A system of practical medicine. By American authors. Vol. 1 (part 4 of 8)

A system of practical medicine. By American authors. Vol. 1 (part 4 of 8)

It appears that conditions of destitution, filth, and intemperance amongst an overcrowded population favor the development of the virus, and hence the epidemics have, as a rule, begun in towns, such as Dublin, Glasgow, Odessa, St. Petersburg, Breslau, etc., where such conditions prevail. Great importance has been attached, in particular, to the scarcity of food and to destitution as powerful factors in favoring the production of the disease. Some of its names (hunger-pest, hunger-typhus, famine fever) have been given with reference to this, and in the case of several outbreaks a careful comparison has been made of the decrease of the food-supply and the consequent advance in price of the staple commodities with the development and progress of the disease. Although this is in all probability true of those centres where relapsing fever originates, it has but a partial application to the secondary centres where the disease is imported and develops.

The presence of destitution and filth, enfeebling the vitality of a section of the community, would favor the spread of this as of any other specific fever, but there is considerable evidence to favor the view that the importance of starvation as a cause of the fever has been exaggerated. This was strongly urged by Parry[5] as the result of his study of the {371} Philadelphia epidemic of 1870, and our own more extended observation showed that the vast majority of the patients appeared to be well fed. On the other hand, the influence of overcrowding as favoring the development and spread of relapsing fever has been clearly established by the study of many epidemics, as in the Breslau attack of 1868, reported by Wyss and Bock, where single tenement-houses furnished as many as seventy-one cases; in the Edinburgh epidemic of 1869 and 1870, where Muirhead found the breathing-space allotted to each individual in the affected houses to vary from 250 to 400 cubic feet; and in the Philadelphia epidemic, where the observations of Parry and ourselves showed the presence of an extreme degree of overcrowding in most of the houses where the disease broke out.

[Footnote 5: Loc. cit., p. 339.]

No age is exempt, but neither can it be said that age exerts any influence upon the occurrence or frequency of relapsing fever. Of 1164 cases in the Philadelphia epidemic of 1869-70 in which the age was noted, the result was as follows:

Males. Females. Under 20 149 76 From 20 to 30 220 140 From 30 to 40 143 101 From 40 to 50 135 67 From 50 to 60 60 34 From 60 to 70 20 6 From 70 to 90 6 7 --- --- Total 733 431 = 1164

The youngest cases were in children two or three years old; the oldest patients were women over eighty-five years old.

Sex exerts no influence, though, on account of the larger proportion of males likely to be exposed to the specific cause, the results of nearly all epidemics show a preponderance of male patients in the proportion of 33 per cent., 66 per cent., or even 85 per cent. (Meschede).

Nationality does not act as a predisposing cause,[6] except in so far as certain countries may present more frequently than others the conditions favorable for the development of this disease. Of 1170 cases in Philadelphia in which the nativity was noted, 219 were Irish, 61 English, 161 German, 729 American. Of the latter 729, about one-half, or nearly 28 per cent. of the whole number, were negroes, while the negro population of Philadelphia was only about 3.3 per cent. of the total. This excessive proportion of cases among the negroes was undoubtedly due in large part to the fact that in Philadelphia overcrowding is notoriously more common and extreme among them than in any other portion of the population, although it is also likely that they present an excessive susceptibility to the virus of this as of many other specific diseases.

[Footnote 6: Hirsch's Geog. and Hist. Pathology, New Syd. Soc. ed., 1883, vol. i. p. 615.]

Attempts have been made to show some connection between the period of the year or the atmospheric conditions and the rise and spread of epidemics of relapsing fever; but, as Murchison clearly showed, these epidemics are wholly independent of such influences. In Philadelphia, of 1176 cases in which the date of occurrence is known, there occurred in September, 1869, 4 cases; December, 1869, 6 cases; January, 1870, 5 cases; February, 1870, 13 cases; March, {372} 1870, 124 cases; April, 1870, 209 cases; May, 325 cases; June, 293 cases; July, 115 cases; August, 19 cases; September, 28 cases; October, 15 cases; November, 1 case; December, 2 cases; January, 1881, 2 cases; February, 1 case; March, 2 cases; May, 7 cases; June, 2 cases; September, 2 cases; October, 2 cases.

Occupation exerts no predisposing influence, but in all epidemics the great majority of cases occur among the vagrant classes, who lead a precarious life and commonly sleep in foul, overcrowded lodgings. Murchison noted that in the London epidemics a considerable proportion of cases occurred among recent residents, but he attributed this, correctly, not to any special local cause, but merely to the fact that this floating population is largely of the vagrant type. In Philadelphia a careful inquiry showed that recent residence produced no special predisposing influence, and a study of other epidemics confirms this view.

Contagion is, however, the essential cause of the spread of relapsing fever when the virus has once been developed. It seems clear from the distinct periods and from the widely-separated localities in which different outbreaks of relapsing fever have occurred that its special poison is capable of being called into existence or activity by favoring conditions. Murchison held the belief that it was very intimately connected with, if not generated by, destitution, and, as already stated, much evidence exists to show that the disease is most apt to break out after periods of scarcity; but no just and convincing proof exists that destitution, any more than over-crowding and other depressing influences, can actually engender a specific contagium capable of being transported to great distances and of originating widespread outbreaks of the specific disease among differently situated populations. It appears necessary to assume the existence of some unknown special virus which finds its suitable nidus for development in the conditions attendant on filth and overcrowding, and which attacks with greatest facility the systems of those who are enfeebled by want and depressed by vitiated air. When once this specific poison has been called into active existence, however, there can be no doubt as to the fact that it can be carried by fomites, and that it is given off from the bodies of relapsing-fever patients so as to affect any who may approach. Although a few observers have doubted this contagiousness of relapsing fever, the evidence in its favor is overwhelming. In many epidemics, as in Philadelphia in 1869, its contagiousness is at least as intense as that of typhus fever. A single case may, indeed, be admitted to a healthy family among the better classes or into the wards of a well-ventilated hospital without propagating the disease, although striking cases of contagion are on record where a patient has communicated the disease to all the members of a family favorably situated and living at a distance from any other possible source of contagion. On the other hand, if admitted to an overcrowded and filthy lodging the disease is apt to spread rapidly. Wyss and Bock report seventy-one cases as having occurred in a single lodging-house during the course of the Breslau epidemic of 1868, and in Philadelphia single houses in several instances furnished more than a score of cases, and several short streets more than one hundred cases each.

In the Philadelphia Hospital twenty-three persons lying sick in the wards with other affections contracted relapsing fever from the patients {373} admitted with that disease; two of the visiting staff, five resident physicians, and nine nurses also suffered attacks of varying severity. This corresponds with the general experience of those connected with fever hospitals during the prevalence of relapsing fever.

As in the case of typhus and other contagious diseases, the distance at which relapsing fever can be contracted by direct contagion through the atmosphere is a very short one, not exceeding a few feet at most.

The poison may be carried by fomites. Instances are on record where persons having visited infected districts have conveyed the disease to others at a distance without contracting it themselves.

When rooms which have been occupied by relapsing-fever patients are subsequently occupied by other persons, these are very liable to acquire the disease. Parry relates two remarkable cases in which relapsing fever was transported to a distance by infected clothes; and it has been more than once observed that during epidemics of this disease laundry-women engaged in washing the clothes of fever patients, but without any means of more direct communication with the sick, were frequently attacked (Cormack, Wyss and Bock).

In connection with the etiology of relapsing fever it is necessary to consider the rôle played by a minute organism which has been frequently detected in the blood of patients suffering with this disease. This spiro-bacterium was first observed in relapsing fever by Obermeier[7] in 1873, and has since been identified as a spirillum or spiroechete. The very numerous observations of Obermeier, Albrecht, H. V. Carter, Motschutkoffsky, Koch, Cohen, Holsti, Enke, Meschede, and others leave no doubt that this peculiar parasite does occur at least very frequently in the blood of patients with this disease. The failure to detect it, which has been reported by several good observers, may readily have been due to the extreme delicacy of the organism, or to the neglect of the proper method of preparing the slides of blood for examination, or to delaying the examination of the blood until after death, when it rapidly disappears. Thus no value can be attached to the negative observations of Rhoads and myself, made prior to Obermeier's discovery, since our method of examination was not sufficiently exact.

[Footnote 7: Centralbl. f. die med. Wissensch., 1873, No. 10.]

The following description of the mode of examining the blood, and of the spirillum, is condensed from H. V. Carter's account: It is necessary to employ magnifying powers of not less than 500 diameters. The fresh blood may be examined immediately after obtaining it by pricking the washed finger of the patient. For preservation dried specimens are needed: a very thin layer of fresh blood is evenly spread with the needle over the glass cover, exposed to the weak fumes of a solution of osmic acid, and allowed to dry under protection from dust; the dried film of blood may then be treated with glacial acetic acid or may be stained.

The spirillum [See Fig. 19] is a colorless, slender, twisted filament, which when quiescent has a length of 2.66 times the diameter of a blood-disc (1/1500 to 1/500 inch = 0.012 to 0.043 millimetre). When unfolded they become distinctly elongated. They are very narrow (not more than 1/40000 inch), and present four to ten spiral turns; when fresh they are in active movement and unfold in part, becoming wavy or bent. They {374} resist the action of concentrated acetic acid, and are readily stained by certain dyes. In number, five or ten may be visible in a field or they may be too numerous to count. They have not been detected either in the secretions or in the evacuations. Both Koch and Carter have succeeded in cultivating this special form of bacteria outside of the body.

To judge from the observations thus far made on this difficult question, the parasite is found first toward the close of the period of inoculation or soon after the beginning of the fever, or it may be detected throughout the febrile stage; but shortly before the cessation of the fever it quickly disappears, to reappear at the time of the relapse. There would seem, therefore, to be some close connection between the febrile paroxysms and this organism, and it is not remarkable that many observers have concluded that this spirillum is the essential and specific cause of the fever, and that it is impossible to have this disease present without the appearance of the parasite in the blood; nor that the name spirillum fever has been applied to the disease by Carter.

Such conclusions appear to be premature, however, and we prefer to regard the undoubted existence of the spirillum in the blood of relapsing-fever patients as at present only an important aid in diagnosis, and to await the occurrence of other epidemics and the repetition of careful studies upon this organism, both within and without the human system, before venturing to decide whether it is merely one of the phenomena of the disease or whether it is its true cause and specific contagious principle.

It must be added that both Carter and Koch have succeeded in inoculating monkeys with relapsing fever, and Motschutkoffsky[8] of Odessa, who had the opportunity of inoculating a human being, asserts that he succeeded in producing the disease, and found the incubation period to be not less than five nor more than eight days. Carter also gives an interesting table[9] of six instances of inoculation, four of them by cuts while making autopsies, with consequent development of relapsing fever in each instance. Some allowance must be made for the fact that in all the instances of this series there had been exposure to contagion by close communication with fever patients, though this exposure had existed for several months previously without leading to the development of relapsing fever.

[Footnote 8: Centralblatt f. d. med. Wissenschaften, 1876, No. 11, p. 194.]

[Footnote 9: Op. cit., p. 403.]

GENERAL CLINICAL DESCRIPTION.--After a period of not less than five or six days from the reception of the contagion the disease begins {375} abruptly with a chill of variable severity, accompanied by headache and aching pains in the back and limbs. The patient feels weak and is often giddy, but is not always obliged to go to bed the first day. Nausea and vomiting are among the earliest symptoms, and distress at the epigastrium, with tenderness, may attend or even precede the chill. Fever quickly follows; the pulse runs up from 110 to 130 in a few hours; the temperature reaches from 103.5° to 106° by the end of twenty-four hours; the pains increase, and there are insomnia and great restlessness; appetite fails; thirst is extreme; the tongue is moist and furred, and the bowels quiet. During the subsequent six days these symptoms persist. The temperature presents a daily remission at some period of the twenty-four hours amounting to one or two degrees, the maximum reached in fully-developed cases varying from 104° to 108°. The pulse continues very rapid, and not rarely exceeds 140; the respirations are hurried and rapid, and cough attends many cases. Delirium is rare, but insomnia, restlessness, headache, and rheumatic pains in the back and limbs may prove constantly annoying. Appetite is variable, more frequently lost; nausea and vomiting are common; thirst is very troublesome; and the bowels are constipated or loose. No characteristic eruption appears, but sudamina are frequently present, since in a large proportion of cases there is more or less sweating, even during the continuance of high fever. Abdominal pain, tenderness in the epigastrium and hypochondria, and demonstrable enlargement of the liver and spleen are almost invariable. The urine is concentrated and dark or bile-stained. Jaundice is a common symptom, though its frequency varies greatly in different epidemics. The same may be said of epistaxis.

While these symptoms are at their height and the patient is suffering severely the paroxysm suddenly ceases, and in a few hours he is entirely relieved. This remarkable crisis occurs usually at the close of the seventh day, but may occur as early as the third or as late as the fifteenth day. It is attended with a critical discharge, copious sweating being by far the most common, though diarrhoea, free epistaxis, or hemorrhage from some other surface may replace it. The patient feels weak and languid; the temperature and pulse have fallen below the normal, and remain so for a day or two. Soon there is a rapid improvement in the appetite and the appearance of the tongue, and the patient regains strength day by day, and often feels so well that it is difficult to persuade him that he must avoid exertion and exposure. The enlargement of the spleen subsides rapidly, that of the liver more gradually; epigastric tenderness subsides, but in many cases some degree of it persists for several days. This interval or apyretic period lasts about a week, when, again without warning or provocation, the patient relapses, and is seized abruptly with the same set of symptoms which attended the first attack. This relapse does not usually last more than three days (one to five are the limits), and is terminated by a similar crisis, after which a slow convalescence is entered upon, or else after an apyretic interval of some days' duration a second relapse ensues, and this may, in rare cases, be in turn followed by a third, fourth, fifth, or even sixth similar relapse. In addition, it must be noted that many serious complications are liable to occur. The total duration of the disease thus varies from eighteen to ninety days. Convalescence is often tedious, and there are many troublesome sequelæ. {376} The mortality, however, is not great, averaging 5 or 6 per cent. Death may occur suddenly from collapse at the close of the first paroxysm or from heart-clot; it may be produced by exhaustion in protracted cases; or be hastened by any serious complication; or the patient may sink into a typhoid condition, with low delirium, coma, and suppression of urine for several days before the fatal termination.

DETAILED STUDY OF SPECIAL CONDITIONS.--It is usually difficult to determine the period of incubation. In the unique case in which Motschutkoffsky is said to have produced relapsing fever by inoculation the initial symptoms occurred seven days after the inoculation. Wyss and Bock had several good opportunities of determining the minimum period of incubation, and found it to be six days. We may assume that the ordinary period is six to eight days, but that it varies, in accordance with the virulence of the virus or the susceptibility of the system, from four to fourteen days. During this time the patient feels as well as usual, or at most suffers for a day or two from slight malaise, with vague rheumatoid pains, headache, giddiness, and anorexia. In only 13 out of 181 of our cases in which this point is noted was the invasion gradual. Examination of the blood prior to the invasion does not discover any spirilla.

The invasion is usually abrupt and during the daytime; the patient can often fix the very hour of its occurrence, a severe chill attacking him while at work or at meal-time. This is the most common initial symptom (138 out of 168 our cases of sudden invasion); less commonly, obstinate vomiting and nausea or sudden vertigo are the first symptoms (each 8 times out of 168), or violent headache (14 times out of 168), or sharp epigastric pain. Parry also observed that the occurrence of obstinate and profuse vomiting as the initial symptom was especially frequent in children.

The physiognomy is carefully noted in one hundred and seventy of our records. The countenance is often flushed, with watery eyes and anxious, suffering expression. The flush is less dingy and dull than in typhus; the eye is comparatively rarely injected; and the expression is much less dull and stupid than in that disease. In cases where grave nervous symptoms supervene and the typhoid condition is developed the facies assumes all the characteristics of that state.

The livid bronzing of the face, described by Cormack in 1843 and by Carter (Bombay epidemic of 1877), was noticed in a moderate degree in only nine of our cases, and seems to be of infrequent occurrence. When we observed it it seemed due to an admixture of a faint jaundice tinge with a deep flush. Jaundice, as already stated, is of common occurrence, though its frequency varies greatly in different epidemics. It was present in 25 per cent. of our cases, rather more frequently in the negro patients than in whites, and in degree varied from a slight tinge of the conjunctiva and skin to the deepest staining of the entire body. The presence of jaundice in combination with the general features of high fever imparts a most peculiar and alarming appearance to such patients.

With the occurrence of the crisis the flush rapidly subsides and the face becomes pale, or, if the discharges have been profuse, it may appear sunken, haggard, and almost choleraic. Parry described a peculiar puffed, velvety look at this stage, as though the skin had been much thickened and softened at the same time.

{377} There is no characteristic eruption in relapsing fever. In 150 out of 180 cases where the condition of the skin was carefully noted there was no eruption of any kind; in 4 cases there were small roseolar spots, with peculiar subcuticular mottling, which resembled the early stages of typhus eruption, but soon faded away without becoming petechial. A similar eruption was noticed by Murchison in 8 out of 600 cases. It appears from the third to the seventh day of the first paroxysm; it may or may not recur in the relapse, or it may occur then only. Eruptions apparently similar to this have been described by others as quite common in certain epidemics. Carter describes minutely an eruption which was noted in at least 10 per cent. of his Bombay cases, the spots of which were at first small, slightly raised, and pinkish or rose-colored, and which either faded away soon or changed into purplish, more persistent stains. In a valuable report on the Königsberg epidemic of 1879-80, Meschede[10] remarks that roseola was observed in cases complicated by exanthematic typhus, which prevailed simultaneously, but in no case of uncomplicated relapsing fever. While, however, this suggestion may apply to some few of the cases of eruption observed by others, it is certainly inapplicable to the vast majority of them. We also noticed an eruption of pale-reddish, slightly elevated papules in seven cases. It must be borne in mind that persons of such a low class as are the great majority of relapsing-fever patients would naturally be expected to present a variety of cutaneous eruptions from filth or vermin, and that in consequence some of the appearances above described may have been of such origin. It is certain that the bites of either mosquitoes, fleas, or bedbugs may in this disease be followed by persistent reddish papules passing into petechiæ. Apart from this, however, true petechiæ have been quite common in some epidemics, while very rare in others. Parry saw "small spots of purpura" once only, in a delicate girl; and we did not observe petechiæ once in several hundred cases, many of which had extensive internal ecchymoses. On the other hand, they have been found in as much as 30 per cent. of all cases (314 out of 1000 cases, Smith at Glasgow). They do not appear on any fixed day, but are more common in the first paroxysm than in the relapses; and although sometimes associated with a tendency to hemorrhages from other surfaces, they have been so often observed in cases of ordinary severity that scarce any unfavorable prognostic value can be attached to them.

[Footnote 10: Virchow's Arch., Bd. lxxxvii., p. 405.]

Vibices and extensive ecchymoses of the surface are of much more grave import, and in cases where fatal sinking is threatened they may appear accompanying a purplish lividity of the countenance.

Herpetic eruptions about the mouth or nostrils were observed in 20 out of 181 of our cases in which this point is noted. They appeared usually toward the close of the febrile stage, and their development was found to have value in determining the approach of the crisis. Bärensprung mentions especially the occurrence of herpes labialis in cases of irregular relapsing fever which bore considerable resemblance to typhus. Sudamina are, as might be expected in a disease attended with so much sweating, of quite common occurrence, though much more so in some epidemics than in others, unless searched for with greater care by the one set of observers. Desquamation was noted in 42 out of 181 of our cases, and {378} invariably at the close of the relapse. It was usually confined to the hands and face, and occurred in the form of comparatively small flakes. This is more frequent than has been the case in most epidemics. Murchison quotes a case in which a piece of epidermis ten inches square separated from the body of a lad convalescent from relapsing fever.

A peculiar odor exhaling from patients with relapsing fever has been repeatedly noticed. A description of this unpleasant symptom, given by Kelly, as quoted by Murchison,[11] accords closely with what was frequently manifest in our own cases: "The smell was peculiar, not fetid or heavy, but somewhat like burning straw with a musty odor." Carter, in describing a similar odor in some of his cases, notes that the skin was not in these instances in a particularly foul state.

[Footnote 11: Op. cit., p. 346.]

From what has already been said, it will be anticipated that the variations of the temperature in relapsing fever constitute the most peculiar and characteristic feature of that disease. A careful study of the accompanying charts will convey a more accurate impression than can be given by any description. The temperature begins to rise before the chill is fully developed, and when there is no initial chill the patient may be found within a few hours of the appearance of giddiness and headache with a temperature of 102.5° to 103.5°. Before twenty-four hours have passed it has risen to from 104° to 106°. During the paroxysm the febrile movement is continued, presenting merely a diurnal variation of one to two degrees, sometimes attended with sweating and partial relief of distressing symptoms, the minimum being observed at different hours in different cases, or even in the same case, though more frequently it occurs in the morning.

In a case reported by Parry a chill recurred at the same morning hour on three successive days. Wyss and Bock report some unusual cases in which a brief intermission occurred, with a fall of pulse and temperature to the normal, most frequently on the day before the real termination of the paroxysm. The highest temperature varies from 104.5° to 108.75°; in our cases the highest observed was 107.5°. This occurs, as a rule, on the last day or the day before the last of the initial paroxysm, and Obermeier has observed a sudden rise of four degrees in half an hour just before the crisis. Meschede,[12] however, found the highest temperature on the corresponding days of the first relapse.

[Footnote 12: Loc. cit.]

The duration of the primary paroxysm is usually six or seven days; but this is subject to considerable variations, as will be seen from the following table of 160 cases in which the duration was accurately ascertained: Initial paroxysm lasted--2 days in 1 case; 3 days in 2 cases; 4 days in 10 cases; 5 days in 19 cases; 6 days in 40 cases; 7 days in 58 cases; 8 days in 18 cases; 9 days in 2 cases; 10 days in 5 cases; 11 days in 2 cases; 14 days in 2 cases; 15 days in 1 case; and Parry, observing the same epidemic, found the duration of the first paroxysm to vary from 4 to 11 days. It is, however, rare for the duration to exceed ten days unless some complication be present.

{379} [Illustration: FIG. 20. Typical case of relapsing fever, with three relapses, terminating in recovery. (From Motschutkoffsky)]

With the beginning of the crisis there is a prodigious and sudden fall of temperature, unequalled in any other condition of disease. Within a few hours it may fall six or eight degrees (going down at the rate of 1.5° or 2° an hour); and falls of 12°, 13°, or even 14.4° (Murchison), in the course of twelve hours have been noted. In our own cases the greatest {380} fall was from 107.2° to 95°, or 12.2°; and this is as low a point as is usually reached, though temperatures of 94°, 93°, or even 92°, have repeatedly been observed. Murchison refers to one case in which collapse supervened, where the rectal temperature was 90.6°. In nearly all of our cases a subnormal temperature occurred at the crisis, and lasted for a day or two subsequently, when it gradually rose and remained normal until the relapse, unless some transient complication caused a temporary rise in the interval.

Occasionally, there is no relapse whatever, but convalescence follows {381} the initial paroxysm. This occurred in 10 out of 181 of our cases, and Murchison found that of 2425 cases reported by various authors no relapses occurred in about 30 per cent. Carter describes these under the name of the abortive form, and found them to constitute 23.8 per cent. of all his cases. It is probable, however, that in many cases so regarded either a relapse of very transient duration has been overlooked, or else that an attack of ephemeral fever has been regarded as of specific nature. In ordinary cases the duration of the intermission averages six or seven days, but here, again, considerable variation occurs. In 139 of our cases where its duration could be accurately determined it was as follows:

3 days in 4 cases. 7 days in 64 cases. 11 days in 1 case. 4 " " 3 " 8 " " 22 " 12 " " 1 " 5 " " 12 " 9 " " 9 " 13 " " 1 " 6 " " 12 " 10 " " 9 " 20 " " 1 "

Despite these variations in the duration of the initial paroxysm and of the first intermission, the average date of the occurrence of the relapse in any large series of cases is about the twelfth day from the primary chill.

The relapse is ushered in with the same striking abruptness as the initial attack. The temperature again rises rapidly to 104° or 106°, and then pursues a continuous course resembling ordinarily that of the primary paroxysm. The difference between the maximum of the two paroxysms is rarely more than 1.5° or 2°, though either may be much milder than the other; as a rule, the highest temperature is attained on the last or penultimate day of the first attack. The duration of the relapse averages three or four days, though it may last but a few hours or a single day, and yet exhibit a rise of 5°, 6°, or 7°; or, on the other hand, it may be prolonged to six, seven, or even more days. Lyons, observing the disease in the Crimea, reports some relapses as having lasted twenty-one days, though it is improbable that a greater duration than seven days occurs without the presence of some complication. The relapse usually terminates by crisis, with an abrupt fall to an abnormally low temperature; though we observed at this time, much more frequently than at the close of the first paroxysm, a gradual subsidence of fever, or lysis. Again the patient regains strength and appetite, but in a considerable proportion of cases subsequent relapses ensue. As a rule, the second, third, and later relapses are attended with a febrile movement of shorter duration and of less severity than the first two paroxysms, and are also separated by intermissions of increasing length. Meschede[13] found from a study of 360 cases that the average duration was for the first paroxysm six or seven days; second paroxysm, four or five days; third paroxysm, three or four days; fourth paroxysm, one or two days; fifth paroxysm, one day.

[Footnote 13: Loc. cit.]

In a remarkable case given in full at page 394, the duration of the paroxysms and intermissions were as follows:

First paroxysm, 8 days; first intermission, 9 days. Second " 5 " second " 1 " Third " 1 " third " 6 " Fourth " 6 " fourth " 8 " Fifth " 5 " fifth " 9 " Sixth " 4 " sixth " 10 " Seventh " 3 " seventh " 11 " Eighth " 3 " followed by convalescence.

{382} The proportion of cases in which more than a single relapse occurs appears to vary in different epidemics. Murchison found that in 1500 cases reported by various authors a second relapse occurred 109 times (1 out of 14); a third relapse, 9 times (1 out of 166); and a fourth relapse, once. Of 182 cases noted carefully by ourselves, a second relapse occurred 24 times (1 out of 7-1/2); a third relapse, 5 times (1 out of 36); a fourth relapse, once; and in the above-mentioned case six or seven relapses.

It follows that the total duration of the morbid process varies from the average of about eighteen or twenty days, in cases with a single relapse, to forty, sixty, or even ninety days. Of course the occurrence of complications may lead to very great modifications of the febrile movement and of the total duration of the disease.

There are several additional points about the febrile process requiring mention. In all the paroxysms there is a greater tendency to local or general perspirations than is met with in other continued fevers, and occasionally there are rigors or slight chills about the same hour on several days after the invasion or on the day preceding the crisis. It has been noted also that, even when the temperature is very high, the quality of the heat, as judged by the feeling of the skin, is different from that in typhus fever, and that the peculiar pungent irritating sensation known as calor mordax is rarely marked. But a more important peculiarity is the fact that the extreme temperatures (106°, 107°, or 108°) that are frequently observed in relapsing fever for several days in succession do not appear to involve any great increase of danger, and in particular are not attended with the production of the grave nervous symptoms so often met with in connection with hyperpyrexia in typhus and typhoid, and often regarded as the direct result of the exalted temperature itself. This striking fact is of much interest in its bearing on the theory of hyperpyrexia, and may possibly be explained by some marked difference in the conditions of heat-dispersion in these different diseases.

The pulse in relapsing fever is very rapid, and on the whole the rate corresponds with the movement of the temperature. It usually rises above 110, the limits being 90 and 140, the lower rate being noticed in the milder and uncomplicated cases and in subjects of phlegmatic constitution. The pulse rises rapidly at the invasion, and may reach 120 in the course of a few hours. Its maximum is usually noticed when the temperature is highest, shortly before the crisis; and when this actually begins the pulse may fall with a rapidity as remarkable as that of the decline of the temperature. Thus, within twenty-four hours it may fall from 152 to 80, or in even a shorter time from 140 to 54, or even as low as 48 (Obermeier) or 44 (Muirheid), or even 30 (Stillé). While this great fall is often noted, it is by no means constant. In our own cases it was frequently observed that the critical fall in temperature was not accompanied by a commensurate fall in pulse. Thus, at the close of a very severe initial paroxysm lasting nine days the temperature was 107°, and fell in the course of twenty-four hours to 99°, and in twenty-four hours more to 96°; during the first day of this fall the pulse was from 96 to 100, and during the second it fell to 76.

This want of correspondence was more marked at the close of the {383} relapse than of the primary attack; thus, in a well-marked case, where the maximum temperature (105.4°) occurred eighteen hours before the crisis of relapse, the temperature fell in four hours from 104.4° to 96.2°, while the pulse, which was 130, fell in twelve hours to 108, and in twelve more to 92. In another case, in a man aged twenty, the temperature at the close of the second relapse was 106.4°, with a pulse of only 100; after the crisis, as the temperature fell, the pulse rose to 120, and did not descend until the end of twenty-four hours; and later, at the close of thirty-six hours, the temperature was 98° and the pulse 72, lower than which it did not go. Carter[14] states that in the Bombay epidemic it was invariably the case that the pulse did not decline to an extent corresponding with the temperature.

[Footnote 14: Op. cit., p. 140.]

During the remainder of the intermission the pulse may be normal, or it may continue accelerated in consequence of some irritative condition; as the time for the relapse approaches it frequently again becomes abnormally slow. In either event it is found that any muscular exertion causes marked acceleration of the pulse.

During the paroxysm the character of the pulse is full and bounding, and there is considerable arterial tension. This is well shown in some of the sphygmographic tracings by Carter;[15] while in one of our tracings from the right radial of a man æt. 32, taken on the fourth day of a severe initial paroxysm, the line of ascent is steep and the summit sharp. During the crisis, and for a day or two thereafter, the pulse may be weak, compressible, and dicrotic, and occasionally irregular.

[Footnote 15: Op. cit., p. 103.]

The sounds of the heart and its impulse are weakened, except possibly during the first few days of the primary paroxysm. Blood-murmurs over the base of the heart and along the great vessels in relapsing fever were first noticed by Stokes, and have been frequently observed in subsequent epidemics. They were found in a large proportion of our cases, not rarely in both paroxysms, and during the early stage of convalescence when anæmia was marked; but during the intermissions they are rarely audible, and when the action of the heart was slow they were replaced by prolongation of the first sound.

It must be further noted that the pulse-rate is not a reliable indication of the danger in this disease, since, just as is the case with the hyperpyrexia, extreme rapidity of pulse may be present when the general symptoms denote no unusual danger, and when the patient ultimately recovers most satisfactorily.

There is a remarkable disproportion and dissimilarity between the cerebral and peripheral nervous phenomena in relapsing fever and those familiar to us in typhus and typhoid fevers. We have seen that patients almost invariably complain of headache. When prodromes are present it is commonly among them, and it may be the initial symptom to usher in each paroxysm. When the attack is fully developed headache is usually very severe, and no symptom is more bitterly complained of. It varies in seat and character. More commonly it is frontal or general; occasionally we found it occipital, and still more rarely it was unilateral, constituting hemicrania. It rarely continues during the relapse. Headache of an equally acute and violent character may be present in typhoid, but the headache of typhus is much more dull and contusive.

{384} The mental condition is only exceptionally affected, a circumstance which greatly increases the patient's perception of his sufferings. Delirium is not present in ordinary cases, even though very severe and attended with hyperpyrexia; or if present is limited to the period immediately preceding the crisis, when there may be violent and noisy delirium of transient character. In some of our cases forcible restraint was necessary under these circumstances.

There are numerous instances on record showing the abruptness with which noisy, demonstrative, or even destructive delirium may appear, and the equal suddenness with which in the course of a few hours, or even of fifteen minutes, the patient may become rational and composed. Such attacks resemble hysteroidal spells, and probably occur more readily in patients of a nervous or hysterical temperament. They were certainly more common when the patients had been of intemperate habits; and, further, we had opportunities of noting that the occurrence of relapses in habitual drunkards who had previously suffered with delirium tremens was apt to develop a form of delirium which was to all appearance of that nature.

Delirium of a different and much more grave type may appear in connection with the symptoms of the typhoid state. In some cases this results from the presence of serious complications which induce a state of great prostration, while in others it is associated with great diminution or entire suppression of urine. The delirium under these circumstances is apt to be low and muttering, with a tendency to pass into stupor or profound coma.

Vertigo is present more frequently and in a more persistent form than in any other febrile disease. It was noticed as among the occasional prodromes, and was especially severe for the first few days of the initial paroxysm, though it often continued throughout this stage and recurred with the relapse. Occasionally it was complained of in the recumbent position, but usually it was excited only by a change of position.

Wakefulness was one of the most distressing symptoms in all cases, and appears to have been noted in all epidemics. Although the severity of the pain in various parts of the body and the absence of blunting of the perceptions would naturally cause much loss of sleep, the degree of the insomnia and the obstinate resistance it offers to the action of anodynes are apparently far in excess of what could thus be accounted for. Parry found that several of his patients could take as much as three grains of opium every second hour throughout the afternoon and night without either inducing sleep or causing contraction of the pupils.

Convulsions are rare and of very grave import. They may occur at the period just preceding crisis, when the nervous irritation is most intense, and are then somewhat less indicative of a fatal result than if occurring in the course of the paroxysm, when they are apt to be associated with extreme prostration of the nervous centres, with a tendency to subsequent fatal coma. No connection has been observed between their occurrence and the presence of albumen in the urine.

General tremor is rare, and was observed only in those of our cases where there had been habitual intemperance, with presumably a tendency to delirium tremens. Muscular rigidity was noticed occasionally, but may have been only apparent, being induced by the hyperæsthesia and {385} soreness which were marked in some cases. The hyperæsthesia which was observed was both cutaneous and muscular, and was attended with tenderness of the body of the muscle, and also of the nerve-trunk supplying it. Meschede speaks of opisthotonos as a rare complication in his cases.

Motor paralysis involving single muscles or groups of muscles is occasionally noticed, as of the deltoid or of one arm (Meschede). Parry observed transient loss of power of the extremities in several cases, chiefly during the intermission or the period of convalescence. In one of our cases temporary hemiplegia occurred, with partial loss of sensation on the affected side.

The bladder and rectum are rarely affected, except in cases where the typhoid state with tendency to coma is present. Disorders of sensation are, however, much more common. When motor palsy occurs the affected part may also be the seat of impaired sensibility, while in a large proportion of all cases numbness of the extremities, with or without a sense of tingling, is complained of; out of 182 cases we noted this symptom in 94, affecting the fingers alone in 62, the feet alone in 6, and all the extremities in 25 cases. Cutaneous hyperæsthesia or partial anæsthesia are also occasionally observed. But the most noteworthy and constant symptom of this class are the pains in the muscles and joints which are bitterly complained of by nearly all patients with relapsing fever. They constitute, indeed, one of the highly characteristic features of the disease, and possess a diagnostic value. They may occur among the rarely present prodromes, but usually they appear with the chill and increase in intensity during the paroxysm; they may persist with even greater severity during the intermission, or, if they have then subsided, recur with the relapse, and may constitute one of the most troublesome hindrances to convalescence. It will thus be seen that in frequency, severity, and persistency they differ widely from the aching pains in the extremities complained of in typhus and other specific fevers. They are one of the most potent causes of the extreme insomnia, and are apt to dwell in the mind of the patient so vividly that he dreads each relapse on this account, and consequently looks back upon his attack of relapsing fever as a terribly painful experience. These pains are usually described as rheumatic in character, and several times patients presenting themselves at the hospital on the second or third day of the initial paroxysm stated that they had inflammatory rheumatism. As a fact, we observed the utmost intensity of these pains in a few cases where the patients were of marked rheumatic diathesis. The nape of the neck, the muscles of the trunk or extremities, or the large or small joints, or lower parts of the spinal region, may be the seat. At times they extend along the course of nerve-trunks. In character they are described as a deep intense aching, with occasional severe or excruciating, sharp, lancinating pains. Pressure or movement increases them. The joints are not red or swollen (though swelling may appear as a sequel), and the pains seemed to us rather to be referred to the joints than to be caused by any local irritation therein. As already stated, there is often tenderness of the body of the muscles, and this was especially marked in many of our cases on pressure along the course of the nerve-trunk.

Murchison suggests that they are due to the circulation in the blood of an {386} abnormal substance, such as uric, lactic, or phosphoric acid; but it appears to us altogether probable that they are rather to be connected with states of congestive irritation of the sheaths of the nerve-trunks (early stage of perineuritis), or possibly in some cases of the spinal membranes also. It is true that they are sometimes shifting in their seat and fluctuating in their severity, but this is not inconsistent with the above suggestion, while the widespread irritative processes found in this remarkable disease, the resemblance of these pains and the frequently attendant numbness and tingling to the sensations caused by other forms of perineuritis, and the occasional development of local palsies of a single muscle or group of muscles, all are in its support.

The special senses are acute, sometimes painfully so. The eyes are watery and occasionally injected, but this latter condition is rare and slight in relapsing as compared with typhus fever. At the crisis and for a few days subsequently wide dilatation of the pupils is not infrequently observed. Dulness of hearing was present during the paroxysm in 14 of our cases, and a few patients complained of tinnitus; but these symptoms are not at all common in the disease, although it will be seen hereafter that affections of the middle ear are among its sequelæ.

Debility is not such a prominent symptom as in typhus and typhoid fevers. Patients manage to drag themselves about for several days during the initial paroxysm with all the symptoms fully developed, and after admission to the hospital will often be able to help themselves, or even to rise from bed, unless prevented by the severe pains or the vertigo. Still, there are many cases, not necessarily of very grave type, in which there is a marked sense of weariness and exhaustion, and of course in all cases of typhoid character the prostration is great. It must constantly be borne in mind that even when the patient feels or seems able to sit up he must on no account be permitted to do so, since the occurrence of sudden and fatal syncope is one of the accidents constantly to be apprehended. It is not only during the pyrexia that this precaution must be enforced; we meet with extreme debility during the intermission in some cases, and syncope has followed exertions made at that period as well as at others.

During the paroxysms the respirations are much accelerated, at times to a greater degree than would correspond with the pulse-rate, while at others extreme rapidity of pulse may be associated with moderate elevation of the rate of respirations.

As examples of the relation between temperature, pulse, and respirations we quote the following from our records of adult cases:

(a) Temperature, 108°; pulse, 124; respiration, 40. In the relapse; no chest trouble.

(b) Temperature, 107.5°; pulse, 120; respiration, 28; falling to temperature, 96°; pulse, 68; respiration, 18, within twelve hours, during which crisis occurred.

(c) Temperature, 107°; pulse, 144; respiration, 31. In the relapse.

(d) Temperature, 107°; pulse, 108; respiration, 44. Initial paroxysm; no pulmonary congestion.

Temperature, 106°; pulse, 116; respiration, 28. Relapse; no pulmonary congestion.

Temperature, 97°; pulse, 76; respiration, 24. Critical fall; cough, {387} congestion of lungs posteriorly, and left one relatively dull on percussion, but pneumonia did not develop.

In many epidemics bronchitis, hypostatic congestion, and pneumonia are of rare occurrence, while in others, as in Philadelphia in 1870, they are comparatively frequent and lead to serious respiratory symptoms. While the pyrexia was high there was very frequently an irritative dry cough, with the fine crepitant and subcrepitant râles attending congestion and imperfect expansion of the lungs heard at the middle and lower portions of the chest posteriorly. In numerous instances the râles would disappear entirely after a few full inspirations in the sitting posture, just as in the corresponding condition in typhoid fever. But in a considerable proportion of all the cases (fully 35 per cent.) there was more troublesome bronchial cough, associated with sonorous, sibilant and subcrepitant râles, with mucous or muco-purulent expectoration.

Bronchitis of this character was a source of serious annoyance to many patients. In several cases there was impaired resonance at the lower margins of the lungs posteriorly, with imperfect bronchial respiration, but without the symptoms of fully-developed pneumonia. Such conditions were regarded as due to hypostatic congestion, and proved amenable to treatment. Pneumonia occurred in eleven cases out of 200 recorded with reference to this complication. It will be more fully discussed under the head of Complications. It was attended with the usual physical signs, and gave rise to extremely rapid and labored breathing, especially when associated with painful enlargement of the liver and spleen. In a case of double pneumonia, with enlarged and ruptured spleen, the respirations were from 80 to 90 for two days, the pulse being 130 to 136. It was a very fatal complication, death resulting in all but two instances.

Leyden[16] has shown that though the percentage of carbonic acid in the air expired during the pyrexia is diminished, the total quantity exhaled is increased, the proportion being as 1.5 to 1 in the non-febrile state.

[Footnote 16: "U. d. Resp. in Fieber," Deutsch. Arch. f. klin. Med., 1870, 536, quoted by Murchison.]

Elaborate investigations have been made of the condition of the urine in relapsing fever by numerous observers, and in the Philadelphia epidemic of 1870 we had the great advantage of being assisted by the distinguished chemist, the late Horace B. Hare, who conducted an extensive series of analyses in our cases. In a number of cases quantitative analyses were continued daily throughout the entire course of the disease.

As a rule, the quantity of the urine is comparatively free during the febrile periods, very scanty at the time of crisis, except in the cases where critical discharges of urine occur, and excessive for some days after the crisis.

Still, there were not rare exceptions, especially to the first of these statements. Thus on four successive days of the relapse of a severe case with delirium, but without albumen, and which ultimately recovered, the analysis gave--

Temperature. Amount in ccm. Sp. gr. Urea in Grm. Na. Cl. 103 400 1024 23.8 2.64 105 300 1025 15.27 1.95 106 500 1024 24.7 4.3 106 to 97 850 1021 24.735 5.525

{388} And in another severe case, also resulting in recovery, the analysis was, for two days preceding the crisis of the initial paroxysm--

Amount. Sp. gr. Urea. Na. Cl. 500 1014 12.9 Traces of albumen. 650 1014 15.85 1.365

After the crisis:

2250 1004 18.9 15.75 No albumen.

And again, in another case at the height of the initial paroxysm, within twenty-four hours of the crisis, no vomiting, purging, or epistaxis being present; temperature 105°; only 500 ccm. was passed of dark reddish colored urine, non-albuminous, and with sp. gr. 1011.

In a fatal case there was total suppression of urine for three days, the catheter drawing off only a few drops of almost pure liquid blood.

When crisis occurs by copious urination the discharges are frequent, large, and of light color and low specific gravity.

The urine of the intermissions is of similar character, and for several days after crisis it is not rare to have 2000 to 2500 ccm. passed. The largest amounts we noted were in a man who recovered, and who passed at the crisis of the relapse and during the following days the amounts here given.

Amount. Sp. gr. Urea. Na. Cl. 1000 ccm. 1010 14.9 2.6 2000 " 1003 20.2 42.8 3550 " 1002 26.625 130.995 2600 " 1002 19.24 27.30 2800 " 1005 24.96 22.66 2500 " 1013 47.25 11.25 2700 " 1014 59.13 7.29

Carter reports a case where the patient continued for two weeks after the relapse to pass 130 oz. of sp. gr. 1002.6.

The amount of urea varies considerably, and is evidently under the influence of complicated conditions. The rule appears to be that it increases during the paroxysms, diminishes during the crisis, increases during the few days following crisis, and then falls off again. These results are stated upon the authority of Murchison, quoting from Pribram and Robitschek, Wyss and Bock, and others. Our own observations, however, while agreeing in the main with these, show that there are numerous and important exceptions, especially to the occurrence of the post-febrile increase in the elimination of urea.

The largest amount of urea excreted in twenty-four hours by any of our patients was 59.13 grammes, or 912 grains, on the sixth day after the end of the relapse, but as much as 74 grammes (1142 grains) have been found.

Deposits of urates were very common in the urine of the paroxysms and of the crisis. The uric acid has been found increased, and so also have the phosphates, crystals of which are frequently found mixed with the urates.

The chlorides diminish during the paroxysms, until just before the crisis their amount is very small, or they may even have disappeared. Immediately after the crisis they reappear slowly or quickly, and even {389} very large amounts may be discharged, as seen in the figures given by Hare's analyses: 2.6 grm. on day of crisis, 42.8 grm. the following day, and the enormous amount of 130.995 grm. on the next day. A copious flow of urine corresponds with great augmentation in the amount of the chlorides.

Bile-pigment was constantly present in jaundiced cases, the amount being proportioned to the depth of the jaundice and the quantity of the urine. Bile-acids have been detected (Carter and Schmidt), and also leucin and tyrosin (Pribram and Robitschek).

Albumen, with or without tube-casts, is not uncommonly found, and traces of sugar have been detected in a few cases. More careful consideration will be given to these under the head of Complications.

The following appearance of the tongue has been repeatedly described, and when present may be regarded as possessing some diagnostic value: The body of the tongue slightly swollen, so as to show the impressions of the teeth, and by the second day the central part of the dorsum covered with a peculiarly white fur, while the edges and a small triangular space at the tip are clean and red. Such a tongue was seen in many cases at the beginning of the Philadelphia epidemic, but later it was present in but a small proportion. We find it specially mentioned in 97 of our recorded cases, or about 50 per cent., the general description being given that it was moist, rather large, with pink, clear edges, and a triangular clear space at the tip, and with heavy white fur in the centre.

Some accurate observers, as Wyss and Bock, did not notice anything peculiar about the tongue, but merely described it as moist and coated with a thick white fur. The tongue often remains moist throughout the case, the coat becoming yellowish, and later brownish. Of course if there is nasal obstruction from epistaxis or catarrh, and the patient breathes through the mouth, the tongue will soon become dry and brown; but in addition, this state of the tongue with sordes on the teeth and lips, appears in a small proportion of cases (3 per cent., Zuelzer; 12 per cent. of our own patients) in conjunction with grave typhoid symptoms.

During the intermissions the tongue clears off quite rapidly, unless marked gastric disturbance persists, but regains its former state as soon as the relapse occurs.

In rare cases the tongue is red and glazed, and Parry and ourselves observed peculiar painful cracks continuing obstinately after the relapse. It is apparent, therefore, that the tongue presents evidences of vitiated secretions, of local catarrh of the buccal mucous membranes, and of the high grade of gastric irritation so constantly attendant on this disease.

As a rule, there is complete anorexia during all of the febrile paroxysm, while in the intermission the appetite soon returns, and is sometimes truly ravenous. We did not, however, observe in any case a voracious appetite during the febrile paroxysms, such as was very often present during the London epidemic of 1843 and the Irish epidemic of 1847, and is particularly mentioned by Murchison.[17]

[Footnote 17: Op. cit., p. 360.]

Thirst is constant and intense, and is excited not only by the high temperature, but by the irritation of the stomach; it may continue through {390} the intermission, when natural appetite and the power of digesting solid food have returned.

Nausea and vomiting are always prominent symptoms, and most especially so in children. In some cases nausea occurs among the prodromes; and occasionally the attack is ushered in by profuse and uncontrollable vomiting instead of by a chill, and the stomach continues entirely non-retentive throughout the paroxysm. Vomiting is not usually so obstinate and severe, however, and with extreme care in feeding and medication it will often be allayed after two or three days. It occasionally recurs profusely immediately before the crisis, as in the case given in full at page 394, where after a violent attack of vomiting the patient fell asleep, and awakened in a profuse sweat.

This symptom was present in 146 out of 182 of our cases, was usually confined to the febrile stages, and was, as a rule, worse in the initial paroxysm.

The matters vomited consist of the ingesta colored with bile, of glairy mucus tinged with bile, or of green bile, sometimes in considerable quantity. Small particles of blood may occasionally be noticed in the matters vomited, and in rare instances true hematemesis occurs. Judging from the frequency with which in fatal cases we find ecchymoses of the gastric mucous membranes with blood-stained mucus in the cavity of the stomach, we should expect black vomit to be more often observed than is the case. Murchison (p. 361) states that it was not noted in any British epidemic except that of 1843, and then it occurred in only a few cases, although it seems to have varied in frequency at different places. Arrott at that time described the symptoms as "quite common" in the fever at Dundee; and W. Reid of Glasgow recorded the case of a girl in the same epidemic who vomited large quantities of clotted blood, and who also had hemorrhages from the bowels and from the ears. It has occasionally been observed in the continental epidemics. It was observed in four of our cases. By all who have observed blood-vomiting in relapsing fever it is recognized as a symptom of almost invariably fatal import. Three of the four cases in which we observed it proved fatal, but one patient, who had copious hematemesis, both at the close of the first relapse and during the second relapse, recovered after a desperate and protracted struggle.

The bowels are not so often constipated as in typhus, and it is not rare for diarrhoea and constipation to alternate, or for the bowels to be loose throughout the paroxysms. They are noted in 181 of our cases as regular in 32, loose in 61, and constipated in 88 instances. Meschede states that diarrhoea was present in nearly one-half the cases of the Königsberg epidemic of 1879, though usually as a late symptom, the early stage being marked by constipation, which in a few cases persisted throughout. The stools may be consistent and dark or thin and bilious, or occasionally, when gastric or intestinal hemorrhage has occurred, they contain black coffee-ground matter. Occasionally, the diarrhoea has a critical character, and occurs at the close either of the initial paroxysm or of the relapse, though it may not entirely substitute sweating. This mode of crisis occurred in two of our cases, but Douglas observed it in 6 out of 33 cases.

The abdomen may appear enlarged, but this is as much the result of the {391} enlargement of the liver and spleen as of gaseous distension, which is rarely present in a high degree. Abdominal pain is almost constant, and may be very severe. It is especially mentioned as having been present in 148 out of 182 of our cases. It commonly extends throughout the epigastrium and both hypochondria, but may be present on one or the other side, while, on the other hand, there may be general abdominal soreness. It is associated with tenderness on pressure, which may be so great as to hinder the movements of the trunk and to render the descent of the diaphragm in breathing painful. This may be the first symptom to usher in the attack, and it occurs at an early stage in most cases. Many of our patients when admitted to the hospital had already been cupped or blistered over the region of the liver or spleen. This distress was greatest in cases attended with jaundice and marked gastric irritation; and Parry reports that in his cases (occurring in the early part of the epidemic which we studied) jaundice was rare (4 out of 37), and abdominal tenderness was not present. It is not difficult to explain its almost universal presence in view of the severe lesions of the substance of the liver and spleen, the distension of their capsules from the acute swelling of the organs, and the implication of the coats of the stomach.

Enlargement of the liver and spleen probably exists to a greater or less degree in every case of relapsing fever without exception. This statement is based on the concurrent testimony of accurate observers in all epidemics and upon the evidence of post-mortem examinations.

The enlargement of the liver can be demonstrated in nearly all instances by careful percussion. It varies greatly in its degree, however; in mild cases it may be slight, while in severe ones the liver may be found extending at least three inches below the margin of the ribs within three or four days from the initial symptom. In our own fatal cases the weight of the liver averaged between four and four and a half pounds.

The spleen enlarges even more rapidly and to a greater degree than the liver. In fact, its enlargement in relapsing fever is greater than in any other acute disease. It may be detected by percussion by the first or second day, and may then continue to rapidly increase until by the fifth or sixth day a large painful mass is readily recognized by palpation and percussion, or even by inspection. The organ often weighs twelve or sixteen ounces, not rarely twenty to twenty-five, and, as an instance of the extreme limit that may be reached, Küttner reports sixty-eight ounces in one case. This enlargement is greatest toward the close of the first or second paroxysm, and subsides quite rapidly in most cases during the intermissions and as convalescence progresses; we have, however, known a moderate degree of enlargement of the spleen to persist for some weeks after the crisis of the last paroxysm.

The occurrence of jaundice in a considerable proportion of cases of relapsing fever is a clinical fact of much interest. Its frequency varies greatly in different epidemics, and even at different stages of the same epidemic. At times it is rarely met with (1 out of 14, 20, or 35 cases), while in other epidemics it is present in 1 out of every 6, 5, or even 4 cases. Of 182 of our own cases jaundice is recorded in 45, or exactly in 1 out of 4. According to our observation, it occurred in a larger proportion of cases among negroes (14 out of 32) than in whites, and {392} Stillé states that it occurred in nearly every such case that came under his observation. When present it usually occurs during the first paroxysm, and may be limited to that stage; or, again, it may be present in each of three or four successive paroxysms in the same case; or, finally, it may first appear in the relapse. As a rule, it subsides speedily after the crisis, though Carter states that in two or three cases the symptom made its first appearance just after the crisis. It varied from the slightest yellow tinge of the conjunctiva to the deepest staining of the whole surface. The urine is discolored in proportion to the intensity of the jaundice, and the serum of a blister will be deeply tinged. It must be carefully noted, however, that the feces are not decolorized, but, as already described, contain fully a normal amount of biliary coloring matter. This fact has been relied on by Murchison and others to prove that the jaundice in relapsing fever is purely dependent on the morbid state of the blood, and is not due to obstruction of the biliary passages; and we are prepared to admit that the element of blood-dyscrasia may play a part in the production of the jaundice. The anatomical evidence, however, given on page 414, renders it probable that in many cases at least the essential cause is to be sought in an obstructed state of the minute gall-ducts of certain areas of the liver. If the main hepatic duct or the common duct were obstructed, there would of course be paleness of the feces, as the bile would be prevented from entering the duodenum. But when a large amount of highly-colored bile is being secreted, as in relapsing fever, it seems clear that the obstruction of a certain number of minute ducts would cause sufficient resorption of the bile to induce jaundice of varying degrees of intensity, while at the same time allowing a flow of bile through the patulous ducts.

Jaundice must be regarded as an unfavorable or even a grave symptom in relapsing fever, but not to the extent that would be the case were it directly connected with the intensity of the blood-dyscrasia. Many of the most violent cases in all epidemics have been unattended with jaundice, while, on the other hand, many cases in which jaundice has been marked "have had not a single symptom that made them differ from ordinary cases excepting the yellowness" (Henderson). It follows, therefore, that the gravity of a certain proportion of the jaundiced cases does not follow directly from the presence of bile in the blood and tissues, but from the lesions of the liver of which the jaundice is a symptom, or from the existence of widespread irritation of many parts of the body. Thus jaundice is present in an unusually large proportion of the cases attended with marked enlargement and tenderness of the liver and spleen, whether vomiting is also present in extreme degree or not. It was noteworthy that it was disproportionately frequent in negroes, and that in these patients the lesions of the liver and spleen were also unusually pronounced. Again, jaundice is present in an unusually large proportion of the cases attended with low delirium, extreme prostration, defective secretion of urine, and the other features of the typhoid state--so much so that such cases have been described by various writers under the name of bilious typhoid fever.

But, as already stated, it is not legitimate to consider the gravity of these cases as the result of the jaundice, but rather that the jaundice is merely a symptom of the widespread irritative lesions, which in such {393} cases not only involve the liver and spleen, but the kidneys, the lungs, the marrow of the bones, the muscle of the heart, and occasionally the membranes or substance of the brain and cord.

The true prognostic value of jaundice in relapsing fever would then seem to be, that of itself it indicates merely an obstructed state of a certain number of minute bile-ducts, but that its presence justifies the apprehension that the local lesions of the liver may become excessively developed, or that there is a tendency to widespread tissue-changes which at a later stage of the disease may lead to the appearance of grave constitutional disturbance of a typhoid type.

Hemorrhage in relapsing fever is not uncommon, and may occur from various surfaces. Epistaxis is, however, the only form which is frequent enough to justify being regarded as a symptom. It usually occurs in from 5 to 15 per cent. of cases of relapsing fever, but in the Philadelphia epidemic it was much more frequent than this, occurring in not less than 83 out of 182 of our cases. It was not more frequent or profuse in grave cases than in those of ordinary severity, and consequently could not be regarded as a reliable indication of the intensity of the blood-dyscrasia. Although ordinarily moderate in amount, it was occasionally so copious and persistent as to require prolonged plugging of the nostrils, and in at least one case contributed chiefly to cause an intense anæmia, which long delayed convalescence. It occurs at all periods of the paroxysms, but more commonly toward the close. In fifteen of our cases extraordinarily profuse epistaxis attended the crisis, and evidently replaced in part the copious sweating by which the paroxysm more commonly terminates.

SYMPTOMS ATTENDING THE CRISIS.--We have already described the aggravation of all the symptoms which immediately precedes the crisis in typical cases of relapsing fever, and the abrupt fall of temperature, and usually of the pulse, that follows. But this extraordinary change is nearly always attended with some profuse critical discharge, of which sweating is by far the most common, though copious epistaxis, metrorrhagia, diarrhoea, or vomiting may also occur, and to a greater or less degree, but seldom entirely, replace the sweating. In 182 cases in which we carefully noted the mode of termination of the paroxysm there was no definite crisis (termination by lysis or gradual and irregular defervescence) in 76; profuse sweating, 89; profuse epistaxis, 15; profuse diarrhoea, 2.

In most epidemics the proportion of true crises is greater than in the above table--a fact dependent upon the unusually severe and complicated form of the disease which we were studying. The beginning of the sweat may be preceded by chilliness or rigors, by extreme and dangerous prostration, or by violent nervous disturbances; or there may be an attack of profuse vomiting, followed by sleep, during which sweating begins. The sweat may be moderate in amount, but is often extraordinarily copious; the patient is literally bathed in it, the bed- and body-clothing is saturated, and we have seen the mattress saturated. It has an acid reaction, but we do not know of any accurate analyses of it. Some writers have attributed to it a characteristic disagreeable odor, but we did not notice any in our cases that could be considered peculiar to this disease.

CONVALESCENCE.--We have already stated the average duration of {394} relapsing fever to be eighteen or twenty days, while the extreme limits are from eighteen to ninety days. Despite the fact, however, that the mortality is in most epidemics only about 5 or 7 per cent.--greatly less, therefore, than in typhus fever--the convalescence from relapsing fever is frequently slow and protracted. The obvious cause is, just as in the case of typhoid fever, the existence of numerous and serious lesions of the solids and the tendency to many troublesome complications and sequelæ. We have, however, seen many instances of rapid recovery of strength and health, even after prolonged attacks with several successive relapses.

The following case is quoted partly on account of the numerous relapses, and the long duration of the sickness:

B. B. Y., medical student, was much exposed to the contagion of relapsing fever in the wards of the Philadelphia Hospital during the spring of 1870, and in May had an attack apparently of this disease, which, however, subsided in four or five days and was followed by no immediate relapse. He continued his attendance at the hospital during the remainder of May and the whole of June; in July took a trip to the South, where there was no relapsing fever prevailing, and after exerting himself for several days during intensely hot weather, he became sleepless and much prostrated. He returned home, and after recovering from the fatigue felt quite well for about a week, until 3 A.M., August 1st, when he was attacked with a severe chill, followed by great insomnia, obstinate vomiting, intense headache, especially in the back of the neck, occasional sweating, violent fever, recurrence of very severe chill the following day at 11 A.M., epigastric and hypochondriac tenderness, decided jaundice, costive bowels, and scanty, high-colored urine. This paroxysm lasted till the morning of August 9th, when severe vomiting took place, followed by sleep, during which crisis occurred by drenching sweat lasting several hours. Appetite and strength soon began to return, though some jaundice persisted, and by August 17th he felt able to drive out a short distance, and retired feeling somewhat fatigued. He awoke with pain in the back of the neck, which continued increasing till 11 A.M., August 18th (second paroxysm), when a severe chill occurred, lasting three hours and followed by the same train of symptoms, including jaundice, which persisted five days, till Aug. 23d, when crisis again occurred by sweating. On the 24th he felt well enough to use slight exercise, which was followed by prostration and by a return of chill (third paroxysm) the next day at 11 A.M., with subsequent headache, fever, irregular sweats, etc., lasting but one day. Again felt well until Aug. 30th, when he was attacked (fourth paroxysm) at 11 A.M. with severe chill, lasting three hours, followed by severe paroxysm, lasting six days, till Sept. 5th, when crisis again occurred by sweating. Again felt well for eight days, until Sept. 13th, when the fifth paroxysm occurred, lasting five days, ending Sept. 18th by critical sweating. This was followed by an intermission of nine days, until Sept. 27th, at 11 A.M., when the sixth paroxysm occurred, lasting four days, and less severe than the preceding ones. This was followed by an intermission of ten days, till Oct. 11th, when the seventh paroxysm occurred at the same hour of the day, and lasted three days. He then went sixty miles from home to a fine, pine-bearing district, and enjoyed an intermission of eleven days, when the eighth and {395} last paroxysm occurred at the same hour, and lasted three days, until Oct. 25th. His convalescence was very satisfactory, and he was enabled to resume his studies by the middle of November. No sequelæ occurred. In 1878 Dr. Y., who had been working very steadily with a rapidly-growing practice, was attacked with severe typhoid fever, with grave nervous symptoms and with albumen and tube-casts in the urine, and died on the twelfth day.

It will thus be seen that in this unusually protracted case there were seven distinct relapses, one of which was brief and interrupted one of the regular intermissions, while the rest were all severe.

Duration of 1st paroxysm, violent, 8 days. 1st intermission, 9 days. 2d " violent, 5 " 2d " 1 day. 3d " less violent, 1 day. 3d " 6 days. 4th " severe, 6 days. 4th " 8 " 5th " severe, 5 " 5th " 9 " 6th " less severe, 4 " 6th " 10 " 7th " less severe, 3 " 7th " 11 days, 8th " mild, 3 " followed by convalescence.

The total duration of the case, which was entirely free from complications, was therefore ninety days.

VARIETIES.--The foregoing clinical description prepares us to appreciate the varieties of relapsing fever that may be said to exist. They consist of--

The abortive form, in which a single paroxysm of variable length and severity occurs, terminating in a critical fall of temperature and usually with some critical discharge, but not followed by any relapse. There can be no doubt of the existence of such cases, although they are not common; and at times the paroxysm is so slight that were it not for the known exposure of the individual to the prevalent epidemic influence, in the absence of any other adequate cause, the case might readily be regarded as one of non-specific febricula. The caution must, however, be borne in mind as to the occurrence of relapses of such extreme shortness of duration (less even than twenty-four hours) as to readily escape notice unless a careful watch be kept for their detection.

The ordinary or typical form, including the cases with one or two relapses, presenting the usual variations in the severity of the symptoms and in the duration of the paroxysms and of the intermissions.

The multiple or protracted form, if it be thought desirable to thus particularize cases presenting an excessive and unusual number of relapses, as three, four, five, six, or even seven.

The grave or subintrant form, which is designed to include the highly congestive form of Cormack and the bilious typhoid of Griesinger and Lebert.

Under another heading (see relations to other diseases, p. 420) we shall give reasons for regarding the bilious typhoid fever of Griesinger and Lebert as merely a form of relapsing fever, with which a certain proportion of cases of true typhoid fever complicated with hepatic catarrh may have been included.

The characteristics of this grave subintrant form are as follows: Jaundice, occasionally absent, but usually present in an intense degree; marked enlargement of the liver and spleen; a tendency to hemorrhage from various mucous surfaces; extreme prostration; defective or suppressed {396} secretion of urine; hypostatic congestion or inflammation of the lungs in a large proportion of cases; dry brownish tongue; low muttering delirium, often passing into stupor or coma; hiccough; imperfect crisis; and a continuance of some morbid phenomena, so that merely a remission occurs to separate the paroxysms; and a high percentage of mortality. The great modification of the intermission which is so highly characteristic of typhoid relapsing fever is doubtless due in chief part to the serious local lesions developed, and seems to justify the name of subintrant as above suggested. The course of such fever is well illustrated by the following case, in which the characters of typhoid relapsing fever were present in the highest degree, death occurring on the fifteenth day:

Charles Hood, colored, æt. 28, of temperate habits, was taken ill on April 5, 1870, after malaise lasting thirty-six hours, with fever, nausea and vomiting, headache, and general aching throughout body; and was admitted to the hospital April 6th. There was already marked jaundice, and epistaxis had occurred; there were also insomnia; wandering delirium; extreme tenderness over the liver and spleen, both of which were enlarged; dryness of tongue, vomiting, and distension of the abdomen. These symptoms continued, his condition becoming daily more aggravated. Restless delirium alternated with heavy sopor. The jaundice grew deeper. Marked digital formication existed, but the arthritic pains were not so severe as in ordinary cases. The tongue was dry and of a red orange color. Profuse epistaxis occurred on the seventh day of the disease, requiring plugging of both anterior and posterior nares, and followed by great prostration. A gradual fall in the temperature occurred during the sixth, seventh, and eighth days, reaching 99° on the latter day. During this decline the delirium ceased and the mind remained merely dull; the jaundice decreased, as did also the tenderness of the hypochondriac zone. The pulse and respirations improved, and diarrhoea ceased. The improvement was but brief; for about eighteen hours he lay apyretic, with cool hands and feet, and with eyes closed and mind dull but free from delirium. Fever then reappeared and with the ascent of the temperature the unfavorable symptoms recurred. The relapse lasted but two days, and was followed by irregular decline of fever till death occurred on the fifteenth day of the disease. Obstinate hiccough appeared on the eleventh day, and continued, accompanied with occasional vomiting on the fourteenth day. Delirium alternating with sopor reappeared. Jaundice again became marked, and again there was extreme tenderness over the liver and spleen. The pulse grew small and feeble, the respirations shallow and labored, with an expiratory moan. Cough began on the twelfth day, and was soon followed by the physical signs of pneumonia of the lower lobe of both lungs. The urine continued free from albumen. The patient sank into deeper coma, and died on the fifteenth day. Post-mortem examination showed highly-developed characteristic lesions of the spleen and liver, with red hepatization of lower lobe of both lungs. There was no affection of the glands of Peyer. The course of the fever is shown in the following tracing (see Fig. 22).

COMPLICATIONS AND SEQUELÆ.--As would be anticipated from what has been said of the wide range of the symptoms and of the remarkable course of the temperature in relapsing fever, there are many complications and sequelæ liable to occur, and which require special consideration. {397} They may be classified according as they affect the febrile movement, the state of the blood, or one or other of the groups of organs.

We have already described the various irregularities presented by the febrile paroxysms and the intermissions, and no further allusion need be made to mere variations in length, severity, or number of the former. In rare cases, however, a peculiarity is presented, usually in the first intermission, which is difficult of explanation. About twenty-four hours after an apparently complete crisis, with a fall of temperature to a subnormal point, there may be a sudden and rapid rise or rebound of temperature to 104° or 105°, attended with distressing symptoms of high fever, but lasting only twenty-four or forty-eight hours. A good example of this is given in the case described on page 394; and Carter[18] cites several examples of it terminating either in recovery or in rapid death. He asserts that examinations of the blood during such post-critical febrile rebounds invariably showed an absence of spirilla, so that in his opinion such fever must be considered non-specific. Their explanation seems difficult, since the pyrexia is too brief to be associated with any local inflammatory complication.

[Footnote 18: Op. cit., p. 172.]

More frequent and serious is the protracted post-critical pyrexia which we have already described as modifying the interval, so as to produce a subintrant type by maintaining continuous though irregular fever until the accession of the relapse, unless cut short by death. This post-critical fever is non-specific, is unattended with spirilla in the blood, and is to be associated with the extensive irritative processes in the liver, spleen, kidneys, lungs, and other parts that are present in these grave and {398} complicated cases. It is to be noted that the course of those paroxysms which terminate in lysis indicates that they may represent a milder type of the above process.

The peculiarities of the delirium, amounting sometimes to maniacal excitement, which attends some cases of relapsing fever, has been fully described.

Less common are the following: mental hebetude, lasting some days or even weeks after the close of the last paroxysm, or, as in a case of Carter's, gradually increasing mental feebleness, terminating in imbecility. In such cases suspicion must arise of the occurrence of some local lesion of the membranes or substance of the brain.

Partial palsy is mentioned by numerous authors as occurring during or shortly after attacks of relapsing fever. Paralysis of one or both deltoids has been noted, the latter by Cormack, who saw it continue ten days after the patient was well in all other respects. Temporary paralysis of the forearm (Douglas) or of the whole arm (Parry, Meschede) has been observed; and Parry also describes loss of power in the legs lasting for one week. In one of our cases temporary loss of power of the left arm and leg occurred, attended with such impairment of sensibility that the woman had to feel for the fingers of the left hand to assure herself of their existence. This loss of power occurred during the initial paroxysm, and gradually passed away, but she was unable to stand alone on the thirty-first day of the disease. In a case reported by Tennent[19] facial palsy was developed six days after the second crisis.

[Footnote 19: Glasgow Med. Jour., May, 1871, p. 379.]

Various explanations have been offered for these local palsies, but, as already stated (see page 386), it seems probable that they are referable to morbid conditions of the nerve-trunks, or, less commonly, of the spinal cord. It must be noted, however, that in a certain number of autopsies serious intracranial lesions are found, which are evidently the results of the attack of relapsing fever. These consist of abscess of the brain, meningitis, and specially cerebral hemorrhage. This was present in one of our cases, but Carter found copious hemorrhage in no less than 8 out of 54 autopsies, and in 5 others there were minute capillary cerebral hemorrhages. Still, in nearly all the cases of large hemorrhage we have found recorded the effusion was upon the surface of the brain, and this, combined with the absence of true hemiplegia from the forms of paralysis noted in relapsing fever, and the transient character of these palsies, makes it clear that they are not to be explained by any considerable cerebral hemorrhage. On the other hand, however, it must be admitted that an additional possible cause of them is to be found in minute hemorrhage into small areas known to govern the movements of certain groups of muscles. Again, we have had occasion to note the occurrence of both thrombosis and embolism among the lesions of relapsing fever, and it is evident that either of these accidents, if involving a comparatively small branch of a cerebral vessel in certain motor areas, might cause transient paralysis, such as has been described. Nor can we fail to see that, while such symptoms as the delirium, mania, coma, or subsequent mental impairment may receive other explanations, it is possible that they may arise from similar processes of minute hemorrhage, thrombosis, or embolism involving other parts of the brain.

{399} The frequent occurrence of severe rheumatic pains in the muscles and joints during the course of the disease has been dwelt upon (p. 385); but in some cases they persisted during the intermissions and for a considerable time after all other symptoms of disease had passed away. Occasionally they greatly retarded convalescence by interfering with exercise and sleep. These pains were mostly in the legs, and were increased by exercise, and also seemed to be influenced by changes of weather. Patients who suffered thus were also liable, after exposure or in consequence of severe atmospheric changes, to sharp attacks of similar pains elsewhere, and especially in the course of the intercostal nerves. Occasionally violent and persistent headache follows the disease, not improbably associated with changes in the membranes of the brain, although in other cases severe neuralgia occurs in consequence of the anæmia which may remain in an intense degree after the fever. Troublesome numbness and soreness of the soles of the feet and of the palms of the hands, increased by pressure, has been noted as a sequel persisting for several days or weeks.

Affections of the special senses are not rare. The most remarkable among these is the affection of the eyes, which is apt to occur far more frequently in connection with relapsing fever than with typhus or typhoid. The proportion of cases in which this sequel appears varies greatly in different epidemics. In the British epidemics of 1826 and 1843, when this form of post-febrile ophthalmia was first accurately described by Mackenzie of Glasgow, it was very frequent; and it was equally so in Finland in 1867-68, when Estlander[20] again carefully studied it.

[Footnote 20: "U. Choroiditis nach Febris Recurrens," Arch. f. Ophth., 1869, Bd. xv., Abth. ii., 108.]

On the other hand, so far as can be stated in regard to a sequel which may appear after convalescence is far advanced and the patient discharged from medical care, it was very uncommon in the Philadelphia epidemic of 1869-70. This ophthalmia may occur during the course of the fever, but more frequently it begins during convalescence, and even some months after convalescence has been established. It occurs in patients of both sexes and at all ages. Usually it affects but one eye, but both may be attacked simultaneously or consecutively. Patients who were very ill-nourished and debilitated were most apt to present this sequel, and Murchison regards previous starvation as one of its main causes. The exciting cause and true pathology appear obscure as yet, however, and the existence of a neural origin is not improbable. In some cases the ophthalmia has seemed to result directly from exposure to cold. Among our own patients, as already stated, eye symptoms were less common and severe. A careful record of 184 cases was kept in reference to this question. Several patients complained of diplopia during the febrile stage, and one asserted that every object appeared fourfold to him. Conjunctivitis of moderate severity, usually associated with otorrhoea, occurred in about 5 per cent. of our cases; it generally affected only one eye, and occurred in a few instances as late as the third week after the relapse. In a few cases (four) also there was dulness of vision in one eye, noted during the course of the disease and persisting for some time after convalescence began. In only one instance, however, did permanent impairment of vision ensue, and this man had passed through a violent attack of the fever with unusually grave nervous symptoms. {400} It left him with optic neuritis on the right side, which induced partial atrophy of the nerve and great limitation of the field of vision. Meschede reports intraocular affections in 6 cases out of 180 specially examined, though it is not certain that such affections were directly connected with the febrile process. Ocular ecchymosis occurs in a small proportion of cases, especially of the graver types.

Dulness of hearing is not so common in relapsing fever as it is in typhoid. It was present in 14 out of 184 of our cases during the course of the disease, and in a few instances partial or almost complete deafness in one ear persisted after convalescence, owing doubtless to a slight affection of the middle ear. In one case marked deafness appeared suddenly on the day after the termination of the relapse by crisis. Meschede[21] found disease of the middle ear in no less than 8 per cent. of his cases.

[Footnote 21: Loc. cit.]

Purulent otorrhoea from one or both ears is of more frequent occurrence, and without any special exciting cause may present itself at any time during the course of the disease or more commonly after the relapse. In the same manner purulent coryza may occur.

The eruptions occasionally present during the fever have been described. Bed-sores from pressure are much less common than in typhus, but are met with in a small proportion of cases. As a rule, they are of moderate size and heal quickly. Superficial gangrene of the lips, nose, and ears has also been noted in rare cases (Zuelzer) in connection with gangrene of the extremities, probably from embolism. The occasional occurrence of painful boils, of abscesses in the cellular tissues (Wyss and Bock), and the more rare occurrence of erysipelas may be mentioned among the sequelæ.

As already stated, the severe pains in the joints and members which so frequently occur during relapsing fever are, as a rule, unattended by any redness or swelling of the joints. In rare cases, however, there is effusion into the joints during the fever, or more commonly there are attacks during convalescence which simulate subacute rheumatic arthritis. Such attacks may last but a few days, but in several of our cases there was painful swelling of the knees, wrists, and fingers which persisted for several weeks after the fever, being attended with slight crepitation on motion, and altogether behaving like subacute rheumatism.

As would be expected from the severity of the fever, the marked disorder of digestion, and the lesions of the spleen and liver in relapsing fever, anæmia is a common sequel. In cases where there has also been free hemorrhage, usually in the form of epistaxis, the anæmia may indeed reach an intense degree.

The cardiac murmurs which have been described as present in a certain proportion of cases are dependent upon the blood-changes, and when the anæmia is extreme these murmurs are also audible over the large veins and the pulmonary artery, and persist after convalescence is fully established.

Oedema of the lower extremities occurs in a considerable number of cases. It is clearly due in part to the anæmia, but the cardiac debility which follows the fever is also largely concerned in its production. It was, indeed, marked in some of our cases where no anæmic murmurs existed, but where there was great nervous and muscular debility. {401} Usually limited to the feet and ankles, it occasionally extended above the knees, and in one case, where great anæmia and debility from fever and over-exertion coexisted, there was oedema of the hands and wrists, with great distension of the legs up to the hips. It is not associated with albuminuria as a rule, and yields readily to treatment and rest, in the course of a few weeks.

Hemorrhages from various surfaces have already been mentioned, and a full account given of epistaxis, which is by far the most common form. Bloody vomiting has been noticed in a small proportion of cases in various epidemics. It varies in amount, but is always attended with great gravity of the attack, and usually is followed by fatal results. It occurred in four of our cases, two of which presented also black stools containing altered blood, and suppression of urine; while in another it occurred at the close of the first relapse, and during the second relapse was copious and repeated. In this case it was attended with alarming symptoms of collapse, from which the patient rallied, and after a desperate struggle recovered.

Blood may also be discharged from the bowels in such large amount as to constitute actual hemorrhage--a symptom of great gravity; or in small quantity and completely altered, so as to impart an inky black color to the stools--a condition not necessarily attended with urgent danger; or, finally, there may be frequent bloody dysenteric stools.

Hemorrhage has also been observed from the uterus, from the kidneys, from the ears, and from the old cicatrix of a syphilitic chancre. Hemorrhage occurred in 87 out of 183 of our cases, or in nearly 50 per cent. It was from the nostrils in 82 cases, from the uterus in 1 case, from the stomach in 4 cases, and from the cicatrix of a chancre in 1 case.

Sudden collapse occurs with such comparative frequency in relapsing fever as to require special attention as one of its complications. It may occur at any period of the disease, but it is most common at the crisis of the first paroxysm or of the relapse. The symptoms are usually those of cardiac failure, with rapid, small, and feeble pulse; shallow and hurried, or slow, labored, and imperfect respiration; coldness of the extremities, while the central temperature may remain elevated; muttering delirium, rapidly passing into unconsciousness. Occasionally almost instantaneous death occurs from syncope induced by some muscular exertion, as standing up or even rising in bed. In other cases the symptoms indicate the development of cardiac thrombosis, and subsequent examination has verified this opinion. In still other cases the symptoms resemble those which occur in extreme hyperpyrexia dependent upon overwhelming and paralysis of the nervous centres. Copious hemorrhage from the stomach and nose may also induce syncope of alarming and even fatal severity. When from the latter cause, reaction may be induced and the patient may ultimately recover, as we saw in a case where after repeated hematemesis the patient sank into profound collapse. In all of its forms, however, this complication is of extreme and imminent danger, and death follows, as a rule, in a few hours. The cases in which it occurs are usually of severe type, occurring in persons who have previously been in poor health or intemperate, or who have been subjected to privation and improper exposure previous to and during the early stages of their attack. Still, collapse may occur in mild cases {402} also, and whatever the type of the disease there may be no special indication of approaching trouble, when the patient rapidly passes into collapse, to be followed by death in a few hours. It occurred in nine of about two hundred cases under our observation. In one it was the result of hemorrhage from the stomach, and ended in recovery; in one, at the close of the initial paroxysm the patient, who was stupid, with muttering delirium, sank into collapse as the temperature rapidly fell from 105° to 97°, and died in a few hours; in one, on the fourth day of the relapse the temperature suddenly fell from 102° to 96°, with free sweating, but suddenly rebounded to 102°, with very rapid, feeble pulse, distinct basic cardiac murmur, constriction of chest, restlessness and delirium, slight convulsions, and death in eight hours; in one, a man at the end of the initial paroxysm, immediately after his admission to the hospital in apparently fair condition, became violently delirious, with bounding pulse, soon grew comatose, and died in one hour; in one, a man who was in feeble condition, on the nineteenth day, with irregular persistent fever (he had splenic abscess), sat up on the edge of the bed, sank back in syncope, and died in less than an hour; in one, a man who did well until the second day of the relapse, when pleuro-pneumonia and pericarditis were developed, died suddenly four days later: there was considerable pericardial effusion; in one, sudden death from syncope or cardiac thrombosis occurred on the twelfth day in a man who had suppurative parotitis and metastatic abscesses of the lungs; in one, sudden collapse and death occurred in one and a half hours at the end of the initial paroxysm; in one, a drunkard with large fatty liver had pyrexia continuing after the initial paroxysm, and on the ninth day, while in a state of hebetude, with mild delirium and a pulse of 112, coma suddenly occurred, and death followed in two hours.

Pericarditis is a rare complication, and is apt to coexist with pleuro-pneumonia. This combination occurred in one of our cases where pleuro-pneumonia and pericarditis were developed on the second day of relapse, and proved fatal by sudden collapse on the fifth day, with the pericardial sac distended with serum and its layers coated with plastic lymph.

Thrombosis of veins, as in phlegmasia alba dolens, occurs much more rarely than after typhoid fever. Arterial embolism, on the other hand, is not uncommon. Murchison[22] reports a case in which gangrene of the left foot from obstruction of the left femoral artery, together with cerebral softening from obstruction of the left middle cerebral artery, occurred in connection with cardiac thrombosis. Zuelzer alludes to similar cases in the St. Petersburg epidemic of 1865-66, where, in addition to the extremities, the nose, ears, and lips became gangrenous. Other examples of embolism are found in lesions of the spleen and kidneys, where infarctions are of frequent occurrence.

[Footnote 22: Op. cit., p 384.]

Heart-clot, or cardiac thrombosis, appears to occur more frequently than in any other acute zymotic disease, with the exception of diphtheria. Even when the occurrence of passive hemorrhages and of ecchymoses of various tissues indicates marked dyscrasia of the blood, there will not rarely be found firm white clots in one or other of the cavities of the heart. These frequently present unmistakable evidences {403} of ante-mortem formation, and, as already stated, there is a certain proportion of the cases of rapid and unexpected death where the fatal result is directly due to cardiac thrombosis, attended with the usual symptoms.

The constant affection of the spleen has been fully described; it is not therefore surprising that both complications and sequelæ arise in connection with it. At times, in cases which ultimately recover, the pain in the splenic region is so violent and continuous, and is attended with so much tenderness over the enlarged organ, that localized peritonitis is undoubtedly present. Occasionally this perisplenitis persists, and in conjunction with the inflammatory changes in the substance of the spleen maintains an irregular fever after the specific pyrexia has run its course. This was noticed in several of our cases, but especially so in a case where, after the initial paroxysm, an irregular fever was kept up, obscuring the relapse, until the nineteenth day, when death occurred suddenly from syncope on rising on the edge of the bed, and where examination showed splenic peritonitis, with a splenic abscess as large as a pigeon's egg.

The enlargement of the spleen usually subsides during the intermission, and disappears speedily or in the course of a few weeks after convalescence is established. Occasionally, however, it persists, and is attended with marked anæmia. In one case, where death occurred from pneumonia, the sequel of relapsing fever, at about the thirtieth day, the spleen weighed twenty-nine ounces; and in another case, where death occurred from gangrenous pleuro-pneumonia, at the fortieth day, the spleen was still enlarged and presented characteristic changes in its pulp. On the other hand, in a case where death occurred on the twelfth day of typhus, occurring forty-four days after recovery from a very bad case of relapsing fever, making it altogether the one hundredth day, none of the lesions of the first disease were discoverable.

Rupture of the spleen occurs occasionally, and is usually attended with sudden pain, collapse, and speedy death. Murchison refers to two examples recorded by Zuelzer and one by Hudson; Petersen reports fifteen cases, in seven of which sudden rupture occurred with speedy death, while in the other eight the rupture followed local softening from infarction, and resulted in death in a few days from purulent peritonitis.

In one of our cases, where death occurred on the sixteenth day, apparently from double pneumonia and heart-clot, it was found that there was a rupture in the enlarged spleen near its upper end, recent plastic peritonitis in the region of the spleen, and a moderate amount of bloody pulpy fluid throughout the peritoneal cavity.

As we have seen, disturbances within the respiratory tract occur with very different frequency in different epidemics. In many they are rare, while in 1870 we noticed cough and other evidences of respiratory trouble in no less than 90 out of 200 cases.

Severe catarrhal laryngitis is a rare and dangerous complication. It did not occur in our cases, but both Begbie and Paterson report cases of it which required tracheotomy, and Wyss and Bock met with ulcerative laryngitis with perichondritis.

Bronchitis of moderate severity, although rare in many epidemics, {404} occurs so frequently in others, as in Philadelphia in 1870, as to rank as a symptom of the disease.

Pneumonia is one of the most fatal complications. The results of our own observations agree with the statements of Jenner and of Carter, that it is the next most common lesion after enlargement of the liver and spleen. On the other hand, Murchison noted it only in 4 or 5 out of 600 cases. It occurred in at least 11 of our cases, 8 of which were fatal; and unquestionably less extensive inflammation was present in other cases which recovered, in view of the marked respiratory disturbances frequently present. Both lungs were involved in 4 cases; of the remainder, the right and left were about equally divided. Out of 23 autopsies, the lesions of pneumonia were found 8 times. The lower lobes were affected in every case. The form of this disease was croupous in 9 cases; in 1 it was that of metastatic suppuration, and in 1 it was more properly described as splenification. The amount of plastic pleurisy associated with it was usually great, and in one case there was also severe pericarditis. In another case the disease advanced to the stage of gangrene of a circumscribed area of the pleura and of the superficial layer of the lung. In only one instance was albuminuria present. In two cases the pneumonia occurred so late in the course of the disease that it might be regarded as a sequel. Death occurred in one of these on the thirtieth day, and in the other (that in which gangrene ensued) it ran a subacute course, and death did not take place until the fortieth day. In the other cases the disease began at the close of the initial paroxysm, during the intermission, or early in the relapse. As would be expected, the sympathetic fever due to this complication modified and obscured the characteristic course of the specific pyrexia.

This rare termination in gangrene has been noted by other observers; in all five or six times. Parry met with a truly remarkable case of double pneumonia, followed by gangrene, and yet resulting in recovery. Jaundice is apt to attend cases of relapsing fever which are complicated with pneumonia.

Pleurisy is an almost constant accompaniment of pneumonia, and frequently occurs in marked degree. It may also be present in cases of severe splenic inflammation. In all probability, localized plastic pleurisy is not infrequent, and may cause some of the severe thoracic pains so frequently present.

Metastatic abscesses of the lung occur occasionally as a result of the profound toxæmia, and are apparently preceded by patches of infarction, which soften in the centre, as in the usual development of pyæmic abscesses. This condition was found in one of our cases in conjunction with suppurative parotitis. It has been included among the instances of pneumonia.

Acute miliary tuberculosis, involving chiefly the lungs and intestinal canal, occurred as a sequel in one case under our observation, and phthisis has been found to follow by other observers (Carter). It is to be expected that if the patient did not so quickly pass from under observation it would be found that an affection so gravely complicating nutrition as does relapsing fever is frequently followed by serious organic disease.

Parotitis is mentioned by so few authors as to show that it is a {405} rare complication in most epidemics, varying from 1 in 600 to 1 in 50 cases. One gland only is affected at a time as a rule, though both may be involved successively. The inflammation begins either during the intermission or the relapse, and may terminate by resolution or by suppuration. Although a painful and severe complication, it is followed by recovery in a considerable proportion of cases. Carter[23] states "that in some degree it was noted in 2 or 3 per cent. of all cases, and nearly as often amongst survivors as in the casualties." It occurred in three of our cases (185); once it underwent resolution; once suppuration occurred in the parotid and in the masseter muscle, with metastatic abscesses in the lungs, and death; and once the patient, who had previously existing amyloid degeneration of liver and spleen without albuminuria, had severe relapsing fever with two relapses, in the first of which parotitis occurred in both glands, successively terminating in suppuration, after which he did well through an apyretic period of six weeks, when sudden high fever appeared, followed by speedy death.

[Footnote 23: Op. cit., p. 210.]

Pharyngitis and tonsillitis of mild grade occur in from 3 to 25 per cent. of the cases in different epidemics.

Hiccough deserves to be ranked among the complications, because it is of frequent occurrence, obstinate and annoying. It occurred in a considerable proportion of our cases, and much more frequently in those who had jaundice. It was often present both in the initial paroxysm and in the relapse, but disappeared soon after the end of the pyrexia. It bore no constant relation to the severity of the vomiting. Not rarely it lasted several days and nights, causing exhaustion and interference with sleep and proving rebellious to treatment. Hypodermic injections of morphia and atropia, chloroform internally, and extremely careful alimentation proved most serviceable.

Hemorrhage from the stomach has already been spoken of (see p. 390).

Diarrhoea, as already stated (see p. 390), occurs much more frequently than in typhus fever, varying from 1 per cent. (Murchison) to 15 per cent. (Scotch epidemics) or 33 per cent. (Philadelphia), or even 50 per cent. (Königsberg). It is usually of moderate severity, but occasionally is so profuse and intractable as to constitute the main cause of death. In some epidemics the attacks of looseness occur almost exclusively after the relapse, but in others the bowels are frequently loose during the febrile stages. In our cases there were not infrequently from three to eight thin, dark, bilious or light yellowish stools daily after the second or third day of the initial paroxysm, and then the looseness would stop during the intermission, probably to recur in the relapse. Occasionally diarrhoea with very frequent liquid stools occurs at the close of one or both of the febrile stages, assuming a critical character, and substituting more or less of the sweating which is the common mode of crisis, although in several such cases quoted by Murchison from Douglas the sweating, despite the critical diarrhoea, was usually profuse. It can scarcely be said that there is any relationship between diarrhoea and vomiting; both are frequently present, and may even be severe and persistent in the same case, though either may be marked while the other is moderate or slight. Abdominal pain and tenderness in the epigastrium and hypochondria are constant symptoms, but when diarrhoea is marked there are apt also to be griping {406} pains and tenderness in the lower segment of the abdomen. When diarrhoea occurs as a sequel, either beginning after the close of the relapse or continuing in cases where the bowels have been loose during pyrexia, it is apt to prove obstinate and intractable, or even to lead to a fatal result.

The character of the stools varies much; usually thin and dark, they may be light yellowish or even whitish. Thus, in a severe case with deep jaundice we observed seven liquid and decidedly whitish stools in twenty-four hours. In such instances there is undoubtedly more or less complete closure of the biliary ducts by plugs of mucus or by swelling of the mucous membrane. On the other hand, the stools may be inky black from admixture with altered blood, or, lastly, they may consist of mucus and blood, in which event the complication assumes the form of actual dysentery and is attended with increased abdominal pain and with tenesmus. Dysentery was, as would be expected, quite frequent in the Indian epidemics studied by Carter.[24] It is usually of moderate severity, but occasionally it runs into gangrenous inflammation, is attended with perforation of the bowel, or is followed by hepatic abscess. In one instance we noticed a peculiarly fetid puriform discharge from the anus, which occurred during the relapse and persisted for several weeks, gradually subsiding, as though from some unhealthy ulceration which slowly healed.

[Footnote 24: Op. cit., p. 218.]

Jaundice is of frequent occurrence, but has been sufficiently discussed at page 391.

Peritonitis is not rare in its circumscribed form. This statement is based on the comparative frequency with which localized splenic peritonitis, of varying degrees of severity, is found after death in relapsing fever from various causes, and from the great frequency of severe pain and tenderness in the region of the enlarged spleen in favorable cases. In its lesser degrees it may not add materially to the danger of the patient, but in more severe forms, associated with serious splenic lesions, it may run a protracted subacute course and maintain irregular fever.

General peritonitis is, on the other hand, a rare complication, occurring not more than once in several hundred cases. It results from dysenteric perforation of the bowel, from rupture of a splenic abscess, or from rupture of the spleen itself. An example of this latter accident which occurred under our observation has already been given. Speedy death invariably follows, though in the case just referred to the symptoms of peritonitis were totally masked by those of the coexisting double pneumonia, which seemed to be the immediate cause of death.

Suppuration of the mesenteric glands is a rare complication, mentioned especially by Wyss and Bock. As these glands are not usually found enlarged, there being no irritative lesion of the intestines of common occurrence in relapsing fever, it is probable that the collections of pus which have been found were metastatic in origin.

Dyspepsia is not an infrequent sequel, as would necessarily be the case after a disease characterized by so much gastric irritation and by such serious lesions of the liver and spleen. As a consequence, care in diet is often required for a considerable period after the course of the disease has ended; dyspeptic symptoms are frequently complained of, and marked emaciation and anæmia often protract convalescence.

{407} It may be observed that a striking appearance of emaciation is often developed shortly after the crisis of the first paroxysm, or, more particularly, of the relapse. It is partly due to the actual loss of weight during the high pyrexia, but even more to the abrupt transition from a state of extreme febrile turgescence to one of equally extreme relaxation and maceration of the surface.

The amount of urine has been seen (p. 387) to vary greatly in cases distinguished by no special disorder of the kidneys; the extremes in ordinary cases being from twelve or fifteen ounces just before the crisis to from eighty to one hundred and twenty within forty-eight hours after the crisis. Suppression is, however, sometimes noted, and is always a grave symptom, though Parry[25] reports more than one case in which on several successive days there was not more in twenty-four hours than one fluidounce of non-albuminous urine, and in which no symptoms of uræmia occurred, and the sweat had no urinous odor. In one of our fatal cases, with intense jaundice, hematemesis, inky black stools, and oedema of the feet and of the lungs, there was not a drop of urine secreted during the last four days of the initial paroxysm; death occurred on the eighth day, and the kidneys were found intensely engorged, of a deep blackish-blue color, with numerous ecchymoses in the cortex, due to impaction of the convoluted tubules with blood, while the renal epithelium was granular and swollen, and many tubules were filled with epithelial cells and granular matter. At the autopsy the urinary bladder was firmly contracted and contained a very small amount of bloody liquid.

[Footnote 25: Op. cit.]

More frequently, incontinence of urine, with or without retention, occurs during the febrile stages--according to our observation, most commonly in cases attended with mental disturbance and tending to a typhoid condition. The symptom was not of very grave significance, however, and after the use of the catheter for a few days the bladder regained its tone.

Albumen is quite frequently present in small amounts during the pyrexia of relapsing fever. Thus, in 18 cases of ordinary severity, which all recovered, and in which the urine was carefully examined daily, a trace of albumen was found in 5; in 2 cases it appeared both in the initial paroxysm and in the relapse, but in all instances its presence was of brief duration. In one of these five cases the albumen appeared at both critical periods, when the amounts of urine in twenty-four hours were respectively 150 ccm. and 250 ccm.; but in the other cases the transient albuminuria coincided with free secretion of urine (1250 ccm., 1850 ccm.). It is probable that were the same careful search to be made in all cases the presence of albumen would be detected in fully 20 to 25 per cent. On the other hand, in fatal cases the occurrence of albuminuria is by no means constant, although undoubtedly it is present in a larger proportion of such cases than of those of ordinary severity.

Our experience does not confirm that of Murchison, who states that he never met with typhoid symptoms in relapsing fever without albuminuria or some other evidence of retarded elimination by the kidneys. In several of our cases where the typhoid state was developed in the highest degree repeated examination of the urine failed to discover albumen.

{408} Most observers have been struck with the comparative immunity of the kidneys from serious disturbance in a disease presenting such complicated morbid processes and widespread lesions as relapsing fever. To show, however, that these organs suffer specially in certain epidemics, it may be mentioned that Obermeier[26] reports having found albumen with tube-casts of various kinds in 32 out of 40 cases of relapsing fever, thus showing that, in the particular epidemic he was studying, catarrhal nephritis was of almost uniform occurrence. It is true that serious interference with the elimination of urea and other nitrogenous matters may occur without the coexistence of albuminuria, so that it is impossible to deny that severe nervous symptoms may result from impaired renal activity even when the urine contains no albumen.

[Footnote 26: "U. d. wiederkehrende Fieber," Arch. f. path. Anat. u. klin. Med., Bd. xlvii. p. 170.]

Attention has already been called to the variations presented in the amounts of urea, but more extended observations are required to show the precise relations of these variations to the graver nervous phenomena. It will be found, we venture to opine, that, while in one group of relapsing-fever cases of grave type, cerebral symptoms are dependent upon the retention and accumulation in the system of urea and other effete nitrogenous products, owing to interference with renal activity from pre-existing organic disease of the kidneys or from an exceptional degree of congestion of those organs, there are other groups where similar typhoid cerebral symptoms are more directly dependent upon the specific toxæmia, upon the hyperpyrexia, upon exhaustion of the nerve-centres by intense peripheral irritation, or upon congestion or other morbid conditions of the nerve-centres themselves.

In all cases where cerebral symptoms manifest themselves in relapsing fever the daily examination of the urine--which here, as in other zymotic diseases, is a duty in all cases--becomes of extreme importance. Three conditions should be borne in mind in such examinations. In the first place, the attack of fever may have occurred in one already the subject of organic kidney disease, and, considering the classes from which the majority of the cases of relapsing fever are drawn, this possibility cannot be of rare occurrence. Out of eighteen post-mortem examinations in which the kidneys were studied with especial care we found positive evidence of pre-existing organic disease four times. In these cases the albuminuria was marked and persistent, though tube-casts were rarely found, and severe cerebral symptoms of typhoid type were prominently present. In another highly interesting case the patient, who had amyloid disease of the liver, spleen, and kidneys, contracted severe relapsing fever; he had increased albuminuria during both febrile stages, suppurative parotitis, but no grave cerebral symptoms, and apparently recovered. After an apyretic period of six weeks, during which the symptoms of the amyloid visceral disease persisted, a sudden and rapidly fatal pyrexia occurred. Unfortunately, the existence of spirillar infection of the blood was not known at the time.

In the second place, the attack of fever may become complicated with acute nephritis from special localization of the poison, as in Obermeier's cases, or from vulnerability of the kidneys. In such cases careful study of the urine should indicate the event, and the prognosis, though grave, is not so hopeless as in the first instance. An interesting example of {409} this occurred under our observation, where the patient, who had apparently an ordinary attack, was seized with acute catarrhal nephritis, with temporary uræmia, during the relapse, but after a dangerous illness recovered without any organic renal disease as a sequel.

In the third place, may be found the more usual and more readily-determined condition of slight and transient albuminuria (with variations in urea excretion) which has already been discussed, and which has no serious prognostic significance.

The following very interesting case deserves special mention: The patient, a man aged thirty-six, was admitted on the fifteenth day of an attack of acute catarrhal nephritis, with slight ascites, marked oedema of the feet and legs, and highly albuminous urine. In the course of ten days the oedema and albuminuria were much diminished, when on the thirteenth day after admission he was attacked with relapsing fever, the ward in which he lay containing a number of persons ill with that disease. The initial paroxysm was severe, but without any grave cerebral symptoms; the urine grew scanty, dark, and bloody, and the oedema increased and invaded the pelvis. Crisis occurred on the fifth day, temperature falling 9°, sweating copious, urine 473 ccm. in twenty-four hours, color of porter, highly albuminous, and depositing blood, renal epithelium, hyaline, granular and epithelial casts, all stained reddish. Two days later, urine 1600 ccm., light colored, with only a small amount of albumen.

A slight and brief relapse (101° for two days) occurred after an interval of four days; a second imperfect relapse (100.5° for three days) after a further interval of six days; and finally, after a further interval of only two days, a violent relapse (temperature rising rapidly to 106°) with crisis (fall of 8° in twelve hours) at close of fifth day. The oedema gradually diminished from the time of the first crisis, did not increase in the relapses, and disappeared completely and finally about ten days after the last relapse. The urine was very free after the first paroxysm, averaging from 2000 to 2300 ccm. During the subsequent febrile periods it did not decrease, and indeed on the second day of the last relapse, with the temperature at 105°, the amount in twenty-four hours was 3200 ccm. Four days subsequently, during crisis, the amount was only 350 ccm.

The albumen disappeared entirely from the urine in two weeks from the close of the last relapse; there had then been no tube-casts for some days, and the patient was discharged entirely well a short time afterward. The treatment consisted of hot vapor-baths, repeated dry cupping over the kidneys, infusion of digitalis with acetate of potash during pyrexia, and Basham's iron mixture in the intermissions. It seemed that the occurrence of the relapsing fever interfered wonderfully little with the recovery from nephritis.

Hematuria is a comparatively rare and very grave complication. It may occur as an additional evidence of the dyscrasia of the blood in connection with hemorrhages from other surfaces, or as in the case we have before referred to or in that reported by Murchison,[27] it results from intense engorgement of the kidneys. In Murchison's case hematuria, with much albumen and tube-casts, occurred in both paroxysms {410} without any uræmic or typhoid symptoms, and was followed by satisfactory recovery.

[Footnote 27: Op. cit., p. 370.]

Sugar is sometimes present in small quantity as a transient symptom; and diabetes has been observed as a sequel.[28]

[Footnote 28: Tyson, Phila. Med. Times, 1871, i. 418.]

Metastatic inflammation of the kidneys, with centres of suppuration, was observed by Wyss and Bock.

When menstruation occurs during relapsing fever, as it may do at any time, it is apt to be excessive, and may amount to severe hemorrhage. Crisis has been known to occur in this manner.

The numerous cases reported by various observers of relapsing fever occurring in pregnant women establish the rule that abortion almost invariably occurs, whatever may be the stage of the pregnancy. In a large majority of cases the mother recovers, but the child, if viable, is stillborn or dies in a few hours. Only two of our patients were pregnant women, and the result in each was unusual. In one, the patient, already the mother of several children, was in the fifth month of gestation; the initial paroxysm was severe, with delirium, but no symptoms of abortion occurred; the intermission lasted six days, during which she felt very well; the relapse was also severe, and crisis occurred on the fifth day, the temperature falling below normal, and the case promising to do well; but on the following day there was a sudden rebound of temperature, pulse 140, severe præcordial pain, and death occurred in twenty-four hours, the contents of the uterus being partially expelled during the act of dying. In the other case, a girl of eighteen years, who had aborted at the third month of gestation eight months previously, and who was again three months advanced in pregnancy when attacked with relapsing fever, went safely through a bad attack and carried her baby successfully to full term.

MORBID ANATOMY.--The surface of the body often presents patches of livid discoloration, and jaundice persists in cases where it has been present during life. There is but little appearance of emaciation, except in cases where it has been present before the attack.

When death occurs while the temperature is high the body remains warm an unusual length of time. Thus, in one case where death occurred at 11.30 P.M., the temperature at 12 was 103°, and at 1 A.M. it was 101-3/5°, that of the room being 73°; at 6 A.M. it remained at 93°, the room being at 73°; between 9 A.M. and 2 P.M. the room was kept at 55°, but the body was still at 82° at the latter hour.

The voluntary muscles are often jaundiced, and in prolonged cases they may be found flabby and having undergone marked granular degeneration. In many cases, however, they remain quite dark and firm. Ecchymoses of the muscular substance are met with occasionally.

In one case, where during life there had been painful swelling of the left parotid region, with fistulous openings on the cheek, and where death occurred on the twelfth day of the disease, the masseter muscle was swollen, with patches of dark, almost black, discoloration from ecchymosis, and was studded throughout with small collections in its substance. The fluid from these contained very numerous cells indistinguishable from leucocytes. The muscular fibrils were friable and granular, and there was multiplication of the nuclei of the sarcolemma. {411} These unusual lesions seemed to have originated in interstitial disintegrating thrombi, with consequent inflammation of the muscle.

The muscle of the heart is more frequently affected, and in the fatal cases our attention was particularly drawn to those lesions. Ponfick[29] has also described them minutely. The degree of change varies from a partial loss of transverse striation, with slight granular appearance, up to a very high degree of granulo-fatty degeneration. The organ is then flabby, its substance pale gray or brownish, either wholly or in streaks, and microscopic examination shows an extreme degree of fatty granular change. It must not be forgotten, however, that many of the subjects of relapsing fever have been leading irregular and dissipated lives, and that in some instances the lesions of fatty degeneration detected in their organs may have been the result of their previous habits.

[Footnote 29: Virchow's Archiv. f. path. Anat., Bd. lx. Hft. 2, p. 162.]

Lesions of the cardiac muscle were most marked in those of our patients who had been intemperate, and in whom fatty degeneration of the viscera (chiefly liver and kidneys) was also found. They were most fully developed in cases where death occurred at a comparatively late period, while in some very severe cases, in which death occurred as early as the fifth day, the cardiac fibre presented merely faintness of striation without actual granular degeneration.

Ponfick in particular notes that the great majority of the bodies he examined were of persons who had been habitual drunkards.

Pericarditis is occasionally present, and is marked by the usual lesions. In a very severe case in which it contributed largely to the production of the fatal result it was associated with pneumonia. In addition to this, effusions of blood beneath the endocardium and pericardium are not rare; and we have seen them quite large and numerous in cases where the muscular fibre was firmly contracted and the cavities contained quite firm decolorized clots.

Thus in our case No. 62, Series C., "the heart was normal in size, with no appearances of previous disease. There were numerous ecchymoses of both layers of the pericardium. The right cavities contained large, firm, yellowish, fibrous clots, forming a cast of the upper part of the ventricle and of the auricle, and extending both into the pulmonary artery and back into the veins, and so firm that by gentle traction a complete cast of these vessels was drawn out. The clot in the pulmonary artery was throughout firm, fibrous, and yellowish. There were numerous ecchymoses of the pleura and of the mucous membranes of the stomach and urinary bladder, hemorrhagic infarctions in the kidneys and lungs, and granulo-fatty degeneration of the cardiac muscle." Death had occurred in this case about the close of the third week, and was preceded by hematemesis and suppression of urine. We must note in this connection the tendency to embolism that exists in this disease.

Especial interest attaches to the condition of the blood in relapsing fever. Usually it presents no abnormal appearance if drawn during life, though in grave cases it may coagulate imperfectly. We have no knowledge of its minute chemical characters, save that in several cases where there was great diminution in the amount of urine, with uræmic symptoms, urea has been found in considerable amount in the blood (Murchison, p. 368). The red globules present no definite or {412} characteristic changes. In some of our examinations they appeared of light color and became crenated very quickly on exposure. On the other hand, the white corpuscles have repeatedly been observed to be increased in number, at times considerably so (Cormack, Thompson, Zuelzer, Carter, Boeckmann, and ourselves), though this change is not regarded as constant or essential. It has, however, a very great interest in connection with the characteristic lesions of the spleen which will be described hereafter. In several cases we observed that many white corpuscles were small and apparently imperfectly developed. Boeckmann[30] concludes that they increase in number during the febrile paroxysm, reaching their highest number at the crisis, and then diminishing gradually to the normal. The red globules are much decreased during the fever, and return to the normal slowly during convalescence.

[Footnote 30: Deutsch. Arch. f. klin. Med., Sept. 1881, p. 513.]

In addition to these changes, various abnormal elements have been observed more or less constantly. By far the most important of these is the spirillum or spirochete of Obermeier, which has been already carefully described. In proportion as this organism has been carefully looked for it has been found constantly, so that the evidence has become very strong in favor of its uniform presence in the blood of relapsing-fever patients during the febrile stage of the disease.

Ponfick in 1874[31] called attention to the occurrence of large granule-cells in the blood in this disease. They are found during life as well as after death, when they exist in largest proportion in the blood of the splenic, hepatic, and portal veins. Their shape is spherical, ovoid, or elongated; the basis of the cells is a delicate, translucent, albuminous substance; and the granules are of a fatty nature, as shown by the action of reagents. These cells have been found by other observers, and the view is generally received that they are derived from the lymphoid elements of the spleen, and perhaps of other portions of the lymphatic system; and Carter, who has studied them carefully, is inclined to think there is some connection between them and the development of the spirillum.

[Footnote 31: Centralbl. f. d. med. Wissensch., 1874, p. 25.]

Ponfick also first described[32] certain other large, irregularly-shaped, pale, granular, nucleated cells, which occur in smaller number in the blood in relapsing fever, and which he regarded as altered endothelium, derived from the lining of the blood-vessels, of the lymphatics, or of the lacunar spaces of the spleen. Occasionally these cells are found with such highly granular contents as to make them closely simulate the large granule-cells described above. These results of Ponfick have been confirmed by other observers.

[Footnote 32: Loc. cit.]

In several of our reports of examinations of blood there is mention made of quite abundant, free granular matter--an appearance also observed by Carter. Finally, the latter describes the occurrence of thread-like filaments and of short, rod-like bodies.

There are no characteristic lesions connected with the gastro-intestinal canal. The mucous membrane of the stomach may be normal or merely injected, though where there has been much vomiting, and especially bloody vomiting, there is marked injection, and not rarely ecchymosis and submucous extravasations of blood, with softening of the membrane. {413} These extravasations are usually small, but Cormack reports a case where one-third of the mucous membrane of the stomach was the seat of ecchymosis and extravasation. In one of our own cases the extravasations occupied an area of four inches square.

The small intestines exhibit patches of congestion or ecchymosis less frequently than the stomach, though it is usual to find injection of the mucous membrane, especially of the lower portion, in cases where there has been diarrhoea. Carter, observing the disease in India, found in one-half of all autopsies some amount of congestion, hemorrhage, or inflammation of the ileum. In two instances he found a layer of diphtheritic deposit over the mucous membrane of the lower part of the ileum.

There are no special alterations of the solitary or agminated glands, and ulceration never occurs. Even in cases where the constitutional infection is severe, whether diarrhoea has been present or not, it is noteworthy that there is rarely any swelling of the solitary glands or Peyer's patches, such as is met with in many other acute specific diseases. It was not present in any of our autopsies.

The large intestine in like manner exhibits no characteristic lesions. Patches of congestion and occasionally submucous ecchymoses may be observed, and croupous exudation occurs here somewhat more frequently than in the small intestine.

Wyss and Bock[33] speak of enlargement of the mesenteric and retroperitoneal glands as of frequent occurrence, but we did not observe it, and Murchison states that these glands present no abnormal appearance.

[Footnote 33: Op. cit., p. 223.]

Alterations of vascularity of the brain or its membranes are met with, but they are variable and bear no definite relation to the precedent symptoms. Ecchymoses of the membranes are occasionally observed, and in one of our cases extensive meningeal hemorrhage was found. Murchison reported a case in which embolism of the left femoral artery occurred, and subsequently of the left middle cerebral artery, inducing death. The suggestion may be hazarded that in some of the cases where there is severe delirium ending in stupor and death there has been multiple capillary embolism of the cerebral vessels.

There is occasionally the evidence of catarrhal inflammation of the upper air-passages, and in some epidemics diphtheritic exudation in the pharynx and larynx has been noted (Wyss and Bock); and Ponfick found acute oedema of the glottis in a considerable proportion of the fatal cases at Berlin. The lesions of pleurisy are met with in a small proportion of cases; in our own autopsies this complication was more frequent than in most epidemics.

The lungs may be normal, and Murchison concludes that they are more frequently so than in typhus. Still, they often present congestion or oedema, and subpleural ecchymoses, hemorrhagic infarctions, and pneumonic consolidation are not rare. Lobar pneumonia was present in 33 per cent. of our own autopsies, in 28 per cent. of Carter's, and in 20 per cent. of those conducted by Ponfick. The inflammation usually presents the regular stages, and is associated with a moderate degree of plastic pleurisy; but occasionally, as in one of our cases, it terminates in gangrene. In the instance referred to there was an area of gangrene about three inches square and one inch in depth, involving the pleura and a {414} superficial layer of lung on the antero-lateral aspect of the left lower lobe. In another remarkable instance, already referred to on account of the suppurative inflammation of one masseter muscle, the lungs, which were stained yellow throughout, presented numerous deep purplish patches, which on section altogether resembled the secondary metastatic deposits of pyæmia, with yellowish softening or even puriform centres surrounded by a rim of purplish livid discoloration. Very numerous similar patches, varying from the size of a pea to that of a hazel-nut, and presenting every stage of development, were found throughout both lungs. In a few instances we found the lesions of chronic phthisis, which had, of course, existed before the attack of relapsing fever. The bronchial glands were found swollen and infiltrated in cases where inflammatory processes in the lungs have existed.

Much interest attaches to the state of the genito-urinary organs in relapsing fever, but caution is required to distinguish lesions that have existed prior to the attack from those properly referable to it.

Owing to the intemperate and exposed lives of many of the patients, renal lesions might reasonably be expected in no small proportion. The comparative rarity of albuminuria (see p. 407), even in severe cases, is suggestive of the view that when it is present it may at least sometimes be due to pre-existing lesions aggravated by the acute infectious process, and further that the extreme gravity generally presented by such cases may be in part due to the impaired condition of the kidneys.

The morbid changes most frequently referable to the fever are moderate enlargement and congestion, occasionally very intense so that we find it described in our notes as deep blackish-purple or blue; ecchymoses of the capsule or of the mucous membrane of the pelvis; small hemorrhagic infarctions, usually in the cortex; and cloudy swelling of the glandular cells. Less commonly are found hemorrhagic infarctions, or small embolic patches advanced to various stages of disintegration, even to the formation of small puriform collections. In quite rare cases the lesions of acute nephritis are present, while caution must be used in interpreting other changes occasionally met with, such as pallor with granulo-fatty degeneration or other advanced alterations of the glandular cells, or hyperplasia of the intertubular connective tissue, with or without contraction of the kidneys.

The mucous membrane of the bladder, as already mentioned, may present ecchymoses, or, more rarely, croupous exudation (Wyss and Bock). The urine contained may be bloody, or, as in one of our cases where there had been total suppression of urine for over seventy-two hours before death, there may be but a small amount of almost pure blood, containing a few phosphate crystals, but no tube-casts. In this case there were also ecchymoses of the bladder and of the pelvis of the kidneys, with intense congestion and numerous small hemorrhagic infarctions of the kidneys.

The liver is constantly though variously affected. It is found enlarged in the great majority of cases, especially if death has occurred during the febrile stage. The ordinary degree of enlargement in our cases was from four to four and a half pounds, but in a few instances the liver weighed one hundred or one hundred and two ounces, though in most of these extreme cases the patients had been drunkards, and there was such advanced fatty alteration of the liver as to make it probable that the {415} organ had been diseased previously. These figures correspond with the results of other observers.

In many cases, especially when death occurs early and during the febrile stage, the capsule and substance of the liver are congested, at times intensely so; and when ecchymoses are found elsewhere they are apt to be present here also, appearing as purplish patches dotted over the capsule and extending into the superficial layer of hepatic tissue. Not rarely, however, the liver substance is paler than normal, and presents a yellowish tinge, apart from the decided yellowish staining present in cases attended with jaundice. Carter describes a partial mottled paleness of the liver as having been frequently observed in his cases, the circumscribed pale areas presenting a corresponding localized degeneration of the cells, as though from some local interruption of circulation.

Cloudy swelling and fatty degeneration of the liver-cells are indeed very often present, and in some epidemics with preponderance of bilious symptoms are constantly found (Ponfick). The degree of the cell-alteration varies from a slight granulo-fatty change to an advanced fatty degeneration, even with a marked tendency, in rare cases, to disintegration of the cells, so as to produce lesions analogous to those of acute yellow atrophy (St. Petersburg epidemic).

The whitish deposits described by Küttner as due to albuminous or fibrinous infiltration are probably referable to transformed hemorrhagic infarctions, and the minute puriform collections that have been observed at the centre of the acini (Wyss and Bock) may have been metastatic in origin, or attributable to the disintegration of minute thrombi associated with irritative hyperplasia of the adjacent lymphoid elements. The consistence of the liver varies: when death occurs early and bilious symptoms have not been marked, it may be even firmer than normal, but more frequently it is softer, and it may be relaxed, flabby, and friable.

The condition of the bile-ducts is of great interest in view of the frequency of jaundice as a symptom in relapsing fever, and most authorities unite in saying that they present no lesions capable of explaining it.

The gall-bladder is usually found full of dark bile, but there is no such degree of inspissation, except in rare instances, as could interfere with its passage through the ducts. Murchison quotes the statement of Peacock that in some instances the bile was thick and viscid, so as apparently to cause obstruction, but all observations agree in showing that this is exceptional. The mucous membranes of the larger ducts may present evidences of slight catarrhal inflammation, but in nearly all cases where they have been carefully examined, even when jaundice had been marked, they have been found patulous and free, so that the jaundice cannot be regarded as due to obstruction of the larger ducts save in rare instances (Pastau). In further confirmation of this may be stated the fact that there is no want of bile in the duodenum and feces.

On the other hand, a careful consideration of the lesions of the substance of the liver will show that it would be most improbable that the minute biliary ducts in the areas most affected should escape implication. Münch, who investigated this subject carefully, found that there was a catarrhal state of the fine bile-ducts in every case of relapsing fever with jaundice; and Litten found the smallest ducts plugged with bile-stained pellets of mucus. It would appear, therefore, that in many cases at least {416} the jaundice is really obstructive in its origin, the seat of the obstruction being in the too-rarely examined minute bile-ducts, though further investigation of this interesting question is required.

The clinical bearing of these conditions has been fully discussed in the appropriate section.

The changes in the spleen are constant, and even more remarkable than those in the liver. It is enlarged with rare exceptions, and especially so if death has occurred during the febrile stage. Upon the subsidence of the fever the spleen probably returns to its normal size more rapidly than the liver. The more common extent of the enlargement in our own cases was from ten to eighteen ounces, though we found the spleen in one case weighing twenty-nine and a half ounces and in another forty-four and a half ounces. In neither of the latter instances was there any reason to suspect malarial complication. The most extensive enlargement we have found recorded is sixty-eight ounces in a case reported by Küttner.[34]

[Footnote 34: Schmidt's Jahrb., 1865, vol. cxxvi.]

There is usually a correspondence between the stage and extent of the splenic and hepatic lesions, but this is not invariable, and one or the other organ may present a far higher degree of enlargement or much more intense interstitial changes. It may be mentioned, moreover, that in some unusual cases the lesions of the lungs, such as ecchymoses and hemorrhagic infarctions, may be disproportionately marked as compared with those of either the liver or spleen.

The capsule of the spleen often presents a mottled look, with at times large purplish ecchymoses; it is apt to be more or less opaque, and local peritonitis, with thin layers of plastic exudation often forming friable adhesions with the abdominal wall, may exist.

In one of our cases the capsule presented a small perforation or rupture, with an exudation of plastic lymph over an area of four by six inches, and diffuse peritonitis, with effusion of bloody liquid with shreds of lymph throughout the abdominal cavity. This fatal termination is fortunately rare, but there are several other instances on record. The splenic pulp may retain its consistency and firmness, even in cases that have run a long course; but more frequently it is softened, and may be almost diffluent. The pulp is often swollen, so that when cut it projects above the section. The color is darker than normal, and often is of a deep maroon color. This swelling is due to enlargement of the blood-vessels, associated with great increase of the cellular elements of the pulp and with enlargement of the Malpighian corpuscles.

When death occurred early in the disease we found these bodies grayish or grayish-yellow in color and of the size of hempseed, so that the section very thickly studded with them closely resembled shad-roe, and this stage of the lesion is frequently described in our notes as the shad-roe spleen. Subsequently, the Malpighian bodies enlarge still more, and stand out above the section a line or more in diameter, and of a lighter color; not rarely, several of them come in contact, and thus form a considerable mass of irregular shape, resembling the infarctions described below.[35] It is probable that central softening may occur later in the {417} Malpighian bodies, though we are inclined to regard the puriform collections frequently found as chiefly due to the disintegration of hemorrhagic infarctions or of embolic patches. Of these, hemorrhagic infarctions are by far the most common and present the familiar appearances. They may be quite numerous, superficial, or deep-seated, and of variable shape and size. At first dark reddish, firm, and sharply separated from the surrounding pulp, they grew reddish-yellow or yellowish later, softened in the centre, and eventually were transformed into puriform collections. Doubtless, in a large proportion of cases that recover such infarctions exist and are slowly absorbed. Ponfick has shown that these are venous infarctions, the arterioles leading to them being patulous. True arterial embolism does, however, occur, though much more rarely (Ponfick, Murchison), giving rise to firm, wedge-shaped infarctions at the periphery of the spleen, which may undergo degenerative changes similar to those above described. The resulting abscesses may burst into the peritoneum, pleura, lung, or bowel. The microscopic appearances have been most fully described by Ponfick, our own comparatively meagre observations having accorded entirely with his subsequent accurate description. The cells of the swollen pulp contain red blood-discs and pigment, and some present collections of bright granules. The lymphoid cells of the Malpighian corpuscles are at first in a state of cloudy swelling with multiplication of their nuclei, and later show marked granular fatty degeneration.

[Footnote 35: Thus, Wyss and Bock describe "multitudes of minute abscesses as large as poppy or hempseed, and containing a single drop of pus."]

The lymphatic glands present no lesions, and the pancreas is normal.

The peritoneum is not affected as frequently as other serous membranes in this disease. Superficial ecchymoses are, however, quite common, especially so over the solid viscera; and more rarely effusions of blood have been found in the subperitoneal connective tissue, involving the muscular or glandular tissues beneath. We have already mentioned (p. 406) the occasional occurrence of local peritonitis, most frequently of the splenic capsule, and also the rare accident of diffuse inflammation from rupture of the spleen.

The marrow of the bones was carefully examined by Ponfick, who first called attention to the presence of important changes in relapsing fever, which have since been confirmed by other observers. These changes consist in proliferation and subsequent degeneration of the lymphoid cells of the marrow, with multiplication of the nuclei in the walls of the minute vessels and fatty degeneration of their coats. As a result of these changes, spots of puriform softening may form, chiefly in the cancellous tissue of the extremities of the long bones, with the production of localized necrosis, and possibly with extension of inflammation to the neighboring articular cavity.

Considerable space has been devoted to the detailed consideration of the pathological changes in relapsing fever, partly because we believe the fact has not been sufficiently recognized that the disease is constantly attended with important and characteristic lesions. These consist, in brief, of remarkable changes in the blood; of widespread ecchymoses and infarctions, which not rarely undergo puriform disintegration; of hyperplasia and subsequent degeneration of the Malpighian corpuscles of the spleen, with changes in the cellular elements of the splenic pulp; of cloudy swelling of the gland-cells of the liver and kidneys, with a {418} marked tendency to fatty degeneration; of changes in the marrow of the long bones; and, finally, of granulo-fatty degeneration of the muscles, and especially of the heart.

DIAGNOSIS AND RELATION TO OTHER DISEASES.--The entire question of the diagnosis of relapsing fever is dominated by that of spirillar infection. Before Obermeier's discovery the differential diagnosis of the initial paroxysm, and to a less extent that of the subsequent events of a case of relapsing fever, was attended with considerable difficulty. But if, as now seems established, immediately before and throughout the initial paroxysm and subsequent relapses a characteristic spirillum is to be detected in the blood upon proper examination, while it rapidly disappears after the crisis, it is evident that as soon as a suspicion is aroused as to the possible presence of relapsing fever the question may be settled conclusively by the microscope.

None the less is it important to consider carefully, but briefly, the symptoms by which relapsing fever is to be distinguished from various affections which may simulate it, because even the most experienced observers admit that the spirillum cannot be invariably detected; because it is not yet known that a similar organism may not be found in some other affections; and, finally, because on the outbreak of an epidemic of relapsing fever, especially in America, where its occurrence has hitherto been so rare, there is strong probability that the nature of the early cases will not be even suspected until the relapse occurs.

Typhus fever often prevails in an epidemic form simultaneously with relapsing fever, so that it was inevitable they should have been for a time confused. Their essential non-identity is, however, now too well recognized to require any lengthy demonstration. The following statement of the heads of the argument may therefore suffice.

In typhus there is no characteristic spirillum, and the lesions which are truly characteristic of relapsing fever are totally wanting. There are convincing differences in the symptoms, course, and results of the two diseases. There is no evidence to show that when fever has been imported into a locality by a single case, typhus fever has ever produced other than typhus, or relapsing other than relapsing fever. The two diseases often prevail together, and may coexist in the same house, each preserving its own distinct characteristics; and persons exposed to the double contagion may contract one or the other, or first one and then the other at a shorter or longer interval, so that an attack of either exerts no protective power against the other. It must be noted, however, that in a large majority of such cases of successive contagion it is relapsing fever which has been followed by typhus, while the reverse has been observed much more rarely.

In 1869-70 the two diseases were prevalent in Philadelphia, and the wards of the municipal hospitals constantly contained a considerable number of cases of both. Three instances came under our care in which after recovery from relapsing fever the patient contracted typhus. All of these patients were employed as assistant nurses, and were continuously under observation from the early part of their attack of relapsing fever to the end of the attack of typhus. In one case the interval of health between the close of the relapse and the onset of typhus was forty-four days; in the second it was thirteen days. In both cases the original disease was {419} thoroughly characteristic and the subsequent attack of typhus was typical. In both death followed, and the post-mortem examination verified the above statement. The third patient had severe relapsing fever, from which he recovered and returned to work, though with pains in the legs, shoulders, and forehead. After an interval of apparent health of eleven days he developed a well-marked attack of typhus, which terminated on the twelfth day in recovery. It may be added that although typhus is not of frequent occurrence in any portion of North America, there have been a number of epidemics unattended with a single case presenting the features of relapsing fever.

Between well-marked cases of the two diseases there should be no difficulty in making a prompt diagnosis. Relapsing fever is distinguished from typhus clinically by the severity of the initial chill; the rapid elevation of the pulse and temperature; the comparative infrequency and mildness of cerebral symptoms, despite the intense fever; the severity of the gastric symptoms, nausea and vomiting; the enlargement of the liver and spleen, with marked abdominal pain and soreness; the frequency of jaundice, of epistaxis, and of other hemorrhages, and of anæmic murmurs over the heart and large vessels; obstinate insomnia; vertigo; peculiar rheumatoid pains and perversions of sensation; the frequency of sweating during the high pyrexia; by the occurrence of crisis, subnormal temperature, apyretic interval, and relapse; the rarity of measly eruption and of bed-sores; the frequency of pneumonia, diarrhoea, ophthalmia, oedema, and desquamation as complications and sequelæ; the usual occurrence of abortion in pregnant females; the protracted course of the disease, and its remarkably low mortality despite the severity of the symptoms, except in cases of complicated or typhoid type; and, finally, by the modes in which death occurs. Of course to this must be added the specific result of examination of the blood in relapsing fever.

Doubt will arise only in very rare cases where a measly eruption appears on or before the fifth day of relapsing fever, with headache and mild delirium, but without severe gastric symptoms, epistaxis, or jaundice. If no relapsing fever were prevalent at the time, such a case might well be regarded as one of mild typhus until the crisis and the relapse disclosed its real nature. But if the two diseases were known to be prevalent in the community, examination of the blood would properly be made at once and the diagnosis be established.

The diagnosis between ordinary cases of relapsing fever and typhoid is readily made by the gradual onset and peculiar course of the pyrexia in the latter disease, as well as by the frequency of delirium, of abdominal distension, and of diarrhoea, and by the characteristic eruption. The occurrence of epistaxis, bronchial irritation, and splenic enlargement is common to both, and an eruption of small rose-pink spots has been noted by some observers (Carter, pp. 194, 317). But jaundice, enlargement of the liver, hypochondriac pain and soreness, excessive nausea and vomiting, severe rheumatoid pains, and numbness and tingling of the extremities, are very significant symptoms of relapsing fever. Attention has already been called to the grave type of relapsing fever in which the typhoid state is fully developed, and to the fact that in such cases the pyrexia is often modified, the onset less abrupt, the crisis imperfect, and the interval occupied by an irregular post-critical {420} symptomatic fever. It is altogether probable that such cases have not rarely been regarded as of true typhoid character; and indeed the attempt has been made by Griesinger to establish as a separate and independent affection, under the name of bilious typhoid fever, a group of cases which close examination seems to show to be chiefly composed of grave complicated relapsing fever with a certain proportion of true typhoid fever, complicated with jaundice.

The recognition of the bilious typhoid type of relapsing fever is based upon the history of the case; the mode of onset; the greater severity of the pains, arthritic and abdominal; the early appearance and intensity of the jaundice; the more marked enlargement of the liver and spleen; the marked tendency to hemorrhages from various surfaces; the peculiarities which careful study of the temperature curve will show, especially about the time of crisis; the rarity of eruption; the characteristic spirillum;[36] and the totally different anatomical lesions, which are, unfortunately, often demonstrable, as this form of relapsing fever is fatal in from 33 to 50 per cent. of cases.

[Footnote 36: As first demonstrated by Motschutkoffsky.]

Since the discovery of the spirillar test for relapsing fever it may be said that Griesinger's bilious typhoid must be stricken from medical nosology as an independent affection.

The case of Charles Hood, on page 396, is a good example of the bilious typhoid form which occurred not rarely in the Philadelphia epidemic.

Murchison points out that, owing to the frequent occurrence of jaundice in relapsing fever, this disease has been mistaken for yellow fever by such good observers as Graves, Stokes, and Cormack. Difficulty in diagnosis would be likely to arise only in regard to the bilious typhoid type of relapsing fever, and since its clinical history has become so well known, a mistake is not likely to occur. The geographical distribution of the diseases is widely different. Yellow fever is influenced powerfully by season and temperature, while relapsing fever is independent of both. Negroes are but slightly liable to yellow fever, while relapsing fever attacks them with special violence. Yellow fever is not contagious, but infectious, and second attacks are extremely rare; relapsing fever is one of the most contagious of the zymotic diseases, but one attack does not protect against a subsequent one. The mortality, the anatomical lesions, the course of the pyrexia, the leading clinical symptoms, are all widely distinct in the two affections; and, finally, no spirillum has been found in the blood in yellow fever. Yellow fever is an extremely fatal disease; the ordinary form of relapsing fever has a mortality of 2 to 10 per cent.; the bilious typhoid form, one of 33 to 50 per cent. In yellow fever the spleen is but slightly enlarged, and the liver is pale and softened; in relapsing fever the liver and spleen are greatly enlarged, and there is great tenderness over the hypochondriac region. In yellow fever albuminuria is much more common, and the urine more frequently suppressed, than in relapsing fever.

The sudden onset, the severe headache and pains in the limbs, the vomiting, jaundice, epigastric tenderness, enlargement of the liver and spleen, occasional epistaxis, hematemesis, or hematuria, absence of characteristic eruption, liability to herpes facialis, pneumonia, and diarrhoea; the occasional occurrence of remissions in the pyrexia, and even of more or less fully-developed chills for several successive days during the initial paroxysm or {421} the relapse, suffice to explain the difficulty which may arise in distinguishing the bilious form of relapsing fever from bilious remittent fever. But the latter disease arises exclusively from malaria, and is therefore powerfully influenced by season and locality; is not contagious; does not present anything approaching to the crisis, the apyretic interval, or the abrupt relapse of relapsing fever; presents pigmentary changes in the blood, instead of the spirillum; and lesions of the spleen and liver totally unlike those characteristic of relapsing fever; can be promptly controlled by antiperiodic doses of quinine, and therefore should have a mortality far less than that of the grave form of relapsing fever. It is not necessary to pursue this subject further, but a reference to the temperature charts of Carter[37] or of Litten[38] will show that in some epidemics single paroxysms resembling those of quotidian ague might occur during the interval between the initial paroxysm and the relapse, or a series of two, three, or more such paroxysms of quotidian or tertian type might represent an entire relapse. Such phenomena are wholly uncontrollable by quinia, and are presumably dependent upon irregularities in the specific infection, instead of upon a blending of malaria with the poison of relapsing fever. There is some ground for believing, however, that those who have recently passed through an attack of the latter are highly, perhaps unusually, susceptible to malarial infection, as we have already seen they are liable to contract typhus.

[Footnote 37: Op. cit.]

[Footnote 38: Deut. Arch. f. klin. Med., xlii. 1874.]

The chill, the sudden and high fever, the acid sweat, the high-colored urine, the intense pains and soreness, and the occasional murmur over the heart, will in some cases of relapsing fever suggest the idea of severe rheumatic fever, with illy-developed articular inflammation and with a tendency to hyperpyrexia. The urgent danger presented by the latter condition and the necessity for immediate recourse to cold baths and large doses of quinine or of the salicylates, render it highly important that no such error of diagnosis should be made. It will usually be avoided readily by observing that in relapsing fever there are great nausea, repeated vomiting, insomnia, peculiar formication of the extremities, jaundice, early enlargement of the liver and spleen, with abdominal pain and soreness, and a tendency to epistaxis; and, further, that despite the high temperature, cerebral symptoms such as result from rheumatic hyperpyrexia are not threatened, except in grave typhoid cases or just preceding the crisis.

The onset of relapsing fever may suggest forcibly the invasion period of small-pox, with its marked rigors, high fever, lumbar pain, aching in the head and limbs, nausea and vomiting, and if the patient is known to have been exposed to the contagion of both diseases a diagnosis would be impossible until the third day. But such a dilemma can rarely occur, and under ordinary circumstances the patient's antecedents will enable a correct opinion to be formed.

Severe cases of simple febricula with marked gastric disturbance may, as remarked by Jenner, closely simulate relapsing fever; and the same is true of attacks of acute gastro-hepatic catarrh, with severe headache, sharp fever, cholæmic eye, epigastric tenderness, and frequent vomiting. Of course there is no danger under ordinary circumstances of these simple conditions being regarded as relapsing fever, but when the latter is prevalent in epidemic form it is probable that the mistake is frequently made. {422} Although an immediate diagnosis might be possible only by microscopic examination of the blood, the peculiar clinical symptoms of relapsing fever would soon be found wanting, and suitable treatment would bring the simpler affection under control.

Acute yellow atrophy of the liver occurs chiefly in pregnant women, though it is also met with in men and children; but it is so rare that should a case of it come under observation during the prevalence of relapsing fever there is considerable danger that its nature would be overlooked. It resembles relapsing fever in the occurrence of jaundice and other signs of hepatic disorder, of delirium, and of a tendency to hemorrhage from various surfaces. The temperature, however, is more moderate, and does not exhibit the sudden remission of relapsing fever; the liver is usually demonstrably diminished in size; severe nervous disturbances, such as convulsions followed by stupor and then by coma, are more constant; while the occurrence of spirilla in the blood of relapsing fever and of leucin and tyrosin in the urine of acute yellow atrophy serves to distinguish completely the two diseases. Acute yellow atrophy is, moreover, invariably fatal.

With ordinary care there is but little danger that any of the local complications of relapsing fever will so absorb attention as to lead to a neglect of the specific general disease, so that the cerebral symptoms should be readily distinguished from the onset of any acute intracranial affection; the parotitis which occasionally appears early in the disease should not be confounded with idiopathic mumps; and so for other complications. There is far more danger, indeed, lest some of the complications may be overlooked; and this is especially true of pneumonia, one of the most frequent and most important of them all. Its occurrence is the cause of the supervention of grave typhoid symptoms or of the modification of the normal course of the pyrexia in so many cases that nothing but a systematic daily examination of the lungs will avert serious oversights.

MORTALITY AND PROGNOSIS.--The rate of mortality has varied in different epidemics from 2 or 3 to 24 per cent. Murchison shows that out of 2115 cases admitted to the London Fever Hospital during a period of twenty-two years, and embracing two distinct outbreaks, only 39 proved fatal, making 1.84 per cent. mortality. Adding to these the results of Scotch and Irish epidemics, a total of 18,859 cases, with 761 deaths, is reached, giving the rate of mortality for Great Britain as 4.03 per cent. The great Indian epidemics studied by Carter gave 111 deaths out of 616 cases, equal to 18.02 per cent. Recent German epidemics have given from 5 to 10 per cent. The above rates are obtained where all the cases observed during an epidemic are included. If, however, the mortality of the ordinary form of relapsing fever is computed separately from that of the bilious typhoid form, it does not exceed 2 to 5 per cent., whilst the mortality of the latter form rises to from 33 to 50 per cent., or even higher.

In the Philadelphia epidemic, out of a total of 1174 cases there were, as nearly as can be ascertained, 169 deaths, giving a rate of mortality of 14.4 per cent. Taking all the cases admitted to the hospital under our observation, many of which entered at a late period of the disease and not a few when moribund, the mortality was not less than 13 per cent. {423} The mortality among the negroes who were attacked with the disease was considerably greater than among the whites. Finally, if the mortality of the bilious typhus form be considered separately--although from the frequency of jaundice in this epidemic and the numerous gradations of severity presented it is difficult to form a sharply defined group of this character--it was certainly not less than 50 per cent.

The date of death varies with the epidemic, the form of the disease, and the previous condition of vitality of those attacked. Ordinarily, by far the larger proportion of deaths occur during the first relapse or the second interval, but in bilious typhoid cases, presenting grave complications, especially pneumonia or severe hemorrhages at an early date, or in cases occurring in intemperate subjects, or in those previously in impaired health, the mortality is much heavier in the initial paroxysm or the first interval than at later periods.

Youth exerts the same favorable influences upon the result of relapsing fever as it does in the case of typhus and typhoid. Murchison states that of 717 male patients under twenty-five years of age admitted into the London Fever Hospital, not one died, and in most epidemics similar, though not equally marked, results have been noted. In some epidemics the mortality among young children has been considerable. As a rule, the percentage of deaths increases with each decade after thirty years.

Sex does not exert any definite or constant influence upon the mortality. The number of males affected is far greater; they are liable to be exposed to the contagion in its most concentrated form; a larger proportion of them are probably the subjects of intemperance than in the case of females; and thus most statistics agree in making the mortality somewhat greater in the male sex; but, all things being equal, there is no good reason for holding that sex itself has any value in determining the result.

As in other zymotic diseases, the mortality from relapsing fever is highest during the early period of an epidemic, and the type of the disease grows milder as the epidemic declines. Cases of the bilious typhoid form have become notably less frequent during the later stages of some epidemics than at an earlier period.

Marked difference has been observed also as to the action of remedies at different stages of epidemics, the early cases exhibiting an extraordinary resistance to remedies, and especially to anodynes, which passes away later. When typhus and relapsing fevers have prevailed together, and a clear discrimination between the two sets of cases has not been made, it has appeared that the mortality increased as the epidemic advanced, but this apparent exception has been due to the fact that at first the cases of relapsing fever were in the majority, while later those of typhus, the much more fatal disease, preponderated.

Epidemics of relapsing fever prevail at all seasons, but more commonly they are at their height during the colder months of the year. The total mortality will of course correspond, but the actual percentage is not constantly greater during any one season, although it is probable that the greater liability to chest complications during the colder months will render the disease more fatal then.

The gravity of relapsing fever has varied so greatly in different epidemics that it is very difficult to determine what influence upon the mortality {424} has been exerted by mere difference of race. A further source of difficulty is found in estimating the differences in the physical conditions of the poorer classes in the various communities affected. The mortality has been exceptionally high in the Russian and Indian epidemics and in some of the German ones, while in the British epidemics it has uniformly been light. It is interesting to note that in the Philadelphia epidemic, where the great majority of patients were Irish or negroes, the mortality was high, over 14 per cent. The previous condition of the Irish patients must certainly have contrasted favorably with that of the individuals attacked in the Dublin and Belfast epidemics, so that the difference in result seems attributable only to a greater virulence of the disease. As an ample opportunity was here afforded to judge of the relative severity of relapsing fever in the negro and white races when the cases occurred at the same season, at the same stage of the epidemic, and in individuals living under nearly similar conditions, it may be stated that the conclusion of all who studied the question closely was that the disease was much more severe among negroes, and in particular that they displayed a greater tendency to serious complications and to the bilious typhoid form.

Although the degree and virulence of the infection undoubtedly constitute the most important elements in determining the mortality, the previous health and habits of those attacked with relapsing fever exert an influence upon the result. This is especially true of habitual intemperance, which, by disposing to disease of the liver and kidneys, greatly increases the liability to a fatal result. It has been seen (page 409), however, that even when acute catarrhal nephritis existed at the time of the attack severe relapsing fever might terminate favorably. Another observation which we made frequently, and which coincides with what is well known in regard to typhoid and typhus, is that improper exertion and exposure during the stage of incubation and immediately after the invasion produced a highly unfavorable effect on the subsequent course of the disease, and seemed in particular to dispose to dangerous or fatal collapse at the critical periods.

Apart from these general considerations, there are many special points to be considered in regard to the prognosis of relapsing fever:

If after the crisis of the invasion there is not rapid and decided improvement, complications should be suspected.

A sharp rebound of temperature quickly following crisis may be followed by speedy death.

Mere elevation of temperature during the invasion and the relapse, even though to an extreme height, is not attended with the danger which even a somewhat lower degree would indicate in other zymotic diseases.

Increased elevation toward the expected time of crisis should arouse anxiety, as sudden and dangerous cerebral symptoms may occur.

Prolonged duration of the pyrexia, or the substitution of irregular gradual defervescence (lysis) for the characteristic crisis often associated with typhoid symptoms as are these conditions, is significant of complications and of danger.

Wild delirium during the pyrexia, or transient active delirium about the time of crisis, is not necessarily unfavorable, but continuous low delirium, with disposition to stupor, is associated with a typhoid tendency and is frequently followed by death. Excessive muscular {425} tremor or convulsions are highly unfavorable, but not necessarily fatal, symptoms.

Cardiac murmurs are not of serious import. The pulse is not usually as rapid in proportion to the temperature as in typhus or typhoid, and an excessively rapid pulse toward the expected time of crisis, especially if associated with feebleness of the heart's action, points to the danger of sudden collapse at or soon after that time. Previous cardiac disease, especially fatty degeneration in habitually intemperate persons, increases this danger. Continued frequency of pulse after the crisis indicates some complication or the danger of some accident.

Cough of a bronchial origin is not a specially unfavorable symptom, but if associated with the physical signs of pneumonia and with marked disturbance of respiration it indicates extreme danger.

Epistaxis, even when copious, often occurs in favorable cases, but hemorrhage from the stomach or the kidneys is usually, though not invariably, followed by death.

An eruption, measly or of pink spots, with or without minute petechiæ, is rare, and usually occurs in severe cases, but is not of specially unfavorable significance unless associated with the typhoid state or with patches of purpura.

Hiccough is a much less unfavorable symptom in relapsing fever than in typhoid or typhus, and vomiting, even frequent and persistent, may occur in cases of ordinary severity.

Enlargement of the liver and spleen indicates special risk only when persistent for some time after the relapse, in connection with persistent irregular fever. Jaundice has no necessarily unfavorable signification, is frequent in ordinary cases in some epidemics, but when it is associated with the other features of the bilious typhoid form the danger is extreme, at least 33 per cent. of such cases proving fatal.

Slight transient albuminuria may exist without special danger, but if associated with evidences of catarrhal nephritis, or if extreme diminution of urine, with or without albuminuria, exists, cerebral symptoms are apt to ensue, with a high degree of danger.

All serious complications--parotitis, erysipelas, dysentery, abortion, pneumonia, and, above all, peritonitis--greatly increase the risk.

It is not possible to determine in what cases the relapse will fail to occur. Motschutkoffsky's statement, that when a slight post-critical rise occurs a relapse will follow, must be applicable only to a limited number of cases.

In all cases at least one relapse must be expected; the patient in the interval must be regarded as still sick, and after the close of the relapse he must still be treated with rigid care until convalescence is permanently established. It must be remembered in hospital practice that many patients enter toward or after the crisis of the first paroxysm, so that caution is needed in estimating the effect of remedies and the period of the disease.

The undue prominence of certain conditions during the course of the disease is apt to be followed by corresponding sequelæ, and emaciation, anæmia, dyspepsia, diarrhoea, dysentery, enlargement of the spleen and rheumatoid pains may then be anticipated. The liability to ophthalmia and affections of the middle ear is not to be forgotten.

{426} CAUSES OF DEATH.--In fatal cases death occurs from exhaustion dependent on the protracted and severe sufferings of the patient; from cerebral symptoms; from hyperpyrexia; from the virulence of the toxæmia; from uræmic poisoning; from sudden collapse; or from some complication, such as hemorrhagic meningitis, hemorrhages, pneumonia, dysentery, rupture of the spleen, peritonitis, or abortion.

TREATMENT.--The indications for treatment presented by regular cases of relapsing fever seem to be--to moderate the pyrexia; to relieve distressing symptoms, especially pain, insomnia, and gastric irritability; to sustain the strength of the system; to prevent or modify the relapses; and to avoid complications and sequelæ.

It is needless to observe that until the nature of the specific cause of relapsing fever is fully determined, whether the spirillum occupy that relation or not, it is impossible to direct our efforts rationally toward its neutralization or elimination. The various remedies which have been employed for these special purposes have no clinical support to recommend them. And while experiment has shown that the activity of the spirillum is readily destroyed by the direct action of various weak solutions, as of quinine, carbolic acid, iodine, and mineral acids, no special curative effect follows the internal administration of these remedies, even in the largest doses consistent with safety. In fact, there can scarcely be any disease in which treatment is less satisfactory or its results more difficult to estimate. The marked difference between various epidemics, and the wide variation presented by the development of individual symptoms in different cases of the same epidemic, fully account for this.

Quinine, as might be expected, has been largely used, in the hope that it might control the pyrexia or prevent the relapse. Murchison[39] quotes a considerable amount of evidence from various sources to show that it does not possess either of these powers. It was administered to a considerable number of our cases, either in small and frequently repeated doses during the pyrexia or the intermission, or else in large doses repeated several times in immediate anticipation of the expected time of the relapse. Thus in some cases three grains of sulphate of quinia were given every two or three hours until tinnitus was produced, and then this was maintained during the remainder of the pyrexia and of the intermission. The amount given daily was from thirty to forty-two grains. It seemed to rather increase the discomfort in the head, and in some cases it aggravated the irritability of the stomach. The pyrexia was certainly not controlled by it. Given in the same manner during the intermission, it was usually well borne, but was not effectual in preventing the relapse. It is true that in some cases the subsequent relapse seemed to be somewhat modified.

[Footnote 39: Op. cit., p. 408.]

Thus in one case 30 grains were given on the 6th of April; 39 grains on the 7th; 39 grains on the 8th; 42 grains on the 9th; and 60 grains on the 10th; the critical fall had occurred during the night of the 7th, and the relapse began on the evening of the 9th, but the rise in temperature was less abrupt than usual, and the relapse lasted less than five days. It was quite severe, however, so that it is doubtful whether the apparent modification was anything more than is frequently observed in cases where no quinine has been administered.

In another case the fall in temperature at the end of the first paroxysm {427} was from 105.5° to 97° on March 26th: 35 to 40 grains of sulphate of quinine were given daily on April 4th, 5th, 6th, 7th, and 8th; the temperature began to rise on the 3d, but the severe pyrexia and the usual symptoms of the relapse were limited to a period of less than thirty-six hours. This is a less common irregularity, and yet does not afford sufficient evidence of the efficiency of quinine. In other cases, however, as already stated, no appreciable effect followed its administration in this manner.

To illustrate the other method of giving quinia, a case may be quoted in which 20-grain doses every three or four hours were given from April 25th to April 29th, so that in four days 575 grains were taken. The initial paroxysm was of average severity, and terminated at the end of the seventh day, April 20th. The quinine did not postpone the relapse, which occurred on April 28th, but was of much less than the usual duration.

In no other case in which these large doses were given was there even as much reason as in the above instance to attribute to quinine any positive influence upon the course of the disease.

In order to demonstrate that the failure of quinine was not dependent upon a want of absorption, Muirhead injected large amounts subcutaneously with no better results.

In conclusion, it may be said that the evidence shows positively that quinine possesses no specific influence whatever upon relapsing fever; that in only occasional cases, if at all, will even enormous doses given during the intermission postpone or modify the subsequent relapse; and that it is not effective in reducing the temperature. In view, therefore, of the usual gastric irritability and tendency to vertigo and headache, which seem to be increased by large doses of quinine, and, further, in view of the small mortality, and of the fact that when death occurs it usually comes from causes over which large doses of quinine could exert no influence, it seems clear that this drug should be prescribed only in tonic doses and only in cases where it is well tolerated by the stomach.

Arsenic was used in a considerable number of our cases with the view of determining if it possessed any power of relieving the severe pains or of influencing the relapse. It was administered in the form of Fowler's solution (Liq. potassii arsenitis), and was given exclusively by the mouth. If given during the intermission, it was well borne in doses of five to ten drops every four or even every three hours, given freely diluted with water and immediately after food. In several cases it quickly induced puffiness about the eyes, but no effect whatever was produced on the pains or on the succeeding relapse. In more than one such case there was an unusually profuse crop of sudamina during the relapse, many of the vesicles breaking and being followed by brownish stains. When given during the pyrexia it aggravated the nausea and vomiting, so that it had to be suspended. In one unfortunate case, indeed, although promptly suspended, the arsenical solution seemed to have assisted in the establishment of vomiting and purging, which proved uncontrollable and contributed greatly to the fatal result. Hypodermic injections of arsenic have been used considerably with no better results. There seems, therefore, to be no reason whatever for any further use of this drug in relapsing fever.

{428} The high pyrexia and the severe rheumatoid pains have naturally suggested the use of salicylic acid and the salicylate of soda. We were not sufficiently aware of their antipyretic properties in 1869-70 to have recourse to them, but in more recent epidemics Unterburger[40] and Riess[41] have found that large doses of the latter substance (one hundred grains or more daily) will reduce the temperature either in the initial paroxysm or in the relapse, but that the disease is not cut short nor are the lesions of the blood or solids prevented.

[Footnote 40: Jahrb. f. Kinderheilk., v. x., 1876.]

[Footnote 41: Deutsch. Med. Wochnsch., Dec., 1879.]

It must be borne in mind here, as in connection with the action of quinine, that apparent modifications of the relapse are to be viewed with great distrust, since such great irregularities therein naturally present themselves. Care must further be taken lest such attempts to reduce the temperature aggravate the irritation of the stomach, and by lessening the power of taking food induce more serious exhaustion than would have resulted from the unchecked pyrexia. The evidence in our possession is not sufficient to justify a positive decision as to the therapeutic value of the salicylates in relapsing fever, but, apparently, they are applicable to only a portion of the cases, and in these are of but limited utility.

The same failure which has followed the use of quinine, of arsenic, and of salicin and the salicylates has attended the effort to prevent the relapse by berberine, benzoate of soda, tincture of eucalyptus, and other reputed antiperiodics.

Digitalis, veratrum viride, and aconite were used by us quite freely as antipyretics. The first two of these were often suspended on account of the irritability of the stomach, and no valuable results followed their use when well tolerated. Aconite in small doses, frequently repeated, as one drop every two hours, seemed to aid in allaying nausea and to exert some slight influence upon the fever. In cases where there was a distinct tendency to heart-failure, digitalis was given freely with advantage.

Cold baths were not used to reduce the temperature in any of the cases under our observation. They have been employed in other epidemics, but, as far as we know, with no other effect than to cause merely temporary lowering of temperature, without any decided relief to the other symptoms and without any apparent influence upon the course of the disease. Frequent spongings with cool water and the application of ice to the head gave only slight and temporary relief.

Simple febrifuge remedies, such as effervescing draught or spirit of nitrous ether with solution of acetate of ammonium, were well received by the stomach, and appeared to promote perspiration and the more free secretion of urine.

Finding all our efforts to control the pyrexia so unsuccessful, recourse was had in a large proportion of our cases to the hyposulphite of soda, given, dissolved in two ounces of water, in doses of twenty grains every two or three hours. In two cases it seemed to increase nausea, and at times it caused some purging, but otherwise it was well borne by the stomach, and, indeed, frequently appeared to aid in controlling vomiting. The records show that this drug was given in only two or three of the fatal cases, so that although the patients who took it regularly presented every grade of severity of the disease, they did well uniformly. It is certain, however, that the hyposulphite of soda exerted no specific effect {429} upon the disease; it did not reduce temperature, it did not prevent or modify the relapses nor relieve the severe pains; it may have promoted more free and healthy secretions, and, by tending to prevent vomiting, may have aided in maintaining nutrition; but, on the whole, it may fairly be doubted whether this remedy merits any more extended trial.

One chief reason of the failure of antipyretics in relapsing fever is to be found in the existence of widespread irritative lesions of the glandular and mucous tissues, which combine with the specific blood-changes in causing and maintaining the high temperature. It is not surprising, therefore, that the remedies which afford the greatest relief in this disease are opiates and sedatives to the gastro-intestinal mucous membrane. Opium, or morphia, must indeed be regarded as the basis of the rational treatment of relapsing fever. It is called for by the insomnia, the severe headache and the pains in various parts of the body, the nausea and vomiting, and the pyrexia. It does not appear to have been as prominent a feature in the treatment of other epidemics as we found it necessary to make it in Philadelphia. Parry[42] used it very freely, chiefly in the form of opium, by the mouth, and found a singular tolerance exhibited by his patients, several of whom took as large a dose as three grains every two hours during the afternoon and night without producing any sleep or even any contraction of the pupils. This resistance to the action of opium was observed chiefly in the early part of the epidemic, and we may add that it was exhibited chiefly when opium was given by the mouth. When morphia was used hypodermically we found that one-fourth of a grain, given at intervals of six to twelve hours, afforded very great relief to the pains, aided and relieved vomiting, and often induced quiet, refreshing sleep. Its use was not contraindicated by jaundice, by cough or pulmonary congestion, or by moderate contraction of the pupils. It was frequently given so as to maintain decided drowsiness throughout the pyrexia. When the pains persisted during the intermission the morphia was continued in smaller doses or at longer intervals. It occasionally happened that when patients were thus kept continuously under opium influence no relapse occurred; but here, as in regard to the action of quinine, it may safely be asserted either that what was regarded as the initial paroxysm was in reality the relapse, or else that the absence of a relapse was a mere irregularity, and in no way to be attributed to the action of the opium. On the other hand, in cases presenting a tendency to the typhoid state, with a disposition to stupor, or where the urine was scanty and albuminous, no opiate was administered.

[Footnote 42: Loc. cit.]

We have already stated that in our cases quinine in acid solution was frequently ordered, and it answered very well to add to each dose of this a suitable amount of morphia.

Atropia, in the dose of gr. 1/60 to gr. 1/40, was usually associated with the hypodermic injections of morphia. This was done particularly in cases where the pains were very severe, when the pupils were disposed to be contracted, or when there was continued profuse sweating. In addition to this, atropia was continued without morphia during the intermission in a few cases. The patients proved susceptible to its influence, and dryness of the mouth with dilatation of the pupils was readily {430} produced by gr. 1/60 every six hours. In one case gr. 1/40 every four hours for two days caused delirium, with the usual symptoms of belladonna action, all of which passed away quickly after withdrawal of the drug. But in none of these cases was the relapse influenced in the least.

Other remedies may be used for the relief of the insomnia, which is always one of the most distressing symptoms. Chloral and bromide of potassium have been found serviceable in various epidemics, and some observers have preferred them to opium for the relief of headache and insomnia. They did not prove reliable in the Philadelphia epidemic of 1869-70. Bromide of potassium, even in large doses, produced scarcely any effect, and, while in a few cases chloral in doses of gr. xx. gave positive relief, in the majority of instances 40 grains failed to cause sleep or relieve suffering. It must not be forgotten also that, as there is a special tendency to cardiac failure in this affection, the action of chloral must be closely watched.

In a small series of our cases where muscular pains, hyperæsthesia, and twitching were marked succus conii was given quite freely, but without any apparent benefit.

The condition of the stomach required attention in almost every case. Nausea, vomiting, and epigastric and hypochondriac soreness were the prominent symptoms. Anorexia was usually complete during pyrexia, and not rarely patients were admitted to the hospital who asserted that for one or more days they had not taken any nourishment whatever. Under such circumstances, and in a disease where the tendency to prostration and cardiac failure calls for stimulants and food, it is evident that strict care must be given to the diet. In many cases skimmed milk with lime-water, meat broths, arrowroot, or gruel, could be taken in small amounts at short intervals, and retained. But whenever these are rejected, no attempt should be made to persist in their use, but koumiss, whey, or chicken-water should be substituted, and continued until the stomach grows retentive. Equal care must be paid to the selection of a suitable form of stimulus. It may be proper to employ a mild and relaxing emetic if the patient be seen at the onset of the disease and if there is reason to suspect the presence of indigested food in the stomach, but under any other circumstances there seems no reason for its use in a disease where vomiting is so common and gastric irritability one of the most troublesome symptoms. Nor should purgatives be given save when very positive indications exist for their use.

Constipation is rarely obstinate; the amount of nourishment taken is very small; in a considerable proportion of cases there is diarrhoea, or at least a sensitive state of the bowels; and as a consequence it is preferable in nearly every case to dispense with laxatives entirely, and, if the bowels must be opened by assistance, to administer a simple enema.

When irritability of the stomach is marked, benefit may be derived from very small doses of calomel frequently repeated, as, for example, gr. 1/8 or 1/4 every one or two hours. Subnitrate of bismuth may be used in combination with this or as a substitute for it. In several instances more prompt relief was obtained from nitrate of silver given in the dose of gr. 1/12 every three or four hours, dissolved in thin mucilage of acacia.

Stimulants were remarkably well borne, and their administration in such form as was acceptable to the stomach was clearly of service, {431} even from an early period of the disease. As a rule, whiskey was employed, given in the form of milk punch. By carefully graduating the amount of alcohol, and when necessary diluting the milk freely with lime-water, the stomach usually received it well. If circumstances favored, dry champagne, or brandy or sherry in carbonated water would often prove preferable. The exhausting nature of the disease, the marked tendency to cardiac failure, and the inability to digest an adequate amount of nourishment, all indicate the early use of stimulants. In cases where a tendency to the development of the typhoid state existed alcohol was freely given, even to the extent of sixteen ounces of whiskey in twenty-four hours. Other stimulants were usually given in these cases, such as carbonate of ammonium, especially if pulmonary congestion existed; turpentine, especially if tympany was marked; or Hoffmann's anodyne or spirit of chloroform, if muscular twitchings, hiccough, or insomnia with wandering delirium were prominent symptoms. In all cases of severity the use of tonics and stimulants should be maintained in reduced doses during the intermission and for some days after the final fall of temperature.

It remains to allude briefly to certain special remedies and to certain symptoms requiring special treatment. Formerly, much diversity of opinion existed as to the propriety of venesection or local depletion in relapsing fever, but Murchison concluded, after a careful examination of the evidence, that it had not been shown to be of service; and certainly the disease as it occurred in Philadelphia in 1869-70 presented no indication whatever for even the mildest depletory measures. This corresponds with the recognized plan of treatment in all the specific fevers.

Blisters are not so objectionable in relapsing fever as in either typhus or typhoid, and there are several conditions in which they have been found decidedly useful. In cases where the headache has obstinately resisted cold applications, bromide of potassium, and opiates, a blister to the back of the neck has afforded marked relief, with no unfavorable result. Again, in cases where the vomiting and epigastric distress were severe and obstinate the application of a blister three inches square to the epigastrium is to be recommended.

Chloroform has proved of value for the relief of various symptoms in relapsing fever. As already stated, it was found the most useful remedy for the hiccough which was so troublesome in a number of our cases, and especially in those where jaundice was pronounced. It also seemed serviceable in controlling the peculiar chills which in varying degrees of severity were present in a few cases, recurring at about the same hour on successive days. These rigors or chills were uninfluenced by very large doses of quinine or other antiperiodics, but were apparently controlled by full doses of chloroform given in advance of the expected hour of recurrence.

Jaundice, which, as has been stated, is partly of hæmic origin, but is probably also due in part to obstruction from catarrhal swelling of the mucous membrane of the bile-ducts, is not influenced by mineral acids, and still less should mercurials or purgatives be administered for its relief. It would seem proper, in cases where this symptom is marked, to observe special care in diet and the use of stimulants, and to employ local sedative {432} astringents, such as small doses of nitrate of silver combined with opium and belladonna.

Muscular soreness, pains, and tremor may call for special treatment on account of their severity. The only remedy which has proved useful in relieving the first two of these symptoms is opium, conjoined with the external use of anodynes. Iodide of potassium fails even in doses as large as can be borne, and the same is true of muriate of ammonium and cimicifuga, which we used thoroughly without any effect. In the muscular pains, however, which torment the patient during convalescence, the ammoniated tincture of guaiacum was found of service. Atropia hypodermically and chloroform internally have been found useful for the relief of severe muscular twitchings.

Upon the whole, therefore, it will be seen that in ordinary cases a supporting and expectant plan of treatment is all that is required. Abandoning the idea of forcibly controlling the fever or of preventing the relapse, care should be given in the first place to the diet and to judicious stimulation.

Opium or morphia should be used to control pain, excitement, and insomnia, aided, as far as the latter is concerned, by bromide of potassium or the cautious use of chloral. Cooling drinks should be allowed, cool applications made to the head, and the body should be repeatedly sponged with cooling and disinfecting lotions. If the stomach is retentive, quinine in moderate doses may be given in acid solution, alternating with a simple fever mixture; but if nausea and vomiting are present, the first purpose will be to allay them by the appropriate measures already discussed.

Epistaxis is a frequent symptom, but usually requires no special attention. Occasionally it is profuse, and then should be promptly checked, since serious exhaustion may follow its continuance. If, therefore, mild astringent applications do not arrest it, recourse must be had to the tampon saturated with diluted Monsell's solution.

The urine must be closely watched and frequently analyzed in relapsing fever. In some epidemics serious alterations in this secretion are rare; in others it is not uncommon for the urine to be scanty, and to contain albumen or blood. When this latter condition is presented, especially if at the same time uræmic symptoms exist, dry cups should be applied over the kidneys, to be followed by the use of dry heat, and free perspiration should be promoted by hot-air baths or by the hot wet pack. It is probable that jaborandi given in repeated small doses, so as to avoid any depressing effect on the heart, will be found valuable in such cases. Infusion of digitalis, with spirit of nitrous ether or with acetate of potassium, may also be used with advantage.

Absolute rest must be insisted on throughout the entire period of paroxysm and relapse. The records of every epidemic present instances of sudden death from cardiac syncope following trifling exertions. The patients should therefore be kept strictly quiet in bed from the initial rigor until their strength is fully restored after the relapse. As the danger of collapse is especially great at the time of the critical fall in temperature, the patient should be closely watched as the end of the initial paroxysm and of the relapse approaches. If there is any sudden rise of temperature, with head symptoms due to hyperpyrexia, large doses {433} of quinine, ice to the head, cold spraying, or the cold bath must be promptly used. As sweating begins the body must be covered with a warm blanket and warm stimulating drinks be administered. If any marked tendency to collapse is observed, the subcutaneous injection of strychnia or of ether and digitalis, conjoined with diffusible stimulants internally and hot applications externally, are to be employed immediately. The special remedies required for the various complications and sequelæ have already been sufficiently indicated.

I desire in conclusion to acknowledge the important assistance received from Drs. Geo. S. Gerhard, Louis Starr, Charles Shaffner, and R. G. Curtin, who, under the supervision of my colleague, the late Dr. Edward Rhoads, and myself, recorded the histories of most of the cases which serve as the basis of this article, and also tabulated them for statistical purposes.[43]

[Footnote 43: Reference must also be made to the interesting observations on spirilla published by Mülhaüser in Virchow's Archiv for July 9, 1884, after this article had been printed. His results go to confirm the view that the spirillum of Obermeier is the essential cause of relapsing fever.]

{434}

VARIOLA.

BY JAMES NEVINS HYDE, M.D.

Variola is an acute, febrile, contagious, and systemic affection, preceded by an incubative period, characterized by the evolution of symptoms in a relatively determinate order, with a cutaneous efflorescence successively papular, vesicular, and pustular in type, followed by crusting, and terminating either fatally or by complete convalescence, with or without sequelæ in the form of multiple, circumscribed, and superficial cicatrices.

SYNONYMS.--Lat., Variola; Eng., Small-pox; Fr., Petite Vérole; Ger., Pocken; Ital., Vajuolo.

HISTORY.--Small-pox is a disease which, there is reason to believe, was first developed in the earliest ages of which the human family has record. Originating probably in China, India, and the adjacent countries of the Asiatic continent, its extension over Europe and America was, without question, in the line of progress pursued by the advancing centres of traffic and population. The earliest traces of its ravages can be dimly recognized in the descriptions of writers in the middle and latter parts of the sixth century. In the early years of the tenth century, however, a remarkably accurate picture of the disease was drawn by Rhazes, a physician of Bagdad. His treatise, translated by Greenhill for the London Pathological Society,[1] sets forth the views of an Egyptian physician named Ahron, who wrote in the sixth century. After these dates the remarkable political and social changes in Europe, which are to be attributed either directly or remotely to the Crusades, contributed largely to the opportunities for the spread of the disease and to the occurrence later of those decimating epidemics which became veritable scourges. In the last century the resulting mortality in some of the countries of Europe was often equal to the entire population of one of their largest cities. If a modern traveller could find himself transported to the streets of the city of London as they appeared in the early part of the present century, it is probable that no peculiarities of architecture, dress, or behavior would be to him so strikingly conspicuous as the enormous number of pock-marked visages he would encounter among the people at every turn. In the face of all cavil and sophistry, medical science will always count among its greatest triumphs the modifications which variola has undergone since its preventive treatment was established upon a satisfactory basis by the discovery of the immortal Jenner.

[Footnote 1: A Treatise on the Small-pox and Measles, by Abu Becr Mohammed Ibn Zacaríyá Arrází, London, 1848.]

{435} The bibliography of the disease is extensive, and the list of authors contributing to the subject is enriched by the names of such men as Boerhaave, Van Swieten, Sauvages, Willan, E. Wagner, Johanny Rendu, Hebra, and, more lately, Kaposi.

ETIOLOGY.--Respecting the etiology of variola, it can scarcely be affirmed that our knowledge has been greatly extended since the date of the experiments of Jenner. There is no historical knowledge of its generation de novo; and the earliest cases of the malady must therefore be classed with the exceedingly rare instances of spontaneous cow-pox which have proved such a boon to the vaccini-culturists. To-day every case of small-pox is justly regarded as having been directly or indirectly transmitted from one or more individuals affected with a similar disorder. It is thus recognized as specifically infectious, contagious, and inoculable, its transmission occurring, first, without contact, by atmospheric conduction of a volatile contagious principle of unknown nature; second, with contact either by (a) actual transference of dry or moist infectious secretions deposited upon a susceptible surface, immediately or through the medium of garments, bed-clothing, paper money, and similar material substances; or (b) by inoculation of unprotected persons with the pathological product of an infected organism. There is no doubt but that the contagious principle displays its greatest activities in connection with the contents of the lesions undergoing a change from the vesicular to the pustular phases, though from the beginning to the end of the disease it is probable that all the tissues and fluids of the infected body are in various degrees capable of producing the malady in those who are unprotected. Furthermore, whether associated or not with an organic substance, the contagium of the disease is known to preserve the power of reproducing itself for a period lasting for weeks, months, and even a longer time. A field for its activities once secured, there is a period of time during which few if any evidences of its progress are declared, this period being abruptly terminated by distinct and characteristic symptoms. This is known as the period of incubation.

The nature of the contagium in small-pox has been the subject of much speculation, careful investigation, and experiment, the results having established but few facts of any practical value. There is at present no proof that any bacteria, vegetable germs, or other minute organisms foreign to the human body are the essential causes of the disease. It is certain that in health the human body is completely enveloped in a volatile medium emanating from the secretions of the glands of the skin, which can be recognized by some of the keen-scented lower animals when it is wafted through the air at a distance of several hundred feet from a single individual. It is reasonable to conclude that not only in small-pox, but in other contagious and infectious diseases, these emanations possess a pathological character, and become capable of transmitting such maladies from diseased to healthy organisms. Certain also it is that when the subjects of these diseases are crowded together, as in prisons, hospitals and camps, this contagious element gathers an unwonted intensity. By far the larger number of all transmissions of variola occur after inhalation of the infective medium--in other words, by the avenue of the lungs. It is probably for the same reason that the disease spreads more widely and with greater virulence during the cold seasons of the {436} year, in this latitude especially from December to February--a time when the ventilation of inhabited dwelling-houses is usually much less perfect than in warmer weather.

The disease affects individuals of all ages and both sexes, not sparing the foetus in utero, and, in the case of the latter, occurring both with and without previous infection of the mother of the unborn child. Nowhere are its ravages so extensive and followed by such fatal results as among those who have long been unprotected by previous vaccination. Among the debilitated, as also among the very young and the very old, small-pox is liable to be followed by severe complications and a fatal result. Negroes, possibly in consequence of tendencies inherited through generations of unvaccinated ancestors, are particularly prone to the disease. Lastly, there is occasionally noted an individual idiosyncrasy, in consequence of which either a remarkable susceptibility to the disease exists or a no less singular immunity against its encroachment is conferred.

Thus, physicians, much exposed to its influences in the discharge of their professional duties, are known to be relatively exempt, while other individuals, few in number it must be admitted, have either had repeated attacks of the malady itself, or, after each exposure to its contagious principle, a recurrent illness of variable type. In the immense majority of all cases, however, one attack confers immunity upon the sufferer against subsequent invasion of the disease for the remainder of life. Upon a few occasions I have known variola to occur in individuals previously affected with cutaneous diseases, especially the eczematous--a fact which merely suggests that such pre-existing disorder of the integument conferred no immunity against infection.

SYMPTOMATOLOGY.--The earliest symptoms of small-pox may be occasionally recognized during the stage of incubation, which, as described above, embraces a period of from ten to fifteen days, though these limits are not absolutely fixed, since both shorter and longer incubative periods have been at times established. During the interval the patient may appear to enjoy perfect health, or, on the other hand, suffer from an ill-defined malaise, with anorexia, languor, insomnia, and allied symptoms. Close observation of the patient thus affected will often reveal the existence of a peculiar pallor of the face, accompanied by a skin-color which suggests a slight degree of sallowness of the complexion. These rather indeterminate symptoms are naturally most marked toward the completion of the period of incubation.

The latter terminated, the period of invasion follows, and extends from the conclusion of the incubative stage to the moment when the first cutaneous lesions of variola appear upon the surface. The symptoms which characterize the onset of this period of invasion are conspicuous and characteristic. There is often a sharp vespertine rigor or a more or less continuous chilliness, accompanied by sensations of "creeping" over the surface, lasting even for several hours. Meantime, the temperature rises to 103° or 105° F., the pulse running up to 120 or 130 beats per minute. In this febrile condition there is commonly complaint of a characteristic aching in the head and back, intense, scarcely intermittent, and so peculiar as to have frequently furnished a clue to the diagnosis of the approaching malady. These sensations are quite analogous to the substernal and other pains which frequently precede the first explosions {437} of syphilis, and are all, without question, due to the circulation of a poisoned blood, the influence of which is in this manner confessed by the nervous system. In the case of infants and young children the invasion of small-pox is frequently ushered in by delirium and convulsions--symptoms which are to be explained by the facts just named.

This complexus of febrile and nervous symptoms, varying somewhat in intensity and possibly interrupted by sensations of chilliness, may be recognized as continuing on the second and third days of the period of invasion. Meantime, there may be noted a dusky hyperæmia of the pharynx and tonsils, the surface of which may even display elevated points which develop later into papules. In exceptional instances the intensity of the poison is such that the system fails to rally before the violence of the onset, and a fatal result ensues before the characteristic exanthem appears upon the skin.

On the second and third days of the invasion stage of the disease, if they are displayed at all, the variolous rashes appear. Too much attention can scarcely be paid to the importance of their recognition on the part of the diagnostician. Often indeed have practitioners been deceived by their occurrence, having been either completely blinded to the serious nature of the malady in progress, or, as Bartholow[2] has well shown, having supposed that they were dealing with a concurrence of variola and scarlatina or rubeola.

[Footnote 2: "The Variolous Diseases," Med. News, Mar. 4, 1882, p. 232.]

Hebra was the first to point out the significance of the rash known as roseola variolosa or erythema variolosa. Occurring at about the dates named above, it is in a few patients pronounced and vivid, even in solitary instances rivalling in severity the exanthem which succeeds it. In others, the majority of all patients in some epidemics, it may be entirely wanting. The writer has certainly observed its most typical development in women who were either menstruating or in the puerperal state. It is said also to be relatively frequent in subjects of a tender age. Kaposi[3] has recognized it in all its manifestations at every age.

[Footnote 3: Consult the admirable chapter on variola in his treatise, Path. u. Therap. der Hautkrankt, Wien, 1882.]

It appears in the form of puncta, striæ, or diffuse and uniform blushes covering extensive areas of the integument, livid red, purplish, or brownish-red in hue, paling under pressure, but never leaving upon the skin over which the finger-nail is quickly drawn the characteristic whitish streak by which many practitioners test the scarlatinal rash. The surfaces involved may be either not raised or slightly elevated above the general level of the skin, and are usually circumscribed. The regions chiefly involved have been carefully described by Th. Simon, and are hence sometimes called Simon's triangles. Thus the groin, the internal face of the thighs, and the hypogastric region may be involved at once (femoral triangle of Simon); the surface of the axilla, the pectoral region, and the inner face of the arm (brachial triangle of Simon), as also the extensor faces of the knees and the elbows, the dorsum of the feet, and indeed every portion of the surface of the body.

In the midst of these rash-covered areas may also appear petechial or hemorrhagic, dark-red, pin-head to bean-sized maculæ, which undergo color-changes both in lighter and deeper shades as the invasion period {438} lapses. In lieu of these, however, transient wheals may come and go over the surface, and even the erythema described above may assume an erratic phase and appear in one part only to disappear and recur at another. None of these flash-light warnings of the oncoming exanthem are proportioned to the latter in the matter of extent and intensity of development. They may be followed by grave or mild manifestations of the disease. The subsequent eruption may also be much more abundantly developed in regions where the invasion rashes have not appeared, and the latter completely fade before the former have advanced to occupy the field thus deserted.

The invasion stage of variola commonly occupies three days. Rarely it extends into the fourth, fifth, and even the sixth, day after the premonitory chill and fever.

Upon its subsidence the exanthem of the disease as a rule promptly appears. Simultaneously, the temperature abates, the rapidity of the pulse diminishes, and there is marked amelioration of the general symptoms. The patient, frequently deceived by the completeness of this defervescence, is apt to conclude that he is convalescent from his disorder, and is thus often astonished at the discovery of the exanthem upon the person, usually the face. In other cases, more commonly those of a grave character, there is failure of this defervescence, the febrile symptoms continuing or even increasing in severity.

The eruption first appears in the form of pin-head sized and larger, firm, conical, discrete, coherent or confluent, reddish papules, sometimes accompanied by mild sensations of a pricking or painful character, often exciting no subjective symptoms by which their presence could be declared. To the touch they are characteristically indurated, and suggest the hardness of small shot imbedded in the skin. They appear first and in greatest abundance upon the face and scalp, involving later and progressively the trunk, the extremities, and the palmar and plantar surfaces. It is at this moment that the eruption most resembles that to be recognized in measles (the distinction between the eruptive symptoms of the two diseases will be considered later). At times a reddish areola surrounds each lesion, especially those appearing upon the trunk. All are situated about the orifices of the follicles and glands of the skin.

On the first and second days of the eruption the papular lesions multiply in number, involve an increasingly large area, and individually augment in size; so they appear first upon the head, and are successively presented to the eye upon the lower portions of the body. The older lesions are usually recognized upon the scalp, face, neck, and shoulders; the more recent upon the extremities. By the third day of the eruptive stage there is usually evident at the apex of the older lesions a minute vesicle containing a drop of pellucid serum, which rapidly changes in character and size till a distinct vesicle is formed with cloudy or lactescent contents. Early in their career an apicial depression can be seen, which later deepens into a characteristic umbilication. This umbilication in the vesicular stage is somewhat peculiar. It is more than a mere depression of the summit, such as might be made by thrusting a blunt-pointed pin centrally and downward so as to carry the roof-wall before it. It is made clinically most distinct by the fluting or puckering of the peripheral part of the roof-wall, giving the lesion a crenated appearance which is not {439} assumed by any other cutaneous efflorescence of multiple development. It may be regarded as pathognomonic of variola.

The pock is usually mature by the sixth day of the eruption. It is pea-sized and globular in shape; its umbilication has been usually quite removed by the complete filling of its chamber with distinctly purulent contents; it is often surrounded by a halo due to hyperæmia or exudation; and, the total number of individual lesions being then fairly determined, it is often closely set against its fellows, islets of unaffected integument having meantime become fewer and more contracted. The face, covered with this eruption, then exhibits a typical aspect. The entire integument becomes swollen and brawny or oedematous. The eyes are thus closed by the tumid lids, which are separable with difficulty, and this, too, even though they be the seat of comparatively few lesions. The nose, lips, cheeks, and ears are by similar processes deformed and given a most repulsive unsightliness. Mucus and puriform secretions gather and dry about the mucous outlets. The skin of other parts of the body (hands, feet, genitalia, and the entire extremities) is in a similar condition, merely most noticeable in the exposed and disfigured visage.

The fever of maturation or suppuration, or, as it is often called, the secondary fever, is lighted to activity with the onset of the suppurative process. The temperature rises to a point ranging between 101° and 105° F., the pulse-rate simultaneously rising to 100 and even 150 in the minute, varying of course with the age of the patient and the severity of the attack. During its continuance, from the eighth or ninth to the eleventh or twelfth day of the disease, the victim of the malady is in a deplorable and critical condition. The intense grade of cutaneous inflammation, with its resulting subjective sensations of burning pain and tension, the soreness of the mouth (tongue, pharynx, inside of lips, and palate), due to the existence of pus-filled pocks upon the buccal membrane, and, for similar reasons, the dysphagia and irritation of the larynx and tracheal membrane, are all sufficient to account for the general condition. In cases of mild grade the patient lies conscious, but in a stolid apathy, listlessly accepting the services of his attendants. In others there is delirium of low or high grade, often sufficient to demand constant surveillance, lest in consequence the patient do serious injury to himself.

The behavior of the pustules which appear upon the mucous surfaces accessible to the eye is modified somewhat by the heat, moisture, and friction to which these surfaces are exposed. Typical, fully-distended pustules occasionally persist upon the soft palate and the inside of the lips. Soon, however, the macerated roof-wall yields, leaving a reddish floor where the mucous membrane is exposed, denuded of its epithelial layer or covered with a new tender and hyperæmic pellicle. In grave and severe cases these pustular lesions may extend deeply into the mucous tracts, involving the trachea, bronchi, or alimentary canal. In an autopsy made by the writer on the body of a male subject dead of unmodified variola, there was no portion of the alimentary canal from the mouth to the anus which was not studded by thickly-set pustules. The urethra, vagina, vulva, external auditory canal, and conjunctivæ are, in severe cases, similarly involved. According to Kaposi, the tympanum is usually exempt.

The period of desiccation begins usually on the thirteenth or fourteenth {440} day of the disease, and, according to the severity of the previous pathological processes, requires for its completion from one week to a fortnight. Its onset is characterized by a second marked but gradually developed defervescence. With a diurnal temperature successively less elevated above the normal standard there is a corresponding fall of the pulse-rate. As the disease has by this date taxed the vital resources of the system to the utmost limit, the exhaustion resulting may be declared by a pulse which is flagging, weak, and even in the matter of frequency much below the standard of health.

The cutaneous lesions now again undergo a change. Some of the pustules rupture, and their viscid contents, oozing forth, concrete into a yellowish crust which gradually assumes a brownish hue. Others desiccate en masse, the roof-wall first collapsing upon the contents, thus producing an appearance which again suggests umbilication of the lesions. This is sometimes termed a secondary umbilication. The desiccation en masse is doubtless due to the evaporation of a portion of the fluid exuded into the superficial strata of the integument, and the consequent inspissation of the pus. Often the face at this moment is totally concealed by a dense, dry, brownish or even blackish mask, composed of the crusts furnished by numerous individual lesions. At the same time the tumefaction of the skin subsides, and the subjective sensations to which it gave rise gradually disappear. Beneath the crusts cicatrization advances till the former are lessened, and finally, becoming detached, fall in quantity from the surfaces subjected to friction. Beneath them are seen brownish and violaceous blotches, the integument thus stained slowly losing its abnormal color. It is thus seen to be the seat of multiple, slightly depressed, shining scars of a dead white color, which in the course of time lose somewhat of their disfiguring prominence, but which when typically distinct persist for a lifetime. This exfoliation of crusts continues till the skin is completely rid of its pathological products, the process being completed with entire restoration to health about the conclusion of the fourth or fifth week of the disease. Meantime, in favorable cases, convalescence progresses pari passu. The patient has a returning appetite, decadence of symptoms originating in impairment of function of the mucous membranes, and gains in weight till the restoration to sound health is complete.

Such is the history in outline of what may be regarded as a typical form of uncomplicated variola. It should not be forgotten, however, that in different epidemics there are marked differences in the career and manifestations of the malady, and that even among the cases observed in a single locality visited by the disease the same divergence of symptoms is no less conspicuous. This diversity is due to several causes, irrespective of the remarkable modifications displayed in the variolous who have been previously vaccinated. Individual susceptibility is doubtless to be considered in this connection, as also the temperament, bodily vigor, and hygienic surroundings of those who are infected. It is possible also that the intensity of the poison may be subjected to occasional modifications in its transmission from individual to individual. In this way the following types of variola present themselves in clinical forms with divergent features:

CONFLUENT VARIOLA (variola confluens).--This virulent form of {441} small-pox is ushered in by a relatively short incubative period, followed by a severe invasion of the disease. The premonitory chill is violent; the cephalic and lumbar pains are excruciating; the fever, rising to a high grade, 106° to 110° F., with few and slight remissions, scarcely subsides, if at all, with the appearance of the eruption, the latter developing early, and, to borrow an expression from syphilographers, exploding with violence over large areas of the surface of the body. The initial lesions of the exanthem are dense and deeply-set papules, so closely coherent even at this moment that they scarcely leave between them interspaces of sound skin. During the vesiculo-pustular transformation which they promptly undergo on the second day there is a more or less complete coalescence of the elements of the eruption, which circumstance has given this form of the disease its name, confluent variola. This confluence is most conspicuous upon the face and hands, where large flat vesicles run together, form pus-filled bullæ, and finally convert the surface on which they rest into a single, large, many-chambered pustule. All this occurs upon an enormously swollen and inflamed skin, disfiguring every feature of the face and wellnigh obliterating every external distinction between the scalp, nose, eyes, and mouth. Here and there the mass is elevated by the quantity of exuded pus to a more notable projection from the surface. Pustules filled with blood may appear at several points. At others, the suppurative inflammation may be seen to have eroded the derma, which is covered with a diphtheritic membranous exudation similar to that covering the mucous membranes lining the mouth, nose, and ears. Naturally, the skin in its totality often yields to these destructive processes and in large patches falls into gangrene.

The confluence of the lesions is less marked in other parts of the body than the face and hands, yet the entire surface may be covered with a coherent exanthem which becomes elsewhere, in large areas, confluent. The writer has seen patients in whom the head of a pin could not be placed upon an unaffected patch of skin in any portion of the body. The parts subjected to pressure in the reclining posture, such as the back, shoulders, and buttocks, are especially liable to this coalescence of the pustular lesions.

In confluent variola too, as already intimated, the mucous surfaces suffer proportionately. Pasty accumulations of muco-pus and diphtheritic exudation, like macerated chamois leather, cover the tongue, which is often so enormously swollen as to bulge between the teeth and project from the mouth. These exudations line the mouth, pharynx, larynx, and even the bronchi. Beneath these masses the eroded mucous surface is dry, livid red in color, and has a varnished aspect. Gangrene here may lead to necrosis of the cartilages of the larynx. Aphonia is often complete, deglutition impossible, respiration difficult. The stench arising from the patient is intolerably fetid and pervading, and a single exhalation will poison the best-ventilated apartment. The submaxillary and sublingual glands are enlarged and the neighboring lymphatics swollen.

The patient who is plunged into this grave condition is the victim of a fever which is unquestionably septicæmic in character; he has a small, frequent, and often fluttering pulse; his mental condition is betrayed by a delirium of varying grade or he lies comatose. In this state a fatal {442} result is often induced by either exhaustion of the vital forces or an intercurrent malady, such as pleurisy, pneumonia, cardiac inflammation, oedema of the glottis, or an uncontrollable diarrhoea. In yet other cases the patient falls into a typhoid state, and, after surviving for a fortnight or more with a low fever, a broncho-pneumonia, or a diarrhoea, succumbs to an inevitable exhaustion, the surface of his body being yet covered with a dry, blackish, and fetid crust.

The expression of an intense variolous poison is known as hemorrhagic variola; also as purpura variolosa and black pox. A large number of such cases have been designated and treated as black measles, the real nature of the malady having been mistaken.

The law readily observed by the diagnostician of diseases in general must here be recognized. There are no hard and fast lines in nature. Hemorrhagic variola occurs, without question, in different types. At the one extreme are classed the inevitably fatal cases, where the patient sinks smitten by the malady even before the exanthem is developed; at the other are found the cases of confluent variola, not necessarily fatal, in the course of which hemorrhagic lesions appear in variable number, blood either filling the pustules after the latter have arrived at maturity, or forming ab initio purpuric pocks intermingled with the typical lesions of the variolous exanthem. However ill-defined the limits between these classes may be, the symptoms of hemorrhagic variola are sufficiently characteristic to require separate description. According to Kaposi, it occurs in the two following types:

The first form is termed variolic purpura. Its incubative period is brief and distinguished by unusual conditions of malaise and lumbar pain. On the fourth day there is an intense fever with rapid pulse, and this is speedily followed by a deep purplish-red staining of the face, neck, trunk, and extremities, the skin thus affected being slightly tumid and quite dry. Minute maculo-papules can be distinguished here and there over the surface, often closely set together, and presenting the characteristic color described above. At this stage of the disease the eruption greatly suggests an intense rubeolous exanthem, and has been, as a result, repeatedly mistaken for the so-called black measles. But the excruciating pains persist, there is often coincident delirium, and the pin-head sized maculo-papules noted above become lenticular in shape, cease to lose their color under the pressure of the finger, extend peripherally even in a few hours, flatten and become purpuric patches of a bluish-black shade, palm-sized and even larger, covering extensive areas of the integument, new lesions forming in unaffected islets of the skin; conjunctival ecchymoses appear at the angles formed by the lids, and finally encircle the cornea with an annular purplish-black cushion. The mucous surfaces become dry, crack, and bleed where the epithelium is torn, and become covered with offensive crusts. The odor exhaled by the patient is intolerably fetid. He lies stupid as the march to a fatal issue is hourly hastened. Hemorrhages occur from the larynx, bronchial membrane, intestinal surfaces, and even into the parenchyma of the viscera, the muscles, serous membranes, periosteum, and neurilemma. The urine is retained in the bladder; the respirations rapidly increase in frequency; the pulse flutters; and death closes the scene between one and two days after the onset of the malady. In several cases observed by the writer, {443} occurring in infants and children, the entire course of the malady was completed in twelve hours.

In the second and much rarer form of hemorrhagic variola there are the usual unfavorable portents of intense prodromic symptoms. On the fourth day the skin is swollen and indurated in consequence of the development within its structure of numerous firm, roundish, slightly acuminate papules, so thickly set together that it is wellnigh impossible to distinguish between them. These are early in betraying the bluish-black hue significant of hemorrhage into their mass. They multiply in number and increase in size, while their hemorrhagic stains widen and sweep from each as a centre, like the waves that spread from a pebble thrown into smooth water. In these cases, more often than in those first described, pus-filled pocks may develop over some portions of the surface, while in others a species of gangrene occurs in consequence of the separation of the derma from the subcutaneous tissues by effused blood. At times pustules of somewhat typical aspect are formed and subsequently filled with blood by a hemorrhage from below. The accompanying symptoms are grave, but less rapidly fatal than in the other types of the disease. Delirium, stupor, an intense fever, and a rapid, feeble pulse are commonly noted. A fatal result is usually reached in from four to five days.

Hemorrhagic lesions, isolated or confluent, are seen also in severe forms of variola, not of the two types described above. Thus, in confluent small-pox, especially when occurring among the unvaccinated, some of the pustules on the face, the back, or possibly the legs, where varicosities of the veins permit a passive engorgement of the tissues with blood, may become the seat of a hemorrhage. For these local causes are often etiologically effective. In other cases the appearance of the hemorrhagic lesions seems to be due to a dyscrasia, such as that recognized in phthisis, chronic alcoholism, and hæmophilia.

Aside from the trivial accidents to which the exanthem may be subject, the hemorrhagic types of variola may be regarded as necessarily grave and in a large proportion of cases inevitably fatal. That they are all truly the results of variolous poisoning is shown, first, by the occurrence of intermediate forms; second, by the occasional transmission of the disease in its typical aspects to the partially protected.

VARIOLOID is that form of variola in which the disease is modified, either in its course, duration, or intensity of symptoms, such modification usually resulting, directly or indirectly, from the protective influence of vaccination or from a previous attack of variola.

The symptoms of the class of patients commonly regarded as suffering from varioloid are all those of variola, modified, however, in the direction of a mitigation of their intensity and dangerous character. It is thus evident that there is no strict line of demarcation between the very mildest physical expression of the variolous poison and that variola vera which presents atypically benign symptoms in any stage of its career. Within this wide range of possibilities cases of varioloid occur which certainly differ from each other by very marked degrees.

The invasion stage of varioloid may be shorter or longer than that occurring in variola vera, and may be insignificant or intensely marked as regards the severity of its symptoms. According to Bartholow[4] the {444} invasion rashes are here of common occurrence; and the more extensive the latter, the less copious the subsequent eruption. It must be admitted that a personal experience has not confirmed us in this view.

[Footnote 4: Loc. cit.]

After the high fever and severe cephalic and lumbar pains of this stage there may follow, in the case of varioloid, a complete defervescence and the appearance of a very copious exanthem. With this, however, the apogee of the disease may be reached, and the subsequent symptoms be altogether insufficient in comparison with those which have preceded. Thus, the maculo-papules may never reach a vesicular stage, or, having attained this, the vesicles may not be umbilicated, or may shrivel after their contents have assumed a lactescent color, and be succeeded by light superficial crusts which in a few days fall. Or, again, the pustular stage of the lesions may be fully developed, even with the production of a halo about the pocks, while yet there is no swelling of the skin and but trifling subjective sensations experienced by the patient. The pustules in the course of from four days to a week desiccate and are shed, leaving behind them violaceous pigmentations of the surface without persistent cicatricial sequelæ.

Other cases, again, instead of producing the impression upon an observer of being illustrations of a malady aborted or cut short at some period of its career, seem to exhibit merely a modification in the intensity or distribution of symptoms betrayed in a wellnigh typical career. Thus, there may be a total absence or insignificant reminder of the septic fever usually known as the secondary fever of variola, and the elements of the eruption may be few or appear in scanty number upon the face and more copiously elsewhere. The latter may, however, pursue a perfectly typical career and be followed by characteristic scars.

There is yet another type of varioloid with which many practitioners become familiar who have experience in epidemics of small-pox. The patient exhibits distinct symptoms of malaise in the period of incubation. The fever of invasion, with its characteristic pains and nausea, is equally well marked. Defervescence occurs with a trifling eruption of maculo-papules, which in two days have wellnigh completely disappeared. There is no secondary fever, but the patient is far from well. There is a period of anæmia, mental depression, marked languor, and unmistakable evidences of physical prostration out of all proportion to the precedent symptoms. In these cases it may well be believed that the poison has at last produced a strong impression upon the nervous centres. The most characteristic feature of these cases is the tedious convalescence from an apparently trifling form of the malady.

The identity of varioloid with variola is abundantly shown--first, by the occurrence of intermediate forms of every grade, from the mildest evidence of variolous poisoning to typically developed cases of variola vera; second, by the fact that patients affected with varioloid are capable of transmitting variola to the unprotected; third, by the anatomico-pathological fact that the structure of the pock, when it appears, is the same in all.

A variation as to the form and contents of the lesion of modified variola occasionally occurs as a consequence of individual peculiarities or of the special surroundings of the patient. A number of useless terms have been employed to designate these peculiarities, the most of which {445} are relics of the superstitions of the past. In variola siliquosa the pocks are said to contain air only; in v. pemphicosa, bullous lesions predominate; in v. verrucosa, the papules, after partial evolution and involution, leave minute wart-like papillary masses upon the face; in v. crystallina, there are superficial vesicles only filled with clear serum, which somewhat resemble those recognized as sudamina. The older English writers with as little reason described cases of horn-pox, swine-pox, etc., differing only from those of variola by the anomalous behavior of the exanthem in the course of its evolution.[5]

[Footnote 5: Besides the terms given above, Hebra gives the following list of Latin adjectives which have been employed to describe special varieties of small-pox, none of which requires special explanation: variola papulosa, conica, acuminata, globosa, globulosa, tuberculosa, cornea, fimbriata, miliaris, lymphatica, vesiculosa, pustularis, rosea, morbillosa, carbunculosa, etc.]

COMPLICATIONS AND SEQUELÆ.--The complications and sequelæ of variola are fewer in number and more restricted in range than those of many other maladies. This results from the remarkable unity of the disease as it occurs in its several manifestations among the unprotected, its relatively rapid progress, and its absolute disappearance on the completion of its curriculum. There is no chronic form of variola lingering for weeks and months after the violence of the fever has abated.

Furuncles and abscesses occasionally result during or after the pustular stage of the disease has been reached, sometimes of such extent as to give exit to large quantities of an ill-conditioned pus. The tissues, weakened by the suppurative process which the skin has undergone, may then necrose, and thus lay bare periosteum, cartilage, or bone. Erysipelas, especially about the face, may close the eyes, encroach upon the scalp, or spread extensively over other regions. Muscular paralyses, hemiplegic and paraplegic attacks, albuminuria, diarrhoea, and the inflammations of chronic type affecting the thoracic organs may each supervene, and either greatly prolong convalescence or precipitate a fatal issue. None of them is perhaps more common than a low typhoid and febrile state, in which the patient lies after his variola is practically ended, his skin struggling to regain its normal tone, a fever of remittent type taxing his energies, his bowels in frequent movements discharging a thin and fetid feculent matter, while a low delirium renders him insensible to the gravity of the situation.

Reference has been made above to the implication of the eyes of the variolous, and the possibility of the disorder terminating, after an otherwise favorable convalescence, in total blindness, should not be forgotten. The cornea may be the seat of pustules or a diffuse puriform infiltration resulting in ulceration, and eventually perforation with hernia of the iris. At times it is merely macerated by the pus continually covering it, and in that condition yields to even moderate pressure. At others the deeper portions of the globe fall into inflammation, and there is a resulting cyclitis, irido-cyclitis, or parophthalmia.

In the nose severe destructive effects may follow the pustular involvement of the Schneiderian membrane, including necrosis of the nasal bones and profuse epistaxis.

In a similar way, the external ear may be involved, the tympanum disappear, a severe otitis media supervene, and the mastoid cells become filled with pus and detritus of necrosed tissue.

{446} In the larynx, which may be well lined with pustules, as indicated above, complications may arise in the shape of oedema of the ary-epiglottic folds,[6] laryngo-oesophageal abscess and various diphtheritic deposits lining every portion of the mucous membrane.

[Footnote 6: J. William White, "Surgical Aspects of Small-Pox," Medical News, March 4, 1882, p. 241.]

Other disorders noted as complicating variola are hydrocele and orchitis in the male, ovaritis in the female, gangrene of scrotum or labia, hæmaturia, peritonitis, adenopathy and lymphangitis and arthritis, as well as peri-arthritic suppurative inflammation.

PATHOLOGY AND MORBID ANATOMY.--Ours is a day in which bacteria, special to each of a number of infectious diseases (lepra, pemphigus, tuberculosis, etc.), are constantly reported as coming to light under the persuasive influence of modern staining solutions. With respect to variola, it may be said that while Cohn, Klebs, Weigert, and others have, without question, recognized microsphæra, micrococci, and similar organisms in variolous pus, their causative relation to the pathological process has certainly not yet been demonstrated.

The pathological anatomy of the cutaneous lesions of variola has been very carefully studied by Auspitz and Basch,[7] and Heitzmann.[8] The following is a condensed account of the results reached by these observers:

[Footnote 7: Virch. Archiv, Bd. 28.]

[Footnote 8: Trans. of Amer. Derm. Ass., Aug., 1879.]

First appear circumscribed patches of hyperæmia, in which the papillary layer of the corium is concerned, and which is followed by some thickening of the rete, the epithelia involved becoming coarsely granular. This granular condition is due to an increase of living matter within the protoplasmic bodies, evident at the points of intersection of the reticulum of which they are composed, the nuclei becoming solid and shining, and the threads traversing this cement-substance between them becoming also increased in thickness. The papillæ beneath increase in size in consequence of their vascular engorgement, and in consequence of the change experienced by the connective-tissue bundles, which are partly transformed into protoplasm, while the protoplasm between them increases also. There is, in brief, a liquefaction of the glue-giving basis-substance, which makes visible the reticulum of living matter formerly hidden within it. In this way the epidermis is raised into the flat solid papules which are the early lesions of the disease.

Then follows an exudation of a serous fluid at one or more points in the papule, the meshes of the reticulum being so stretched and torn that small chambers are formed filled with the liquid exudate containing granules. Between these chambers the separating strata of epithelia are compressed so as to form septa or partition walls. The neighboring epithelia become granular, divested of their cement envelope, and transformed into protoplasmic clusters still connected with the living reticulum by slender threads. An irregular cavity is thus formed in the thickened rete traversed by septa, the contained exudation being filled with granules, coagulated fibrin, and lymph. A few protoplasmic bodies are here also distinguishable, which Heitzmann regards as either débris of destroyed epithelia or colorless blood-corpuscles.

In these changes the connective-tissue beneath participates. The papillæ eventually disappear, the superior portion of the corium being replaced by {447} clusters of medullary or inflammatory elements uninterruptedly connected by threads of living matter.

The pus-corpuscles which eventually appear originate mainly from transformed epithelia. In the process of transformation the increased protoplasm of the epithelia first exhibits shining homogeneous lumps, which, after an intermediate stage of vacuolation, undergo an endogenous metamorphosis into nucleated bodies with a reticulum in each. To the number of these there is possibly an addition by the immigration from below (diapedesis) of leucocytes.

The question of repair with or without the production of cicatrices rests upon the behavior of the connective-tissue elements. If these are not torn asunder, but remain in connection with each other, the re-formation of a glue-giving basis-substance is possible, and new bundles of fibrous connective-tissue take the place of the old. If, on the contrary, the latter are completely destroyed, their place is filled with the cicatricial new growth. The pigmentation, which is such a common transitory sequela of the skin lesions, is due both to the imbibition of the coloring matter of the blood by the epithelia and by direct hemorrhagic exudation into both the rete and derma.

The umbilication of the mature pock is doubtless due to the situation of such lesions at the orifices of the excretory ducts of the skin-glands. The epidermis, in one or more of its strata, dips downward to form a living investment for such glands, and in this situation ties down the centre of the roof-wall of the pustules. Eventually, it too, as a result of the maceration and tension incidental to the complete filling of the pock with pus-elements, is ruptured or stretched, and the umbilication of the pustule disappears.

The anatomy of the exanthematous lesions in hemorrhagic variola is not different from that described above. The pocks in such cases are merely filled with blood instead of with pus or sero-pus. In some forms of hemorrhagic variola, as indeed would be suggested by their clinical observation, there is hemorrhage directly into the tissues of the integument, or, more probably in severe cases, a mere passive leaking of the sanguineous fluid with its coloring matter through the relaxed and weakened vascular walls.

The morbid changes occurring in the viscera are described by Curschmann as follows: The mucous surfaces may be the seat of pustules, diffuse purulent infiltration, and catarrhal, croupous, or diphtheritic inflammation. As regards the extent of diffusion of the pustular lesions, they occur, according to Wagner, in bronchi of the second and even of the third order, rarely in the stomach and intestines, and in the rectum only in its lowest portion. The bladder, urethra, and serous surfaces are always exempt. The lungs, breast, liver, spleen, brain, and spinal medulla are variously involved. Often the tissues of these organs are quite unchanged as regards their macroscopical appearance. At other times the tissues appear swollen, granular, and undergo a fatty degeneration. In purpura variolosa the spleen and walls of the heart, however, are seen to be firm, dark-red, and more or less indurated.

DIAGNOSIS.--The establishment of a correct diagnosis where there is question of variola is one of the most critical and important of the duties of a physician. Upon such decisions have turned, again and again, {448} professional success or disaster. To pronounce that case to be variolous which is not of such a nature is to subject one to the indignation of the few and the ridicule of the many. On the other hand, to be guilty of treating a patient with small-pox, and of remaining ignorant of the nature of the malady, is to subject many ignorant people to the danger of exposure to the disease and to render one's self liable for the redress sought by recourse to the civil authorities and the law. It is difficult to decide which predicament is the graver.

Typical variola vera is readily recognized by its characteristic features. As usual, it is the atypical and modified forms where the difficulty most often arises and where the danger to the physician is proportionately increased.

In the invasion stage of the disease it is often impossible to recognize any symptoms characteristic of variola. High fever with severe lumbar pain, considerable gastric distress, and the appearance of one of the invasion rashes (roseola variolosa) would, however, put the observant practitioner on his guard. I have often noticed in these cases a symptom which, apparently insignificant, has on more than one occasion preceded the eruptive period. It is the occurrence upon the centre of the two cheeks of a vivid damask-red blush, occasionally having a purplish-red hue, and with a very remarkable circumscribed area. This may be recognized in children and adults of both sexes when it occurs in typical aspect, and is undoubtedly a hyperæmia of the character of that producing the rashes in Simon's triangles.

When the variolous exanthem first appears the practitioner should secure as soon as practicable a history of the invasion stage if this has not been subject to his personal observation. He should then make careful inquiry as to the possibility of a neighboring source of contagion, and ascertain by inspection whether the person of the patient exhibits the evidences of successful vaccination. In this connection it is always well to estimate the value of the elements represented by (a) the period ascertained as having elapsed since the last successful vaccination; (b) the typical or atypical character of the existing cicatrices of vaccinia; (c) the unicity or multiplicity of the cicatrices simultaneously resulting from vaccinations performed at one and the same date.

Without question, the first papular lesions of variola resemble those of rubeola or measles to an extent which has often deceived the most expert diagnosticians. The distinguishing points are--(1) In measles, catarrhal symptoms (conjunctival, nasal, laryngeal, bronchial), which are usually absent in the early stages of variola, and later are obviously associated with the irritation set up of the pustules of the maturing period. (2) The difference in the temperature record, that noted in the invasion stage of variola varying from 104° to 105° F., while in rubeola it is rarely registered above 103° F. Moreover, in typical variola the defervescence is marked and characteristic on the appearance of the exanthem, while in rubeola, when the rash appears, the temperature is usually sustained at a maximum, and may even rise. (3) The differences in the rashes of the two disorders. The papules of variola, even in its confluent forms, are, when first observed, remarkably discrete and exhibit not the slightest tendency to grouping, while the maculo-papules of rubeola are (a) developed simultaneously on the face and trunk, while those of variola {449} commonly appear first on the face and afterward on the trunk, the older, and larger therefore, in the site of earliest appearance; (b) are set in clusters or groups having a distinct tendency to crescentic arrangement, a symptom decidedly best appreciated by the eye when the eruption is viewed in totality or in large areas with the eye of the observer somewhat removed from the surface; (c) are often made to disappear or pale beneath the pressure of the finger, while there is greater persistence of color in the variolous papules; (d) are surrounded by little or no halo, each elementary lesion of the eruption being abruptly defined upon the sound skin, while the variolous papule is apt to rest upon a circlet of hyperæmic integument.

Even with careful observation of all the specific differences between the two diseases, they may, for a brief time, so resemble each other as to defy the skill of the expert. In all doubtful cases the physician should invariably admit the doubt and defer an exact diagnosis for twenty-four hours. During the delay the variolous exanthem should betray its individuality by the formation of a minute vesicular apex at the summit of several papules.

In scarlatina the uniform diffusion of the exanthematous blush, the absence of papules and vesico-papules, the continuance of the fever after the rash has appeared, the characteristic scarlet or boiled-lobster color of the skin, and the anginose condition of the throat, are all significant symptoms. In hemorrhagic small-pox the color of the integument is a much more purplish and lurid-reddish hue, rapidly reaching that stage where it refuses to pale under the pressure of the finger, and never leaving in the track of the finger-nail quickly drawn over its surface the peculiar transitory yellowish-white line which can be usually obtained in the skin of the patient with scarlatina.

The pustular stage of variola might be confounded with the pustular syphiloderm. But in the latter there should be a history of a chronic rather than of an acute affection, and, as a result, the simultaneous appearance of lesions in very different stages of their career, some distended with pus, others ruptured and crusted, yet others which have recently formed in the immediate vicinity of the oldest lesions, while the latter have been in full involution or have been replaced by superficial losses of tissue.

The resemblance of pustular variola to certain suppurative and other disorders of the sebaceous glands is well attested by the name given by certain French authors to molluscum epitheliale (M. contagiosum, M. sebaceum)--viz. acne varioliformis. But in the case of acneiform disorders the concurrence of comedones, the chronic course of the disease, the absence of fever and systemic disturbance, and the particularly irregular distribution of the lesions upon the face, with failure to appear elsewhere,--all these facts forbid the confusion of the affection with variola. In medicamentous acne, accompanied by the sudden appearance of numerous pustular lesions symmetrically displayed upon the surface, there will indeed be a source of error. In such cases, of course, a history of the ingestion of a medicament capable of producing a rash will afford valuable aid in the diagnosis. In pustular forms of dermatitis medicamentosa there will usually be found a more abundant development of the pus-containing lesions upon the head and both arms and forearms, with {450} no tendency to extension over very large areas of the trunk and lower extremities--a circumstance which a delay of but a few hours will often substantiate.

The absence of marked defervescence is the most characteristic difference between variola in its eruptive stage and typhus, typhoid, and relapsing fevers. Pneumonia, cerebro-spinal meningitis, acute miliary tuberculosis, and gastric fever are all to be differentiated from variola by the occurrence of symptoms characteristic of the involvement of the several organs which in these diseases respectively are more particularly impaired.

PROGNOSIS.--The prognosis of variola is wellnigh inseparably associated with the question of protection by vaccination. Variola vera in the unprotected is an exceedingly fatal malady, the death-rate varying in different epidemics according to the severity of each and the ages and hygienic surroundings of the victims of the disease. Certainly, from 15 to 50 per cent. of unprotected individuals affected with the disease occurring in epidemic form in any given community will perish. This number may, however, be enormously increased, as, for example, among a large number of unprotected negroes crowded together in a filthy prison, or when the malady makes a periodical visitation to an insular community where long isolation has begotten a carelessness with respect to vaccination.

With respect to individual cases it may be asserted, first, that an intense series of prodromic symptoms, followed by the appearance of an unusually large number of cutaneous lesions, is often unfavorable. Confluence of the latter adds to the gravity; hemorrhagic and purpuric symptoms are in the highest degree portentous, and commonly indicate a fatal result. Women pregnant or in the puerperal state, infants at the breast, and persons of both sexes at advanced ages, are little able to resist the ravages of the disease. According to Kaposi, women recently delivered prematurely or who have lately suffered from an abortion succumb more often than others of their sex. Chronic alcoholism among male subjects and the cachexia induced by all chronic visceral and systemic disorders are sources of weakness which largely increase the death-list by adding to the heavy strain upon the vital energies. The prognosis is rendered uncertain or unpromising by extensive involvement of the mucous as well as of the cutaneous surfaces, by marked visceral complications, by evidences of shock or exhaustion before the apogee of the exanthem is reached, by grave sequelæ, and even by simple complications of the malady when, instead of entering promptly upon convalescence, the patient lingers for weeks in a typhoid condition. An unfavorable symptom in any case is the sudden cessation of the processes actively pursued upon the surface of the body. The swelling of the integument then suddenly diminishes and the crusts by which it was covered shrivel. The eruption, in brief, seems to undergo what may be described as a collapse. The pulse at such moments usually flutters feebly, and there are other portents of dissolution which the eye of the physician will hardly fail to interpret correctly. The fluids in such instances mechanically drain away from the surface of the body to seek the deeper parts. This is not peculiar to small-pox. Similar phenomena occur even in the case of other than exudative affections of the skin. In pityriasis rubra the {451} patient dies leaving an integument apparently unaffected, and I have seen a patient dead of even multiple sarcoma of the skin when the tumors were reduced fully one-half in bulk as the result of a similar cause.

On the other hand, the practitioner should never forget that even apparently desperate cases of variola rally and are won back to life. That the exudative process should be in full evolution at the surface of the body is, cæteris paribus, certainly so far a good omen. The most hideous, extensive, and stench-emitting crusts have hidden for a time the forms that have for many subsequent years not only known the enjoyment of life, but have made that life of inestimable value to others. The physician in the presence of this most loathsome and formidable disease should never despair.

PROPHYLAXIS AND TREATMENT.--The loftiest end to be reached by the physician of our day with respect to variola is its complete removal from all civilized countries, and indeed from the face of the earth, by the practice of universal vaccination and revaccination. The evident modifications which the disease has undergone in late years as a consequence of the extraordinary attention given to this subject is an earnest of the future. The day is probably not far distant when the man, woman, and child unprotected by vaccination will properly be regarded as an enemy of the human race, and treated accordingly. Evidences of the most satisfactory character as to successful vaccination should be imperatively required of all applicants for admission to schools, academies, colleges, charitable institutions, public libraries, art-galleries, and places of labor controlled by incorporated institutions; of all members of conventions, legislatures, political, religious, and deliberative bodies; of every purchaser of a ticket for purposes of travel; and of every voter. In addition, there should be in every district a systematic and periodical inspection of all persons registered in the census by persons qualified and competent to perform compulsory vaccination. This is the scientific treatment of variola.

Respecting the therapeutic management of variola, it must be admitted that there are no remedies known to exert the slightest influence in either cutting short the curriculum of the disorder or in checking its progress in any stage. When vaccination is practised after the disease is fully developed, the two disorders, vaccinia and variola, apparently concur, and proceed pari passu to the evolution peculiar to each. Quinia, the sarracenia purpurea, the salicylate of sodium, emetics, diaphoretics, purgatives, and other remedies and methods vaunted as efficacious, have again and again failed to establish the claims which have been put forth respecting the value of each.

The most important of the considerations to be regarded at the outset of the management of the small-pox patient relate to his hygienic surroundings and nursing--considerations which scarcely differ from those recognized as of general importance in the case of all septic, contagious, and filth-producing diseases.

The timid, the fearful, and the unprotected are to be at once dismissed from the bedside, and trustworthy attendants secured who have received protection by either recent vaccination or a prior attack of the malady. The sick chamber should be sufficiently large and capable of the most thorough ventilation by free access of air. Solar light should be excluded {452} as rigidly and completely as possible, since it is reasonably certain that its access to the face has an etiological relation to the pitting of that part, often the most serious sequel of the affection. It is an interesting fact that pitting is much less frequently noted on those parts of the body from which light is excluded by the covering of the clothing. The temperature of the sick room during the febrile stages of the disorder should not rise above 70° F. nor be permitted to fall below 60° F. Between these extremes a variation may be made in accordance with the sensations of the patient.

During the invasion stage of the disease the patient can rarely assimilate food, but if this be possible it should be given throughout the entire course of the disease in the form of animal broths, eggs, nutritious soups, and milk. Iced and acidulated beverages are often grateful to the palate, and small lumps of ice should be permitted to dissolve slowly in the mouth. Lime-water may be required by unusual gastric irritability. As the disease progresses and the palate and buccal membrane become painful and sore by reason of the localization there of pustular and other lesions, various mouth-washes and gargles may be ordered, such as those containing the chlorate of potassium, the tincture of myrrh, the tincture of cinchona, or even the milder demulcent fluids made by the addition of flaxseed, gum acacia, or powdered elm-bark to water. In almost all such cases the skilled nurse will accomplish a grateful result by frequently cleansing the mouth of the sufferer (especially before the deglutition of aliments) by covering the finger with a soft handkerchief, dipping it in pure hot water, and then thoroughly and gently cleansing the entire buccal cavity. The spray of a saturated solution of boracic acid in rose-water may then be directed over the parts.

Applications of cool and iced water to the skin are commonly grateful, and, as a rule, are accompanied by no danger to the patient, though in the early periods of the disease they unquestionably retard the full evolution of the cutaneous symptoms. For the pain in the back, therefore, which is often the most urgent symptom of the invasion stage of the disease, it is usually preferable to make hot applications. The large rubber bags now in common use, filled with hot water and from time to time applied to the lumbar region, may be employed with good effect simultaneously with iced, spirituous, or camphorated applications to the head.

Numerous indeed have been the topical applications made to the surface of the skin in the pustular stage of the malady, both with a view to assuage the soreness and pain and to obviate the tendency to pitting. The opening of the pustules and the evacuation of their contents (practicable only in other than confluent forms of the disease) has been practised from an early date, but is ineffectual from the standpoint of any practical results thus obtainable. The same may be said of the subsequent cauterization of the floor of the pustular chamber, which only adds to the distress experienced by the sufferer in his skin. Medicated unguents, applied to the skin, containing mercury, iodine, and other substances, are not known to be followed by any better results. It may indeed be laid down as a general rule that fatty applications to pus-producing surfaces where the pathological product is virulent are apt to undergo decomposition and otherwise act unfavorably upon the tissues--a fact first pointed out by Ricord in connection with the treatment of the {453} chancroid. Vaseline, as not liable to undergo chemical decomposition, is not open to this objection.

Curschmann, Kaposi, and other authors are in agreement respecting the value of water-compresses over the surfaces invaded by the eruption--a method of topical treatment which I desire to fully endorse after personal observation of its value. Curschmann recommends compresses dipped in iced, Kaposi those moistened with tepid water. The sensation experienced by the patient will prove the best guide to the temperature of this fluid. I prefer a solution containing one drachm of boracic acid to the pint of water as hot as can be discovered to be productive of comfort, a drachm or two of glycerine being added to the solution. The compresses dipped in this (or a carbolated solution, if the latter is preferred by either physician or patient) should be assiduously moistened and changed regularly by the attendants just as long as they can accomplish good. They operate, first, by protecting the part; second, by keeping it moist; third, by maintaining the surface temperature at the point most pleasant to the patient; fourth, by exercising the gentlest degree of equable compression over the surface. When desired, this may be covered with the Lister protective material or a piece of oiled silk to prevent evaporation at the surface.

In Vienna warm baths, administered either by the process of continuous immersion so generally practised there or by immersion for from two to three hours of each day, have been found to furnish the greatest amount of comfort to the patient. The skin is thus speedily relieved of its tension, the exfoliation of the crusts is hastened, and the time required for the evolution of the cutaneous lesions, if not shortened, is at least not retarded by the accidents of exposure to the desiccating influences of the air--ends which for the patient are practically one. In this country, and especially in private practice outside the larger charities with their ampler provision for these emergencies, nearly the same result may be reached by wrapping the patient completely in sheets wrung out of water of the temperature desired.

From first to last in the treatment of variola, all indications should be made subordinate to that most prominently set forth by the general character of the symptoms--viz. the conservation by every possible means of the vigor of the patient. The tax upon all reserves of vital energy is here so enormous and constant that he will gravely err who for a moment loses sight of this fact. Hence it is that anodynes, chloral, opium and its alkaloids, the bromide of potassium, and similar medicaments, introduced either by the stomach or by hypodermic injection, are to be jealously reserved for emergencies when it would seem cruel to withhold the temporary comfort they may impart. Stimulants are of course to be freely employed whenever they are indicated by exhaustion as this may be shown by a weak pulse and other failing functions of the body, but are certainly best reserved for such emergencies. In general, it may be remarked that the fewer the medicaments ingested by the stomach, and the larger the restriction of the labor of this organ to the task of sustaining the nutrition of the body, the better are the chances of a favorable issue.

It is unnecessary to add that all other indications presented in any given case are to be met, subject to the conditions indicated above. Abscesses {454} are to be opened and antiseptically treated; delirious patients are to be sedulously prevented from doing themselves injury; daily movements of the bowels are to be secured; while the diarrhoea of the typhoid state, occasionally resulting from the exhausted condition of the system when the force of the disease is spent, demands proper control.

Cleanliness is to be enforced by every judicious measure. The skin of the patient is to be washed in tepid water and soap as often as practicable in the course of the disease, and under no circumstances are applications of ointments, washes, or lotions to be allowed to collect in strata upon the surface commingled with the pus and crusts of the disease. At the time of such ablution, and occasionally oftener, the linen and other garments of the patient are to be changed. When the crusts are regularly exfoliating from the surface of the body general warm baths may be ordered, after each of which the surface of the body may be anointed with vaseline or covered with a finely-sifted dusting-powder, such as the corn-starch farina sold by grocers.

Inasmuch as hemorrhagic variola is usually hopeless in character, and remedilessly fatal, Kaposi's liberal use of opiates may be recommended when euthanasia is all that can be expected. So long as there is the narrowest chance of recovery resort may be had to ergot, turpentine and the mineral acids internally, combined with the external use of styptics and ice. But little confidence can, however, be placed in these measures, which will prove entirely ineffective in the great majority of all cases.

In all fatal cases of variola the duties of the physician are not ended by the death of the patient. It is for the benefit of the living that he should require destruction or disinfection and long disuse of all domestic articles that were employed upon or about the patient. The lifeless body should be disposed of by cremation, and medical men should exert their influence in favor of legal enforcement of such a wholesome practice.

{455}

VACCINIA.

BY FRANK P. FOSTER, M.D.

SYNONYMS.--Vaccina, Variolæ vaccinæ (Jenner), Cow-pox, Cow-pock, Kine-pox, Kine-pock; Fr. Vaccine; Ger. Kuhpocken, Schutzpocken, Impfpocken, Schutzblattern; It. Vaccina; Sp. Vacuna.

DEFINITION.--An eruptive disease characterized by a cutaneous lesion closely resembling that of small-pox, going through the stages of papulation, vesiculation, pustulation, incrustation, and cicatrization; differing from small-pox in the mildness or almost total absence of the constitutional symptoms, by being communicable only by inoculation, and by the fact that the lesions, as a rule, are developed only at the points of inoculation and in their immediate neighborhood.

This definition holds good for the great majority of cases, but in each of its parts we must take account of exceptions. For example, the lesion does not always follow the regular sequence of changes described. It may stop short at the stage of papulation, constituting the so-called raspberry excrescence, which will be further referred to hereafter; it may pass directly from the stage of vesiculation into that of incrustation, without any such change in its liquid contents as can properly be said to form a pustule; desquamation may take the place of incrustation; and, after an evolution otherwise normal, there may be no formation of a scar, simply because the destructive effect of the lesion has not extended deeper than the epidermis. The constitutional symptoms are sometimes severe, but they are always of very short duration. The disease is said to have been communicated otherwise than by inoculation in the case of some of the lower animals. Thus, Chauveau succeeded in producing some of its phenomena in the horse by causing the virus to be inhaled in the form of spray. It is doubtful, however, if it is possible to eliminate all sources of fallacy in such experiments. Finally, a generalized eruption is occasionally observed, although with great rarity. In stating these exceptions no reference is intended to cases in which complications occur.

NATURE OF THE DISEASE.--Many considerations warrant us in classing cow-pox among the varioliform diseases--chiefly its general resemblance to variola, and the fact that individuals who have been affected by it are thereby more or less fully protected against small-pox. It has been thought, indeed, that cow-pox was in reality but a modified form of small-pox; and this idea has been the basis of one of the theories that have been held as to the origin of vaccinia. Before enumerating and discussing those theories it will be well to mention that cow-pox is spoken of as spontaneous, casual, or inoculated, according to its mode of origin, known or assumed, in individual instances.

{456} Spontaneous or original cow-pox is the name commonly applied to the disease as it is met with in the cow in instances in which its mode of origin is unknown. Strictly interpreted, this expression implies a belief that the affection is capable of being developed in a cow independently of contagion or infection--a notion that seems to be held by many physicians, but not, so far as the writer is aware, by those whose study of the subject has been such as to lend any considerable weight to their opinions. Ordinarily, however, the term spontaneous cow-pox is employed simply as a convenient expression to denote the disease as it occurs naturally in cows, without implying any belief or theory as to its mode of origin.

Casual cow-pox is the term applied in cases that have been contracted by accidental inoculation, whether in the cow or in man. It is manifest that the so-called spontaneous cases are really casual, unless we accept the doctrine that infection is not necessary to the development of the disease.

The term inoculated cow-pox implies that the affection has been produced by intentional inoculation. Here, again, we are confronted with an illogical expression, for a disease that is inoculated accidentally is still inoculated, as much as if it had been conveyed purposely. It may be said, indeed, that the casual disease is due to some other form of infection than inoculation, but for such an assertion there is not a particle of proof.

Passing from this unsatisfactory nomenclature to a consideration of the theories that have been held as to the nature of cow-pox, we are first met with that of its being a disease sui generis, like small-pox, measles, scarlet fever, and the like, and, like them, originating only by its own specific contagion, not being capable of development by a modification of any other contagion, however closely it may thus be counterfeited. This seems the most rational theory of the nature of cow-pox, but it cannot be demonstrated except by disproving all opposing theories; and that has not yet been accomplished.

Another theory is, that cow-pox is really small-pox modified, as the phrase runs, "by passing through the system of the cow." It has been thought possible, indeed, to specify in what way the cow's system could impress such decided changes upon the virulent disease small-pox as to convert it into the mild affection that we know as vaccinia; in other words, it has been imagined that the function of lactation accomplished this remarkable result. This notion may have been due to the observation that so-called spontaneous cow-pox is met with only in cows that are in milk. The significance of this fact, however, is really nothing more than that cows in milk are more exposed to accidental inoculation than other bovine animals--namely, at the hands of the milkers. The fact that in such cases the lesions are almost always confined to the teats and the udder, far from affording any ground for the notion that there is some mysterious connection between cow-pox and the function of lactation, is but another proof that the disease is the result of inoculation. The lesions appear at the points of inoculation, the teats and the udder being the parts handled by the milkers. Moreover, there is no difficulty in inoculating young calves or adult bulls, and the lesions so produced do not vary in a single particular from those observed in so-called spontaneous cases.

{457} Men have been so carried away with this milk theory, however, as even to believe that the virus of small-pox might be shorn of its dangerous properties, so that it would produce only the vaccinal lesion when inoculated simply by mechanical mixture with milk. During the late Civil War one of the Confederate Army surgeons actually put this notion to the test of practice on quite a large scale, inoculating large numbers of persons with a mixture of small-pox virus and milk, terming the practice mitigated inoculation. We can scarcely suppose that he did anything else than variolate these persons, just as he would have done had he used variolous lymph without the addition of milk. His experiments show nothing new; they merely furnish a recent confirmation of the well-known fact, familiar to the old inoculators, that inoculated small-pox is sometimes exceedingly mild in a series of cases.

This theory of the variolous origin of cow-pox, and of the practicability of converting small-pox into cow-pox at will by "passing it through the system of the cow," has taken deep root in the minds of men, especially in Great Britain, where the late Mr. Ceely's experiments and Mr. Badcock's experience seemed to give it some color. Some years ago, however, the question was investigated most practically and thoroughly by a commission appointed for the purpose by one of the medical societies of Lyons, Chauveau being the recorder. Their conclusion was--and their reasoning seems to the present writer incontrovertible--that small-pox and cow-pox were wholly distinct from each other under all circumstances, and that it was impossible to convert the one into the other. But the doctrines of the English investigators, reinforced as they were by the ingenious arguments of the late Dr. Seaton, were not easily to be overturned in their own country or in America; consequently, the practice of variolating cows has been resorted to from time to time for the purpose of obtaining a stock of vaccinal virus of unquestionable authenticity--the so-called variola vaccine. This practice is utterly fallacious, and it is also dangerous, since the disease so produced, however mild it may seem to be, is nothing more nor less than small-pox, with its infectiousness by effluvium and its liability to prove serious even when carefully inoculated.

Quite recently the experimental investigation of the question has been undertaken de novo by a well-known English veterinarian, Mr. Fleming; and, since his conclusions coincide with those of the Lyonnese commission, it is to be hoped that we have seen the last of this rough-and-ready method of improvising a case of genuine cow-pox--a method that, in the light of our present knowledge, can only be characterized as downright malpractice.

The third and last theory we have to consider is that which ascribes the origin of cow-pox to infection from the horse. So far back as Jenner's time it was conjectured that cow-pox was due to the accidental conveyance of the virus of the grease (the eaux-aux-jambes of the French) by reason of the cows being milked by persons who were also employed in the care of horses affected with that disease. Grease is an eruptive disease of horses' heels. Doubtless it has often been confounded with a mere eczematous affection by those who have repeatedly failed in their persistent attempts to inoculate cows with it, and, on the other hand, a localized eruption of horse-pox may have been mistaken for it by those who have {458} supposed themselves to have succeeded in producing cow-pox by inoculating cows with the virus of grease, and have consequently given in their adhesion to the grease theory of the origin of cow-pox. At all events, so far as the writer is aware, that theory is not now held by any well-informed writer.

Still regarding the horse as the originator of cow-pox, we must turn our attention to horse-pox (equinia). Several years ago Depaul of Paris took great pains to establish the fact that horse-pox (an affection totally distinct from grease) was an eruptive febrile disease of horses, an exanthem; that the eruption was generalized, and, being for the most part concealed by the hair, generally overlooked; and that it was capable of being conveyed by inoculation, the lesion being indistinguishable from that of cow-pox. He believed himself to have demonstrated also that it was the contagion of horse-pox that gave rise to cow-pox in the cow.

Depaul's investigations were very keen and his conclusions were exceedingly plausible, but they cannot be called convincing, notwithstanding the fact that Constantin Paul succeeded for a time in popularizing a stock of horse-pox virus as material for vaccination. At about the same time the Beaugency case of cow-pox was discovered, and the perfectly satisfactory use that has been made of that stock may have thrown Depaul's theories and Paul's practice undeservedly into the background.

We can only say, in summing up, that the small-pox theory is utterly untenable, that the horse-pox theory has not been disproved, and that the theory that regards cow-pox as derived neither from small-pox nor from horse-pox, but as a disease sui generis, although not proved, is the most rational of all, and the most in keeping with known facts.

ETIOLOGY.--Nearly everything that could be said under this head has already been considered. It may be added that meteorological conditions have been supposed to favor the prevalence of the disease among cows. More precise observations are needed to enable us to determine whether or not there is any truth in this supposition. It has been said that the affection is most apt to prevail during warm and moist seasons. This is contrary to what we might have imagined, as warmth and moisture are quite destructive of the vaccinal virus. Under ordinary circumstances, however, the contagium often proves wonderfully tenacious of life, and the disease, once introduced among a herd of cows, is prone to linger for months, or even years, attacking animals recently added to the stock and young cows during their first lactation. As has already been stated, age, sex, and parturition can be regarded as etiological factors only in so far as they favor the occurrence of accidental inoculation. In the human subject vaccinia occurs generally as the result of intentional inoculation, as will be more fully referred to when we come to the consideration of vaccination. Insusceptibility is occasionally met with, both in the cow and in man, but it is very rare. Perhaps it may be explained in some instances by the subject having really had the disease, or indeed small-pox, either before or after birth, in so mild a form as not to have left the characteristic marks. Certain it is that the lesion does not always leave a permanent scar, especially in the cow.

GENERAL COURSE OF THE DISEASE.--This is best studied in cases that have followed intentional inoculation, for here we know the {459} chronological sequence of events. Depending somewhat upon the method of inoculation, and perhaps also to some extent upon the state of the skin at the site of the inoculation, or even upon a systemic condition (since some vaccinators hail it as a harbinger of success), at the time of the operation a ring-like erythema may be seen surrounding the inoculation. This is exceedingly evanescent, being doubtless due to vaso-motor action, and is not often witnessed.

Ordinarily, no effect whatever is observed until after the lapse of two or three days, when a red papule is formed. This papule increases in superficial area, but not in height, and gradually loses its redness. It assumes a circular form, or, in the case of a compound pock (for that is the proper name for the lesion), a configuration representing segments of several circles, and as it increases in area it becomes more and more raised at the border (the bourrelet of French writers), while the central portion, which also increases in size pari passu with the peripheral annular vesicle, does not become more elevated, but remains depressed, giving the pock as a whole the peculiar shape termed umbilication. Up to the eighth or tenth day, inclusive, the marginal elevation contains a limpid fluid termed lymph, and consequently presents a pearl-like lustre. At this period a rather sudden increase takes place in the corpuscular elements contained in the lymph, causing that liquid to become thick and opaque, so that the elevated margin of the pock, which before had shown the pearl-like lustre alluded to, now comes to look as if made of tallow.

At the same time what is known as the areola forms around the pock, and constitutional symptoms show themselves. The areola is a circumscribed redness of the skin, perfectly circular in form and of five or six times the diameter of the pock itself. It is sharply defined and of a vivid red hue. Usually it is a mere hyperæmia of the skin, but in some instances, especially where the process of pock-formation is decidedly pronounced, a few papillary elevations are to be seen in the immediate neighborhood of the pock, and at that situation there may also be some lividity. After a few hours' persistence in the form of a disc the areola begins to disappear, the redness fading first at the central portion, so that in its declining stage it assumes the shape of a ring which constantly grows narrower and narrower at the expense of its inner portion, and finally disappears altogether. In the cow the areola is only a faint line immediately around the pock.

Constitutional symptoms are invariably present in cases that follow the regular course. The temperature rises one or two degrees Fahrenheit, the appetite becomes impaired, and sleep is somewhat disturbed. In many cases, mostly those of secondary inoculation, the symptoms are more severe; the fever runs higher, and may be accompanied with transient delirium; nausea is experienced, perhaps with actual vomiting; and severe pain is felt in the head and along the spine, the latter being most marked in the cervical region. These symptoms usually last but a few hours, and they are apt to be accompanied by a modification of the areola whereby it loses its disc-like outline and becomes diffused irregularly, especially, if, as is usual, the inoculation has been done on the arm, in a downward direction toward the elbow.

Along with these phenomena intense itching is often felt at the situation of the pock, being an aggravation of the pruritus that in a mild {460} form accompanies the greater part of the whole course of the lesion. Supposing the arm to have been inoculated, the lymphatic glands of the axilla now become swollen and tender, but their suppuration is unusual, and is to be regarded as a complication.

To go back to the pock: some time before the contents of the marginal elevation become opaque the central portion is converted into a crust of a brownish color, and finally, from the tenth to the fifteenth day, the bourrelet itself, having ceased to increase in size, takes part in the process of incrustation, the completed crust representing the form of the pock, having a circular ridge at the border, at which part its color is not so deep as at the centre. The crust usually falls off between the fifteenth and the thirty-fifth day. It is hard, translucent, and of a prune-juice color; thick at the centre and thin at the periphery; smooth on its attached surface and somewhat wrinkled on its outer aspect; surmounted at the centre by the epidermal débris produced by the operation of inoculation, mingled perhaps with more or less dried blood.

After the crust falls off a reddened surface is left of a cicatricial nature, usually somewhat depressed below the level of the surrounding skin, and frequently showing lesser pits, which latter appearance is termed foveolation. Instead of these pits, radiated striæ are frequently left. Gradually the scar loses its red color, and, like other scars, finally becomes paler than the surrounding skin. It is usually permanent.

IRREGULARITIES IN THE COURSE OF THE DISEASE.--Ever since cow-pox first became the subject of medical study deviations from its typical course have been noticed, and have been the theme of a good deal of speculation. The older writers, indeed, bestowed no little attention upon what they considered to be not irregular forms of vaccinia, but distinct affections with which it was liable to be confounded. Their descriptions of these diseases, which they termed spurious cow-pox, are, however, so vague as to possess but little more than an historical interest. In regard to affections met with casually in the cow, we can often determine their nature only by test-inoculations, and even that criterion is not always thoroughly convincing; for, on one account or another, we may fail in the attempt to propagate true cow-pox, and on the other hand, if we admit that there is a radical difference between cow-pox and small-pox, it is manifest, bearing in mind the errors into which experienced investigators have fallen, that we may propagate small-pox through a long series of experiments without once suspecting it to be anything but cow-pox. We may, nevertheless, always determine, provided we succeed at all, whether we are dealing with a disease that protects against vaccinal and variolous inoculation.

In the human subject we seldom meet with affections that counterfeit vaccinia, although, if we take only the lesion into consideration, there are certain contagious forms of herpes that may give rise to doubt, and possibly the same may be true of impetigo contagiosa.

Turning, then, to the irregularities properly so called, we have first to consider the absence of constitutional infection. This must not be confounded with the mere lack of obvious constitutional symptoms; what is meant by the expression is, that in certain instances the local lesion may appear typical, and yet no such impression be made upon the system as to render it proof against subsequent inoculation. Early in the {461} century the possibility of this lack of systemic infection was insisted upon by Mr. Bryce of Edinburgh, who invoked it as an explanation of the occasional failure of vaccinia to protect against small-pox. The practical question was, how to decide, in a given instance, whether general infection had or had not taken place. In the opinion of many observers--and that notion has cropped out every now and then up to the present day--absence of the areola furnished at least presumptive evidence that the constitution had eluded infection. But, whatever may be held theoretically, it must be conceded either that the general system very rarely fails to feel the impress of the disease, or else that the criterion is fallacious. For in an experience of seventeen years the present writer has not known of a single instance in which a vaccinal lesion that pursued a regular course in other respects has failed to be accompanied by the areola. And certainly Mr. Bryce himself must have attached little if any importance to it, for he took great pains to establish a means of determining the presence or absence of constitutional infection--the so-called Bryce's test. This consists in repeating the inoculation at a certain period in the evolution of the disease, the theory being that systemic infection does not take place at once, but only after the lapse of a number of days from the time of the inoculation. Up to that time a repetition of the inoculation is possible, and, if systemic infection results from the first one, both lesions will mature at the same time, the second one following an accelerated course, reaching its acme rapidly, although dwarfed in size. If, on the other hand, the first inoculation failed to infect the constitution, the second one will pursue its course in the usual manner. Moreover, at a certain time, generally about the fifth day, a repetition of the inoculation will fail altogether if the original insertion has really infected the system. The present writer can testify that Mr. Bryce's statements are correct; he has applied the test in many cases, but in no instance has he been led to the conclusion that constitutional infection had failed to take place. He is inclined to think, therefore, that such failure is exceedingly rare.

Passing over the multiplicity of irregularities in the lesion that were described by the older observers, it seems that there are a few that are of practical importance. In the first place, there is a variety of pock to which it is not easy to give a definite name, but which is characterized by a lack of decided elevation above the surrounding skin (a deficiency for which it makes up in superficial area), by the early formation of a thin, flimsy, straw-colored crust, and by the utter failure of the characteristic firm brown crust of the typical variety to become developed. This form of irregular pock has not been seen by the writer of late years, but before animal vaccination came into general use he met with it frequently, mostly in cachectic children. Notwithstanding its sprawly, unsatisfactory appearance, it is undoubtedly genuine, for the typical lesion may be produced by inoculation with its contents.

Another irregularity of the pock is what is familiarly termed the raspberry excrescence. A red elevation forms at the seat of inoculation, and at first promises to follow the typical course, although it may be tardy in making it appearance; but it never advances to full development. It becomes indolent, and may last for several weeks, or even months, in the form of a hard, flat nodule of a bright-red color, not unlike a small {462} nævus. In many instances it has a succulent look, but no lymph can be obtained on puncturing it. No areola appears at any time, and finally the lesion slowly disappears, leaving no trace of its existence. It is probably an abortive form of pock, in which only the papillary layer of the skin takes part, without any exudation into the epidermis. It is seldom, if ever, protective against small-pox, for it constitutes no bar to a subsequent vaccination. This irregular pock has been observed from time to time ever since the early days of vaccination, but for the past six years it has been seen more frequently in New York than for many years before. Now, however, it seems to be growing less common. The writer is not aware of any satisfactory explanation of its occurrence. It is seen in all sorts of subjects, and seems to follow the use of one variety of virus as much as the employment of any other.

What has been termed generalized vaccinia is another form of irregularity. The expression is a vague one, covering as it does not only the very rare cases of true eruptive vaccinia, in which a general eruption of pocks takes place as a consequence of constitutional infection, playing the part of an exanthem, but in addition those instances, not very uncommon, in which pocks are formed here and there on the body, probably as the result of the accidental transfer of the virus from the pock by scratching. Under such favorable conditions--the immediate transfer of lymph from a pock in which the specific evolution is going on vigorously--the slightest penetration of the epidermis with the nails is enough to secure self-inoculation. In view of this facility with which it may be effected, we should be very careful not to jump hastily to the conclusion that in any given case of generalized vaccinia the supplementary pocks are truly eruptive; as a matter of fact, the present writer has never seen an instance in which he was convinced that such was the case. Where the pocks are very numerous, especially in subjects with an irritable skin, much distress may be caused by the itching and by the consequences of scratching, and marked febrile reaction may accompany the process; so that, in view of the great similarity of the lesions to those of the variolous eruption, much doubt is sometimes entertained as to whether the disease is not really small-pox. This question cannot always be definitely settled at first, but the failure of the secondary fever of small-pox, together with the fact that the disease does not spread by infection, will generally suffice to decide it.

Concerning those cases of generalized vaccinia that are manifestly not eruptive, it sometimes happens that the cutaneous receptivity is not exhausted for several weeks, or even months. Such cases set Bryce's test at defiance, in consequence, probably, of an idiosyncrasy. In some of these instances the pocks appear in clusters of successive formation, looking not unlike patches of zoster. Small supplementary pocks in the immediate neighborhood of the original lesion are not at all uncommon.

PATHOLOGICAL ANATOMY.--Avoiding the minute histological details for which the prescribed length of this article gives no scope, but little is to be added to what has already been said in the section on the clinical features of the disease. The lesions of vaccinia are wholly cutaneous. Confining ourselves to cases that follow a regular course, there is, indeed, but one, the pock--a term that seems preferable to vesicle and {463} pustule, since the latter apply only during certain phases in the development of the lesion.

A pock may be regarded as essentially a lesion of the epidermis, for it is in that structure that its most striking features are developed, and in some cases, although doubtless the papillary layer of the derma is congested, there is no permanent alteration of tissue below the Malpighian layer of the epidermis. These are the catarrhal pocks of Rindfleisch, and it is in such cases, if in any, that no scar (even of temporary duration) results. The term catarrhal pock, however, is not vitiated by an extension of the morbid process deep enough to produce a permanent cicatrix, and it is probable that in most cases the catarrhal type predominates. By the term diphtheritic pock the same author refers to cases in which the congestion of the papillary layer is so intense as to block the supply of blood to the apices of the papillæ, as a result of which they become exsanguinated and necrosed, forming a white pultaceous layer on the floor of the pock, which is undoubtedly what Ceely referred to when he spoke of a false membrane. In some cases even the subcutaneous tissue undergoes necrosis, a sort of core being included in the substance of the crust that ultimately forms.

Whichever of these forms of pock we take into consideration, always excluding irregularities and complications, we find certain definite changes in the epidermis. The dome of the pock is formed by the unbroken transparent horny layer of the epidermis, unaffected by the morbid process. The cavity of the pock is formed by the squamous cells of the epidermis being forced out of their normal relations by an exudation of lymph between them, some of them being tilted up edgewise while still retaining their connection with the surrounding cells, thus accounting for the multilocular structure of the pock; for it is a fact that the circular bourrelet consists not of one ring-like cavity, but of many separate chambers. The result of this structure is, that the liquid contained within the pock--the lymph--escapes only partly through a puncture made in the wall of the vesicle. In order to evacuate the pock thoroughly it is necessary to make a great number of punctures or a circular incision following the ring-like ridge of the bourrelet.

The lymph contained within the cells of the pock is a liquid which in its gross physical properties differs but little from the lymph which exudes from any traumatic surface shortly after the injury has been inflicted, as in the glazing process that takes place in wounds. Examined microscopically, however, it is found to contain not only the fibrin, the salts, the corpuscular elements, and the débris that ordinary tissue-juice presents, but also certain minute spherical bodies--termed microspheres, microzymes, vaccinads, etc.--that give it its characteristic infective quality and justify the title of virus commonly applied to it. That these minute bodies really constitute the virulent element of the lymph, or at least that they are the vehicle of the contagium, is not a mere matter of conjecture, but has been demonstrated abundantly, notably by Chauveau and Sanderson's diffusion experiments. Inoculation with the supernatant liquid, containing none of these bodies, always fails to convey the disease, but it is not absolutely essential that they should be present in large proportion in the lymph to render the latter virulent, for Chauveau found that lymph diluted with thirty times its bulk of water was not without infective {464} power. It scarcely need be said, however, that the greater the proportion in which they are present, the greater is the probability that the lymph will prove infective on inoculation. These bodies have been supposed to be of a vegetable nature, and Hallier, Kohn, and others have bestowed no little study upon their botanical characteristics. Under favorable circumstances they retain their virulent properties for a long time, especially if kept perfectly dry and not subjected to a high temperature. The present writer has met with success in the use of vaccinal virus seven years old.

The lymph differs somewhat in its gross appearances according as it is produced in man or in the bovine animal. In the former it is clear and limpid, and exudes freely in great drops when the pock is punctured in its peripheral portion; in the latter it is more straw-colored and more viscid, exuding sluggishly, or even refusing to flow without the aid of pressure. Moreover, the vaccinads seem endowed with different properties in the two cases: in man they have a tendency to remain equably diffused through the liquid, while in the cow they tend to separate from it and to be deposited upon any solid surface at hand.

The phenomenon termed umbilication, common to the vaccinal pock and to that of variola, has given rise to some differences of opinion as to the mechanism of its production. The term implies a depression at the centre of the pock. This appearance is not invariable, but it is constant enough to have met with general acceptance as a characteristic feature, notwithstanding the undoubted fact that it is found in lesions that have nothing whatever to do with any of the varioliform diseases. Not to waste space in discussing the various theories that have found supporters, it may be said that they have all been proved to be defective, save only the simple explanation that as the process of evolution advances the centre of the pock undergoes desiccation, whereby that portion of the tissue involved is so glued and drawn together as to become incapable of the swelling that is still going on in the growing peripheral portion of the lesion.

The crust into which the pock ultimately becomes converted is not, as is commonly supposed, mere dried lymph and nothing else; it is dried tissue enclosing concrete lymph. It generally includes also various sorts of débris--broken-down epithelium, blood-corpuscles, pus-corpuscles, and even, in rare cases, a core of sphacelated tissue like that of a furuncle.

As has already been said, the cicatrix is to a certain extent peculiar in that it is usually depressed and foveolated. Too much stress has been laid upon these features, however, and the truth is that some traumatic scars cannot be distinguished readily from that of vaccinia, while, on the other hand, many a genuine pock leaves no permanent trace behind it. Indeed, in the cow it is the exception for a noteworthy scar to form.

SEQUELÆ AND COMPLICATIONS.--The most important sequela of vaccinia is the fact that it protects the subject against small-pox, and on that circumstance hinges the chief practical interest of the disease. This leads us at once to the subject of vaccination, and therefore under that head we shall pursue our consideration of this curious affection.

{465} Vaccination.

SYNONYMS.--"The new inoculation;" Fr. Vaccination; Ger. Kuhpockenimpfung, Schutzpockenimpfung; It. Vaccinazione; Sp. Vacunacion.

HISTORY.--Before giving the history of vaccination itself (meaning by that term the intentional inoculation of vaccinia for the purpose of protecting the subject against small-pox), it may be well to devote a few words to a practice that preceded it--that of the intentional inoculation of small-pox (or simply inoculation, latterly called variolation). In very early times various Oriental peoples became aware of the fact that small-pox might be very decidedly mitigated by inoculation. This was practised in various ways, all of which may be reduced to the process of inserting small-pox virus into a solution of continuity. Lady Montagu, the wife of an English ambassador to Turkey, brought the practice back to England with her, where it soon made its way into popular favor, and whence it spread rapidly over Europe and America. Thus contracted, small-pox was shorn of a great part of its terrors; the eruption was usually trifling in amount, and in every way the disease was mild as a rule. Still, the mortality was something worth considering, and, worse than that, the inoculated disease was communicable by effluvium, so that an inoculated person had to be secluded carefully for fear of spreading the disease in the ordinary way. In all cases, too, careful medical treatment was thought necessary. On the whole, then, while inoculation was undoubtedly a boon, it was fraught with many grave perils. So great, indeed, were these perils, and so thoroughly were they appreciated, that the practice was interdicted by law in most civilized countries so soon as vaccination had become established in popular favor.

In several European countries the common people--at least those of them who had much to do with dairies--gradually became aware of the existence of the disease termed cow-pox, and of the fact that those individuals who had accidentally contracted it were rendered proof against the infection of small-pox. There is even fair testimony to show that some of these people, particularly the English farmer, Benjamin Jesty, relying on their observation to this effect, employed intentional cow-pox inoculation as a protective measure. These facts, however, do not detract in the least from the credit that all Christendom has awarded to a man who subjected the popular impression in question to the test of scientific investigation, proved its truth, and demonstrated its value to the world. That man was Edward Jenner, an English country physician. It was in the last quarter of the eighteenth century that he entered upon his course of inquiry, and on the eve of the present century he published his demonstration to the world. It was not a discovery; it was not an invention: it was more than either, "a matchless piece of induction," to quote the words of Mr. John Simon. Filled as he must have been with the consciousness of his great achievement, Jenner set this good example to all investigators: that he did not make haste to convert the world; he first convinced himself. It may almost be said, indeed, that, like Minerva from the head of Jove, the rational and perfected practice of vaccination sprang complete from Jenner's hands. Doubt and ridicule he had to encounter at first, and afterward envy and detraction; but the force of {466} his facts and the symmetry of his deductions were such that the new inoculation soon spread through the broad world, and has ever since maintained its sway, save with a few fanatical scoffers.

That vaccination really does protect against small-pox observation has taught the whole civilized world, if we leave out of account the few conscientious and intelligent doubters (made such, doubtless, quite as much by the extravagant statements often put forth by those who from time to time think it incumbent on them to defend vaccination, as by their own misinterpretation of facts) who are to be found associated with the noisy little body of actual opponents of the practice. One of the most injurious statements ever made in the advocacy of vaccination is, that it always protects if properly done. When one of these illogical defenders of that proposition is confronted with an instance that disproves his assertion, he falls back on the allegation that in that instance the vaccination was not properly done. The manifest absurdity of such an argument strikes the doubter most forcibly, and inclines him to say to himself, Falsus in uno, falsus in omne. Unbelief founded on this ground would never have arisen if the plain truth had always been adhered to: that the protection afforded by vaccination is not invariable, and that very often it is not permanent. In the infancy of the practice these facts were not known, but it is now many years since they became obvious to every fair-minded observer. The misapprehension of facts lies chiefly in the false deduction from the circumstance that the great majority of cases of small-pox occur in persons who have been vaccinated. But the explanation of this is very simple. Suppose that, of one hundred persons vaccinated, twenty fail to be protected permanently; that all persons not vaccinated are unprotected; and that throughout the civilized world the proportion of vaccinated to unvaccinated persons is as ninety to ten. Making no pretence of arithmetical accuracy, it may certainly be said that all these suppositions are well within the truth. It follows from them that in a community of ten thousand persons there will be nine thousand who have been vaccinated, and one thousand who have not. Of the former, eighteen hundred will have failed to secure lasting protection. Therefore in case of an epidemic there will probably be a proportion of eighteen cases of small-pox in the vaccinated to ten in the unvaccinated; and yet this should not obscure the fact that of the nine thousand vaccinated more than seven thousand were absolutely protected, whereas of the one thousand not vaccinated not one could escape the disease if exposed to it. When we add the further observation that of the eighteen hundred cases of small-pox among the vaccinated not more than thirty or forty would probably prove fatal, while of the one thousand cases in the unvaccinated about two hundred would end in death, we have a striking demonstration of the efficiency of vaccination. As a matter of fact, statistics show that the figures here given err rather in allowing too little than in asserting too much in favor of vaccinal protection.

The question naturally arises, Why it is that vaccination protects some persons and does not protect others?--reference being had, of course, to permanent protection, for it is exceedingly rare for temporary immunity to be attained if we exclude those instances in which the variolous infection has taken place before the operation is resorted to. This {467} question cannot be answered with any certainty, but various theories have been brought forward, some of which call for notice.

In the first place, it has been thought that the revolution of the system termed puberty was fraught with such a radical change as to do away with the mild modification due to vaccination. While this theory has an air of plausibility, it seems to lack proof and not to be upheld by analogy, for we do not find that children who have had scarlet fever, measles, and the like often undergo those diseases a second time on arriving at the age of puberty.

The only remaining theory that our limits will allow a consideration of is that put forward by Marson of London, that the degree and duration of vaccinal protection are proportionate to the perfection of the vaccinal lesion and to the number of insertions made. In a large experience with small-pox Marson found that the disease was more fatal among those whose vaccinal scars were imperfect or few in number than among those who bore evidence that several pocks had been produced and had run a typical course. As to the influence of a perfect evolution of the lesion, but little doubt can be entertained, for we have already seen that in some instances its course is so different from what it should be that no protection whatever seems to result. When we come to consider the number of the pocks as affecting the degree or the duration of protection, however, an obvious source of fallacy arises in the fact that we cannot always be sure that some of the scars on a person having a number of them were not the products of a repetition of the operation several years after the first--that is to say, a revaccination, the efficiency of which in restoring lost immunity is now well established. Nevertheless, as long as the doubt remains the best course to pursue seems to be to act as if Marson's theory were in all respects correct, and vaccinate by multiple insertions.

We have, then, no positive means of ascertaining who those persons are that are likely to fail of lasting protection, or how long a time will elapse before the cessation of their immunity will take place. The only safety lies in revaccination. But after how many years should revaccination be resorted to? It has been thought that this question might be settled by noting at what age, or at what period after primary vaccination, large numbers of people became susceptible of revaccination. This test, however, is not altogether trustworthy, for a renewed susceptibility to vaccinia by inoculation does not necessarily imply that the liability to take small-pox by effluvium has been regained. If it did, modified small-pox (varioloid) would be far more common than it is, for it is certain that revaccination can be made to succeed in a very large proportion of children long before they have reached the age of puberty. The fact is, contrary to the notions of the last generation, that success in revaccination is the rule, not the exception. Formerly it was not expected to succeed, and therefore no special pains were taken to ensure success.

Definite rules cannot be laid down as to the time that should be suffered to elapse before vaccination is repeated, but in the great majority of instances safety may be attained by revaccination every five or six years, and always in the presence of an epidemic, regardless of the lapse of time; also whenever one's mode of life is to undergo a noteworthy change, {468} as in emigrating to a foreign country, on entering the military service, and the like.

To sum up, then, vaccination almost invariably protects against small-pox for the time being; generally for a long term of years; sometimes for a lifetime. Often the protection is absolute; as a rule, it is very nearly so; in rare instances it is trifling. In general terms, it may be said that it is scarcely less protective than variolous infection itself, for death from a second attack of small-pox is by no means rare. Here the question comes up: Is vaccination less protective, either in degree or in duration of effect, than it was at the time of its adoption? Given a typical vaccinia, we may unhesitatingly answer, No; but do we now so invariably produce the disease in all its essential features as was done in Jenner's time? Yes, provided we use proper virus and employ as much care as was taken by the older physicians, who, trained to the practice of variolation (the inoculation par excellence of bygone days), did their work with a gusto now seldom witnessed. But there was a time, now happily at an end, when it was not easy to obtain thoroughly good virus, and when, therefore, the result was apt to vary materially from the standard. This may be conceded without entering upon the vexed question of the general deterioration of the Jennerian stock of vaccine.

Besides immunity from small-pox, there are one or two sequelæ of vaccinia that deserve mention before we proceed to consider what it is better to class as complications. In the first place, vaccination has been supposed to confer temporary protection against whooping cough. The writer is not aware, however, of any precise data going to prove either the truth or the falsity of this supposition.

Secondly, by virtue probably of the inflammation that attends the evolution of the vaccinal pock, vaccination practised in the immediate neighborhood of a small nævus often cures that blemish, and it has been done for that purpose in many cases. It has no advantage over many other measures, however, and there is the disadvantage that the nævus may so mask the pock as to give rise to some doubt as to the satisfactory character of the latter. The practice, therefore, is not to be urged.

COMPLICATIONS.--These are local and systemic. Those of them that are at all serious are rare, and can generally be traced to fortuitous circumstances.

Inflammatory complications are usually due to undue traumatism at the time of the inoculation, to injury of the pock, or to the previous existence of a cutaneous disease or of some dyscrasia. Dermatitis is the most common. It is usually a mere erythema, but in some instances lymphangitis, lymphadenitis, phlegmonous inflammation, with diffuse suppuration, may result. From injury of the pock ulceration and gangrene may take place, and septic absorption may follow in their train. These complications are to be treated as if they had occurred from any other cause. Generally, the mere vaccination is not responsible for them, but in some instances putrescent vaccine may be adduced as their source. In such cases the complications, if they can still be called so, are apt to make their appearance long before the pock matures, even within forty-eight hours of the vaccination. Inflammatory complications supervening on the full development of the pock may invariably be set down as due to some cause not connected with the quality of the virus employed.

{469} An undue amount of dermatitis is best treated with some mildly astringent and anodyne application. The following liniment is excellent for the purpose: Rx. Unguenti Stramonii oz. j; Liquoris Plumbi Subacetatis fl. drachm ss; Olei Lini fl. oz. iv.--M. fiat linimentum. As a rule, it is best to avoid poultices applied over the pock itself, for they soften the tender structures that make up its dome and render it prone to rupture, with all the consequences that may follow its conversion into an open sore. When the latter accident has occurred, dusting powders will ordinarily suffice to absorb the discharge, and thus prevent putrefaction--either the ordinary toilet powder or salicylized or carbolized powders, the basis of which may be starch with a small proportion of the oxide of zinc. Besides the antiseptics mentioned, iodoform, boric acid, etc. may be used to advantage. Liquid applications are not usually so appropriate, but the writer has known the proprietary preparation termed Listerine to answer admirably.

Circumscribed collections of pus are to be treated as under other circumstances, and burrowing is to be guarded against. It is only in the worst cases that constitutional treatment of any sort is demanded, and in these it should be of a supporting nature.

Passing from the simple inflammatory complications to those of a specific character, we will first mention erysipelas. Genuine erysipelas following vaccination is quite rare, but when it does occur it is prone to prove serious. The writer believes that it always depends on secondary infection--i.e. that the vaccinal wound becomes the nidus of an erysipelatous contagium already existing in the patient's surroundings, just as any other traumatic surface might, and that the vaccinal virus has nothing whatever to do with it. Admitting that improper virus is apt to give rise to dangerous inflammatory complications, the latter are not really erysipelatous, whatever guise they may put on. Erysipelas following vaccination calls for no other treatment than what is proper for traumatic erysipelas under ordinary circumstances.

We now come to the subject of vaccinal syphilis. The question of the possibility of conveying constitutional taints along with vaccinia was raised long ago, but, partly relying on certain theoretical tenets, and partly because of the rarity of well-ascertained facts to shake the blind confidence felt in the utter harmlessness of vaccination, the profession fought the suggestion without properly investigating it. In regard to syphilis, the broad assertion was maintained that two infectious diseases could not affect an individual at one and the same time: either syphilis would be communicated alone or vaccinia alone; moreover, it was affirmed that the juices of a syphilitic person were not capable of giving rise to the disease by inoculation unless they happened to proceed from a syphilitic lesion. There was never sufficient basis for the former of these two doctrines, and the latter received a rude shock when it was shown by Pallizzari and the anonymous physician of the Palatinate that the blood of a syphilitic subject was capable of conveying the taint. Meantime, certain horrible outbreaks of syphilis were reported, chiefly in Italy, that could not reasonably be imputed to the ordinary occasions of syphilitic infection. Even these occurrences, however, failed to shake the general incredulity, especially in Great Britain, where until quite recently men's orthodoxy in medical matters was gauged by their obstinacy in refusing to {470} investigate, far less believe, the slightest proposition unfavorable to vaccination, and where, also, observations from beyond the limits of the empire were looked upon as in all probability fallacious.

To a Frenchman, M. Viennois, we are indebted for the first systematic and fair-minded study of the subject of vaccinal syphilis. This writer demonstrated that the Rivalta cases and those of other like outbreaks were certainly due to vaccination, but he concluded that they owed their occurrence not necessarily to the use of lymph from syphilitic subjects, but to the fact that that lymph contained blood. By this time it had come to be recognized that syphilis was inoculable by the blood. But even Viennois's masterly essay, and the facilis descensus it offered to those English authors who found themselves confronted with proof positive of their error, failed to make any noteworthy impression beyond the concession that syphilis might possibly be communicable in vaccination, but that, if it were, the catastrophe might easily be escaped by avoiding the use of lymph contaminated with blood, and that, therefore, the danger was practically no danger at all, for no one in England would think of using bloody lymph! In all this the English were slavishly followed by our own countrymen. It is proper to add, however, that Ballard of London did his best to present the matter in a proper light to the British profession, and that it is largely due to his labors and to those of Jonathan Hutchinson (the latter of whom supplemented Ricord's discovery that vaccine lymph is never free from blood with abundant clinical evidence of the existence of vaccinal syphilis unavoidable by the mere observance of Viennois's safeguard) that we are now freed from the clog of error in this matter. Nor was it the English alone that so long baffled the recognition of the truth; in the French Académie de Médicine, Jules Guérin and his adherents fought desperately against it.

At the present day we know that syphilis is liable to be communicated in vaccination, and that, too, without regard to visible blood in the lymph employed. There are two ways of avoiding it. One is, to use non-humanized lymph, since the lower animals are insusceptible to syphilis.[1] This is simple. The other is, to select a human vaccinifer that is free from syphilis. This is difficult. Too great reliance, however, should not be placed upon the vaccinifer; it is possible to convey syphilis even in the use of bovine virus. Suppose two persons, A and B, are to be vaccinated at one sitting, A being syphilitic. If A is vaccinated first, and the same lancet, imperfectly cleansed, is used on B, it is plain that B will be inoculated not only with vaccine lymph, but also with A's blood. It is of the first importance, therefore, that this form of vaccinal inoculation of syphilis should be carefully guarded against; and that can be accomplished most certainly by using a fresh instrument for each patient.

[Footnote 1: Practically, this is certain, although there is some reason to believe that the disease may be conveyed to monkeys.]

From a medico-legal point of view it is important to note that constitutional syphilis may follow vaccination, and yet have nothing to do with it. Suppose an infant to be born syphilitic, but with no visible manifestations of the taint. Let that child be vaccinated, and let the syphilitic dyscrasia afterward break forth. The ordinary inference would be that the syphilis was due to the vaccination; and in most instances this view would certainly be urged by the syphilitic parent, since it would {471} free him from suspicion. It is always easy to disprove such an allegation, however, for syphilis communicated in vaccination always shows itself first in the form of a chancre at the site of the vaccination. Therefore in any given case, unless this mode of onset can be proved, the syphilis is manifestly not of vaccinal origin. Some observers, it is true, are of the opinion that vaccination may evoke a pre-existing syphilis, to use Lanoix's term--i.e. that it may hasten the appearance of the characteristic manifestations, and even determine their localization at the site of the vaccinal inoculation. But, even allowing the truth of that proposition, in such a case the lesion would be constitutional, not chancrous.

It is well, nevertheless, to take precautions against being placed on the defensive in this way; and it may commonly be avoided by declining to vaccinate infants under three or four months old, since inherited syphilis generally manifests itself by that time. This prudence on our own behalf should not be carried so far, however, as to lead us to deny the benefit of vaccination to very young infants whenever the prevalence of small-pox is such that they are in obvious danger of exposure.

As regards its management, vaccinal syphilis does not differ from the ordinary form of the affection, and hence demands no other treatment than what is proper for the disease contracted in the usual way. It simply originates in an extragenital chancre.

Concerning the conveyance of other constitutional taints in vaccination our knowledge is very limited. The present tendency of pathological investigation is, however, to accord inoculability to many diseases that formerly were not imagined to possess that quality, so that in regard to other affections than syphilis it is prudent to use the utmost care in the choice of lymph. There is one supposed safeguard that does not seem to have the slightest title to be so regarded--namely, the notion that a typical pock cannot be developed on a person affected with a specific cachexia. There is no truth in the doctrine. Over and over again the writer has seen perfect vaccine pocks on persons whom he knew to be syphilitic.

Cutaneous affections of a non-specific character are sometimes observed to result from vaccination; that is to say, they follow close upon its performance, without any other known exciting cause. It may fairly be supposed that in many instances they would have shown themselves even if the vaccination had not been performed, for it is often the case that we are unable to speak positively in regard to the exciting cause of an eruption. Several years ago a striking case in point was related to the writer by a well-known physician of this city, S. S. Purple, in whose practice it occurred. Purple had engaged to vaccinate a child on a certain day, but for some reason the vaccination was not done. In about a week from the appointed day, however, erysipelas made its appearance, beginning on the left arm at the usual site of vaccination, and pursued its course to a fatal termination. To be sure, we are now speaking of non-specific affections, but erysipelas illustrates the proposition perfectly, notwithstanding its specific character.

Children with a tendency to eczema are prone to suffer an outbreak of that disease as the result of vaccination. In Jenner's time, indeed, it was considered not only that there was great risk of causing an aggravation of any slight eczematous eruption by vaccination, but that the mere {472} existence of the eczema, even in the most trivial form, was likely to interfere with the success of the vaccinal inoculation. This has been the general feeling of the profession. Quite recently, however, many observations have been recorded tending to show that the old dread of vaccinating an eczematous child was not altogether warranted. The question needs further study, and, while it is probably best to postpone the operation under ordinary circumstances, nothing should induce us to withhold its protective influence where there is any manifest danger of actual exposure to small-pox.

Although eczema is the most common of the cutaneous affections called forth or aggravated by vaccination, there are various forms of skin disease, some of them difficult to classify, that occasionally result. They are usually vesicular, pustular, or furuncular--that is to say, irritative. In the majority of instances it will be found either that the pock itself has followed an irregular course, being whitish, diffuse, and ending in an exaggerated although superficial incrustation, or that it has been subjected to injury. Still, in some cases neither of these conditions is the precursor of the skin affection. In many instances the latter can only be called nondescript. There seems to be some occult connection between vaccination and the curious skin disease described by the late Tilbury Fox of London under the name of impetigo contagiosa; and, indeed, Piffard of this city has found certain microphytes to be common to the crusting period of vaccinia and that of contagious impetigo. What the relation of the two affections is to each other, however, it is difficult to say.

Apart from impetigo contagiosa, the cutaneous complications that follow in the wake of vaccination possess no distinctive features, and their management differs in no wise from that of the same manifestations due to other causes.

THE TECHNICS OF VACCINATION.--This aspect of our theme involves a number of separate considerations. It will be convenient to give our attention first to the matter of the choice of virus. The question arises at once as to the selection between animal vaccine and the humanized variety. In a broad sense the term animal vaccine includes--1. Virus derived directly from a case of so-called spontaneous cow-pox. 2. Variola vaccine--i.e. the virus of an affection of the cow resulting from variolation. 3. The virus of horse-pox (not strictly vaccinal). 4. Retro-vaccine--i.e. the virus of an affection produced in the cow by the inoculation of vaccinia from the human subject. 5. The virus of a disease (true vaccinia) propagated through a series of bovine animals from the so-called spontaneous cow-pox, being the virus now commonly understood by the term, and the variety here referred to when it is not stated to the contrary.

By humanized vaccine we understand that which is obtained from the human subject, no matter how short or how long its descent from the cow. As regards animal vaccine, we may practically exclude from consideration all but the last variety mentioned, that being the one to which, in the great majority of instances, the term is now restricted. This narrows the question down to the choice between virus that has been propagated through a number of bovine animals (practically, calves) from the spontaneous disease in the cow, and that which, whatever its original source, has already passed through the human system.

{473} The variety first mentioned, sometimes called primary vaccine, is generally spoken of by authors as not very trustworthy as regards its infective power (that is, not to be counted on to take), and as prone to give rise to undue inflammatory complications when its use does prove successful. These unpleasant qualities might be explained by the supposition that primary vaccine is not apt to be at its best when it is now and then obtained. Practically, however, it may be dismissed without further consideration, for it is seldom to be had.

The second form--variola-vaccine--is manifestly improper to be used whenever genuine vaccine is to be obtained, unless, indeed, we shut our eyes to the accumulating evidence that variola-vaccine, so called, is not vaccine at all. Furthermore, it is a question whether its use, as well as all attempts to produce it, should not be forbidden by law.

The third variety, if such it may be called, it does not seem legitimate to use in the present state of our knowledge, since it is not yet proved satisfactorily that horse-pox possesses the full protective power of cow-pox, or is free from objections that do not arise in connection with the latter.

As to retro-vaccine, while the writer is unable to see any positive reason against its use, neither can he see any reason why it should be superior to humanized vaccine, as such, save that during the period of its bovine propagation it is not liable to become contaminated with the poison of syphilis. The idea that an enfeebled stock of humanized vaccine can have new life infused into it by passing through the system of the cow is not reasonable primâ facie, and there are no particular facts to support it. By ensuring freedom from the danger of communicating syphilis retro-vaccination doubtless served a good purpose at one time, but now, since the remarkable and enduring excellence of the Beaugency stock is so well established, there seems to be no excuse for a further resort to the practice.

The last of our five forms of animal vaccine, that produced by the continued propagation of spontaneous cow-pox through calves, is what is now known as animal vaccine par excellence. Its advantages over the other forms are so obvious that it alone should figure in any comparison between animal and humanized vaccine. That being understood, what are the relative merits of animal and humanized vaccine? It should be stated, in the first place, that bovine virus should be compared with virus that has long been humanized, for lymph of but a few removes from the bovine animal does not show any noteworthy differences from animal vaccine itself.

In behalf of humanized virus it is maintained--1, that it is a more trustworthy preventive of small-pox; 2, that it is superior in its infective property, so that it is surer to take; 3, that it is more prompt in its action, thereby affording more speedy protection to persons who have actually been exposed to small-pox; 4, that its virulent property is easier of preservation, wherefore it is more to be depended on when it is necessary to keep it on hand for a long time or to transmit it to great distances; 5, that its use requires less skill, or, rather, less special knowledge of the peculiarities of the animal virus; 6, that it is less violent in its effects; 7, that it is less apt to give rise to irregular, and therefore more or less abortive and non-protective, forms of pock.

{474} The first of these propositions, which asserts that humanized vaccine confers greater protection against small-pox than the animal virus, was warmly maintained by those who opposed animal vaccination on its first introduction into this country; but now the record of the past thirteen years, during which period bovine virus has more and more borne the brunt of the fight against small-pox, has disproved it in the judgment of all competent and fair-minded observers. So far, indeed, as the facts have been analyzed, they go to show that the reverse is the case--that bovine virus confers a more complete and a more lasting protection. Direct observation on this point is strengthened by the collateral fact that revaccination became at once astonishingly successful when the use of animal vaccine first gained currency, whereas now it is again declining in success; the explanation of which latter circumstance is, that it is now found difficult to revaccinate those whose primary vaccination was done with bovine virus--a striking indication of the permanence of the protection accomplished with the latter.

The second assertion--that humanized virus succeeds more readily than the bovine variety--is still maintained by many, but, it may confidently be said, by few if any whose experience with good animal vaccine has been large. The truth is, that every large public vaccination service in the country is now carried on almost solely with bovine virus, and that results are thus achieved that were not dreamed of in former times. Individual experience cannot weigh against this fact, but may be explained, rather, by what modicum of truth there may be in the fifth proposition, or by the assumption (surely a legitimate one, in view of the number of irresponsible and ignorant purveyors of animal vaccine that have thrust themselves before the profession since the advantages of the practice were established by the labors of others) that those whose observation leads them to a conclusion at variance with that reached by the great majority of trained observers have really been unfortunate in the quality of the virus with which they have been supplied. Whatever the explanation may be, however, there is nothing more certain than that the use of animal vaccine, properly carried out, is daily furnishing results that have never been excelled, if they have been equalled, in the employment of humanized virus on a like scale.

The third suggestion--that the humanized virus acts the more promptly of the two, and is therefore to be preferred for immediate protection--is plausible, since the areola (the alleged sign of systemic infection) forms somewhat later around a pock produced by animal virus than around one that is the result of vaccination with the humanized variety. The difference is one of a few hours only at the most, and it is not by any means a general occurrence; still, we may concede that in this respect the use of humanized virus is to be preferred under certain circumstances.

As to the fourth statement--that humanized virus is more tenacious of its infective property--strictly speaking, there is not a particle of truth in it. In the case of liquid lymph preserved in capillary tubes it has the semblance of truth, but, for reasons that will be more fully set forth hereafter, that is because it is difficult to get the virulent portion of bovine lymph out of the tube. In the form of dried lymph (the only form that ought to be used) animal vaccine may be sent to all parts of the world, and may be kept any reasonable length of time and without {475} special care, without undergoing sensible deterioration, if tested by one who is familiar with its peculiarities and aware of the care that should be taken in using it. Under ordinary circumstances there is no difficulty about preserving animal vaccine with its energy practically unimpaired.

The statement that the use of humanized virus demands less special knowledge than that of bovine virus is conceded at once. That special knowledge is easily mastered, however, and no man fitted to practise medicine will look upon its acquirement as a bugbear or a hardship.

The impression, almost universal thirteen years ago, that humanized vaccine is less severe in its local and constitutional effects than the animal virus has been eradicated from the minds of all but those who still follow the teachings of the older writers rather than yield to what daily experience has been teaching during these thirteen years, or those who reason from exceptional cases rather than from a general drift. The truth seems to be this: with revaccinated adults animal vaccine acts somewhat more severely than the humanized virus; in infants, on the other hand, its action is not so violent as that of the humanized variety.

Concerning the seventh and last claim put forward in behalf of humanized vaccine--that it is less apt to give rise to irregular or spurious pocks--we may say that no form of irregularity has been observed by those who have lately used the bovine virus that was not well known to the older writers, who founded their observations wholly, or almost wholly, on the use of the humanized virus; nor is there any proof that such irregularities are more common now than formerly. The truth seems to be, that these irregular forms of pock seem to prevail at certain times, and not at other times, regardless of the particular stock of virus used, other things being equal. Why this should be so we do not know, but the fact is beyond dispute.

To sum up, then, we can only say that in barely one particular--that of promptness of action--can humanized virus justly be credited with any superiority, while in every other essential respect it is inferior, so far as any difference is to be observed.

What, on the other hand, are the points of superior excellence attaching to bovine virus? Setting aside certain extravagant assertions that have sometimes been made in its behalf, such as that it far exceeds the humanized virus in its protective virtue (which may be true, but is not yet proved), they may be put in general terms in the form of a denial of all the particular claims that we have enumerated as having been put forth for its rival. Such a denial, it has been seen, seems to the writer to be justified, save in the one particular that perhaps we should accord to humanized virus the merit of speedier action, and consequently greater certainty of protection, in cases of actual exposure to small-pox.

Besides these negative points in its favor, the foremost advantage of animal vaccine is the guarantee it gives that, properly used, no syphilitic contamination will result. On this point no argument is needed, for the cow is insusceptible to syphilis.

A second consideration in its favor is, that it can always be had in large quantities at short notice. The young practitioner of the present day can scarcely appreciate the importance of this fact, but whoever remembers the comparative helplessness in which, in past years, he has found himself in the face of a sudden outbreak of small-pox, not knowing which {476} way to turn for an adequate supply of vaccine, will at once concede its force.

On the whole, then, it must be said that bovine virus is entitled to the preference as a rule, but that possibly it is well to resort to humanized lymph of early removes under the special circumstances above referred to. On no account should long-humanized vaccine be used so long as our present stocks of animal virus maintain the excellence they have thus far preserved, nor should humanized virus of any sort be preferred in the general run of cases.

Passing now to a consideration of the various forms of vaccine, disregarding its source, there are practically these three: the crust, liquid lymph preserved in capillary tubes, and dried lymph.

Until recently the crust, or scab, was much used in this country. Its capability of being preserved unimpaired for a long time was a valid excuse for this, especially in regions remote from the great channels of communication, and it was in such districts that the use of the crust was chiefly practised. That excuse scarcely exists now, for there are few physicians who cannot obtain a better form of vaccine within a very short time. The objections to the crust are two: 1. Most crusts are inert. Especially is this true of bovine crusts, which are wellnigh worthless. It must be confessed, however, that when once a crust has proved itself active it may be trusted to retain its infective property for a very long time. The writer has made successful use of crusts seven years old that had made the voyage to Japan and back; and they were bovine crusts too. Still, the rule is, that crusts are untrustworthy. 2. Their use is apt to be followed by undue inflammation, probably of septic origin, for they almost invariably contain putrescent or readily putrescible elements. It has even happened to the writer to cut open a crust that to all appearance was typical and innocent, and to find in its interior a cavity occupied by a pulpy, stinking slough. Manifestly, such material is unfit to be introduced into the system of any human being.

In regard to liquid lymph in tubes, it is not much used in this country, and its employment elsewhere is on the decline. At first thought, it would seem to be the best form of all, but experience does not bear out this view. In this form humanized lymph is vastly superior to animal lymph, but with every possible care in charging and sealing the tubes it is not uncommon to find their contents putrid. There are low vegetable organisms that are supposed to prey on the vaccinad. If there is any truth in this supposition, those organisms are certainly favored in their destructive luxuriance by keeping the lymph liquid, thus furnishing them with the best possible culture-fluid. Be this as it may, the fact is well ascertained that tube-lymph does not keep well. It has been mentioned already that bovine lymph stored in tubes is decidedly inferior to the same form of humanized lymph. This was long ago recognized by propagators of animal vaccine, but the cause remained a mystery until Warlomont of Brussels suggested that it was due to one of the physical peculiarities of animal lymph--that, namely, as already hinted at, by virtue of which its formed elements tend to attach themselves to any surface presented to them, leaving the supernatant liquid a mere inert compound of water, albumen, and salts; so that in the case of tube-lymph the virulent elements remain attached to the glass, and only the inert constituents {477} are really used. This theory is exceedingly ingenious and plausible, but the writer is not aware that it has been proved. He does know, however, that in some South American countries, where calf lymph in tubes is used with success, the custom is to grind the tubes to powder, and inoculate with the resulting magma, glass and all. This practice is certainly not to be commended.

Dried lymph is the most efficient of all forms of vaccine, and, kept as it ought to be, it retains its infective power long enough to answer all ordinary requirements. The writer has used it three years old with success. It may commonly be counted on for six weeks. One fact should be borne in mind, however: the longer dried lymph has been kept the more care is necessary in its use, for by long keeping it becomes very hard, so that it is a work of patience to dissolve it off from the surface on which it was deposited. Failure to accomplish its solution is the most common cause of a lack of success in its employment.

The various forms of stored vaccine are esteemed by the writer in the following order: 1, dried bovine lymph; 2, dried humanized lymph; 3, humanized tube-lymph; 4, humanized crusts; 5, bovine tube-lymph; 6, bovine crusts.

The age and other circumstances under which it is best to vaccinate children constitute a point for practical consideration. It may first be mentioned that pre-natal vaccination has been advocated by some authors; that is to say, the vaccinal infection of the foetus in utero by vaccinating the mother during gestation. There seems to be respectable testimony going to show that the end may thus be accomplished, but a weighty objection arises in the fact that this mediate vaccination of the foetus produces no physical sign of its success, so that doubt must always be felt as to whether or not the procedure has been efficacious. Moreover, it is seldom indeed that a child needs protection before its birth, provided we protect the mother, for it is well known that vaccinia will overtake and destroy the variolous infection, even when the latter has had two or three days' start. The practice has been chiefly urged by Bollinger. It is not likely to come into general use.

There is no special objection to vaccinating an infant at any time after birth, but usually it is well to defer the operation until the child is about three months old, unless there is actual danger of exposure to small-pox. Yet it is not well to postpone vaccination until the period of dentition, for the combined irritation of the two disturbing elements may prove decidedly uncomfortable if not serious.

Something is to be said as to the time of the year to be chosen. In New York the bad custom prevails, especially among the poorer classes, of having children vaccinated only in April, May, or June--just the part of the year in which erysipelas is most rife. The hot months should not generally be chosen, for any source of irritation is apt to be felt more severely by infants during the summer heat. However, no circumstances should be looked upon as a positive bar to vaccination in case of actual danger of exposure to small-pox, and in large towns children should never be taken into public conveyances or carried into any promiscuous assemblage until they have been protected by vaccination.

The next question is as to the part of the body that should be selected for the inoculation. The region of the insertion of the left deltoid muscle {478} is usually chosen--the left rather than the right, because most nurses habitually carry an infant on their own left arm, so that the child's left arm is uppermost, and hence less exposed to injury. The region of the deltoid insertion is comparatively free from the irritation of muscular contraction, and it is easily accessible. If two insertions are made, it is well to make one of them over the deltoid insertion and the other at a point about an inch distant on the line of the posterior border of the same muscle, for there the lymphatic connection with the axillary glands is less free, so that adenitis is not so much to be feared. To avoid a scar in a locality that may be exposed to view on certain occasions some mothers prefer that their daughters should be vaccinated on the lower limb. To this there is no special objection, further than that the lower limb is rather more exposed to rough handling than the arm. If the leg is chosen, the point of junction of the two heads of the gastrocnemius is an eligible situation.

The actual operation is performed in various ways. The old inoculators generally made an incision through the whole thickness of the skin, so that a pellet of subcutaneous fat rolled up into the little wound. This is wholly unnecessary; furthermore, it is objectionable, for it decidedly increases the risk of inflammatory complications. Still more to be avoided are the methods by inserting a seton imbued with the virus and by hypodermic injection or other like procedures. The best way is, simply to remove the horny layer of the cuticle, so as to expose the succulent portion of the epidermis. This surface is somewhat red, and from it a slight exudation of lymph will be observed, but there need not be the least flow of blood. By this procedure it is not uncommon to vaccinate a sleeping child without waking it. It is not only admissible, but preferable, not to wound the derma at all. Such an abrasion is easily made with an ordinary lancet, which, contrary to the advice sometimes given, should be very sharp; but no cutting or scratching should be done with it, only scraping with the convex part of its edge, precisely as in using an ink-eraser. Scratching instruments (such as the rake-like vaccinator often used or a row of needles set in a handle) are not easy to adapt to varying degrees of plumpness of the arm, and are apt to make too deep scratches, one at either side, while the skin between the two is scarcely touched. Whatever instrument is chosen, it should not be used again until it has been thoroughly cleansed--made chemically clean--which can be accomplished only by heating it or by wiping it off and then dipping it into a strong disinfectant solution.

Some individuals are refractory to vaccination, but complete insusceptibility is exceedingly rare. Various expedients have been resorted to in rebellious cases, such as vesication with ammonia-water, maceration of the skin for some hours with glycerine, and the like. The writer has known these devices to succeed, but he has not seen the slightest advantage in the plan recommended by Ceely, that of using a wound some hours old rather than one just made, although he has tried the experiment many times. It is not necessary to make a large abrasion; one as large as the little finger-nail is ample.

The next step is to apply the virus, and it should be so applied as to bring it into contact with every part of the denuded surface. In what is known as arm-to-arm vaccination, or its equivalent, calf-to-arm {479} vaccination (by all means the most successful method, although not often practicable in this country), the liquid lymph, fresh from the vaccinifer's pock, is simply applied, when it will at once become diffused over the abraded surface without any special pains being taken to accomplish that end.

If dried lymph is used, particular care should be taken to see that it is actually dissolved and transferred from the substance on which it was dried to the abraded surface. Failure to accomplish this is the cause of almost all the lack of success that inexperienced vaccinators meet with. The lymph should be moistened with water, or, if it is quite old, with glycerine, before the abrasion is made, so that it may have time to dissolve. It should then be rubbed upon the abraded spot vigorously, and at least for the space of a full minute.

In the use of tube-lymph no other precautions are necessary than in arm-to-arm vaccination, but, simple as this method is, its results are unsatisfactory.

Crusts should be reduced to a powder, and then made into a thin paste with water or glycerine. A convenient way of powdering a crust is to rub it on a file or between two files. The paste is to be well rubbed upon the abrasion. The insertion of a solid piece of crust into a valvular incision is not to be recommended.

When the operation is finished it is well to keep the arm bare for about five minutes, but not necessarily until the spot has become dry. It is not well to apply any sort of plaster, but means should be taken to prevent the underclothing from sticking to the abrasion. For this purpose there is no objection to the shields that are furnished by the surgical instrument-makers. Usually, however, nothing of the sort is necessary.

THE STORAGE AND PRESERVATION OF VACCINE VIRUS.--Lymph should usually be taken on the eighth day, inclusive--never after the areola has formed. On the other hand, the writer's experience does not lead him to coincide with those who state that the earliest lymph that can be obtained is the most energetic. If it is to be dry-stored, the substance to be coated with it (slips of quill, ivory, wood, whalebone, glass, and the like) should be laid gently in the pool of lymph that exudes on puncturing the pock, and allowed to dry, preferably without the aid of artificial warmth. The layer of lymph should be plainly visible after it has dried. A second coating is advisable, as it serves to preserve the first.

Capillary glass tubes are either cylindrical or furnished with a bulbous expansion at the middle, the latter form being most commonly used. To charge a tube make sure that both ends are open, and then submerge one end in the pool of lymph. Capillary attraction will cause the tube to fill, and the process may be facilitated materially by inclining the tube toward a horizontal direction, so that the capillary attraction is not opposed by that of gravitation. Care should be taken to keep the applied end of the tube constantly submerged, or bubbles of air will enter it. The sealing may be done with a blowpipe, by simply holding the ends in a flame, or by means of sealing-wax or some similar substance. The satisfactory charging of tubes demands some practice, but a little patience will enable any intelligent person to succeed.

In regard to crusts, they should never be removed until the surface beneath has become cicatrized and they have been partially detached by the natural process. A crust torn off prematurely should never be used, {480} and the same may be said of secondary crusts--i.e. those that form by the desiccation of the discharge from the raw surface left when the primary crust has been removed forcibly.

For the preservation of vaccine in these various forms tubes need only be kept in a cool place. Dried lymph and crusts should be guarded against dampness even more than against warmth. Their preservation may be decidedly favored by over-drying, either in an exhausted receiver or by keeping them in a closed vessel in the presence of sulphuric acid, chloride of calcium, or some other substance having a strong affinity for water. It is needless to say, however, that they should not come into actual contact with any such agent. While this artificial desiccation tends powerfully to preserve dried lymph, it makes it more difficult to use. When dried lymph or a crust is to be sent by mail or other conveyance, it should be wrapped in some impermeably envelope, for which purpose gutta-percha tissue is very convenient. Both these forms of virus should be kept in a cool place. There is no objection to keeping them on ice, provided they are well protected against moisture.

* * * * *

In conclusion, the writer wishes to say that the limited space at his command has compelled the assumption of a dogmatic rather than an inductive form in the construction of this article. To the reader who may wish to pursue the subject further--and it will well repay thorough study--he would recommend the following bibliography:

Ballard: On Vaccination: its Value and Alleged Dangers, London, 1868.

Bousquet: Nouveau traité de la vaccine et des éruptions varioleuses, Paris, 1848.

Bryce: Practical Observations on the Inoculation of Cow-pox, Edinburgh, 1809.

Ceely: Observations on the Variolæ Vaccinæ, Worcester, 1840.

Chauveau et al.: Vaccine et Variole, Paris, 1865.

Depaul: Nouvelles recherches sur la véritable origine du virus vaccin, Paris, 1863; De l'origine réelle du virus vaccin, Paris, 1864; et al.: De la syphilis vaccinale, Paris, 1865.

Hardaway: Essentials of Vaccination, Chicago, 1882.

Hering: Ueber Kuhpocken an Kühen, Stuttgart, 1839.

Jenner: An Inquiry, etc., 2d ed., London, 1800.

Sacco: Trattato di Vaccinazione, Milano, 1809.

Seaton: A Handbook of Vaccination, London, 1868.

Steinbrenner: Traité sur la vaccine, Paris, 1846.

{481}

VARICELLA.

BY JAMES NEVINS HYDE, M.D.

Varicella is an acute disorder of infancy and childhood, in the course of which appears a cutaneous exanthem of vesicular type, accompanied at times by systemic symptoms of moderate severity, terminating in the course of from three days to a fortnight, after the formation of relatively few crusts upon the skin, with occasionally persistent cicatrices.

SYNONYMS.--Eng., Chicken-pox; Ger., Windblattern, Schafpocken; Fr., Varicelle; Lat., Variola notha, seu spuria; Ital., Morviglione.

HISTORY.--The literature of the disease which is now best recognized under the title of varicella has been, in the history of medicine, wellnigh inextricably confused with that of variola. In the latter part of the seventeenth and the early part of the eighteenth century the distinction between typical forms of the two disorders became apparent, and was described by Willan and Harvey in England, and other writers in Germany, France, Holland, and Belgium. Among those who have contributed to its literature may be named Hebra, Kaposi, Trousseau, Simon, Thomas, Güntz, Henoch, Kassowitz, and Boeck.

ETIOLOGY.--Varicella is essentially a disease of early life, occurring almost exclusively in infants and young children. It is a contagious disorder, and at times, especially in hospitals and asylums for children, occurs in apparently epidemic forms. The question relating to the inoculability of the contents of its vesicular lesions is still open, positive and negative results being recorded by different experiments.[1]

[Footnote 1: The writer has purposely avoided, in the brief space here devoted to the disease under consideration, entering into a discussion of the question respecting the relation sustained by varicella to variola. On one side are the views entertained by the Vienna school of dermatologists, according to which there is but a single virus in these several forms of disease--the variolous poison. On the other are the opinions and the practice, largely based upon the latter, of most English and American physicians, who deny the existence of any relation between the pathological states recognized by them as occurring in two entirely distinct affections.

My personal view may be briefly formulated as follows: Practically and clinically, it is useful to regard these disorders as of a distinct nature. The arguments, however, in favor of such absolute distinction are not irrefutable. There is probably in both forms of disease but a single virus, that of variola; but this, modified by evolution among generations of vaccinated children, has, in this process of natural cultivation or attenuation, produced a malady of tender years whose attacks do not protect from variola and occur irrespective of vaccination.]

SYMPTOMATOLOGY.--The period of incubation of the disease cannot be said to be definitely established. At times, without question, an entire fortnight elapses between the dates of exposure and the evolution of the disease, but both longer and shorter intervals have been recorded.

{482} If there be a prodromal stage of the disease, certainly in the vast majority of the little patients it cannot be recognized. During the last month the writer has observed the evolution of the disease in twenty children gathered together in the Chicago Home for the Friendless, no one of whom was recognized as ailing before the eruption appeared. Occasionally the disease is preceded by mild or even severe febrile symptoms, accidents sufficiently common in this class of patients.

The exanthem, commonly the first symptom of the disorder, occurs in the form of reddish puncta, from which rapidly develop rosy-colored maculations, and these become tensely distended, transparent or slightly yellowish vesicles, of the average size of a split pea, though they are occasionally smaller or may enlarge to the dimensions of a bean or small nut. The eruption appears first upon the upper segment of the body, implicating the chest in front and behind, the neck, the scalp, particularly the extremities, and quite sparingly the face also, which may, however, entirely escape. In cases where the eruption is profuse it may be completely generalized, involving largely the trunk and extremities, the lesions, upon the back particularly, being as closely set together as in discrete variola. In many, even the majority, of cases the exanthem is much less profusely developed, not more than a dozen or twenty vesicles springing from the surface.

The vesicles are superficial in situation, the firm papule which precedes the variolous rash being altogether wanting. They are at first transparent, their contents plainly showing through their translucent roof-wall, composed only of the stratum corneum of the epidermis. They are both acuminate and globular, and occasionally rest upon a slightly hyperæmic integument. Umbilication rapidly occurs at the apex, and simultaneously their contents become lactescent and gradually sero-purulent. Occasionally vesicles are transformed into genuine, coffee-bean-sized, pustules. Intermingled with these are often seen illy-developed and abortive vesicles.

By the end of a period lasting from twelve hours to the second or third day involution has usually begun, and the lesions, with and without rupture--more often the latter--desiccate, and are thus transformed into yellowish or yellowish and brown, circular, circumscribed crusts resting upon an apparently unaltered integument. These crusts are often so firmly attached that they do not fall spontaneously before the lapse of from five to eight days. When this exfoliation is ended there are left slightly hyperæmic pigmented patches of corresponding size where the crusts had rested. A destructive process occasionally results upon the surface of the face at the base of such vesiculo-pustular lesions as have formed there, in consequence of which a small depressed and superficial cicatrix is left, which does not differ from that resulting from discrete variola. These scars may be superficially seated and transitory in character, or much deeper and persistent through life.

Throughout the course of the disease systemic symptoms may be altogether wanting, or may occur in a mild, and much more rarely in a severe, type. In some cases the temperature is increased by one or two degrees upon the appearance of the exanthem, and often a febrile movement of moderate grade may persist for forty-eight hours or somewhat longer. Defervescence, however, is always rapid and perfect. In very {483} rare cases there is a subsequent successive new development of scanty vesicles, whose appearance is heralded by mild exacerbations of fever.

Occasionally the vesicles may be recognized upon the mucous surfaces of the lips, inside of the cheeks, tongue, palate, conjunctivæ, and progenital regions of both sexes. Still more rarely the glands of the throat become slightly tumid and painful.

The complexus of symptoms, in the large majority of all these little patients, is that which pertains to a disorder of distinctly mild type. The eruptive lesions are scanty and productive of but trifling subjective sensations. Occasionally they are picked or scratched, and thus become the seat of either pain or pruritus. In the febrile stage the child is noticeably fretful for a period of perhaps twenty-four hours. At the end of that time older children are frequently observed engaged in their customary amusements in the nursery.

Severe types and complications of varicella are in general limited to the little patients who are recognized as suffering from hospitalism. Among these we see erysipelas, severe vaccinal eruptions, lesions of inherited syphilis, and the sequelæ of morebilli and scarlatina, which the disease both precedes and follows.

PATHOLOGY.--The anatomical structure of the lesions in varicella is largely a matter of inference, since there has been but small opportunity of studying the disorder as displayed in sections of the morbid integument. Manifestly, the exanthem is exudative in type, the serum in circumscribed areas lifting the superficial layer of the epidermis from the deeper parts of the derm. Unquestionably, septa occur in typically developed varicella chambers, similar to those seen in variola--a pathological fact which is the corner-stone of the doctrine relating to the unity of the two disorders. The serum contained in these septa possesses an alkaline reaction. The formation of a cicatrix is evidently due to the intensity of the process in certain exceptional lesions, as a result of which the papillæ of the corium are superficially destroyed. These sequelæ are often due to the picking and scratching of the lesions.

DIAGNOSIS.--Varicella is to be distinguished from eczema pustulosum by its mild febrile symptoms, the discreteness of its pustular lesions, the absence of itching, and of infiltration of the skin in patches, and its tendency to symmetrical development.

From impetigo and the impetigo contagiosa of Fox of London it will often be scarcely differentiated. Inasmuch as these disorders are frequently recognized among children suffering from varicella or varicella convalescence, it can scarcely be doubted that these diseases have been in the past often confounded, and that in many cases it is practically impossible to distinguish between them. Decided elevation of bodily temperature, umbilication of symmetrically-disposed lesions, and a rapid involution of the disease point to varicella. The two forms of impetigo occur without fever, are usually scantily developed, and are much more apt to be pustular in type, lacking, moreover, the halo of the varicella lesions. The latter are also, on an average, smaller and more numerous. The two forms of impetigo, finally, never display the generalized eruption of severe varicella. The non-contagious variety of impetigo is much more decidedly pustular in its lesions, and the latter spring from a deeper plane of the epidermis.

{484} As to the eruptions due to vaccinia and vaccination, there can be but little doubt that these also have been frequently confounded with varicella. Efflorescences having origin in this way are very largely impetiginous in type, and the conditions named above are then to be regarded as distinctive differences, so far as any distinction can, under these circumstances, be recognized. Impetigo, impetigo contagiosa, and varicella are all sufficiently common accidents after vaccination. No reliance can be placed upon characteristics described as connected with a certain stuck-on appearance of the crust regarded by Fox as characteristic of the crusts in impetigo contagiosa. In all these vesiculo-pustular disorders of childhood desiccating serum and sero-pus upon the surface result in the formation of crusts which have a similar (so-called) stuck-on appearance.

Variola and varioloid of infants and children are to be distinguished from varicella by the evidence of origin from such contagious maladies; by the occurrence of prodromal symptoms; by the greater rise in temperature during the febrile stage; by the typically papular stage of the exanthem at its outset, and no less typically pustular stage before the occurrence of desiccation; by the confluence of lesions in confluent cases; and by the much longer and evidently graver stadium of the disease. Distinctions between mild varioloid and severe varicella in infancy and childhood will always tax to the utmost the skill of the diagnostician. The sooner it is generally understood that intermediate forms occur which cannot be positively assigned to the one or to the other category, the better it will be for both the profession and the laity. The fact that in the one case there is generation of a variolous poison capable of producing a contagious disease in adults, and in the other a malady which is known to affect children only, renders the decision important. Scattered papulo-vesicular and vesiculo-pustular lesions appearing after a high fever, and pursuing a period of evolution longer than forty-eight hours, should always awaken suspicion. Superficial lesions, on the contrary, distinctly vesicular on the third day, or commingled with minute, very superficial pustules, should be regarded as characteristic of varicella.

The so-called varicella prurigo of Hutchison of London[2] includes several of the disorders considered above under the titles impetigo, impetigo contagiosa, and the vaccine rashes. The irritable condition of the skin resulting from several of the exanthemata leaves it prone to the development of a long list of cutaneous lesions, some of them accompanied by pruritus in various grades, to each of which might be given, according to the caprice of authors, a separate name.

[Footnote 2: Lect. on Clin. Surg., Lond., 1878, p. 15 et seq.]

PROGNOSIS.--The prognosis of varicella, per se, is always favorable. Only in the hospital cases, complicated by erysipelas and scarlatina convalescence, may grave results be anticipated. The milder attacks may leave persistent relics of their career in the form of one or more depressed and persistent cicatrices, which become less conspicuous as the patient approaches adult years.

TREATMENT.--Varicella is, in a large proportion of cases, successfully treated by domestic management and the simpler remedies familiar to those in charge of the nursery. Confinement for a brief time to the {485} cradle or bed, and a proper regulation of the temperature of the room and of the diet, are usually all that is required. Special remedies may be indicated in isolated cases, but certainly none such are demanded by the varicella. Efforts should be made to protect the face lesions from the traumatism of picking and scratching, with a view to prevent pitting.

Isolation of patients is not requisite, nor any process of disinfection other than that which is incidental to a fresh supply of pure air. Vaccination should be practised alike in the case of children who have and who have not suffered from the disease.

{486}

SCARLET FEVER.

BY J. LEWIS SMITH, M.D.

HISTORY.--The terms scarlet fever and scarlatina are used synonymously to designate one of the most common and fatal of the eruptive fevers. Whether this malady occurred prior to the Christian era is uncertain. It is believed by some that the plague of Athens, 430 years before Christ, vividly described by Lucretius, and by Thucydides, who was attacked by it, was scarlet fever of a peculiarly malignant type (Richardson); but, as will be seen from the following extracts from Thucydides, the plague differed in important particulars from scarlatina of the present time: "Internally, the throat and the tongue were quickly suffused with blood, and the breath became unnatural and fetid. There followed sneezing and hoarseness; in a short time the disorder, accompanied by a violent cough, reached the chest.... The body externally was not so very hot to the touch, nor yet pale: it was of a livid color, inclining to red, and breaking out in pustules and ulcers." Loss of sight and gangrene of the extremities were common results in those who recovered, and adults appear to have been affected as frequently as children. "The dead lay as they had died, one upon another, while others, hardly alive, wallowed in the streets and crawled about every fountain craving for water. The temples in which they lodged were full of the corpses of those who died in them." Lucretius says of this plague, "If any one for a time escaped death (as was possible, either by reason of the foul ulcers breaking or by means of a black discharge from the intestines), yet consumption and destruction awaited him at last; or, as was often the case, an excessive flux of corrupt blood, attended with violent pains in the head, issued from the obstructed nostrils, and by this outlet the whole strength and substance of the man passed away. He, moreover, who had escaped this violent flux of foul blood was not certain wholly to recover, for still the disease was ready to pass into his nerves and joints, and into the very genital organs of the body. And of those who suffered thus, some, fearing the gates of death, continued to live, though deprived by the steel of the virile part, and some, though without hands and feet, and though they lost their eyes, yet persisted to remain in life, so strong a dread of death had taken possession of them. Upon some, too, came forgetfulness of all things, so that they knew not even themselves."

Gangrene of the extremities, loss of sight, a violent cough, loss of memory, etc. are not symptoms of scarlet fever, so that in my opinion {487} the plague of Athens, if correctly described by the historian, was a different malady.

Caspar Morris, in his essay on scarlet fever, states his belief that Seneca, who lived in the first century of the Christian era, described an epidemic of the malignant form of scarlatina in his portrayal of the pestilence that visited Thebes during the half-mythical age of Oedipus, six centuries before Christ. Seneca's description of the symptoms of this plague is as follows:

Piger ignavos Alligat artus languor, et ægro Rubor in vultu, maculæque caput Sparsere leves; tum vapor ipsam Corporis arcem flammeus urit Multoque genus sanguine tendit Oculique regent, et sacer ignis Pascitur artus. Resonant aures, Stillatque niger naris aducæ Cruor; at venas rumpit hiantes.

Languor, redness of the face, light spots upon the head, distension of the cheeks with blood, distortion of the eyes, a flushed appearance of the limbs, tinnitus aurium, and a discharge of black blood from the nostrils, certainly indicated a very malignant form of disease, but to believe that it was identical with the scarlet fever of the present time requires considerable credulity. From the fact that it devastated Thebes we infer that it occurred largely among adults, differing, therefore, from the modern scarlet fever, whose victims are chiefly children. The same uncertainty hangs over epidemics during the first centuries of the Christian era.

The first clear and undoubted portrayal of scarlet fever is found in the medical literature of the sixteenth century. Sydenham and his contemporaries in the seventeenth century witnessed epidemics of it, studied its nature more thoroughly, and consequently acquired a more accurate knowledge of it than that possessed by their predecessors. It was in this century that measles and scarlet fever were differentiated. During the last two hundred years scarlatina has been the subject of monographs too numerous to mention. It has long been regarded as one of the most important maladies of childhood, on account of its frequency and the great mortality that attends it, so that numerous cases and many epidemics are every year related in the medical journals. By this vast accumulation of observations and the patient and thorough use of the microscope our knowledge of scarlet fever has become full and accurate.

As with most of the infectious maladies, scarlet fever extended to the Western World through European shipping. It was brought to North America about the year 1735. Tardily it spread to South America, where it appeared in 1829, and more recently it has been established in Australia. It entered Iceland in 1827, and Greenland in 1847.

ETIOLOGY.--The evidence is strong that scarlet fever does not originate de novo--that it does not spring from certain atmospheric or telluric conditions, but is produced by a definite specific principle, since countries have been free from it for centuries till it was imported by commerce. That it appears in certain localities without any known exposure is attributed to the fact that the poison is so subtle and transmissible that it is {488} conveyed long distances in articles of merchandise, even in small packages, so that those who chance to open them or come in contact with them are infected. It is believed that reading matter transmitted through the mails has in many instances been the medium of infection.

The theory that the acute infectious maladies are caused by micro-organisms, or, as they are now designated, microbes, commonly discarded at first and believed to be chimerical, is rapidly gaining ground in the profession, and appears to be fully established as regards certain of them. These parasites, barely visible under high powers of the microscope, and ascertained to be vegetable by their behavior under certain chemical agents, exist in immense numbers in the blood, tissues, and secretions of patients suffering from the infectious maladies, especially in the graver cases of them; and the microscope shows that these organisms vary in shape and appearance so as to admit of classification.

The germ theory has now become so important that it cannot be ignored in a monograph relating to so important an infectious malady as scarlet fever. The relation of microbes to the infectious diseases has been made the subject of investigation by Pasteur, Toussaint, and others in France, and by many in Germany, with most interesting results. The belief held by many, and which seemed very plausible, was that the microbes, instead of sustaining a causative relation to the maladies in which they occur, were the result of these maladies--that they sprang into existence in consequence of the vitiated state of the blood and tissues, just as fungi appear on decaying substances or as the Oidium albicans appears in certain morbid conditions of the buccal surface and secretions. Obviously, in order to elucidate this matter and determine the relation of these parasites to the diseases in which they occur, it was necessary to experiment on animals, but, unfortunately, as a bar to successful experimentation many of the most important infectious maladies which afflict the human race, as typhus and typhoid fevers, the marsh fevers, and syphilis, do not occur in animals, or they occur in a changed and mitigated form. Others, however, can be produced in their typical character in animals, as diphtheria, and others still originate in animals and are transmitted from them to man, as anthrax or splenic fever of the herbivora and hydrophobia. Very interesting and important results have been produced by experimental researches with the microbes of certain of these diseases, which, if applicable to the common and fatal infectious maladies of an analogous nature in man, may yet result in immense benefit in mitigating the virulence of those affections which are the scourge of childhood and which sensibly diminish the increase of population. It has been found possible to cultivate the microbes contained in the blood, tissues, and secretions in certain of the infectious diseases, and after a series of cultivations, so that these organisms are far removed from the animal substance which contained them, and with which they were so intimately associated in the individual, they have been employed for inoculation--with this important result, that the primary disease was reproduced. This seems to indicate beyond question the causative relation of these parasites to the diseases in which they occur. Experiments with the result which I have stated have been made with the microbes of splenic fever, chicken cholera, murrain, and certain other maladies.

Pasteur employs as the media for cultivation--(1st) urine neutralized {489} by a few drops of potash solution; (2d) a liquid prepared by boiling for twenty or thirty minutes the yeast of beer in water, neutralizing, and filtering; and (3d) chicken tea, prepared by boiling equal parts of water and the lean of muscles a quarter of an hour, filtering, and neutralizing. A small drop of infected blood is placed in the liquid of cultivation, and the microbes which it contains multiply so abundantly that the liquid becomes turbid in a short time, and they are found in all parts of it. A drop of this liquid is added to another portion of the medium, and this also soon becomes turbid from the immense development of organisms which have the same microscopic appearance and character as those in the drop of blood. The process is repeated many times, until the microbes are far removed from their original source in the blood and tissues, and a drop of the last cultivation, whether it be the fiftieth or the hundredth, is inserted under the skin of a healthy animal selected for the experiment. If it be true, as stated by the experimenters, that the original disease is thus reproduced with the microbes of at least three or four distinct maladies, this age is distinguished by one of the most important discoveries ever made in pathological studies. It remains to determine whether this great discovery is of general applicability to the infectious diseases with which man is afflicted. If so, it is not improbable that we are on the eve of finding a method by which some at least of these maladies may be prevented or mitigated, as small-pox has been since the time of Jenner. The result of experiments made by Pasteur with the microbes of that fatal malady of the herbivora, known under the various names of splenic fever, anthrax, wool-sorter's disease, and charbon, encourages this belief. Originating among the herbivorous animals, it has in many instances been contracted by individuals who have rapidly perished. Many engaged in assorting alpaca and mohair have lost their lives by it, some with all the symptoms of profound blood-poisoning, without external lesions, and others with redness and swelling at some point of infection where a sore or abrasion existed, but with speedy blood-contamination.

The microbe of this malady, the Bacillus anthracis, occurs in the form of straight filaments with little movement or only with oscillation, and producing bright-shining spores. Now comes a very interesting and important result of experimentation: Pasteur states if several days elapse between the cultivations the virulence of the parasite diminishes, so that he has been able to produce by inoculation with it a mild and never fatal form of charbon, which affords immunity in the animal from any subsequent attack. This opinion was sustained by a trial experiment on sixty sheep. Toussaint and Chauveau claim that they produce a similar attenuation of the virus by defibrinating infected blood, heating it to 55° C. (131° F.) and filtering it. These experiments awaken the hope that the time will come when the acute infectious maladies in man, scarlet fever among others, will be rendered less virulent. That one of them--to wit, small-pox--has for nearly a century been under our control certainly encourages the belief that there is some way to mitigate others of the same class which are equally fatal if not so loathsome.

As yet, observers do not agree in regard to the parasite which is supposed to sustain a causative relation to scarlet fever. Klebs states that it is highly probable that both measles and scarlet fever are produced by {490} micrococci, and he has sketched the design and described the development of a microbe which he designates the Monas scarlatinosum.

The London Medical Times and Gazette for Jan. 28, 1882, contains an account of the supposed discovery of the scarlatinous microbe by Eklund of Stockholm, an authority in the microscopic examination of parasites. He says that scarlet fever is rarely absent from the Swedish capital and from the barracks and dwellings on the isle of Skeppsholm. In the urine of scarlatinous patients he has constantly found a prodigious number of discoid corpuscles, oval or round, their diameter being less than 1/1000 millimetre and from 1/30 to 1/10 that of a red blood-cell. They are colorless or yellowish white, surrounded by a distinct cell-wall, each containing a well-defined nucleus of a deeper hue. Sometimes one or more microbi may be seen. They exhibit rotatory or oscillatory movements, especially observed when a drop of water is added to the fluid. They multiply, as he has frequently seen, by fission--first in the microbes, next in the nucleus, and lastly in the cell-wall. He cannot say whether they develop into a mycelium. At any rate, the development of fine filaments seems to be exceptional. He has never seen them adhere in moniliform chains nor massed as zooglæa. He considers them to be veritable schizomycetes, and proposes the name Plox scindens.

Eklund asserts that he has found these same organisms in vast numbers in the soil- and ground-water of the isle of Skeppsholm, in the mud of the trenches dug for the water-mains, and in the greenish mould upon the walls of the old barracks, where scarlet fever was most rife. He states that scarlet fever has occurred in children after drinking milk mixed with the ground-water of the island, and he observed a case which followed immersion in one of the trenches of the island and the drying of the clothes in a small room. In another instance scarlet fever broke out in a block immediately after exposure of the ground-water by excavations.

It is evident that the discovery of this microbe under such circumstances does not prove that it is the cause of the disease. This can only be determined by inoculation, or by experiments which furnish the conditions of scientific exactness. Although great progress has been made in parasitology during the last decade, it is evident that several years of observation and experimentation must elapse before it is clearly and definitely ascertained whether or to what extent microbes cause scarlet fever and the other exanthematic fevers with which it is classified.

Whether the specific principle of scarlet fever be a micro-organism or a chemical substance, its mode of action and effects have been ascertained by clinical observations. Without doubt it commonly enters the system by the breath, but it may enter in the ingesta, and it infects the blood. That it resides in the blood has been ascertained by inoculation with this liquid, by which scarlet fever has been reproduced in its typical form. From the blood it enters the tissues and secretions. Hence handkerchiefs or linen containing the saliva or mucus of a patient, the epidermic scales shed abundantly in the desquamative period, and probably also the urinary and fecal evacuations, contain the poison, so as to be highly infectious. Even the discharge of a scarlatinous otorrhoea is thought by some to be contagious for a considerable time.

Scarlatina is communicable not only by direct exposure to a patient, {491} but also by exposure to objects which happen to be in his room during his illness, and to which the poison becomes attached, such as clothing, books, and toys; small packages, even letters, it is believed, from cases which have occurred, sometimes convey and disseminate the contagious principle.

In England observations have been made which show that scarlatina has been communicated by infected milk. The disease occurred in the family of a milkman, and the milk, before it was distributed, remained for a time in a kitchen which had been occupied by the patients. This milk was taken by twelve families, and in six of these the disease occurred almost simultaneously at a time when few cases were occurring in the locality. There had been no direct exposure to the carrier of the milk nor to members of the affected family (Taylor). In another instance a woman and her son had scarlet fever while they were serving milk to several families, and the disease appeared in all these families except one, which consisted of old people (Bell). It is known that milk absorbs volatile substances so as to be flavored by them, as is shown in the experiment of placing it in an open vessel in a box with a pineapple; and it may in a similar manner become infected by the specific principle of scarlet fever, or it may be infected by detached particles of epidermis; which is not improbable when one convalescing from scarlet fever is allowed to milk the cows or prepare the milk for distribution.

The scarlatinous virus surpasses that of any other eruptive fever except small-pox in its tenacious attachment to objects and its portability to distant localities. Hence in the literature of the disease are the records of many cases in which the poison was conveyed long distances, retaining its virulence to the full extent and causing an outbreak of the malady in the localities to which it was carried. In New York, so frequently has scarlet fever as well as measles and diphtheria been contracted from the persons or clothing of well children who come from infected houses, that the Health Board now excludes from the public schools all children who come from such houses, even though they live on separate floors from those occupied by the sick. In one instance that came under my notice a washerwoman whose child had scarlet fever communicated the disease to an infant in the household where she was employed, by placing her shawl over the cradle in which it was lying. A physician of my acquaintance went from a scarlet-fever patient to a family several streets distant, and took one of their children upon his lap. After the usual incubative period this child sickened with a fatal form of the malady, and the remaining children of the household were in time affected. In New York scarlet fever has seemed to me to be not infrequently communicated through school-books, which, profusely illustrated by pictures and rendered attractive to the young, are often allowed to lie upon the bed of a scarlatinous patient and be handled by him during convalescence, or even during the course of the fever if it be mild. The young librarian of the circulating library of a Sunday-school, whose pupils came largely from the tenement-houses, was occupied a considerable part of a day in covering and arranging the books. After about the usual incubative period of scarlet fever he sickened with the disease. His two sisters were immediately removed to a rural township three hundred miles away, and to an isolated house where scarlatina had never occurred. About one {492} month after his recovery, and after his room had been disinfected by burning sulphur and his bed-clothes and linen had been thoroughly washed, and all articles suspected to hold the poison had been either disinfected or destroyed, the brother visited his sisters in the country. Three weeks subsequently to his arrival one of these sisters sickened with scarlet fever, and a week later the other also. It seems that the exposure must have occurred several days after his arrival in the country from some book or other infected article in his possession. About two months elapsed after the last case; the family had returned to the city, the infected room in the country-house had been thoroughly fumigated by burning sulphur from morning till evening, when a little girl from an inland city remained a few days in this house, and probably often entered the room where the young ladies had been sick. In a few days she also sickened with a fatal form of scarlatina. Such histories and experiences are not infrequent. They are common during epidemics of scarlet fever. They indicate an extraordinary attachment of the scarlatinous poison to objects, and show that it is not gaseous nor readily volatilized.

A striking example of this fixity of the poison occurred in the practice of the late Kearney Rogers, formerly a prominent and much esteemed surgeon of New York City. Six children in a family had scarlet fever. Three and a half months subsequently another child, living at a distance, was allowed to return home and occupy the apartment in which the sickness had occurred. One week subsequently to the date of the return this child sickened with the same malady. Elliotson states that a patient with scarlet fever was admitted into one of the wards of St. Thomas's Hospital, and for two years subsequently young persons who were admitted into the ward were apt to take the disease. Richardson of London relates the following experiences of a family whom he attended in a rural district: "At a short distance from one of our villages there was situated on a slight eminence a small clump of laborers' cottages, with the thatch peering down on the beds of the sleepers. A man and his wife lived in one of these cottages with four lovely children. The poison of scarlet fever entered the poor man's door, and at once struck down one of the flock." The remaining children were now removed some miles away, and after several weeks one of them was allowed to return. Within twenty-four hours it also took the disease, and quickly died. The walls of the cottage were now thoroughly cleaned and whitewashed, the floors scoured, and all the wearing apparel either destroyed or washed. Four months elapsed after the last sickness when one of the remaining children returned. "He reached his father's cottage early in the morning; he seemed dull the next day, and at midnight I was sent for, to find him also the subject of scarlet fever. The disease again assumed the malignant type, and this child died." Richardson believes that the contagium was attached to the thatch, which could not be thoroughly disinfected. The fact of this remarkable long-continued attachment of the poison to objects, indicating by this fixity that it is a solid, is consonant with the theory that it is an organism.

INCUBATIVE PERIOD.--The duration of the incubative period varies in different cases. It is sometimes less than twenty-four hours, as in {493} the above case reported by Richardson; in the following well-known case, observed by Trousseau, it was one day. A girl arrived in Paris from Pau, where there was no scarlet fever, and occupied the same apartment with her sister, who was sick with this disease. Twenty-four hours after her arrival she also was attacked with the same malady.

Russeberger attended a child who was exposed at noon to scarlet fever, and took the disease on the following night. B. W. Richardson (Clinical Essays, 1861, vol. i. p. 94) gives his own experience: He had applied his ear to the chest of a patient suffering from scarlet fever, and was conscious of a peculiar odor emitted from the patient. He was immediately nauseated and chilly, and from that moment he dated the beginning of an attack of scarlet fever. In the Transactions of the Clinical Society of London, vol. xi. 1878, the late Charles Murchison gives the statistics of 75 cases, showing the incubative period, as follows:

In 4 cases it was not more than 24 hours. " 2 " " " " 30 " " 3 " " " " 36 " " 4 " " " " 40 " " 1 " " " " 41 " " 4 " " " " 58 " " 1 " " " " 54 " " 1 " " " " 2-1/2 days. " 31 " " within (time not accurately ascertained) 4 days. " 2 " the incubation did not exceed 4-1/2 days. " 17 " " " " " 5 " " 2 " " " " " 6 "

In three cases Murchison believes that the incubation was precisely fixed at thirty-six hours, three days, and four and a half days.

Watson says that a man reached Devonshire on mid-day to see his daughter, who had scarlet fever. Two days later he was also attacked. Rehn saw a child who was attacked two days after its grandmother returned from a case of scarlet fever; and Zengerle, a girl of ten years, residing at Wangen, where there was no scarlet fever, who took the disease two days after her mother had returned from visiting a family affected with it. Loochner states that a boy aged four and a half years was attacked one and a half days after admission into the infected wards of a hospital. Armistead, in his annual report on the health of the Newmarket rural district, states that three children, coming from a different part of the district, visited Westley, and stayed next door to a child who had scarlet fever six weeks previously, and who was allowed to play with these children on the evening of Aug. 13th and morning of the 14th. The family then returned home, and on the 18th, four days after the exposure, all three children sickened with scarlet fever (Brit Med. Jour., Sept. 30, 1882).

Ordinarily, therefore, the incubative period, though varying in different cases, is within six days. Many cases, however, occur in which it seems to be longer. Thus in my practice scarlet fever appeared in a family on April 26, 1882. The patient was immediately removed to the third floor and the other children to the basement. All communication between the infected room and the basement was forbidden, but on May 8th, twelve days after the separation, one of these children sickened with the disease. {494} Many observers--among whom may be mentioned Niemeyer and Copland--believe that the incubative period may be longer than one week, but, on account of the subtlety of the poison and the many modes of transmission, it is possible that in the instances of an apparently long incubative period there were other and unsuspected exposures. When scarlet fever has been communicated by inoculation, as in the experiments of Rostan and others, the incubative period has been about seven days, but Gerhardt states that a man was attacked four days after an abscess was opened by a knife used upon a scarlatinous patient. This variation in the incubative period, which also occurs in some other infectious diseases, as diphtheria, is probably due mostly to individual differences, some being more susceptible than others; but it may be due partly to those obscure meteorological conditions which we designate the epidemic influence. Probably, as a rule, when the disease is quickly developed after exposure, the attack is more severe than when several days elapse.

CONTAGIOUSNESS.--The area of the contagiousness of scarlet fever is small. It apparently embraces only a few feet. Therefore, close proximity is the necessary condition of its propagation. Hence many who are exposed, particularly of those who are remotely exposed, do not contract the disease. There is also an idiosyncrasy in some children, so that they resist infection even when repeatedly and closely exposed. In the New York Medical Record for March 23, 1878, C. E. Billington states that of 90 children in 26 families who were exposed to scarlet fever, 43 contracted the disease and 47 escaped; whereas, as is well known, comparatively few unprotected children escape pertussis, variola, varicella, or measles if exposed to either of these diseases. By strict isolation, therefore, the spread of scarlet fever is more easily prevented than that of most other acute infectious maladies. In the New York Foundling Asylum for a number of years children with scarlet fever were isolated in a small room attached to one of the wards. The door between the two rooms was closed, and not opened during the continuance of the sickness. Entrance into the small room was through another door, and a nurse was assigned to the scarlet-fever cases, with strict directions that she should not mingle with the other children. These simple precautions were found sufficient in the various epidemics of scarlet fever which occurred in the city to prevent the spread of the malady through this institution; whereas, similar measures were much less effectual in arresting the spread of measles and pertussis. Consequently, an outbreak of scarlet fever in this institution was usually limited to a few cases, while the extension of measles and pertussis was arrested with difficulty till a more efficient quarantine was established.

VARIATIONS IN TYPE.--The type of scarlet fever varies greatly in different epidemics, and frequently also in cases which occur in the same epidemic, even in the same family. One child may have scarlatina so mildly that little treatment is required and convalescence soon begins, while another has the malignant form, and soon succumbs, notwithstanding the prompt employment of the most efficient and appropriate measures. Ordinarily, however, if the first case in a family be very severe, subsequent cases will present a similar type; but there are notable exceptions. This variation in type in different years and different epidemics is probably not equalled in any other infectious malady. Consecutive {495} epidemics may present this variation, or the same type may continue for a series of years, and then, from some unknown cause, change to one milder or more severe. In England, during Sydenham's life, scarlet fever was so mild that he regarded it as a trivial affection, requiring little attention, like rötheln of the present time, but after the death of Sydenham, Morton and his contemporaries in London found, to their sorrow, that the type of scarlet fever was very different from that described by Sydenham's pen. The late Graves of Dublin and his contemporaries treated a mild type of scarlet fever with a very small percentage of deaths--much less than that during the preceding generation--and they attributed their success to their greater knowledge and more appropriate use of remedies than their ancestors possessed and employed. By and by the type changed, the mortality of former years was restored, and they discovered that their previous success in saving life had been due not to their skill, but to the mild form of the malady. A distinguished physician of New York treated more than fifty cases of scarlet fever in one of the institutions without a single death. A few months afterward the type of the malady changed, and his own son perished from it.

SURGICAL AND OBSTETRICAL SCARLATINA.--After surgical operations, and sometimes in surgical cases not requiring operative measures, a scarlatinous efflorescence occasionally appears upon the whole or nearly the whole body, and remains for several days. The following were cases of the kind alluded to. They occurred in Guy's Hospital, and were published by H. G. Howse in Guy's Hospital Reports for 1879: On March 15, 1878, Jacobson performed osteotomy upon a child suffering from extreme rachitis. The operation was followed by a moderate febrile movement (100° to 101°), and after three days by the appearance of an efflorescence, with sore throat and the strawberry tongue. The osteotomy had been performed under carbolic acid spray and with all the details of antiseptic surgery. The rash soon faded, the temperature fell, and the child, temporarily separated from the other patients from the suspicion that the disease was scarlet fever, was brought back to the ward. The subsequent history confirmed the diagnosis of scarlet fever, for the skin desquamated, and on April 1st abundant albumen was found in the urine. The case terminated favorably. Three months previously the same operation had been performed on the other leg, with no unfavorable symptoms. On April 5th, three weeks after the osteotomy, a lipoma was removed from another patient aged twenty-one years. The following day the temperature rose to 101°, and remained at that till April 8th, when it suddenly increased to 103°, and a rose-rash occurred over the body, with sore throat. On April 9th, Howse excised the elbow-joint of a girl of sixteen years having pulpy disease. On the 10th her temperature began to increase, and on the 11th reached 105.8°. Toward evening a roseoloid eruption appeared over her body, and she was isolated. On April 12th, Dr. H. excised a fibroid bursa patellaë from a woman of twenty-nine years. On the following day her temperature was 99°, but on the 14th it rose to 100°, and on the evening of the 15th she had rigors and headache. On the morning of the 16th the temperature was 102.5°, and a roseoloid eruption occurred over the face and chest. The surgeons now perceived that an epidemic of the so-called surgical scarlatina was occurring, so as to justify the postponement of other operations.

{496} In the same volume of Guy's Hospital Reports, James F. Goodhart gives the histories of nearly thirty cases of this disease occurring during a series of years in the same hospital. The patients were chiefly children, having the most diverse surgical ailments, among which may be mentioned hip disease and abscess, genu valgum without operation, necrosis of femur, hydrocele with explorative operation, a scald, a sinus over the great trochanter, spinal disease with abscess, tenotomy for club-foot, and vesical calculus with operation. The most common disease was caries or necrosis with abscess. In cases operated on the intervals between the operations and the occurrence of the efflorescence varied from two days to more than two weeks. Goodhart, after a careful examination of these cases, came to the conclusion that they were for the most part examples of true scarlet fever, especially as a considerable proportion of them occurred in groups, and there was a known exposure of some of the patients to children admitted into the hospital with the sequelæ of scarlet fever.

In the British Med. Jour. for Jan., 1879, George May, Jr., reported a case of efflorescence in surgical practice which appears to have been scarlatinous. A child was operated on for the radical cure of hernia on Dec. 4th. Toward the close of the same day he became restless, vomited, and his pulse on the following day rose to 136. Forty-eight hours after the operation a rash appeared on the chest and arms, the abdomen became tense and painful, and on the following day he died. The poison, however, in this case may have been septic.

Hillier remarks (Diseases of Children): "In the hospital for sick children, of the children who contract scarlatina a very large proportion have been the subjects of a surgical operation within a week before the rash appears." Gee says (Reynolds's System of Medicine): "It has been doubted by some whether the scarlatiniform rash which sometimes follows operations is really scarlatinal. The eruption appears from the second to the sixth day after the operation, and in the cases which have caused the doubt is very fugitive and the first and only symptom. Yet that the disease really is scarlet fever would seem to be proved by the following observations: first, that the disease occurs in epidemics; secondly, that in a given epidemic a severe case occasionally relieves the monotonous recurrence of the very mild form; thirdly, that a precisely similar scarlatinilla attacks in the same epidemic patients who have not been subjected to operation and who have no open sore; and lastly, by way of a veritable experimentum crucis, that, however freely these patients are exposed to ordinary scarlet fever contagion afterward, they do not contract that disease." Paget and other distinguished London surgeons who have observed this complication of surgical cases, believe that the patients have been previously exposed to the scarlatinous poison, and that the surgical diseases or operations furnish favorable conditions for the occurrence of scarlet fever, so that the exposure, which probably would have been without result in ordinary health, causes an outbreak of the malady.

Those who have reported cases of this form of efflorescence have for the most part neglected to state whether the patients had had scarlet fever previously, knowledge of which would have aided in the diagnosis; but from an examination of the histories of cases, especially those {497} published in the London journals in the last four or five years, there can, I think, be little doubt that surgical maladies of a certain kind, especially traumatism, do produce a state of system which predisposes to scarlet fever, so that this class of patients are especially liable to contract it. Therefore, in my opinion, a considerable proportion of reported cases of surgical scarlatina are genuine, but in a considerable number, perhaps an equal number of such cases, the histories and symptoms indicated a septic rather than scarlatinous efflorescence, and in not a few instances, when consultations have been held, opinions differed, some diagnosticating scarlet fever, others septicæmia. In some of the cases I find it stated that the fauces presented the normal appearance. Now, faucial redness is so generally present in scarlet fever, antedating that of the skin and coexisting with it, that its absence is strong evidence that the disease is not scarlatinous. Moreover, when, as was true of certain of the reported cases, the rash appeared irregularly upon the surface, and faded away in two or three days with the abatement of the fever, and the conditions for septic absorption were present, the efflorescence was probably septicæmic.

The following were apparently cases of septicæmia efflorescence: A child aged five years (Brit. Med. Jour., Feb. 15, 1879) had inflammation of the lymphatic glands in the groin, which suppurated. At the time when the abscess was fully formed a rash appeared over the entire body. It consisted of numerous red points, but was paler than that of ordinary scarlet fever; temperature never above 99°; no sore throat nor desquamation of cuticle. No child exposed to her took scarlet fever, and her sickness could not be traced to infection. In the British Med. Jour., Jan. 4, 1879, L. Braxton Hicks states that his son, attending school at Reading, was seized with a severe attack of pyrexia, accompanied on the second day by delirium and the occurrence of a rash like scarlet fever over the entire surface. He had no decided redness of the fauces, though it was perhaps slightly flushed. The right buttock was swollen from inflammation, and a large, deep-seated abscess formed near the tuberosity of the ischium. When the delirium abated the boy said that he was standing the day before the fever began with his legs far apart, when a schoolfellow stretched them farther by suddenly pulling on one of them. The rash, which was nearly universal, lasted three days, and was not followed by desquamation. No case of scarlet fever occurred in the school before or afterward. In the same volume of the British Medical Journal, Surgeon Frolliott of the East India Service relates the case of a private, aged twenty-three years, and three years in India, who, when on duty in the Punjab, was injured by the explosion of an Afghan powder-magazine. The accident occurred Dec. 21, 1878. On Dec. 25th a bright scarlet rash appeared upon the abdomen and spread over the entire body. The following day the eruption was very vivid, like a boiled lobster, and it lasted five days. The temperature, which in the beginning had been 101°, abated to the normal after the rash appeared. No soreness of throat nor redness of the buccal surface occurred, but the epidermis desquamated even from the palms of the hands and soles of the feet. Now, the febrile movement of scarlet fever does not cease while the efflorescence is distinct. It does not even diminish when the eruption appears, while in the above case it fell to the normal--a common {498} occurrence in septicæmia, even when the blood-poisoning is profound. Moreover, scarlet fever is so rare in India that Frolliott, after twelve years' service, had only heard of one case among Europeans and natives. The surgeons who consulted over the case of this private disagreed in opinion, some regarding the disease as septicæmic, others as scarlatinous. But a better knowledge of the clinical history of scarlet fever on the part of these army surgeons would, I think, have removed all doubt as to the diagnosis.

It is the opinion of some reputable surgeons that the exposure of traumatic patients to the scarlatinous poison sometimes aggravates the inflammation of wounds, causing them to assume an unhealthy appearance even though no scarlatina be produced. The late Solly made the remark, "Whenever a case of surgery in private practice takes on a highly phlegmonous appearance I am always sure to find break out, in the inmates of the house, either erysipelas or scarlet fever" (British Med. Jour., Feb. 15, 1879). We will see that the scarlatinous poison sometimes causes pharyngitis or nephritis without producing the general disease. In a similar manner it seems that it may aggravate open wounds, intensifying the inflammation in them, while there is no efflorescence or other symptom to show that scarlatina itself is present. The poison appears to act entirely locally in such cases.

Paget, in his Clinical Lectures, says: "I think it not improbable that in some cases results occurring with obscure symptoms within two or three days after operations have been due to the scarlet-fever poison, hindered in some way from its usual progress." Playfair, in his remarks on the puerperal state, adds: "Mr. Spencer Wells informs me that he has seen cases of surgical pyæmia which he had reason to believe originated in the scarlatinal poison; and his well-known success as an ovariotomist is no doubt, in a great measure, to be attributed to his extreme care in seeing that no one likely to come in contact with his patients has been exposed to any such source of infection." Opinions like these, held by such prominent members of the profession and sustained by many observations, should certainly induce physicians to prevent, so far as possible, any exposure of their surgical patients, especially if they have any sores or wounds, whether by traumatism or the scalpel, to the scarlatinal poison.

OBSTETRICAL SCARLATINA.--Women during convalescence after childbirth are very liable to contract scarlet fever. In the New York Infant Asylum, which has maternity wards, a woman was admitted from a house in which scarlet fever was prevailing, and assigned to a cot next that occupied by one of the waiting women, who was confined soon afterward. Her labor was favorable, but three days afterward she took scarlet fever, and another lying-in-patient contracted it from her. The sore throat and desquamation were characteristic. It has come to my knowledge that a physician of New York, in whose family scarlet fever was occurring, attended three women in succession in their confinement, and all contracted scarlet fever, which presented the characteristic symptoms, and two of them died. Experienced and cautious physicians of New York, aware of the danger, do not go directly from a scarlatinous patient to an obstetrical case, but avoid the risk by intermediate visits to other patients or by remaining for a time in the open air.

{499} Playfair, remarking on this subject, says: "There is good reason to believe that the contagium of zymotic diseases may produce a form of disease indistinguishable from ordinary puerperal septicæmia, and presenting none of the characteristic features of the specific complaint from which the contagium was derived. This is admitted to be a fact by the majority of our most eminent British obstetricians, although it does not seem to be allowed by continental authorities, and it is strongly controverted by some writers in this country. It is certainly difficult to reconcile this with the theory of septicæmia, and we are not in a position to give a satisfactory explanation of it. I believe, however, that the evidence in favor of the possibility of puerperal septicæmia originating in this way is too strong to be assailable. The scarlatinal poison is that regarding which the greatest number of observations has been made. Numerous cases of this kind are to be found scattered through our obstetric literature, but the largest number are to be met with in a paper by Braxton Hicks. Out of 68 cases of puerperal disease seen in consultation, no less than 37 were distinctly traceable to the scarlatinal poison. Of these, 20 had the characteristic rash of the disease, but the remaining 17, although the history clearly proved exposure to the contagium of scarlet fever, showed none of its usual symptoms, and were not to be distinguished from ordinary typical cases of the so-called puerperal fever. On the theory that it is impossible for the specific contagious diseases to be modified by the puerperal state, we have to admit that one physician met with 17 cases of puerperal septicæmia in which, by a mere coincidence, the contagion of scarlet fever had been traced, and that the disease nevertheless originated from some other source--a hypothesis so improbable that its mere mention carries its own refutation."

Parturition, like traumatism, furnishes in an eminent degree the conditions in which septic poisoning occurs, and the efflorescence which often accompanies septicæmia bears, as we have seen, a very close resemblance to that of scarlet fever. Hence in many instances the same difficulty is present in making a differential diagnosis between septic and scarlatinous blood-poisoning in obstetrical cases which occurs in surgical practice. But, according to my observations, an efflorescence occurring during the week following parturition is in most instances septic. It is only in exceptional cases that it is scarlatinous, and there is little danger that the accoucheur, engaged in general practice and visiting scarlatinous patients, will communicate scarlet fever through his person or clothing if he exercise proper precautions. His short stay in the sick room and his out-door exercise in visiting cases prevent infection of his person or dress. But if, as Playfair believes, the scarlatinal poison sometimes produces in parturient women a puerperal fever in which the characteristic scarlatinal symptoms are lacking, and which, in the present state of our knowledge, is not distinguishable from ordinary septic fever, certainly the scarlatinous virus sustains a much more frequent causative relation to childbed fever than has been heretofore supposed.

Infants under the age of six months do not ordinarily contract scarlet fever, although fully exposed, and those under four months nearly possess immunity. Still, this disease has been observed in new-born infants, contracted, apparently, through the placental circulation. {500} Tourtual states that a woman waited upon her own husband and child, both of whom had scarlet fever, during the eighth and ninth months of her pregnancy, till near her confinement. Though she had no symptoms of scarlet fever, her infant had unusual redness of the skin and buccal surface and difficulty of swallowing up to the fifth day. On the ninth day desquamation began, and at a later stage the nails of the fingers and toes separated. A case having a history in some respects similar is related by Megnert, but the symptoms were anomalous for scarlet fever, and the disease may have been ordinary septic fever. On the other hand, in one instance in my practice a mother had scarlet fever, beginning about the third day after her confinement, and although she suckled her infant and it was constantly in bed with her, it had no symptoms of scarlet fever, although it became affected immediately afterward by a severe form of eczema, probably from the altered quality of the milk; and in two instances observed by Murchison new-born infants remained healthy, although their mothers suffered from scarlet fever.

After the age of six months the liability to scarlet fever increases till the close of infancy, children between the ages of six months and one year being less liable to contract the malady than during the second year, and those in the second year being less liable to it than those in the third year. Murchison collected the statistics of deaths from scarlet fever in England and Wales during a series of years ending with 1861. The number of deaths aggregated 148,829, and the percentage of deaths at different ages was as follows:

Deaths under 1 year, 6.7 per cent. " between 1 and 2 years, 14.09 " " " " 2 " 3 " 16.00 " " " " 3 " 4 " 15.13 " " " " 4 " 5 " 11.9 " " " " 5 " 10 " 25.9 " " " " 10 " 15 " 5.8 " " " " 15 " 25 " 2.6 " " " " 25 " 35 " 0.8 " " " over age of 35 years, 0.8 " "

Among the deaths were ten cases above the age of eighty-five years, so that scarlet fever, though especially a disease of childhood, may occur in any decade of life; but old age, like early infancy, almost possesses immunity from it.

I have preserved the records of the ages of 145 consecutive cases occurring in private practice. If we add to these 58 cases observed by Prof. Octerlony (Amer. Jour. of Med. Sci., July, 1882) we have the statistics of the ages of 203 cases, which are embraced in the following table:

Under 1 year, 3 From 1 to 2 years, 25 " 2 " 3 " 43 " 3 " 5 " 57 " 5 " 10 " 53 " 10 " 15 " 13 " 15 " 20 " 3 " 20 " 30 " 4 " 30 " 40 " 2 --- Total, 203

{501} CLINICAL FACTS REGARDING SCARLET FEVER.--As a rule, scarlet fever occurs but once, one attack conferring immunity from the disease for life; but there are exceptions. In 1869, I attended a child with fatal scarlet fever who three years previously, it was stated, had passed through a first attack with all the characteristic symptoms. The following case occurred in a family attended by the late Dr. Herzog: R----, a boy of six years, had scarlet fever in a mild form in January and February, 1875, followed by moderate desquamation. In July of the same year he was kicked by a horse in the street, receiving a deep scalp-wound which required three stitches. Three days afterward he had, to appearance, a second attack of scarlet fever, attended by high febrile movement, and followed also by desquamation. It was believed by Dr. H. to be a genuine case, and was so treated. I am not able to state as regards the presence of soreness of the throat, and doubt arises whether this second attack may not have been septicæmic. In April, 1876, a third attack occurred, which I saw from the beginning. It was accompanied by all the characteristic symptoms--injection of the fauces, an efflorescence continuing the usual time, followed by desquamation and albuminuria, the latter continuing several weeks. Richardson states that three distinct attacks occurred in his own person, and a student attending the lecture at which this was mentioned informed the doctor that he also had had scarlet fever three times.

Sometimes a second attack occurs so soon after the first that it has been described as a relapse. The following was a case in point in the practice of Godneff (Meditz. Vestnik., No. iv., N.Y. Med. Rec., April 30, 1881): A youth of seventeen years contracted scarlet fever while taking care of a child. It began with a chill, and he had the usual efflorescence, sore throat, and tumefaction of the cervical glands. An exudation appeared upon his tonsils and uvula, and his temperature reached 104°. The urine contained a trace of albumen, the rash in due time faded, and the epidermis exfoliated. On the fifteenth day, when he was about ready to leave the hospital, he again had a chill, followed by fever. The temperature reached 105.2°, the rash reappeared over the entire surface except the face, diphtheritic exudations occurred upon the fauces, and the urine, the quantity of which was diminished, again became albuminous. This second efflorescence faded on the twenty-fourth day, and on the twenty-seventh exfoliation began. Hillier says: "I have seen a young woman in the fever hospital suffering from a second attack of scarlatina, the first attack having occurred five weeks previously. She had quite recovered from her first illness, and was acting as nurse. In both seizures the rash, the sore throat, and other symptoms were characteristic. The relapse or recurrence was less severe than the primary disease." Cases of a fourth, or even of a greater number of attacks, have been reported. The first seizure is sometimes milder, but in other instances is more severe, than those which follow.

Exposure to the scarlatinous poison not infrequently produces pharyngitis without the occurrence of scarlatina, and the inflammation is apt to be severe, accompanied by pain in swallowing and marked febrile movement. This phlegmasia is distinguished from scarlet fever by its shorter duration and the absence of the efflorescence. It occurs in adults as well as in children, and in those who have had, as well as in those who have not {502} had scarlatina. So far as I have observed, it is very seldom accompanied or followed by any of the complications or sequelæ so common in and after scarlet fever. It cannot be distinguished from ordinary pharyngitis except in the manner in which it occurs, and one attack does not preclude another. The late George B. Wood made the remark that he never attended a case of scarlet fever without suffering from sore throat. The following were examples of this form of pharyngitis: On Jan. 17th, 1882, I was called to a boy of three years with severe scarlet fever, ushered in by convulsions. On the following day his sister, aged seven and three-fourths years, whom I had attended a year previously during a severe attack of scarlatina, and who had been almost constantly with the brother, became very ill, with a temperature of 103.5°. Examination revealed severe inflammation of the fauces, without pseudo-membrane or any other exudation except muco-pus. On Jan. 19th an older brother, nine years, whom I had attended in scarlet fever three years previously, was affected in the same way, his temperature being 104° and his respiration guttural and noisy, especially during sleep, in consequence of the great amount of faucial swelling. At times he was delirious. The inflammation in both cases began to abate about the third day, and had disappeared by the close of the week. That the contagium of scarlet fever may be received into the system and cause pharyngitis, while the patient has immunity from scarlet fever through a previous attack, and that this inflammation may occur any number of times, as in the case of Dr. Wood, are remarkable facts.

Now and then cases occur which appear to show that the scarlatinous poison may affect the kidneys, producing nephritis, while there is no other manifestation of its influence. Thus in my practice a lady of about forty-five years constantly attended her son, sleeping by his side, during an attack of scarlet fever. Her health had previously been good. When the boy was convalescent, as her appetite failed and she was indisposed, a careful examination revealed the fact that she had albuminuria, although she had had no sore throat or other symptom of scarlet fever. After several weeks of treatment her disease was removed, and she has remained well since. In the British Med. Jour. for Nov. 29, 1879, it is stated that in a family four girls were found to be suffering from desquamative nephritis. One of them had recently had scarlet fever, but the other three had presented no symptoms whatever of this disease. Such cases, although probably rare, appear to show that, as the scarlatinous poison may produce inflammation of the fauces without the occurrence of scarlet fever, so it may cause nephritis without producing the general disease, or apparently disturbing the functions, or changing the state of other parts, except the kidneys.

SYMPTOMS.--ORDINARY FORM. Scarlet fever usually begins abruptly, so that the exact time of its commencement can be fixed. If any premonitory symptoms occur, they are slight, so as scarcely to attract attention, as languor or the appearance of fatigue. A dusky aspect of the surface may occasionally be observed during the few hours preceding the attack. In some children the first symptom is chilliness, and occasionally a distinct chill occurs. In the adult a chill is ordinarily the first symptom. With or without the initial chilliness, febrile movement occurs, of variable intensity according to the severity of the type, and {503} accompanied by such symptoms as usually arise in a febrile state of system, as cephalalgia, anorexia, and thirst. The pulse rises to 110, 120, or more per minute, the temperature to 102°, 103°, or 104°; the skin is hot, face flushed, and the eyes bright. Even in cases that are not malignant or grave, and that give indications of a favorable result, there is often more or less stupor, with transient delirium and sudden starting or twitching of the extremities, showing that the cerebro-spinal axis is involved.

Vomiting is a common symptom in the beginning of scarlet fever, occurring before the appearance of the efflorescence. It therefore has diagnostic value when the nature of the case is still doubtful. In some patients it is an initial symptom, but in others some hours have elapsed when it occurs. I recorded its presence or absence in 214 patients, with the following result: present in 162 patients, absent in 52. In severe forms of the disease it is rarely absent, and if it do not occur it is probable that the case will be mild, requiring little treatment and having a favorable termination. In epidemics of unusual mildness the number of cases without vomiting may be in excess of those in which this symptom occurs. It appears to be due to functional disturbance of the cerebro-spinal system, and it may therefore be properly regarded as a nervous symptom. In severe cases the vomiting is apt to be repeated, not only on the first but on subsequent days, and we shall see that in cases of great gravity, in which a fatal termination is not improbable, persistent vomiting, by which the food and stimulants so urgently required are rejected, interferes seriously with successful treatment. In a few cases embraced in my statistics nausea without vomiting was recorded. The bowels in ordinary scarlatina act regularly or are slightly constipated. Diarrhoea, which so commonly accompanies the persistent vomiting in malignant cases, if it occur in this form of the malady is slight and transient and due to accidental causes. The food, if it be given in the liquid form and cool, is usually taken readily, on account of the thirst, except when deglutition is rendered painful by the pharyngitis.

The symptoms pertaining to the nervous system vary according to the severity of the disease and the temperament of the patient. Many children during the progress of the common form of scarlet fever present a dull or apathetic appearance. They lie much of the time with their eyes closed; others are more restless, and not a few, if the fever be considerable, have occasional twitching of the limbs and more or less headache. Eclampsia sometimes occurs on the first day, especially in those predisposed to it, even when the subsequent course of the disease is mild and favorable. This complication, very grave and usually fatal when it occurs at a later stage, is in most instances, when it takes place on the first day, readily controlled by proper remedies and with little detriment to the patient. But if it be attended by high elevation of temperature and marked drowsiness, approaching the comatose state, it is very serious upon the first as well as upon subsequent days. Nervous symptoms occurring in the beginning of scarlet fever, when it has the ordinary favorable type, begin to abate in three or four days, but if they supervene at a later date, and especially in the declining stage, they possess more gravity, since they then not infrequently result from and indicate renal complication.

{504} Early in the disease, nearly as soon as the commencement of the fever, the faucial and buccal surfaces become inflamed, as shown by redness, swelling, and tenderness. The physician summoned in the beginning of an attack will already, at his first visit, observe hyperæmia of the fauces, with points of deeper injection than over the general faucial surface, and soon the buccal surface also participates. The inflammation at first produces preternatural dryness, and this is followed by a viscid secretion. The papillæ of the tongue enlarge and become prominent, giving rise to the appearance known as strawberry tongue which is so common in scarlet fever. This state of the buccal and faucial membrane continues throughout the disease. A thin fur appears upon the tongue on the first day, and it increases on the second and third days, after which it is apt to be detached, exposing the surface of the organ, which has a deep red hue, but in not a few patients the fur remains or is reproduced as soon as shed. Except in the mildest cases the Schneiderian membrane also participates in the inflammation as the disease advances, so that a thin, irritating discharge, containing leucocytes or pus-cells, flows from the nostrils. The skin is hot and dry, and cutaneous transpiration nearly checked. The respiratory system is rarely involved in any notable manner unless there be a complication. Many have no cough whatever, while others have a slight cough, due to the fact that the inflammation, of a catarrhal form, has extended from the fauces to the surface of the glottis. Slight acceleration of respiration, corresponding with the degree of fever, may also be observed. The kidneys commonly act regularly and normally during the first days, any serious impairment of their functions being rare before the close of the first week.

When the symptoms described above have continued from six to eighteen hours the efflorescence appears. It is first observed about the ears, neck, and shoulders, in reddish patches fading into the normal hue. These patches extend and unite, and in the course of a few hours the trunk and upper extremities, and finally the legs, are covered. The scarlatinous rash usually, when fully developed, resembles that produced by external heat or the application of a sinapism. It has been likened to the appearance of a boiled lobster, but there are numerous minute points of a deeper or duskier hue than the surface generally. In many patients the rash appears, especially over the abdomen and lower extremities, as minute, thickly-set points, with the skin of normal appearance between them. Henoch of Berlin says of scarlet fever: "In general, the moderate grades of eruption prevail, the skin, when seen from a distance, presenting a diffuse, more or less scarlet redness, while on closer inspection it is found that this redness is composed of innumerable red points closely situated together, and separated from one another by very small paler portions of skin. The dark-red points appear to correspond to the hair-follicles." On passing the finger over the efflorescence no distinct prominences are observed, but a sensation of roughness is sometimes imparted from engorgement of the cutaneous papillæ. The rash disappears on pressure, but it immediately reappears when the pressure is removed. Its slow return is evidence of sluggish circulation, and it indicates a grave and dangerous form of the malady. The color is then usually a dusky instead of a bright red. The efflorescence is most marked in dependent parts, as along the back, over the chest and {505} abdomen, and in the flexures of the joints. Parts pressed upon by the bed-clothes, which confine and intensify the heat, present a deeper coloration than other portions of the surface. Often, especially in mild cases, the rash is absent from portions of the surface where it commonly appears, while it presents a typical character elsewhere. Tardy and incomplete establishment of the rash when the symptoms indicate an attack of ordinary or more than ordinary severity is commonly due to some perturbating cause, especially diarrhoea. In the London Lancet for Aug. 16, 1879, cases are related of supposed scarlet fever without the rash, cases in which pharyngitis and stomatitis with the strawberry tongue occurred, without efflorescence upon the skin; but it is to be remembered, as stated above, that the inflammations which commonly attend or follow scarlet fever, particularly the pharyngitis and nephritis, not infrequently occur in those who have already had scarlatina, and occur more than once from fresh exposure to scarlatina patients. These inflammations, occurring under such circumstances, appear to be purely local maladies, produced by the scarlatinous virus; and it seems to me a question whether, in the so-called scarlatina without efflorescence, the inflammations which are present, and which undoubtedly have a scarlatinous origin, are not local in their nature, instead of being local manifestations of the constitutional disease. The burning and itching sensation produced by the rash increases the restlessness of the patient, and is sometimes the most annoying of the symptoms.

The temperature in the common favorable forms of scarlet fever usually varies from 101° in the mildest cases to 103° or 104° in those more severe. If it attain 105° or over, the case is properly designated grave or severe. The febrile movement commonly fluctuates but little from day to day till the fourth or fifth day, when, if the case be favorable and no complication occur, it begins to decline. The temperature is as high in the beginning of the attack as subsequently.

The symptoms pertaining to the digestive system during the initial period of scarlet fever have been sufficiently described. The subsequent symptoms referable to this system do not differ materially from those present in the beginning, except the absence of vomiting. The lips are dry and often cracked. The inflammation of the mouth and throat continues, with anorexia and thirst. With the decline of the disease the appetite gradually returns, but it is not till the close of the second week that it is fully restored. Great and continued disturbance of the digestive apparatus, seriously interfering with the nutrition, pertains to the malignant forms of scarlet fever.

The urine is high-colored, and in robust children during the first days of scarlet fever it frequently deposits urates on cooling. Gee, who has carefully investigated the state of the urine in scarlet fever, says that the quantity of water is diminished and the urea is not necessarily increased during the pyrexia; that the chloride of sodium is diminished till the fourth, fifth, or sixth day, and that the phosphoric acid is diminished during the climax of the pyrexia, though not during the first three or four days. In one case he made a daily estimation of the amount of uric acid, and found it greatly diminished on the second and third days, normal on the fourth, and much increased on the fifth. He believes that similar variations are common in the quantity of the products excreted {506} in the urine. Bile may also appear in the urine, coincident with a yellow tinge of the conjunctiva.[1]

[Footnote 1: Article on scarlatina in Reynolds's System of Medicine.]

The duration of scarlet fever varies in different cases. If the attack be very mild, with little efflorescence, the febrile movement may decline by the fourth or fifth day; but if the disease be severe, little or no amelioration of symptoms may occur before the twelfth or fourteenth day, even when no complication has occurred to increase the temperature or cause aggravation of symptoms. Octerlony, who estimated the duration of scarlet fever from the commencement of febrile symptoms to "the disappearance of fever, with marked improvement in leading symptoms," ... "found that the average duration of the disease in forty cases was six and one-sixth days. The minimum duration in a very slightly-marked case was three days: the maximum duration was fourteen days." In general, prolongation of fever beyond the usual time is due to some complication--more frequently to unusually severe pharyngitis, with accompanying cellulitis, than to any other cause.

The malady whose commencement was so abrupt declines gradually. In ordinary cases, by the close of the first week or in the beginning of the second the rash becomes less and less distinct, and finally disappears, as do also the redness and swelling of the buccal and faucial surfaces. The engorgement of the tonsils and of the papillæ of the tongue subsides, the appetite returns, the countenance brightens and becomes natural, and the child, who during the height of the fever scarcely noticed objects or noticed them with indifference or even repugnance, can be amused as before his sickness.

Desquamation succeeds. This begins at about the sixth day, and is not completed till the tenth or twelfth day; often not till the close of the third or in the fourth week. The amount of desquamation corresponds with the intensity and duration of the efflorescence, or rather of the dermatitis which produces the efflorescence. If the efflorescence have been slight and partial, it will be slight, perhaps scarcely appreciable, but if the rash have been general, full, and protracted, exfoliation occurs upon every part. It begins about the face and neck, and within a day or two appears upon other parts. Where the skin is thin the epidermis as it is detached presents a furfuracous appearance; where it is thick, as upon the palms of the hands or soles of the feet, it separates in layers of considerable thickness.

Such is a brief description of scarlet fever when it pursues its normal course without any disturbing element, but there is no other disease in which complications and sequelæ so frequently occur. The liability to them renders the prognosis in every case doubtful. They largely increase the percentage of deaths. They occur both in mild and severe forms of scarlatina.

The difference in type in different cases and epidemics has already been alluded to. Scarlet fever is sometimes so mild, and its symptoms so slight, that the diagnosis is necessarily uncertain. In the spring of 1866 I was called to an infant thirteen months old who had slight pharyngitis and an indistinct rash over a part of the surface. In two days the eruption had disappeared, and the health within a day or two later was apparently fully restored. Diagnosis would have been doubtful except for sequelæ {507} which clearly indicated the scarlatinous nature of the attack. In another instance two children passed through the entire course of scarlet fever playing every day in the street. Although the intelligent grandmother saw the rash upon them, its nature was not suspected, as it was midsummer and cases of prickly heat common, till nearly two weeks afterward, when one of the children had nephritis and anasarca ending fatally. In cases so mild as these the heat of surface is but slightly increased, the pulse but little accelerated, and the rash usually does not occupy so much of the surface as in ordinary cases; the appetite is not lost, though diminished, and the thirst is moderate.

Between scarlet fever so mild that it terminates in four or five days, and that of the grave or malignant type presently to be described, all grades of severity exist. Scarlet fever occurs in all forms from mild to severe, but certain symptoms characterize grave or malignant cases--symptoms which are absent or much less prominent in ordinary scarlet fever. Therefore the grouping of cases according to the type is proper, and facilitates the studying of the disease.

GRAVE FORM (malignant scarlet fever).--This form of the disease is in some epidemics common, while in others it is rare. The symptoms which characterize it are severe from the beginning, those of the nervous system predominating at first, such as intense cephalalgia, restlessness or stupor, sudden twitching of the muscles, and perhaps delirium, or even convulsions. Many pass rapidly into coma and die within two or three days, succumbing to the intensity of the scarlatinous poison while the malady is still in its commencement. The rash is dusky. It disappears by pressure, and returns slowly when the pressure is removed, showing extreme sluggishness of the capillary circulation. Some patients are very drowsy, lying in a semi-comatose state except when aroused, and if aroused are very restless. Others are constantly restless. If placed in one position on the bed, they throw themselves in another in a half-conscious or unconscious state. They do not speak, or they mutter like those affected by the graver forms of typhus, calling the names of playmates or talking incoherently about things which interested them when well. The thermometer placed in the axilla is found to rise above 103°, which is a safe average, to 105° or even 107°, and the heat of the surface is pungent except when the case approaches a fatal termination, when the extremities, ears, and nose may be cool while the trunk and head are extremely hot. The pulse from the first is rapid, ranging from 130 as the minimum in a malignant case to a frequency which can scarcely be counted. A very frequent pulse is nearly always feeble and compressible. Irritability of the stomach is one of the most common symptoms in grave cases, so that many patients immediately reject the nutriment and stimulants which are so urgently required to sustain the vital powers. The vomiting, therefore, if frequent and severe, greatly increases the danger, and in not a few instances this symptom is associated with diarrhoea, which also tends to increase the prostration.

Severe and dangerous nervous symptoms, due to the intensity or activity of the scarlatinous poison, occur chiefly within the first three or four days. Grinding the teeth, sudden muscular twitching, delirium, convulsions, and profound stupor occur for the most part within this time. Afterward the danger is mainly from exhaustion, unless in the {508} second week or subsequently, when nervous symptoms may arise from uræmia.

Those who survive the onset of malignant scarlet fever often have in the course of a few days severe pharyngitis, with extension of the inflammation to the lymphatic glands and connective tissue around the angle of the jaw. These inflammations cause more or less external swelling. The faucial turgescence around the entrance of the larynx, with the accompanying secretion of viscid mucus or muco-pus, often causes noisy respiration, and many at this stage of the attack breathe with the mouth constantly open to facilitate the ingress of air.

Ordinarily, no discharge occurs at first from the nasal surface, but as the disease continues, if the type remain severe, defluxion of thin muco-pus takes place from the Schneiderian surface, which frequently excoriates the cheek. The lips also are apt to be sore and swollen.

In malignant cases the disease is more protracted than when the type is mild. Thus in a recent case in my practice the rash was still distinct at the close of the second week, though the temperature had fallen from 105° to 102° and some desquamation had appeared. Long continuance of the febrile movement is, however, oftener attributable to some inflammatory complication than to the primary disease.

In all epidemics of a severe type cases now and then occur in which the poison is so intense, or it acts with such frightful energy, that death occurs even within the first day. The patient is overpowered at the outset of the disease by the virulence of the specific principle, perishing in coma, preceded perhaps by convulsions. The autopsy in such cases reveals hyperæmia of the brain and cranial sinuses, blood of a dark-red color, capillary hemorrhages in various parts, a flabby heart, and perhaps some engorgement of the spleen and kidneys.

Usually, malignant scarlet fever exhibits its severe type from the first, but cases sometimes occur which seem mild and favorable for a few days, when severe symptoms suddenly supervene. This change from a mild to a dangerous disease is, however, most frequently, I think, due to some complication.

IRREGULAR FORMS.--Deviation from the normal type in scarlet fever is usually due to some perturbating cause, which is often a pre-existing or co-existing disease, or a disordered state of system through causes distinct from the scarlatinous disease. Thus, a little girl in my practice had the symptoms of scarlet fever, such as febrile movement and inflammation of the buccal and faucial surfaces, nearly a week before the scarlatinous eruption appeared. During this time the patient had an intestinal catarrh, with diarrhoea, which declined when the rash occurred. This intestinal disease was the apparent cause of the irregularity in the malady. If scarlatina occur during a severe attack of entero-colitis attended by purging, the defluxion from the external surface may be such that no efflorescence appears. Severe scarlet fever itself sometimes appears to cause gastro-intestinal catarrh so as to produce an afflux of blood toward the intestinal tract and away from the skin. Practitioners occasionally meet cases like the following, which I recall to mind: In a family where scarlatina was prevailing a little child early after the commencement of symptoms which seemed to be plainly referable to this exanthem was seized with vomiting and purging, which continued till death {509} occurred on the third day. No efflorescence appeared upon the skin, but the symptoms indicated the presence of severe intestinal catarrh, complicating and masking scarlatina. We are aided in the diagnosis of such cases by observing the faucial redness, and we may discover a faint efflorescence upon parts of the surface, as about the groin or in the flexures of the joints. In another instance an infant in the warm months having protracted entero-colitis, the usual summer epidemic of the cities, had the characteristic symptoms of scarlet fever, which was present in the family, but the diarrhoea continued and no rash appeared.

In one who is much reduced by an antecedent disease, as phthisis, or who has a disease, chronic or acute, which produces a decided afflux of blood away from the surface and toward the interior of the body, the eruption is commonly tardy in its appearance, indistinct, or wholly absent. Thus, severe inflammations of internal organs not infrequently render scarlet fever irregular. On the other hand, some maladies occurring in connection with this exanthem do not change its symptoms, but themselves undergo modification. Pertussis may be cited as an example, the cough of which is sometimes modified by an intercurrent attack of scarlet fever, the symptoms of the latter disease undergoing little change.

Scarlet fever may also be irregular without any apparent perturbating cause. In 1867 I attended a young lady whose previous health had been good, and whose brother was sick at the time with scarlet fever. She had considerable febrile movement, with severe pharyngitis, and, though her surface was repeatedly examined, no efflorescence was seen. Two weeks subsequently she was affected with severe nephritis, anasarca, effusion into at least one of the pleural cavities, oedema of the lungs, and probably hydro-pericardium, the case ending fatally. Rilliet and Barthez state that a second attack of scarlet fever is more apt to be irregular than the first. Probably this opinion is correct, especially if only a short time have elapsed between the two seizures. Still, as we have already stated, both seizures may be typical, and the second more severe than the first.

It would be impossible to make a clear and positive diagnosis of certain cases of irregular scarlet fever, in which cerebral, pulmonary, or gastro-intestinal symptoms predominate, were it not for the fact that they occur in connection with other cases of scarlet fever or are followed by sequelæ which evidently have a scarlatinous origin.

Occasionally, the eruption, if it be intense or if a certain condition of system be present in the patient, is accompanied by more or less extravasation of blood-corpuscles from the capillaries, so that the redness does not entirely disappear on pressure, usually in points. In rare instances certain of the exanthematic fevers present an extreme hemorrhagic character, so as to be beyond the reach of remedies, and of necessity speedily fatal. Hemorrhagic cases of this severe form are probably more common in variola than in the other fevers, but I have met a notable case in what was diagnosticated scarlatina. In June, 1881, a man in his thirty-second year, whose previous health had not been good, though he had no defined ailment and had been able to follow his occupation of harness-maker, suddenly became very ill, with high febrile movement and faucial inflammation, attended by marked prostration. After some hours an intense eruption of a scarlatinous appearance covered nearly the entire surface, and on the following day hemorrhages began to occur. The urine {510} contained a large proportion of blood; each conjunctiva was raised by hemorrhages underneath (ecchymosis), so that its natural color was lost and the eyelids closed with difficulty; and blood flowed from the nostrils, gums, and under the skin, forming hemorrhagic points and blotches. One of the consulting physicians, perceiving the resemblance to hemorrhagic variola as described by Hebra, suspected that we had a case of this formidable malady to deal with, but the time for the appearance of the variolous eruption passed by without its occurrence. Death took place on the fifth day. The temperature during the sickness was high, though the record of it has been mislaid. Fortunately, such severe hemorrhagic cases, which are necessarily fatal, are rare.

COMPLICATIONS AND SEQUELÆ.--Scarlet fever, if its type be severe, is in itself dangerous to life. Many, as we have seen, perish from its direct effects when it produces profound blood-poisoning. But, while the ordinary epidemics of this malady are necessarily attended by a large mortality from the virulence and depressing effect of the specific principle, unfortunately, of all the diseases of modern times, scarlatina ranks first as regards the number and gravity of its complications and sequelæ, so that nearly or quite as many perish from these as from the direct effect of the poison.

Nervous accidents occur chiefly at two periods--to wit, in the first days, when they are due to the severity and malignancy of the malady and to the impressible nervous temperament of the child, and in the declining stage, or after the termination of the fever, when they occur from uræmia. If the type be malignant, delirium, jactitation, profound stupor, and convulsions frequently occur on the first and second days; and they are symptoms which properly excite the utmost alarm and demand all the resources of our art, since they indicate a form of the disease which is apt to end in speedy death. The eyes have a dull or wild expression, the conjunctiva is suffused, the heat of surface pungent, the pulse rapid and compressible or feeble, rising above 150, even to 200, per minute, and the temperature is always elevated to a degree that involves danger, the thermometer not infrequently indicating 105° or 106°. But this severe form of scarlet fever, attended by so great elevation of temperature, is much less dangerous than in former times, even though it be complicated by delirium and convulsions, since we no longer hesitate to reduce bodily heat, when excessive, by the free use of cold baths, and have discovered potent agents in the bromides and chloral for controlling convulsions. Nevertheless, not a few perish in the commencement of scarlet fever with predominating cerebral symptoms, as delirium or eclampsia, followed by coma, under the best possible treatment. Sometimes the symptoms have closely simulated those of acute meningitis, and if the rash have been delayed and the sore throat is as yet slight, the physician may suspect that he is dealing with this disease; but autopsies in such cases show no inflammatory lesions, but only congestion of the cerebral and meningeal vessels.

As is stated in a preceding page, in every case of normal scarlet fever inflammation of the faucial surface is present, as indicated by redness, tenderness, and increased secretion of mucus or muco-pus. It precedes the efflorescence on the skin, and is announced by pain in swallowing and on pressure with the fingers behind and below the angles of the jaw. In that form of scarlet fever which has been designated anginose the {511} pharyngitis is severe, and is a prominent element in the malady, the uvula, the pillars of the fauces, and the faucial surface in general being infiltrated and swollen. Nevertheless, this inflammation, with the accompanying tumefaction, is properly a part of the disease, rather than a complication, if it abates with the subsidence of the scarlet fever or begin to abate soon after, and if it produce but slight destructive change in the tissues of the neck. The secretions from the fauces may be foul and offensive; even superficial ulcerations or gangrene may occur upon the faucial surface, causing it to present a dark brown or jagged appearance, and the tissues of the neck may be infiltrated to a certain extent, and we designate the disease a form of scarlet fever under the title anginose. But when this condition is greatly aggravated, so that there is extensive infiltration and swelling of the tissues of the neck, with an amount of ulceration or gangrene which in itself involves danger, continuing after the primary disease abates, prolonging the fever and reducing the strength, it is proper to regard the state of the throat as a complication. In addition to the pharyngitis, which is severe as described above, the sides of the neck around the angles of the jaw become swollen, hard, and tender. The inflammation has been propagated to the deeper structures of the neck. Poisonous substances, the result of decomposition or vitiated secretions, traverse the lymphatic vessels from the faucial surface, and, being intercepted in the lymphatic glands, cause adenitis, and the inflammation extends from the glands to the adjacent connective tissue, which becomes hard, tender, swollen, and infiltrated with inflammatory products. This tumefaction sometimes begins by the second or third day, but it is usually about the close of the first week or in the beginning of the second week that it becomes so considerable as to constitute a source of danger and anxiety. It is in most cases bilateral, though one side may begin to swell before the other and remain larger throughout.

In severe cases of this complication the tumefaction extends from ear to ear, filling up the space below and around the angles of the jaw and under the chin. Not only is deglutition difficult, but it is difficult to open the mouth sufficiently to inspect the fauces, and attempts to do so cause much pain. The lymphatic glands, which lie in the inflamed area and participate in the inflammation, are greatly enlarged by hyperplasia, the round granular lymph-cells multiplying so abundantly that the glands increase to many times their normal size. Most of the tumefaction is, however, due to extension of the inflammation to the connective tissue of the neck. The cellulitis, which resembles that occurring in other conditions, is attended by distension of the capillaries, the abundant formation of young round cells, and transudation of serum (Billroth). A moderate amount of tumefaction may disappear by resolution, but if it be considerable it seldom abates in this way, but by the tedious and exhausting process of suppuration or gangrene. If the swelling at its most prominent point present a reddish hue, all hope of producing resolution must be abandoned; it cannot be effected by any medicine or appliance within the resources of our art. The abscess which forms is apt to be diffuse, so as to involve danger of pyæmia, unless it be soon opened and properly washed out. With the discharge of the pus the swelling gradually softens and declines. In other cases gangrene results. The vessels in the inflamed part are compressed by the inflammatory products, so that {512} they no longer convey the blood which is required for the purpose of nutrition. It is a law of the economy that whenever the circulation ceases, the tissues which receive their nutritive supply through the obstructed vessels lose their vitality. Hence gangrene occurs in all that portion of the swelling in which the circulation is arrested. The skin over it peels off, the dead tissue underneath is brown or dark, and soon, if life be prolonged, the slough begins to separate. The prognosis as regards this complication depends largely on the size of the slough. If it be large, death will probably result, since the strength of the system is already reduced by the primary disease, and the reparative process will necessarily be slow, while abundant suppuration tends to increase the exhaustion. In some of the worst cases of cervical gangrene which I have seen the slough has laid bare the muscles and vessels of the neck, producing in one case a cavity or excavation sufficiently large to admit a hen's egg. Often the slough extends under the skin, so that the deepest recesses of the cavity are not visible, and occasionally in cases which have ended fatally in my practice severe hemorrhage occurred from the concealed vessels. If the ulcerative or gangrenous process extends so deeply into the tissues of the neck that hemorrhages occur, death is the common result; but if the destructive action be of moderate extent and other conditions favorable, we may expect recovery through cicatrization, with perhaps some deformity by contraction of the cicatrix.

When the inflammation of the connective tissue of the neck is extensive, involving both the lateral and anterior regions of the neck, the patient is in a perilous state. The cellulitis, when extensive and accompanied by much swelling, may produce oedema of the glottis, may obstruct respiration by compressing the air-passages or the laryngeal nerves, may cause compression of the jugular veins, and thus give rise to dangerous cerebral symptoms, or may lay bare and injure important muscles and nerves, as we have seen. If the ulceration or gangrene be extensive, and death do not occur by hemorrhage from arterial or venous twigs, septic poisoning may occur, increasing still more the fatal nature of the malady.

Some cases of this complication are melancholy in the extreme, as one related by Cremen, in which ulceration of the pharynx occurred, allowing the escape of food and preventing deglutition. In severe scarlatinous pharyngitis the inflammation is apt to extend along the Eustachian tube, causing its occlusion. This accident will be considered when we treat of otitis media, another grave complication. It often also extends into the nares, causing catarrh of the Schneiderian mucous membrane, with discharge of muco-pus from this surface. Not infrequently ulceration or gangrene occurs in the faucial surface, producing more or less destruction of tissue and forming excavations which connect with the throat, while the cutaneous surface retains its integrity and is not even reddened. The following case shows how grave the complication which we are now considering sometimes is when the external surface of the neck is not involved, and how the inflammation by extension outward from the fauces may involve the middle ear.

Case 1.--Annie K----, aged two and a half years, an inmate of the New York Foundling Asylum, was well, except an eczema of the scalp, until the night of April 3, 1882, when she was attacked with vomiting and {513} diarrhoea. She was feverish and drowsy, and at 2 P.M. on the 4th the scarlatinous efflorescence appeared upon her neck, body, and lower extremities; tongue coated; pharynx red; temperature (axillary) 103°; pulse 160. The symptoms and aspect indicated a grave form of the malady, and the usual sustaining treatment was ordered. On April 5th the temperature was 102°, pulse 144, tongue less coated, eruption fading, less stupor, no albumen in urine. April 6th, morning temperature 102°, pulse 160; passed a restless night; stools thin and too frequent; has grayish patches in the throat: P.M. temperature 103-1/5°, pulse 150. April 7th, the diarrhoea continues, and she has a copious muco-purulent discharge from the nostrils; P.M. temperature 103-3/5°, pulse 160. April 10th, the temperature has continued at about 103°; the patient is very sick, with a constant foul-smelling discharge from the nostrils; breath very offensive; temperature 103.5°, pulse about 180. April 12th, general appearance a little better, but the posterior surface of the fauces is completely covered by a thick pseudo-membrane; had four loose stools last night; temperature and pulse the same as at last record; a dark, offensive, and jagged coating over the fauces, and a dark, foul discharge from the nostrils, as before; examination of the chest negative. April 14th, is much prostrated; temperature 104.5°, pulse rapid and weak; respiration noisy, diminished resonance over lower two-thirds of left side of chest; ulcers upon the mouth and tongue; fauces red and ulcerated. April 17th, pulse 150, temperature 100.5°; general appearance somewhat better, but the diarrhoea continues, and patches of a diphtheritic character have appeared upon the lips; moist râles in left side of chest. The symptoms continued nearly the same until April 23d, when she died. A dull percussion sound and distinct bronchial respiration were observed in the left scapular region during the last days of her life.

Autopsy nine hours after death by the curator, Dr. W. P. Northrup: Body well nourished; the tissues have a jaundiced hue; lips sore; on turning the head to one side pus runs from the left ear and dirty muco-pus from the mouth. Brain normal; on opening the petrous portion of the left temporal bone the middle ear is found full of pus, which communicated freely with the external ear through a perforated membrana tympani; the Eustachian tube cannot be traced in the sloughy tissue, and a passage filled with pus extends from the ear to the fauces; opposite the greater cornua of the hyoid bone are two deep ulcers, each having about the diameter of a ten-cent piece, with sloughy and offensive base and sides; the left ulcer communicates by a ragged and wide sinus with a dark and sloughy cavity of about four drachms capacity; this cavity is located in the neck under the angle of the jaw, apparently occupying the site of a disintegrated gland, and it opens upon the surface of the fauces. The surface of the larynx has a dusky, dirty appearance, sprinkled with little cheesy-looking spots, and covered by a dirty, foul-appearing liquid, as if some of the ichorous pus had escaped into it from the neck; about one and a half inches below the vocal chords there is an unmistakable pseudo-membrane; below this, near the bifurcation, the trachea has a bright-red color, as if a pseudo-membrane had been peeled from it, leaving the surface raw. The detachment of a pseudo-membrane from this part, if it did occur, must have been ante-mortem, for the organ had been carefully handled {514} in making the autopsy. Between the apex of the left lung and the median line the tissues of the neck, dissected upward, are found indurated, yellow, and giving an offensive odor, showing that the cervical cellulitis had extended downward farther than usual. The bronchial glands have undergone hyperplasia, being enlarged and hard. The right lung is normal; about one-half of the left lower lobe is consolidated, and when cut is found to be gangrenous and offensive. The liver is apparently somewhat enlarged; spleen normal in size; gastric mucous membrane has a congested appearance and is covered with mucus; mesenteric glands enlarged, pale, and firm; Peyer's patches swollen and pale; at lower end of ileum some pigmentation of these glands; in large intestine the solitary glands are enlarged, and a few of them pigmented; kidneys pale, cortex thickened, and markings indistinct. Microscopical Examination.--In the pia mater perhaps a little increase of cells; meninges of brain otherwise normal. The trachea shows well-marked diphtheritic inflammation; it contains a film of pseudo-membrane; evidences of inflammation occur also upon the laryngeal surface, though less marked than in the trachea. The solidified portion of the lung exhibits the ordinary lesions of broncho-pneumonia, with some interstitial change. In the kidneys we find parenchymatous nephritis, with some cell-growth in the Malpighian bodies.

The above case has been related at length, not only because it shows how severe and destructive the inflammation of the throat, extending into the tissues of the neck, sometimes is, but because four other complications or sequelæ were also present--to wit, otitis media, diphtheria, nephritis, and pneumonia. We see from the above case how formidable a disease scarlet fever sometimes is when attended by the inflammations to which it so frequently gives rise, for a child older and stronger than this, if thus affected, would necessarily have perished with the best possible treatment.

In localities where diphtheria is endemic, as in New York City and Paris, scarlet fever is often complicated by a pseudo-membranous inflammation of the fauces and air-passages. In severe cases of scarlet fever the Schneiderian as well as the faucial surface is covered with it, so that it can be readily seen on inspecting the anterior nares. Occasionally, the pseudo-membrane appears upon the laryngeal and tracheal surfaces, as in the case which I have related above and in others presently to be related, causing dangerous embarrassment of respiration. This complication sometimes begins almost at the commencement of scarlet fever, but in most instances it does not occur before the third or fourth day, and it sometimes does not appear till in the declining stage of the fever. When it begins, it intensifies the febrile movement and produces general aggravation of symptoms.

The common opinion is, that whenever a pseudo-membrane occurs upon the inflamed mucous surface in scarlatina true diphtheria has supervened; but there are those who hold that scarlet fever itself, when the inflammations which attend it are severe, may give rise to pseudo-membranes, so that what seems to be diphtheritic is but an element in the primary disease. My convictions are strong that when pseudo-membranes occur on any of the inflamed mucous surfaces in scarlet fever, true diphtheria has, with few exceptions, supervened if the patient live in a {515} locality where diphtheria is prevalent. That scarlet fever may occur in an individual along with another acute infectious malady is shown by abundant cases. It often occurs with varicella, and J. Herzog relates the following case, in which measles and scarlet fever coexisted:[2] A boy aged eight years had measles, with the usual catarrhal symptoms, and on the fourth day, as the temperature was returning to the normal, it rose again suddenly, and the scarlatinal rash and sore throat appeared. In due time these subsided, and desquamation occurred. I have seen a similar case in consultation during the current year, so that there is nothing improbable in the theory that scarlet fever may coexist with other infectious maladies; and it is admitted that diphtheria, like erysipelas, may complicate the most diverse constitutional diseases. Moreover, when a child with pertussis, measles, typhoid fever, or tuberculosis suddenly develops a high fever with the occurrence of a pseudo-membranous inflammation upon the fauces or air-passages, all admit that diphtheria has supervened, since such inflammation is not an element in any form or type of either of these diseases; and I see no reason in the nature of the disease why scarlet fever should not be equally liable to this complication.

[Footnote 2: Berl klin. Woch., 1882, No. 7.]

The elaborate treatise by Sanné of Paris on diphtheria contains a chapter entitled "Secondary Diphtheria." In it the author says, what all who are familiar with diphtheria will agree to, that secondary diphtheria does not differ in nature from the primary form, and that it exhibits a tendency "to occupy the organs which are themselves the seat of the more pronounced local determinations of the primitive malady.... Diphtheria is seen in the course or sequel of numerous diseases. Some appear to have a special proclivity for engendering diphtheria; these are specific maladies: measles, scarlet fever, pertussis." I have tabulated as follows Sanné's statistics of secondary diphtheria:

Cases Deaths Cures Doubtful ----- ------ ----- -------- Diphtheria complicating measles, 100 83 15 2 " " scarlet fever, 43 22 17 4 " " pertussis, 20 12 6 2 " " typhoid fever, 8 8 " " tuberculosis, 19 19

Sanné's statistics relating to the seat of scarlatinous diphtheria are as follows:

Fauces alone attacked, 15 cases. " with larynx " 4 " " " nasal fossa " 8 " " " larynx and nasal fossa " 4 " " " larynx and bronchi " 1 " " " nasal fossa and lips " 1 " " " lips and skin " 1 " " unaffected, 3 " Diphtheria generalized, 2 " Larynx only affected, 2 " Nasal fossa " 1 "

The opinion of so good an observer as Sanné, that when in scarlet fever, pseudo-membranous exudation appears upon the mucous surfaces which are the seat of scarlatinous inflammation, diphtheria has supervened, and not a croupous form of scarlatinous phlegmasia, carries with it great {516} weight. That it was diphtheria in four instances in my practice I had sufficient proof, for this disease became dissociated from scarlet fever, and extended to other members of these families as idiopathic diphtheria.

Nevertheless, one of the most difficult problems which we have to deal with in certain cases is to distinguish diphtheritic from non-diphtheritic inflammation; and I see no reason why the scarlatinous inflammation when intense may not be sometimes membranous; and those no doubt err who ignore this, and consider every inflammation attended by a pellicular exudation diphtheritic. We know that in some cases of dysentery a fibrinous exudation occurs upon the surface of the colon; that in croupous pneumonia fibrin exudes into the bronchioles and alveoli of the lungs; and that physicians in localities where there is no diphtheria meet, though at long intervals, cases which they designate croupous pharyngitis and laryngitis; and it seems to me that the intense inflammation of anginose scarlatina probably sometimes produces the same exudation. Moreover, it is very difficult to distinguish in the swollen fauces between a membranous exudation and ulceration or superficial gangrene so common in malignant scarlet fever. The grayish-white surface, jagged and foul, may be the one or the other, an exudation or a sphacelus, and in certain instances it is impossible to discriminate between the two conditions at the bedside.

Diphtheria complicating scarlet fever sometimes begins nearly simultaneously with the latter. Henoch states that exceptionally he has observed suspicious patches upon the fauces before the appearance of the scarlatinous eruption upon the skin; and he adds: "I have had repeated opportunities of observing this unusual beginning. In such cases we must ask ourselves whether the first affection was really connected with the second, or whether the former was a true primary diphtheria, rapidly followed by scarlatina. This opinion is favored by the fact that I have only observed such cases in the hospital, in which infection with various forms of contagion can scarcely be avoided."

But usually it is not till the third or fourth day of scarlet fever that this complication begins. The patient has been progressing favorably with the scarlet fever, till on a certain day a marked aggravation of symptoms occurs. A higher temperature, more pungent heat, and the physiognomy of a more serious malady are present. On inspecting the fauces to discover the cause we observe a pellicle forming over the tonsils and perhaps other portions of the faucial surface. Often the entire aspect of the case changes by the occurrence of this complication, a mild case of scarlet fever becoming grave and fatal in consequence. Thus in a case which I saw with Dr. Hardy of New York the membranous inflammation of diphtheria, commencing upon the fauces on the third day of scarlet fever, extended to the Schneiderian membrane, and thence along the left lachrymal sac to the eyelids, producing redness and swelling along the side of the nose and upon the cheek like that of erysipelas. A thick diphtheritic pellicle occurred upon the under surface of each eyelid on the left side, with great tumefaction of both lids, gangrene of the cornea, and destruction of the eye. The case soon ended fatally.

The diphtheritic inflammation sometimes extends to the larynx and trachea, producing hoarseness and more or less obstruction to {517} respiration. A thin film or flakes of fibrinous exudation, rendering the respiration noisy, developed on the laryngeal or tracheal surface, is, I think, not infrequent in diphtheria complicating scarlet fever, but the rapid development of a thick and firm pseudo-membrane, so as to imperil the life of the patient from the stenosis in the air-passages, has been much less frequent in my practice than it is in primary diphtheria and in diphtheria complicating measles or pertussis. The following were cases of this severe complication occurring in a recent epidemic in the New York Foundling Asylum. In these cases the respiration was noisy, but the obstruction to breathing seemed to be due to infiltration and swelling around the aperture of the glottis, rather than to diphtheritic croup, which the autopsies showed to be present.

Case 2.--A child aged three and a half years, who previously had symptoms of mild catarrhal croup, with moderate redness of the fauces, sickened with scarlet fever on Oct. 1, 1882, the rash being profuse and soon covering nearly the entire body. The axillary temperature was 103°, pulse 140; slight stridor in breathing and some cough; fauces very red, but free from membrane. Oct. 2d, restless, sleeping but little; has vomited four times. Oct. 3d, temp. 103.5°, pulse 120; fauces much swollen; still vomiting; rash abundant. 4 P.M., temp. 104.3°, pulse 128; tongue clean; some discharge from nares; urine not albuminous, but its quantity diminished. Oct. 4th, aspect that of very severe sickness; profuse discharge from nostrils; fauces of a deep red color, and a diphtheritic pellicle over tonsils and uvula; tumefaction along the sides of the neck; temp. 104°, pulse 140; breathing moderately stridulous; urine is passed more freely than yesterday; evening temp. 105°. Oct. 6th, croupy symptoms more marked; tonsils and uvula greatly swollen, so that the fauces are almost occluded; temp. 103.5°; breathing difficult, but apparently sufficient oxygen is received; profuse nasal discharge, and other symptoms as before. About 1.30 P.M. he was raised to take some milk, and suddenly became asphyxiated. His face was dusky, his eyes protruded, and he voided urine and feces. Dr. Swift, who attended the child, and to whom I am indebted for this history, immediately performed tracheotomy, which gave temporary relief by the expulsion of a considerable quantity of pseudo-membrane through the opening. On the following day the respiration again became obstructed at some point below the canula, so that it could not be removed; the features grew livid, and death occurred in convulsions twenty-six hours after the tracheotomy.

The autopsy was made by Dr. W. P. Northrup, curator of the asylum, who found the pharynx covered by a membrane which was traced to the posterior nares; larynx, trachea, and bronchial tubes as far as the third divisions also covered with membrane; portions of the tracheal surface denuded, and the mucous membrane underneath of a bright red color and smooth; tonsils sloughy and fetid; mucous membrane of smaller bronchial tubes very red and covered with viscid mucus and pus; a portion of the left lung, extending from the root posteriorly to the surface, gangrenous, discolored, and honeycombed; two or three intensely hyperæmic spots, as large as a bean, in left lung; right lung congested, but not consolidated; slight catarrh of stomach; circumscribed areas of congestion in intestines; solitary glands of intestines swollen, and some {518} of them ulcerated; spleen of normal size, rather pale; liver congested and somewhat enlarged.

Case 3.--Katie, aged six and a third years, was returned to the asylum on Nov. 18th. Three days later (Nov. 21st) she had sore throat, reddened fauces, coated tongue, and a faint rash upon the neck, chest, and arms; eyes injected; temperature 102°. In the afternoon temperature 103°; eruption still faint. Nov. 22d, temperature 103.5°; an eruption on chest, abdomen, arms, and legs in patches. Evening, temperature 104°; voice clear. Nov. 23d, temperature 103.5°; tongue red; fauces deeply reddened, but without any visible pseudo-membrane; eruption of a scarlatinous appearance over the back and abdomen; on the extremities dusky, livid patches. P.M., temperature 104°; is slightly delirious; eruption abundant. Nov. 24th, temperature 103.5°; eruption well out on abdomen; it is the same as yesterday upon the extremities, except perhaps a little more dusky; still no pseudo-membrane to be seen upon the fauces; is restless and delirious. P.M., during the day has been very restless, suffering from dyspnoea; no croupy voice nor croupy cough, though the dyspnoea continues, and a pseudo-membrane is now visible over the tonsils and adjacent faucial surface; eruption dusky; skin cool; pulse very frequent and feeble. From this time she sank steadily, and died at 11.30 P.M. During her sickness her urine seemed to be diminished, but it was not properly examined.

Autopsy Nov. 25th by Dr. W. P. Northrup, curator: Points of redness, apparently a hemorrhagic eruption, over the face, shoulders, and parts of the trunk; a few of the same on the extremities; no pseudo-membrane visible in nostrils or in buccal cavity; brain not examined. Naso-pharynx covered by a thick fibro-purulent membrane. Larynx contains a well-marked pseudo-membrane, but not continuous. Trachea covered by a pseudo-membrane, continuous over most of its surface, but in places broken and flaky. Where it is detached the mucous membrane is seen underneath, dusky and deeply injected. At the root of the lungs the pseudo-membrane can be traced along the tubes about an inch in all directions. Lungs oedematous, with deep congestion in places, but apparently no pneumonia; about two drachms of clear, straw-colored fluid in pericardium; a few stringy decolorized clots in the cavities of the heart; left ventricle contracted. The heart-fibres, carefully examined, microscopically, in the laboratory, are found to be normal, not having undergone granular or fatty degeneration. Liver normal in size; pale-yellow areas upon the superior surface, either from anæmia or fatty deposition. Kidneys of usual size, capsule not adherent; pyramids congested; cortex pale; markings distinct. Spleen enlarged about one-third; consistence normal. Stomach and intestines not examined.

Case 4.--Scarlet fever complicated by diphtheria, nephritis, and broncho-pneumonia. (History by house physician, Dr. Swift.) Phoebe, aged three and a quarter years, was delicate, but in her usual health till Oct. 29, 1882, when she became languid and vomited several times, and her tongue was coated. Oct. 30th, occasional vomiting; fauces reddened; tongue coated. Oct. 31st, remains languid; fauces deeply reddened; a faint scarlatinous eruption over back, wrists, and feet; temperature 100.5°. P.M., eruption of scarlet fever well out over the surface; tongue cleaner. Nov. 1st, {519} rash over entire body; temperature 100.2°. Nov. 2d, fauces deep-red; tonsils and uvula swollen; diarrhoea and vomiting. Nov. 3d, temperature 102.5°; the eruption, which has been bright red, is now more dusky. Nov. 5th, temperature 104.5°; dusky-red color of the eruption; skin beginning to desquamate in places; urine normal; a discharge from nostrils. Nov. 6th, temperature 103.5°; eruption still present, but skin of abdomen and back desquamating; has otorrhoea on both sides; fauces deeply hyperæmic, but no pseudo-membrane visible upon them. Nov. 7th, temperature 103°; respiration and cough have a slight croupy character; other symptoms as yesterday. Nov. 8th, temperature 101°. A careful inspection of the fauces shows that it contains no pseudo-membrane; nostrils discharging a dark-brownish liquid; examination of urine negative. Nov. 11th, eruption, which appears to have been hemorrhagic in points, is fading and the desquamation is less. Nov. 14th, nostrils still discharging; glands of neck swollen. Nov. 16th, temperature 103°; sp. gr. of urine 1010, no casts, nor albumen; the chest seems clear; less discharge from nostrils; fauces clean and but slightly inflamed. Nov. 17th, 18th, temperature 103.5°; vomits; lungs healthy, but breathes with considerable effort, though without stridor; urine diminished; its sp. gr. 1020, albuminous, contains blood-corpuscles and granular casts. Nov. 19th, is very pallid; temperature 104°; very restless; vomits; urine diminished; bowels freely open. Nov. 20th, respiration still embarrassed; subcrepitant râles over the entire chest and percussion resonance not clear; temperature 102.5°. Nov. 21st, physical signs the same; temperature 103.5°; respiration 80. Nov. 22d, urgent dyspnoea; dulness on percussion over top of right lung and over lower part of left lung; is delirious; no perspiration; urine scanty; bowels freely open. From this date the dyspnoea became more urgent, and death occurred at 4 P.M. on the 23d.

Autopsy by Dr. W. P. Northrup, curator: Body well nourished; slight oedema of both legs; swelling at angles of jaws, most marked on left side. Vessels of brain moderately injected; otherwise appearance normal. Cicatrizing ulcers on both sides of fauces; a diphtheritic pseudo-membrane on septum of nose, larynx normal. Trachea, upper half apparently normal; a thin film of pseudo-membrane extends from just above the bifurcation upward to nearly the middle of trachea. About an ounce of fluid in each pleural cavity; on the right side a few loose flakes of fibrin floating in the serum, and consolidation of lung at apex; collapse in one or two places. Left side, recent adhesions over whole of posterior surface and base; surface of lower lobe dark, and when it is detached strings of fibrin adhere to it, and it is consolidated. The cut surface shows marked oedema, injection, increase of mucus in bronchi, and disseminated miliary tubercles in every part; no tubercles in the pleura, and none elsewhere in the body except in the left lung; tubercles in the lower lobe larger and more thickly grouped than in the upper lobe. Decolorized clots in heart, extending from ventricles into auricles of both sides. The capacity of the ventricles seems normal. Liver and spleen, normal. Kidneys rather large; capsules not adherent; superficial veins injected. The cut surface shows congested pyramids and pale cortex; markings indistinct and irregular; about four ounces of clear straw-colored fluid in abdominal cavity, and the solitary follicles of {520} large intestines show pigmentation; two simple intussusceptions, each three-fourths inch in length, in small intestines.

Coryza frequently commences at or about the time of the pharyngitis. The inflammation of the Schneiderian membrane is continuous posteriorly with that of the fauces, and is announced by redness and swelling, inability to breathe freely through the nostrils, and an irritating ichorous discharge. Simple coryza in itself involves little danger, though it is an unpleasant complication, and in the nursing infant it may interfere with sucking. Diphtheritic coryza, on the other hand, which is frequently present when diphtheria complicates scarlet fever, involves danger, since it is apt to cause ulcerations, hemorrhages, and septic poisoning. When the local symptoms are unusually severe and the discharge abundant, it is probable that inflammation has in some cases extended to the antrum of Highmore.

Inflammation of the middle ear is another unpleasant and not infrequent complication. It is attributed to extension of the catarrh from the pharynx along the Eustachian tube to the tympanum. In a considerable proportion of cases of otitis media this tube is occluded by the infiltration and swelling of its mucous membrane, so that the muco-pus escapes with difficulty or is retained. Hence severe earache, an increase of the febrile movement, and outward bulging of the membrana tympani occur. Sometimes headache or other cerebral symptoms arise, probably from the fact that the meningeal artery, which supplies the meninges, is connected by anastomosing branches with the tympanum. In one of the cases related above it will be recollected that the ulceration and abscess extended from the fauces to the middle ear, the entire Eustachian tube having disappeared in the ulcerative process.

Frequently, the otitis escapes detection, its symptoms being masked or obscured by the general disease, until the membrana tympani is perforated and otorrhoea begins; but by careful examination the nature of the complication can usually be ascertained before the ear is injured to this extent, for a patient too young to speak will often press with the fingers against the painful ear or lie with the ear pressed upon the pillow, evidently having an increase of suffering if placed in any other position. One old enough to speak and in proper mental condition makes known the earache as soon as it occurs.

The mucous membrane of the tympanum, red and swollen from inflammation, secretes muco-pus abundantly; and this, pent up in the cavity, must obtain an exit before relief occurs. It is well if this secretion escape, though with difficulty, down the Eustachian tube. The destructive action of the pus upon the delicate structure of the ear is often such that, within a few days, irreparable harm is done and more or less deafness results. Relief can occur, if the Eustachian tube remain closed, only by perforation of the membrane and the discharge of the secretions into the external meatus. When this occurs the inflammation in the most favorable cases gradually abates, the aperture in the drum closes, and the integrity of the auditory apparatus is preserved. In severe cases the mastoid cells participating in the inflammation become filled with muco-pus and tender to the touch, and often the collateral oedema causes tumefaction and narrowing of the external ear, which subside with the discharge of pus from the tympanum.

{521} Unfortunately, there is for many a more melancholy history--a more destructive inflammation, involving permanent impairment or total loss of hearing. This is especially apt to occur in strumous and feeble children. All grades of inflammation and destructive action occur in different cases. The perforation in the drum-membrane may be large or the membrane may be completely destroyed, and the detached ossicles escape one by one into the external meatus, and in a few instances, fortunately rare, this occurs in both ears, producing complete and permanent deafness. In my own practice this has never occurred, but I have met one or two adults who were totally deaf from this cause.

The mucous membrane which lines the bony wall of the middle ear has the function of the periosteum, and therefore, when inflamed and subjected to pressure, is liable to ulcerate. As in other parts of the skeleton under similar conditions, superficial caries or necrosis of the underlying bone is apt to occur. The carious or necrotic process may extend to the mastoid cells. An offensive otorrhoea, continuing for months or years, indicates the persistence of this pathological state of the tympanum, which is rendered so obstinate by the presence of dead bone. A moment's survey of the anatomical relations of the middle ear shows the danger to which these patients are liable. A thin bony septum, perforated with blood-vessels and sometimes containing congenital apertures, separates the tympanum from the cranial cavity above. Posteriorly lie the mastoid cells, connected with the tympanum by one large and several small apertures. Anteriorly is the commencement of the Eustachian tube and in close proximity to the tympanum lies the carotid canal, and at one point also the superior petrosal sinus. Virchow has shown how inflammation extending from the ear in otitis media sometimes produces such compression of the veins or sinuses by the swelling from the infiltration and exudation that the circulation is arrested, and the fibrin contained in the blood of these vessels is precipitated, forming thrombi, with the most disastrous effect upon the individual. Pus may also burrow in the interstices of the bone, causing great pain, or the pent-up secretions, having no outlet for escape, may in time undergo caseous degeneration, producing the conditions in which tuberculosis so often originates.

Death not infrequently occurs in chronic otitis media in another way. The otorrhoea, after months or years, suddenly ceases, the child complains of constant severe headache and is feverish, and the case ends in coma, preceded perhaps by convulsions. Meningitis has occurred, produced by extension of the inflammation through the thin bony septum which divides the tympanum from the cranial cavity, and at the autopsy hyperæmia of the meninges, fibrin, pus, perhaps softening of the brain and an abscess, are formed in the portion of the encephalon adjacent to the tympanum. Therefore, otitis media, though it often ends favorably, is in many patients an obstinate, dangerous, and even fatal sequel of scarlet fever.

The complication known as scarlatinous rheumatism is regarded by some as a synovitis, but its symptoms, especially its shifting from joint to joint, seem to ally it to the rheumatic affections. In some epidemics it is common. It usually begins toward the close of the first week or in the second week, and its common seat is in the ankle, phalangeal, and wrist joints. It is attended by very little swelling in {522} most patients, though the joints are tender and painful on pressure. It does not seem to retard convalescence materially, though it produces suffering and involves danger as regards the heart. It subsides in a few days with the ordinary treatment of acute rheumatism, and even without special treatment, the chief danger being that, as in idiopathic rheumatism, endocarditis may arise, with permanent crippling of the valves. The following was a case of valvular disease having this origin. It occurred in my practice.

Case 5.--Freddy M., aged four years, sickened with scarlet fever March 6, 1879. The usual vomiting occurred on the first day, and the temperature was 104°. The case progressed favorably till March 14th, when he complained of pain in both wrists, both ankles, and both knees. On March 17th the general condition was good, the urine contained no albumen, and apparently few urates, but he still had pain in the joints of the upper and lower extremities and in the back; pulse 140, temp. 103°; breathes with a slight moan; urates in the urine, but no albumen. A distinct mitral regurgitant murmur is now heard for the first time. Under the use of salicylate of sodium the pain in the joints soon ceased, but the mitral murmur is permanent.

The following prescription is for a child of five years:

Rx. Ol. Gaultheriæ fl. drachm iss; Sodii Salicylat. drachm iii; Syrupi fl. oz. ii; Aquæ fl. oz. iv. M.

S. Give one teaspoonful every four hours.

Of the serous inflammations occurring in scarlet fever, pericarditis has been, according to Rilliet and Barthez, most frequently observed. In this country it is probably more frequent than is usually supposed, but it is less frequently detected than pleuritis, the symptoms of which are more conspicuous. It is apt to occur in connection with endocarditis.

The following case, showing the liability to pericarditis and other serous inflammation which exists in scarlet fever, occurred in my practice:

Case 6.--C----, girl aged five years and ten months, sickened with severe scarlet fever on April 4th. Was delirious; pulse 158; had vomiting and constipation. April 10th, pulse varies from 124 to 153, no delirium; a considerable quantity of urates in the urine. April 11th, has to-day, for the first time, severe pain in the epigastrium, with tenderness and moderate distension. Otherwise symptoms favorable, but severe; pulse 140; respiration moderately accelerated, and vesicular in every part of the chest. From this date the symptoms continued about the same till April 14th, when the dyspnoea became more marked and the action of the heart rapid and tumultuous. The epigastric pain, distension, and tenderness continued; the percussion sound was dull over the lower part of the chest; the dyspnoea became rapidly worse, although the pulse had considerable volume; and at 5 P.M. death occurred. At the autopsy about one ounce of turbid serum, with a soft deposit of fibrin, was found in the pericardium. Each pleural cavity contained from six to eight ounces of transparent serum, and both lungs were readily inflated, except a little of the posterior portion of each lower lobe, which could not be; no fibrinous exudation over the lungs. The liver extended four inches below the margin of the ribs, and upon its convex {523} surface in the epigastrium, corresponding with the seat of the pain, was a rough patch of fibrin about one and a half inches in diameter. The bronchial mucous membrane was moderately injected, as was also that of the colon, and the kidneys appeared hyperæmic.

Among the serous inflammations which complicate or follow scarlet fever, pleuritis is one of the most important. It usually begins in the desquamative stage, and is apt to be suppurative on account of the feeble state of the patient when it commences. It has always, in my practice, been tedious, as all empyemas are, and it does not differ in its clinical history from the idiopathic disease. I have met cases of scarlatinous empyema in which, from opposition of the family or for other reasons, thoracentesis was not performed, and death occurred; others in which this operation effected a cure, and one at least in which the patient recovered by escape of pus through a bronchial tube. The pleuritis is seldom latent, or so masked by the symptoms of the general disease that it is apt to be overlooked. On the other hand, the cough, embarrassment of respiration, and pain referred to the affected side render diagnosis easy.

Dilatation of the heart is common in grave cases of scarlet fever, such cases as are properly termed malignant. It is indicated by a feeble and quick pulse. Acute infectious maladies, especially those of a malignant type and accompanied by high febrile movement, are very apt to cause parenchymatous degenerations in organs, prominent among which is granulo-fatty degeneration of the muscular fibres of the heart. This weakens very much the contractile power of these fibres. But early in malignant cases, probably before the muscular fibres are damaged, the contractile power of the heart is feeble from impaired innervation, the result of the general weakness. Hence this organ, when weakened by structural change and insufficiently stimulated through diminished innervation, may not fully empty itself during the systole, and consequently it becomes dilated. Dilatation of the heart and imperfect contraction of the auricular and ventricular walls are apt to result in the formation of clots in the cavities of the heart; and this appears to be the immediate cause of death in not a few instances. An ante-mortem clot occurring in any of the cavities of the heart necessarily seriously obstructs the circulation, unless it be of small size. Hence the dyspnoea, which may occur perhaps suddenly, and the change of pulse to one of marked feebleness and frequency. Large, firm white clots are most frequently found in the right cavities. They interlace with the chordæ tendineæ, lie even within the auriculo-ventricular opening, and send prolongations into the pulmonary artery and the cavæ. Associated with the white clots are dark, soft clots and fluid blood. The left cavities may be contracted and empty, or they may contain dark, soft clots or white ante-mortem clots. Clots in the left ventricle are sometimes prolonged into the aorta as far as the brachio-cephalic branches, while those in the left auricle may extend to the pulmonary veins. If dilatation of the heart be so great that clots form in its cavities, speedy death is probable. Sometimes a patient passes through scarlet fever and appears in a fair way to recover, when he succumbs to some exhausting sequel distinct from the heart, and at the autopsy the heart is found dilated and containing whitish clots, which are probably ante-mortem, and which hastened {524} death by obstructing the circulation. Under such circumstances this state of the heart is attributable in great measure to the complication which has weakened its contractile power.

The following was a case in point. It occurred in the New York Foundling Asylum:

Case 7.--R. A., aged three years, had scarlet fever, beginning March 23, 1882. The symptoms were favorable at first, but serious complications and sequelæ occurred, which were fatal. The record of April 18th reads: "Appears well nourished, but is anæmic; has otorrhoea; no oedema; skin desquamating; dulness on percussion over upper third of right side of chest, anteriorly and posteriorly; mucous râles and rude breathing over same area; fine râles posteriorly over lower part of left side of chest; pulse 160, respiration 68, temperature 101-2/5°." April 20th, is feeble and takes nutriment with difficulty; tongue thickly coated; pulse 160, respiration 68, temperature 101-2/5°. April 26th, condition about the same as at last record, but he is evidently weaker; the lips are ulcerated and fauces still swollen. May 2d, cannot speak distinctly; a brownish, foul-smelling secretion lodges on the spoon used in depressing the tongue; left side of face swollen. On the following night eight convulsions occurred, attended by orthopnoea, and mucous râles in the chest from pulmonary oedema. Diarrhoea supervened and the patient died about midnight. Autopsy: Body moderately wasted and very white, several dark-blue spots on scalp and face from hemorrhages underneath; lips covered with dry crusts; brain of normal appearance; aperture of the larynx narrowed at the chink by infiltration and swelling of the tissues; surface of the vocal cords covered by a thin white film, apparently a fibrinous exudation; tracheal surface hyperæmic; about a drachm of straw-colored fluid in each pleural cavity; right lung wholly adherent by recent exudation of fibrin; left lung also largely adherent. A careful examination showed the presence of broncho-pneumonia in each lung, with considerable infiltration of the walls of the bronchi, and cylindrical dilatation of many of them; cavities of the heart dilated, so that this organ appears much enlarged, and its shape approaches the globular; its apex is rounded or obtuse; transverse diameter of the right ventricle, when its walls were open and drawn apart, was three and one-quarter inches; that of the left ventricle three and a half inches. Similar measurements of the heart of another child of about the same age, believed to be normal, were about one inch less in each direction. All the cavities contain white firm clots along with soft dark clots. Liver of normal size, pale; the outer surface and all cut surfaces are studded with nodules of the size of a pin's head, of a dull, opaque white color. These white spots, examined microscopically by Professor Delafield, are found to be neither tubercles nor gummy tumors, but to consist of polygonal cells, lying in the meshes of the capillary plexus of veins, which are perfectly preserved. He has not observed a similar case. The walls of the gall-bladder are one line or more in thickness, and the gall-duct is pervious. The microscope shows general hypertrophy of the gall-bladder and hypertrophy of its papillæ. The urine removed from the bladder was found to contain albumen and hyaline casts, and a microscopic examination showed a small amount of parenchymatous inflammation. The spleen was somewhat enlarged. Punctate congestion of small areas of {525} gastric surface, no increase of mucus; mesenteric glands uniformly enlarged; jejunum, ileum, and colon exhibited a slightly increased vascularity. The immediate cause of death appeared to be imperfect contraction of the heart and the formation of clots in its cavities, due, apparently to the pleuro-pneumonia as much as, or more than, to the primary disease, scarlatina.[3]

[Footnote 3: Dr. Goodhart (Guy's Hospital Reports, 1879) reports several interesting cases to confirm his opinion that acute dilatation of the heart is a not infrequent sequel of scarlatinous nephritis, and is the cause of death in some apparently inexplicable cases.]

There can be little doubt that nephritis in its milder form is much more common than was formerly supposed. A few years since little attention was given by a large proportion of physicians to the state of the kidneys, and the urine was not examined till dropsy made its appearance, which only occurs in the more severe forms of nephritis and is a late symptom. It is now known that catarrh of the renal tubes frequently occurs in a mild form early in scarlet fever, without causing albuminuria, dropsy, or any notable symptom. It may produce a smoky color of the urine, and the appearance in it of granular epithelial cells, with an increase of mucus, but no albumen. With careful treatment and no exposure to cold, the renal catarrh abates with the decline of the scarlet fever. It is scarcely severe enough to merit the name desquamative, tubal, or parenchymatous nephritis, though it is a mild form of the same pathological state. Steiner states, as the result of many careful examinations of cases, that hyperæmia of the kidneys was always present in those who died early in scarlet fever, and that in a certain proportion of these cases catarrh of the renal tubules was present in addition to the congestion. Even in some who died on the second or third day he found cloudiness of the epithelium in the renal tubes, although the urine had not indicated such a change. The opinion has even been expressed that catarrh of the renal tubes is as common in scarlet fever as that of the bronchial tubes in measles; that is, that it is a uniform element in the disease; but this appears to be an exaggerated statement, for others have failed to find any evidence of renal catarrh in certain cases.

The nephritis which gives rise to symptoms, and therefore interests the practitioner, commonly begins in the declining period of scarlet fever or during the desquamative stage, and is in many instances plainly attributable to exposure to cold or to currents of air. It originates either during this period, or, if it have previously existed as a mild renal catarrh, it now becomes aggravated. Dropsy, which always attracts attention, does not occur till the nephritis has continued for some time.

Why nephritis, with the subsequent dropsy, so frequently occurs after scarlet fever is not fully understood. Rilliet and Barthez attribute it to disturbance of the function of the skin. The fact has long been observed that the kidneys become affected nearly if not quite as frequently after mild as after severe cases. Indeed, the chief danger in mild cases, when the patients are but a short time in bed and are soon allowed to go about, is from the nephritis. Chilling the surface and checking cutaneous transpiration appear to be the immediate cause of this inflammation in a considerable proportion of cases. Therefore, severe attacks of scarlet fever with abundant rash and desquamation, which require the patient to be kept in bed the proper time and in a warm room two or three {526} weeks, appear to be less frequently followed by this renal disease than are milder cases which are more carelessly treated.

The most thorough and minute microscopic examination of the state of the kidneys in scarlet fever which have come to my notice were those by E. Klein, published in the Lond. Path. Soc. Trans., and illustrated by microscopic drawings. It appears from these examinations that the changes in the kidneys are complex, among which we recognize both those of parenchymatous or desquamative nephritis and interstitial nephritis; but we would infer that the interstitial nephritis is mild in degree and quite subordinate, or else confined to portions of the organ, from the fact that so many permanently and fully recover. The following is a resumé of Klein's examinations in twenty-three cases: We conclude from these microscopic researches that the anatomical changes of both parenchymatous and interstitial nephritis are commonly present in greater or less degree in cases of scarlet fever. If they are mild or confined to portions of the kidneys, no symptoms occur; but if they are sufficient in extent or degree to impair the function of these organs, then symptoms, as albuminuria, diminution of urine, etc., appear.

1. Parenchymatous Nephritis, Proliferation of Nuclei, Hyaline Degeneration of Arterioles, the Glomerulo-Nephritis of Klebs.--Klein found increase of nuclei (probably epithelial) upon the glomeruli and hyaline degeneration of the intima of minute arteries, especially marked in the afferent arterioles of the Malpighian bodies. The intima of these vessels was in places so swollen as to resemble cylindrical or spindle-shaped hyaline masses, and cause narrowing of the lumina of the vessels in which this degeneration occurred. Klein observed in some specimens so great hyaline degeneration of the capillaries of the Malpighian bodies that circulation through them was obstructed. In the more advanced or protracted cases this hyaline substance in the glomeruli began to assume a fibrous appearance. Bowman's capsule was considerably thickened. This hyaline degeneration of the Malpighian bodies Klein discovered in the earliest cases which fell under his observation.

Also in the earliest cases the multiplication or germination of the nuclei of the muscular coat of the arterioles was observed, with a corresponding increase in the thickness of the walls of these vessels. This change in the muscular element was observed in the arterioles in different parts of the kidney, but it was most conspicuous in arterioles at their point of entrance into the Malpighian bodies; and it was distinctly observed in other arterioles, both in the cortex and in the base of the pyramids.

In the glandular portion of the kidneys other anatomical alterations were observed, indicating parenchymatous nephritis. There were swelling of the epithelial lining of the convoluted tubes; multiplication of nuclei of epithelial cells, especially in ascending tubules, which lay close to the afferent arterioles of Malpighian corpuscles; granular matter, and even blood, in the cavity of Bowman's capsule and in the convoluted tubes; cloudy swelling and granular disintegration of epithelium in some parts of the convoluted tubes; detachment of epithelium from the membrane of larger ducts of the pyramids in some cases. These parenchymatous changes are already known to the profession through the observations and writings of Dickinson, Fenwick, Johnson, John Simon, and others.

{527} Klein, in commenting on the hyaline degeneration which he observed, states that Neelsen found the walls of the capillaries of the pia mater thickened, highly refractive, and of a lardaceous appearance in certain acute infectious maladies, as variola, typhoid fever, measles, and in one case of scarlet fever.[4] Usually, only a small portion of the capillaries were thus affected, most frequently at the point of division into branchlets. In a few instances Neelsen observed degeneration of arterioles extending a considerable distance, with fusion of the intima, media and adventitia, and chemical examination showed that the substance produced by this degeneration had similar properties to elastic tissue. Although the examinations by Neelsen relate to the pia mater, two of his observations are especially interesting--first, that the hyaline change affects chiefly vessels near their point of branching; and, secondly, that the hyaline substance is of the nature of elastic tissue, for in the kidney in scarlatinous nephritis the arterioles undergo the change in question chiefly near their point of branching into the capillaries of the glomerulus; and the intima being the part which undergoes the hyaline change, it is probable, in the opinion of Klein, that the same substance is produced by the degeneration in walls of the vessels of the kidney which Neelsen observed in the pia mater, and therefore that it is of the nature of elastic tissue.

[Footnote 4: Archiv der Heilkunde, 1876.]

This hyaline degeneration of the arterioles is also very marked in the spleen in scarlet fever; and in studying the minute anatomy of the intestines and spleen in typhoid fever Klein has found the same degeneration of the intima of the minute vessels. He believes that this hyaline change and the proliferation of muscle-nuclei which thus occur at an early period in scarlet fever in the renal vessels when the kidneys become affected are due to an irritating cause acting similarly to that in typhoid fever.

Klein calls attention to the interesting examinations of the scarlatinous kidney made by Klebs, who attributed the diminished urination and the uræmic poisoning in certain cases in which the kidneys do not exhibit any marked change to the naked eye, to what he designates glomerulo-nephritis. Klebs says: "In the post-mortem examination the kidneys are found slightly or not at all enlarged, firm, ... the parenchyma very hyperæmic. Only the glomeruli appear, on close inspection, pale like small white dots. The urinary tubes are often not changed at all. Occasionally the convoluted tubes are slightly cloudy. The microscopic examination shows that there are neither interstitial changes nor proliferation of epithelium, the so-called renal catarrh generally supposed to be present in these conditions on account of the absence of other perceptible derangements; and there seems, therefore, leaving out the glomeruli, the congestion of the kidneys alone to remain to account for the symptoms during life." But that mere congestion is insufficient to produce the symptoms appears from the fact that it does not produce them under other circumstances. Klebs finds, "on microscopic examination of the glomerulus, the whole space of the capsule filled with small somewhat angular nuclei, imbedded in a finely granular mass. The vessels of the glomerulus are almost completely covered by nuclear masses."

Klein, commenting on these examinations by Klebs, states that in all {528} early cases which he examined he observed great abundance of nuclei of the glomeruli, but a condition like that described and figured by Klebs[5] he has seen in only a few glomeruli; for a general state of these bodies, as described by this observer, and such an excessive proliferation of the nuclei that the blood-vessels are completely compressed, was not seen in one of the twenty-three cases. Klein therefore questions whether the diminished urination and retention of urea in scarlet fever, when the kidneys do not exhibit any conspicuous catarrhal or other change, is due, unless in exceptional instances, to compression of the vessels of the glomeruli by nuclear germination, but believes, rather, that the obstructed circulation, and consequent diminished urinary excretion, is largely due to the changed state of the arterioles. Klein adds that perhaps undue contraction of the arterioles, through stimulation by the blood-irritant, may also be a factor in causing arrest of circulation in the Malpighian corpuscles. As regards cases that perished early, he found the parenchymatous change slight, so that a careful examination was required in order to detect cloudy swelling and granular degeneration.

[Footnote 5: Handbuch der Pathol., p. 646, fig. 72.]

2. Interstitial Nephritis.--A second set of changes Klein observed in cases that died on about the ninth or tenth day. In such cases he found changes due to interstitial, in addition to those produced by parenchymatous, nephritis. Round cells, lymphoid cells, or whatever else they should be called, were seen in the connective tissue of the kidneys. In the kidneys of those that died at the end of the first week after the commencement of nephritis, infiltration with round cells was observed in the connective tissue around the large vascular trunks. At a later stage this infiltration had extended into the bases of the pyramids and into the cortex. The gradual increase in extent and intensity of this infiltration was so decided in the cases which Klein observed that he has no hesitation in concluding that when interstitial nephritis occurs it begins about the end of the first week, in the manner already stated--to wit, as a slight infiltration of the tissue around the large vascular trunks, and gradually extends, so that portions of the cortex, and rarely portions of the base of the pyramids, are changed into firm, pale, round-cell tissue, in which the original tubes of the cortex become lost.

The infiltration of the cortex with round cells, beginning at the roots of the interlobular vessels, spreads rapidly toward the capsule of the kidney, and laterally among the convoluted tubes around the Malpighian bodies.... In the course of this process considerable parts of the peripheral cortex, occasionally of a more or less distinctly cuneiform shape, with the base nearest the capsule of the kidney, become changed into whitish, firm, bloodless, cellular masses, in which Malpighian corpuscles and urinary tubes are only imperfectly recognized, being more or less degenerated. In some cases attended by this infiltration of the cortex Klein observed a more or less dense reticulation of fibres, especially around the interlobular arteries, containing in its meshes lymph-cells, chiefly uninuclear.

In a child of five years that died after a sickness of thirteen days Klein found evidence of intense interstitial inflammation, and also emboli, consisting of fibrin with a few cells, in the arteries, both in those of large size and in the arterioles, chiefly where they enter the Malpighian corpuscles. {529} He states that in the specimens which he examined the more intense the degree of interstitial change, the greater was the enlargement of the kidneys, and the more distinct also were the evidences of parenchymatous nephritis in the urinary tubes, which either contained casts or were in the process of destruction. By being crowded with inflammatory products, especially cells, the Malpighian corpuscles were obliterated, undergoing fibrous degeneration. A very curious fact observed was the deposit of lime in the urinary tubes, first of the cortex, and then also of the pyramids, at an early stage of scarlet fever, when the kidneys otherwise showed only slight change. Several observers, as Biermer, Coats, and Wagner, have each described a case of scarlet fever with interstitial nephritis, which they consider unusual; but Klein has apparently demonstrated, as we have seen, by a large number of microscopic examinations, that this form of nephritis is common after the ninth or tenth day.

Nephritis, in proportion to its extent and gravity, is accompanied by languor, febrile movement, thirst, loss of appetite and strength. At first the patient experiences but slight pain in the head or elsewhere, and the quantity of urine is not notably diminished; but as the disease continues urination becomes less frequent and the urine more scanty. Albuminuria occurs, while the urea is only partially excreted, and therefore accumulates in the blood. If the nephritis be so severe or protracted that this principle accumulates to a certain extent, grave symptoms occur, as headache, vomiting, apathy or restlessness, and, more dangerous than all, eclampsia, which is not unusual in these cases. Microscopic examination of the urine shows the presence in this liquid of blood-corpuscles, granular epithelial cells, and hyaline or granular casts, or both. The specific gravity of the urine is diminished. But a large quantity of albumen in the urine may render the specific gravity as high or higher than in health.

The altered state of the blood soon gives rise to transudation of serum, first observed in most cases as an anasarca occurring in the feet and ankles. The oedema, if not checked by treatment or through mildness of the disease, extends over the limbs, scrotum, and sometimes upon the trunk. It is well if the dropsy remain limited to the subcutaneous connective tissue, but, unfortunately, it is apt to occur, if the nephritis continue, in and around the internal organs, producing, mentioned in the order of frequency, pulmonary oedema, effusion into the pleural and peritoneal cavities, the pericardium, the encephalon, and lastly into the connective tissue of the larynx, causing that very fatal complication, oedema of the glottis. Although this is the common order in which dropsies occur, exceptions are not infrequent. Even the anasarca may not be the first to appear, although in the vast majority of cases it has the precedence. Thus, Rilliet relates the case of a boy of five years who twenty days after the occurrence of scarlet fever, and six hours after the appearance of bloody and albuminous urine, had double hydrothorax, rapidly developed. As long as the hydrothorax continued no anasarca was observed, but as it declined anasarca appeared. Legendre cites a case in which oedema of the lungs occurred without anasarca or other dropsy. Occasionally, the anasarca and internal dropsies take place nearly simultaneously. The nephritis and consequent serous effusions usually appear within three weeks after scarlet fever ends, but cases occur in which the effusions are first observed as late as the fourth and fifth weeks. The patient may be {530} considered to possess immunity from this sequel if he have reached the close of the fifth week after the abatement of scarlet fever without its occurrence.

The dropsy is usually acute, but it may assume the chronic form, since the nephritis which causes it, happily curable in most instances, may, if neglected, become chronic. Whether the dropsy in itself involve danger depends in great part on its location. Anasarca and ascites may exist a long time with little suffering or danger, but a small amount of serum in certain other localities causes alarming symptoms and speedy death. Oedema of the lungs, hydro-pericardium, oedema of the glottis, and intracranial effusions are always dangerous, and the last two are sometimes fatal within twenty-four to forty-eight hours. Oedema of the lungs has been fatal within twelve hours from the occurrence of the first symptoms of obstructed respiration.

Cerebral symptoms occurring during scarlatinous nephritis are probably sometimes due to the irritating effect of the retained urea on the nervous centre. In other cases the cause appears to be cerebral oedema or compression of the brain by effusion of serum within the ventricles and upon the surface of the brain. Headache, dull or severe, dilatation of the pupils or their oscillation in the same degree of light, vomiting with little apparent nausea, are common symptoms of scarlatinous nephritis when it has continued a few days, and the excretion of urea is so diminished that this substance begins to exert its poisonous effect on the system. Such symptoms are apt to be followed by somnolence, threatening coma, or by eclampsia, unless the patients are promptly and properly treated. In some patients that die of scarlatinous nephritis, death occurring in convulsions or coma, no appreciable lesions are observed within the cranium, unless more or less congestion, the fatal ending being attributable to the uræmia. In other instances we find an effusion of serum within the ventricles or upon the surface of the brain. Although the symptoms in scarlatinous nephritis and uræmia may appear very unfavorable, the prognosis is usually good under prompt and appropriate treatment. Thus severe convulsions and a degree of somnolence that bordered on coma may abate, and convalescence be fully established within a few days, and Rilliet and Barthez announce ten recoveries in thirteen patients affected with convulsions due to this renal affection.

ANATOMICAL CHARACTERS.--Scarlet fever being, as we have seen, a constitutional febrile disease of an ataxic nature, and accompanied by certain inflammations, necessarily affects the composition of the blood; but since this disease varies so greatly in type or severity, the state and appearance of this liquid also vary. At the autopsies of the more malignant cases we find the blood dark and fluid, with small, soft, and dark clots in the heart and large vessels. In other cases the clots are large, firm, and solid, as described in a preceding page. In malignant cases that end fatally Rilliet and Barthez state that both the large and small vessels of the cerebral meninges and the brain are found hyperæmic, but in a variable degree. In those who die in coma, preceded by delirium or convulsions, during the eruptive stage, the intracranial congestion is usually marked, with perhaps some transudation of serum, but without inflammatory lesions. The fibrin in scarlet fever remains in about normal proportion, except as it is increased by inflammatory {531} complications. Andral found an increase in the proportion of blood-corpuscles from 127 to 136 parts in 1000.

The respiratory apparatus, except the Schneiderian membrane, is usually normal when no complications exist. Samuel Fenwick[6] made post-mortem examinations in sixteen cases of scarlet fever, and concludes from them that inflammation of the mucous membrane of the stomach and intestines occurs like that of the skin, followed by desquamation of the epithelial cells, like that of the epidermis. I have had the opportunity of examining the stomach and intestines of those who died of scarlet fever in the eruptive stage, and have not found any unusual hyperæmia of the gastro-intestinal surface, except when gastro-intestinal inflammation, usually indicated by diarrhoea, had occurred as a complication.

[Footnote 6: London Lancet, July 23, 1864.]

In some cases the abdominal organs exhibit changes which suggest a resemblance to typhoid fever. The spleen is enlarged and somewhat softened, and Peyer's patches and the solitary glands are thickened and prominent, but less in degree than in typhoid fever. The mesenteric glands also are in a state of hyperplasia. In other patients these parts appear normal.

Klein made microscopic examination of the liver in eight cases, and states that he found granular opaque swelling of liver-cells, and changes in the internal and middle coats of certain arteries similar to those observed in the kidneys, which have been described above. He also found evidences of interstitial inflammation, as an increase of round cells and connective tissue in the liver. He remarks also that he observed hyaline degeneration of the intima of arteries in the spleen. Rilliet and Barthez state that swelling and softening of the spleen are exceptional in scarlet fever, but are sufficiently common to merit attention. In post-mortem examinations which I have witnessed nothing noteworthy has appeared to the naked eye in the state of the liver, nor ordinarily in that of the spleen.

The efflorescence, though one of the anatomical characters, has perhaps been sufficiently described in the foregoing pages. It begins over the neck, chest, and groins as numerous reddish points not larger than a pin's head, closely crowded together, but with skin of normal color between. It is estimated that the aggregate efflorescence and aggregate normal skin over a given area are about equal. If the cutaneous circulation be active and the febrile movement be considerable these spots extend and coalesce, producing an efflorescence like erythema or like the hue of a boiled lobster, to which it has been likened. The efflorescence, less upon the face than upon the trunk, contrasts in this respect with that of measles, in which the rash is full in the face, often causing some swelling of the features. It is also less upon the palmar and plantar surfaces than elsewhere. It scarcely causes any perceptible elevation of the skin, but in certain localities, as upon the backs of the hands and upon the fore-arms, it communicates the sensation of slight roughness. The seat of the efflorescence is mainly in the superficial layers of the skin, but it is said that it sometimes has occurred upon a cicatrix, as that from a burn. In the robust and in favorable cases in which the circulation is active the rash has a scarlet hue, and when the cutaneous capillaries are emptied and the skin rendered pale by pressure with the {532} fingers, the circulation immediately returns when the pressure is removed. In malignant cases the color is not scarlet, but dusky red, and so sluggish is the capillary circulation that the skin when pressed upon recovers the blood very slowly. In grave cases also extravasation of blood in minute points or transudation of its coloring matter is apt to occur in portions of the surface, when of course decolorization is not fully produced by pressure. In cases ending fatally, during the eruptive stage the efflorescence may entirely disappear in the cadaver, or it remains upon parts of the surface, especially depending portions. Desquamation is attributable to the exaggerated proliferation of the epidermis and the loosening of its attachment by the inflammation.

DIAGNOSIS.--In the commencement of scarlet fever, prior to the eruption, no symptoms or appearances exist which enable us to make a positive diagnosis. Positive statement in reference to the nature of the attack should be deferred, for the credit of the physician. Still, if a child with no appreciable local disease sufficient to cause the symptoms a few days after exposure to scarlet fever, or during an epidemic of this malady, be suddenly seized with fever, the pulse rising to 110, 120, or more, and the temperature to 102°, 103°, or 105°, scarlatina should be suspected. The diagnosis is rendered more certain at this early stage if vomiting occur, and especially if the fauces be red, for hyperæmia of the fauces, due to commencing pharyngitis, is one of the earliest and most constant of the local manifestations of scarlatina.

When the eruption has appeared the nature of the malady is in most instances apparent. The punctate character of the eruption before it becomes confluent, its occurrence within twenty-four hours after the fever begins over almost the entire surface, but its absence or scantiness upon the face, and especially around the mouth, serve to distinguish it from other diseases.

Scarlet fever and measles were long considered identical by the profession, and, though the ordinary forms of these maladies can be readily distinguished from each other, cases occur in which the differential diagnosis is attended by some difficulty. But there are differences in the symptoms and course of the two diseases which aid in discriminating one from the other. Measles begins with marked catarrhal symptoms, as if from a severe cold. Mild conjunctivitis, causing weak and watery eyes, coryza, and mild laryngo-bronchitis, with accompanying cough, precede the eruption three or four days and continue during the eruptive stage. The febrile movement in the prodromic stage of measles is remittent, the evening temperature being two or three degrees higher than that in the morning. Contrast this with the invasion of scarlet fever, in which the only catarrh is that of the buccal and faucial surfaces, and there is consequently little or no cough, and the febrile movement, ordinarily high in the beginning, is nearly uniform in the different hours of the day. The scarlatinous eruption appears, as we have seen, within twelve to twenty-four hours about the neck and upper part of the chest, and spreads over the body in a shorter time than that of measles, which appears on the third day. The rash of measles begins to fade at the close of the third or in the fourth day after its appearance, that of scarlet fever not till from the sixth to the eighth day. In nearly all cases of measles, even when the rash is confluent upon the face and a {533} considerable part of the trunk, in consequence of the high febrile movement and vigorous cutaneous circulation, we observe the characteristic rubeolar eruption upon certain parts of the surface, as the extremities, which, in connection with the history, renders diagnosis certain.

Erythema resembles the scarlatinous eruption, but its duration is commonly shorter. It is limited to a part of the surface, and it is accompanied by much less febrile movement. The temperature in erythema does not usually rise above 100°, unless for a few hours, whereas in scarlet fever it continues considerably above 100° for several days. The scarlatinous efflorescence has also a brighter red or more scarlet hue than that of erythema, except in the more malignant cases, in which the severity of the symptoms renders the diagnosis clear. But an important aid in differentiating the one from the other of these diseases is the fact that in erythema there is, with few exceptions, no faucial inflammation, and in the few instances in which it is present it is slight and transient, fading within a day or two.

Scarlet fever is readily diagnosticated from diphtheria, although the affinity is close between these two maladies. The early appearance of the pseudo-membrane upon the fauces in diphtheria, its absence in scarlet fever, and the absence of any appearance resembling it until the fever has continued some days, and the characteristic efflorescence upon the skin in scarlet fever, render diagnosis easy. If scarlet fever have continued some days when first seen by the physician, the diphtheritic pseudo-membrane may be present as a complication, or the fauces may present an appearance like diphtheria from ulceration or sloughing and the presence of foul and offensive secretions, which produce a dark-grayish and fetid mass over the faucial surface. Under such circumstances the character of the disease is ascertained by the history of the case, and especially by the occurrence of the scarlatinous eruption. An erythema transient and limited to a part of the surface sometimes appears in the commencement of diphtheria, and at a later period, as a result of the toxæmia, points of a roseoloid appearance and irregular patches, often located upon the extremities. Both kinds of rash can be readily diagnosticated from that of scarlet fever, for the erythema, as has been stated, is transient and partial, and does not exhibit minute points of deeper injection, while the toxæmic rash differs in form and aspect from that of scarlet fever, and appears at a stage of the case when the scarlatinous efflorescence would have faded or begun to fade.

The efflorescence of rötheln sometimes closely resembles that of scarlet fever, though it is usually more like that of measles; but it is ordinarily accompanied by symptoms which are much milder than those of scarlet fever, and it begins to abate as early as the third, and disappears on the fourth, day. The eyes have a suffused appearance, the temperature may reach 102° or 103°, and the efflorescence may be as general over the body as that of scarlet fever, but there is not the aspect of serious indisposition, and the speedy abatement of the symptoms shows that the disease is not scarlet fever.

PROGNOSIS.--The prognosis depends on the form of scarlet fever, whether mild or severe, the strength of the patient, and the presence or absence of complications or sequelæ. The type of this disease is sometimes so mild throughout an epidemic or during a series of years that {534} death seldom occurs, whatever the mode of treatment; but afterward the type changes, and the percentage of deaths increases and remains high till another mitigation in the type occurs.

Sydenham in the middle of the seventeenth century stated that scarlet fever, as he saw it in London, was so mild that it scarcely deserved the name of disease: "Vix nomen morbi merebatur." Morton some years later, and Huxham in the following century, had abundant reason to regret the change of type, and now throughout Great Britain scarlet fever is one of the most fatal and most dreaded of the diseases of childhood. In Dublin during the present century, prior to 1834, scarlet fever was uniformly mild, so that on one occasion of eighty patients in an institution all recovered. In 1834 the type of the disease totally changed and epidemics of unusual virulence occurred. The type frequently changes from mild to severe or severe to mild, not only in consecutive years, but in consecutive months. A few years since a distinguished physician of New York treated about fifty cases of scarlet fever in one of the institutions without a single death, but a few months later the type of the malady changed, and his own son was among those who perished from it. The prevailing type of the disease should therefore be considered in giving the prognosis when in the commencement of a case we are asked the probability as regards the termination.

Extensive statistics, including those collected by Murchison from various sources, show that in different epidemics the mortality may vary as much as from 3 per cent. (Eulenberg of Coblentz) to 19.3 per cent. (cases seen by myself in New York City in 1881-82, many of which were complicated by diphtheria), or even to 34 per cent. (epidemic in the Palatinate in 1868-69). The hospital statistics of Rilliet and Barthez gave 46 deaths in 87 cases, or about 53 per cent.

Observations have thus far failed to establish any connection in the atmospheric conditions of temperature or moisture and the type of scarlet fever. Grave as well as mild epidemics have occurred in all climates and seasons.

The mortality is nearly equal in the two sexes, but age bears a marked influence on the percentage of deaths. Comparatively few contract scarlet fever under the age of one year, and the period of its greatest mortality, since it is of its greatest frequency, is between the ages of one and six years. The following are statistics bearing on the relation of the age to the percentage of deaths:

From the close of From the 1st till 5th to Under close of the 12th 1 year. 5th year. year. ------- --------- -------- Fleishman, Cases 8 204 260 Deaths 6 88 51

1st to From the close of 6th to 12th to 6th year. 12th year. 20th year. --------- ---------- ---------- Kraus, Cases 13 113 106 40 Deaths 4 29 10 2

7th to 16th year. ---------- Voit, Cases 5 166 109 Deaths 1 24 10

1st to close of Over 5th year. 5 years. --------- -------- Röset, Cases 43 156 88 Deaths 26 31 3

{535} Under 5th to 10th to Over 5 years. 10th year. 15th year. 15 years. -------- ---------- ---------- --------- Rusigger, Cases 101 126 47 27 Deaths 21 20 3 0

These statistics, which I believe correspond with the observations of others, show that although few cases occur in the first year, the percentage of deaths is large, and that a majority of the deaths occur under the age of six years. After the sixth year the greater the age the less the proportionate number of deaths.

Scarlet fever is liable to so many complications and sequelæ that a physician should not predict a certain favorable termination in the beginning, however mild and regular the symptoms may be. But a favorable result may be expected if the attack be mild, the efflorescence appear at the proper time and extend over the entire surface, the angina be moderate and accompanied by little or no cellulitis or adenitis, with pulse under 140, temperature not above 103°, and no marked nervous symptoms.

Whether the complications or sequelæ be dangerous depends upon their character. Rheumatism has never in my practice been dangerous, nor has it materially retarded convalescence, except when it affected the heart, causing pericarditis or endocarditis, when it involves great danger. Nephritis, if it be moderate, attended by little albuminuria and serous effusion, and by the occurrence of few renal casts in the urine, commonly ends favorably under judicious treatment, as we have already stated; but severe nephritis, with abundant albuminuria and casts and serous effusions, soon gives rise to alarming symptoms, and is the cause of death in a considerable number of instances. A similar remark is applicable to the angina, which occurs in all grades of severity. If it be attended by much cellulitis, with considerable ulceration or necrosis, the state is one of danger, in consequence of the difficulty in administering sufficient nutriment, of the diminished assimilation and of the loss of strength from the prolonged inflammatory fever, the septic poisoning, and the occasional hemorrhages. Complication by pharyngeal or nasal diphtheria, now so common where diphtheria is endemic, also greatly increases the danger.

Many cases, even when their course is normal and without complications, involve danger, and some are necessarily fatal, from the direct effect of the scarlatinous blood-poisoning. Such are grave or malignant forms of the disease which the experienced eye recognizes at a glance. Death often occurs rapidly from the toxæmia. Such cases are characterized by high temperature (105° or 106°), rapid pulse, a dusky-red hue of the surface from languid capillary circulation, pungent heat, frequent vomiting, diarrhoeal stools, a dry-brown tongue, and marked nervous symptoms, such as delirium, great restlessness, or stupor. Not a few in this form of scarlet fever take eclampsia, which is apt to be severe and repeated, and to end in fatal coma.

Other inflammatory complications and sequelæ, which have been described in the preceding pages, retard convalescence and jeopardize the life of the patient, such as empyema, endocarditis, pericarditis, and pneumonia. Otitis media is seldom immediately dangerous, although it may be painful and involve serious consequences, even a fatal meningitis, as has been stated above, after months or years of otorrhoea. Anomalous cases are believed to be, as a rule, more dangerous than such as are {536} attended by an early and full efflorescence and have the usual symptoms.

TREATMENT.--PROPHYLAXIS. Since the discovery by Jenner of the prophylactic power of vaccination as regards small-pox, the attention of the profession has been frequently directed to the prevention of scarlet fever. Belladonna has been employed for this purpose by a class of practitioners who believe in the theory that an agent which produces symptoms similar to those of a disease is antagonistic to that disease, and therefore tends to prevent it, or, if it be present, to render it milder; and since this herb causes an efflorescence upon the skin and redness of the fauces, it was selected as the proper preventive and remedial agent for scarlet fever. Its use, however, for this purpose has been fruitless, and it is now nearly or quite discarded.

It is probable, from a considerable number of observations, that scarlet fever occasionally occurs in the domestic animals during epidemics of the disease in children. It is stated that Spinola observed it in the horse; that Heim saw a dog that occupied the same bed with a scarlatinous patient sicken with fever, which was followed by desquamation; that Letheby saw scarlatina in swine, and Kraus in young cattle. Prominent veterinary surgeons, as Williams of Great Britain, admit the occurrence of scarlatina in animals, and the hope has arisen that since small-pox is modified in cattle so as to afford us the vaccine virus, perhaps scarlet fever may also be modified by passing through one of the lower animals, so that a milder and less fatal form of the disease might be produced in man by inoculation from the animal. This theory, though it deserves investigation, is far from being established. It has not yet, so far as I am aware, been shown that scarlet fever is milder in any animal than in man, nor, if we admit that it is modified in the animal, is it certain that the disease could be returned to man in the modified form. In the N.Y. Medical Record for March 24, 1883, some experiments are detailed by S. W. Strickler of Orange, New Jersey. He cites the experiments of Caze and Feltz, who injected scarlatinal blood under the skin of sixty-six rabbits, and of these sixty-two died within eighteen hours to fourteen days, which indicated a highly poisonous state of the blood employed, either septic or scarlatinous, and certainly no mitigation of the virulence of the scarlet fever. Strickler obtained from Williams of Edinburgh nasal mucus from a horse supposed to have scarlatina, and with it inoculated twelve children, all of whom had sores at the point of inoculation, with redness of the skin around the sores, and in some instances swelling of the adjacent lymphatic glands. It is stated that the children thus inoculated did not contract scarlet fever subsequently when they were exposed to scarlatina. Obviously, there is a serious objection to such experiments upon children, so that they may not be repeated, but a movement has been made in one of the New York medical societies looking to the appointment of a competent committee to investigate them. Some of the prominent veterinary surgeons of this city do not attach much importance to the experiments thus far made, as they are in doubt whether the virus employed was that of the genuine disease.

It is a matter of great interest and importance, and one not yet elucidated, whether or to what extent disinfectant and antiseptic remedies administered internally prevent the occurrence of the infectious maladies {537} in those who have been exposed, and aid in curing those who are sick with them. Sodium sulpho-carbolate, from which, by decomposition in the system, carbolic acid is supposed to be set free, has been used for this purpose. It is administered to adults in doses of ten to thirty grains, and to children in doses proportionate to their age. Declat has prepared a syrup of phenic (carbolic) acid as a preventive and curative agent in the infectious diseases. It is now employed by several of the New York physicians, but thus far the statistics of its use are not sufficient to determine its efficacy. It is a question whether the so-called antiseptics can, on account of their toxic properties, be used with safety in doses sufficiently large to be antidotal to the specific principle of any of the infectious maladies.

It is not my intention to recommend in this treatise any remedial agent that has not been fully tried and its efficacy determined; but from observations made by myself in nearly twenty families in which scarlet fever was prevailing, I am convinced that boracic acid (acidum boricum), an antiseptic recently introduced into our Pharmacopoeia, deserves trial as a preventive and antidote of scarlet fever as well as diphtheria. The good result in my practice from the use of this agent, which only extends over about six months, may be due to the present type of scarlet fever, but I have been surprised at the favorable progress of the cases which appeared very grave in the beginning, at the small mortality, and at the large proportion of well children exposed to scarlatinous cases that escaped infection, to whom this medicine was regularly administered. Boric (boracic) acid has been recently used by aurists with remarkable success in suppurating and granulating otitis media, and by oculists as an eye-wash. E. R. Squibbs says of it (Ephemeris, May, 1883): "A solution saturated at ordinary temperatures contains between 4 and 5 per cent.... It is a very bland and soothing application, whether applied in powder or solution, relieving irritation and reducing suppuration.... It has been administered internally in large doses without any disturbing effects." The preparation which I have employed is one found in the shops, with the name listerine, prepared by a Western pharmaceutical firm. It contains, according to the manufacturers, the "essential antiseptic constituents of thyme, eucalyptus, baptisia, gaultheria, and mentha arvensis," and also two grains of benzo-boracic acid in each drachm. The dose of listerine which I have employed for an adult is one teaspoonful, considerably diluted with cold water. A child of five years can take ten to fifteen drops every two to four hours. I call the attention of the profession to the use of boracic acid as an antidote to the scarlatinous poison, without sufficient experience to enable me to speak positively of its efficacy, but with the hope and expectation, from observing its apparent effects in seventeen families afflicted with scarlet fever, that it will be found a useful addition to our means of controlling this much-dreaded and fatal malady.

In the present state of our knowledge the most reliable and certain prophylaxis is the isolation of patient and nurses, and the thorough and judicious employment of disinfectants upon their persons and in the apartments. All furniture and articles not absolutely required should be removed from the sick room, and no one should be allowed to enter it except the medical attendant and nurses. Constant ventilation should be {538} insisted on by lowering the upper and raising the lower sash of the window two or three inches in mild weather. Even in stormy weather sufficient ventilation can be obtained in this way without exposing the patient to currents of air, which should be avoided.

Since the exhalations from the body, the various excretions, and the epidermic cells shed so abundantly in the desquamative period contain the scarlatinous poison, measures should be employed to disinfect them, in so far as the comfort and well-being of the patient will allow. Vessels which receive the excretions should contain carbolic acid, chloride of lime or other disinfectant, and they should be immediately emptied and cleaned after use. By the frequent application of disinfecting washes to the nostrils and fauces the secretions from these surfaces are to a great extent deprived of their contagiousness. If otorrhoea occur, boracic acid, so serviceable in its treatment, acts as a disinfectant, but in addition the ear should be syringed with warm carbolized water, one drachm of carbolic acid to the pint of water, and this should be continued during convalescence, for cases occur which show that the discharge from the ear is probably the vehicle by which the virus is communicated. Even as late as the fourth week after the disappearance of the rash children in scarlet fever experience relief from inunction of the surface, and if carbolic acid be added to the substance which is employed for this purpose, and the inunction be made twice daily over the entire surface, contamination of the air through the exfoliations and exhalations from the skin is in great part prevented. The late William Budd of Bristol, England, was in the habit of recommending inunction of the surface twice daily with sweet oil, which answered the purpose of preventing dissemination of epidermic particles through the air; and we will presently see how successful were his precautionary measures.

A convalescent child should not be allowed to mingle with other children till three or four weeks have elapsed and desquamation has ceased; and all who are liable to take the malady should be excluded from the room in which a case has occurred for a longer period, and until it has been thoroughly disinfected by burning sulphur or other methods.

The New York Board of Health enforces the following excellent regulations to prevent the spread of scarlet fever as well as other acute infectious maladies:

"Care of Patients.--The patient should be placed in a separate room, and no person except the physician, nurse, or mother allowed to enter the room or to touch the bedding or clothing used in the sick-room until they have been thoroughly disinfected.

"Infected Articles.--All clothing, bedding, or other articles not absolutely necessary for the use of the patient should be removed from the sick room. Articles used about the patients, such as sheets, pillow-cases, blankets, or clothes, must not be removed from the sick room until they have been disinfected by placing them in a tub with the following disinfecting fluid; eight ounces of sulphate of zinc, one ounce of carbolic acid, three gallons of water. They should be soaked in this fluid for at least an hour, and then placed in boiling water for washing.

"A piece of muslin one foot square should be dipped in the same solution and suspended in the sick room constantly, and the same should be done in the hallway adjoining the sick room.

{539} "All vessels used for receiving the discharges of patients should have some of the same disinfecting fluid constantly therein, and immediately after being used by the patient should be emptied and cleansed with boiling water. Water-closets and privies should also be disinfected daily with the same fluid or a solution of chloride of iron, one pound to a gallon of water, adding one or two ounces of carbolic acid.

"All straw beds should be burned.

"It is advised not to use handkerchiefs about the patients, but rather soft rags, for cleansing the nostrils and mouth, which should be immediately thereafter burned.

"The ceilings and side-walls of a sick-room after removal of the patient should be thoroughly cleaned and lime-washed, and the woodwork and floor thoroughly scrubbed with soap and water."

By such measures of prevention there can be no doubt that the number of cases of scarlet fever would be greatly reduced.

Budd for years recommended similar precautions in the families which he attended, and the following is his testimony in regard to the result: "The success of this method in my own hands has been very remarkable. For a period of nearly twenty years, during which I have employed it in a very wide field, I have never known the disease to spread beyond the sick-room in a single instance, and in very few instances within it. Time after time I have treated this fever in houses crowded from attic to basement with children and others, who have nevertheless escaped infection. The two elements in the method are separation on the one hand, and disinfection on the other."[7]

[Footnote 7: British Medical Journal, Jan. 9, 1869.]

HYGIENIC TREATMENT.--The room occupied by a scarlatinous patient should be commodious and sufficiently ventilated. Its temperature should be uniform at about 70° during the course of the fever. When the fever begins to abate and desquamation commences, a temperature of 72° to 75° is preferable, so that there is less danger that the surface may be chilled during unguarded moments, as at night, when the body may be accidentally uncovered, since sudden cooling of the surface at this time may cause nephritis or some other dangerous inflammation. Henoch does not believe in the theory that the nephritis is commonly produced by catching cold, but many observations show that those who are carefully protected from vicissitudes of temperature, who remain during convalescence in a warm room, and are protected by abundant clothing, more frequently escape this complication than such as are under no restraint of this kind and are carelessly exposed in times of changeable weather. Nevertheless, it is true that a certain proportion suffer from nephritis however judicious the after-treatment may be. The best hygienic management does not always prevent its occurrence. The patient should not, therefore, leave the house until four weeks after the beginning of the fever, and in inclement weather not till a longer time has elapsed. So long as desquamation is going on and the skin has not regained its normal function the patient should remain indoor, and when finally he is allowed to leave the house he should be warmly clothed.

THERAPEUTIC TREATMENT.--In order to treat scarlet fever successfully it is necessary to bear in mind that it is a self-limited disease, running for a certain time and through certain stages, and that it is not {540} abbreviated by any known treatment. Therapeutic measures can only moderate its symptoms and render it milder. The severity of the disease is indicated by its symptoms, and the symptoms are to a certain extent under our control.

MILD CASES.--A patient with a temperature under 103°, and with only a moderate angina, does not require active treatment, but, however light the disease, he should always be in bed and in a room of uniform temperature, as stated above. Instances have come to my notice in the poor families of New York in which scarlet fever was not diagnosticated, and the patients were allowed to go about the house, and even in the open air, in the eruptive stage, till some severe complication or an aggravation of the type created alarm and medical advice was sought, when it appeared that a grave and dangerous condition had, through carelessness and ignorance, resulted from a mild and favorable form of the malady. The physician, when summoned to a case however mild, should never fail to take the temperature, note the pulse, inspect the fauces, and inquire in reference to the fecal and urinary evacuations, that he may detect early any unfavorable changes which may occur.

Since in all cases angina and more or less blood-deterioration are present, the following prescription will be found useful in mild as well as severe scarlet fever:

Rx. Potass. Chlorat. drachm ii; Tr. Ferri Chloridi fl. drachm ii; Syrupi fl. oz. iv. M.

S. Half a teaspoonful every hour to two hours to a child of three years; a teaspoonful to a child of six years.

Small doses of this medicine frequently administered act beneficially on the surface of the throat and tend to prevent the anæmia which is so common after scarlet fever. If the medicine be given gradually diluted with only a moderate amount of water, the effect is better on the inflamed fauces. Potassium chlorate is known to be an irritant to the kidneys in large doses, causing intense hyperæmia of these organs, with bloody urine or suppression of urine. The melancholy fate of Fountaine, who died from the effects of one ounce of this medicine, is known to the profession. I have seen a similar instance in a child. But doses of one to four grains, according to the age, can be administered with safety to children, so that half a drachm to a drachm and a half are taken in twenty-four hours. A quantity much exceeding this amount involves risk. In mild cases it is not necessary to treat the throat by topical measures, the above prescription producing sufficient local effect, but camphorated oil may be used externally. I ordinarily prescribe quinine in small doses for this form of scarlatina, as in the following formula:

Rx. Quiniæ Sulphat. gr. xvi; Ext. Glycyrrhizæ scruple ss; Syr. Pruni Virginianæ fl. oz. ii. M.

S. One teaspoonful every fourth hour to a child of three to five years, the potassium chlorate and iron mixture being administered twice between.

The treatment of scarlatina by antiseptic remedies will be considered hereafter.

{541} The itching and dryness of the surface, which increase the discomfort of the patient in mild as well as severe scarlatina, are relieved by frequently anointing the whole body with vaseline, cold cream, or butter of cocoa. Carbolic acid is an efficient remedy for pruritus, while it is also a disinfectant. It may be used in the following formula:

Rx. Acidi Carbolici drachm i; Vaseline oz. iv. M.

S. To be applied over the entire surface.

In New York leaf lard has long been employed as an unguent over the entire surface in scarlet fever, and patients experience benefit from it. Alcohol and water or vinegar and water are sometimes employed for the same purpose. The linen should be changed every day and the bed thoroughly aired.

ORDINARY CASES AND CASES OF SEVERE TYPE.--A safe temperature in scarlet fever may be considered at or below 103°. If it rise above this, measures designed to abstract heat are very important--more important even in many cases than the medicinal agents which are commonly used to combat this disease. Since a high temperature retards assimilation, promotes deleterious tissue-change, and causes rapid emaciation and loss of strength, measures designed to reduce it are urgently needed. "The production of heat depends chiefly on oxidation of the constituents of the body" (Billroth). Therefore fever indicates an increase of the oxidation and a molecular disintegration above the healthy standard. Hence the augmentation of urea in the urine and the progressive emaciation and loss of weight which characterize the febrile state. Fever also diminishes the secretions by which food is digested and destroys the appetite, so that repair of the waste is insufficient. Moreover, a high temperature continuing for a time tends to produce degenerative changes, albuminous and fatty, in the tissues, the more rapidly the higher the temperature, so that the functions of organs are seriously impaired. Among the most dangerous of the tissue-changes is granulo-fatty degeneration of the muscular fibres of the heart. In dogs and rabbits that have perished from a high temperature artificially produced by experimenters granular clouding of the elementary tissues has been found after death.[8] A high temperature, therefore, in itself involves danger, and if it occur in an ataxic disease like scarlet fever, and be protracted, it greatly diminishes the chances of a favorable issue.

[Footnote 8: See experiments by Mr. J. W. Legg, Lond. Path. Soc. Trans., vol. xxiv., and others.]

The temperature can be reduced without shock or injury to the child by the judicious use of cold water externally. The cold-water treatment is not necessary if the temperature be under 103°, though useful if judiciously employed by sponging when the temperature is at 102° or 103°; but if it rise above 103° it is required, and the more urgently the higher the temperature. The external use of cold water as an antipyretic in the febrile diseases is now almost universally recommended by physicians, but it still meets with opposition on the part of families, especially in the treatment of the exanthematic fevers, and the directions for its employment are therefore not apt to be fully carried out during the absence of the medical attendant. The old theory that the fevers require warmth and sweating has such a firm hold on the popular mind that some years longer will be required for its removal.

{542} The modes of applying cold water recommended by cautious and experienced physicians are various. Von Ziemssen recommended that the patient be immersed in water at a temperature of 90°, and cool water be gradually added till the temperature fall to 77°. In a few minutes the patient is returned to his bed, his surface dried, and he is covered by the proper bed-clothes, when his temperature will probably be found reduced two or two and a half degrees. If the patient complain of chillness or his pulse be feeble, he should be immediately removed from the bath and stimulants administered, either whiskey or brandy, for if the extremities remain cool and the capillary circulation sluggish, the effect may be injurious, since some internal inflammation may arise to complicate the fever. Under such circumstances increased alcoholic stimulation is required.

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