A treatise on diphtheria

Preface

My first paper on diphtheria, which appeared in the American Medical Times of August nth and 18th, i860, was based on several hundred cases. Since that remote period I have seen thousands, and published my experience several times. After some " Contributions " in the Journal of Obstetrics and Diseases of Women and Children, Feb., 1875, I collected and condensed my views in the second volume of C. Gerhardt's Handbuch der Kinderkrankheiten, 1877. Thus the present little book may be considered as an augmented edition of that monograph, with this exception, that it contains less literature and more therapeutics.

While thus admitting the claims of the practitioner as paramount, I was ever of opinion that a careful physician and therapeutist required the very latest and soundest results of exact scientific investigations as the foundation and safeguard of his practice. For the physician's science is no longer mere formula, and his art no routine. As the important questions of the identity and non-identity of " croup " and diphtheria, and of the parasitic or chemical nature of the diphtheritic poison are not yet iv PREFACE.

settled to the satisfaction of all, their discussion is still in order. I am bound to say, however, that anxious though I be for a possible future success of a parasitic theory of nosogenesis, I have not been able to change my attitude in regard to the prevalent bacteria doctrine of diphtheria. I cannot look upon the bacteria epidemic in the medical journals, particularly of Germany, with the hasty conclusions and gratuitous assumptions of scores of experimenters and writers, as anything but a calamity which, I trust, is but temporary. The safest verdict of the sober critic is still : " not proven." Fortunately, the non-acceptance of the bacteria doctrine does not at all interfere with the success of the rational practitioner.

The cases of diphtheria in every physician's practice are so numerous that, with very few exceptions, I shall abstain from detailing histories. What I hope to present in #iis little book is a condensed but tolerably extensive report on the present state of what is known about diphtheria, with my personal views on its pathology and treatment.

A. JACOBI, M.D.

New York, October 15th, 1880.

When the above was written and printed, I came into possession of Supplement No. 7 of the National Board of Health Bulletin. It contains a " research on the effects of inoculating the lower animals with diphtheritic exuda-

PREFACE. V

tlon," by Drs. H. C. Wood and Henry F. Formad, with the signature, " University of Pennsylvania, July ist, 1880." In thirty-two experiments, in which inoculation of diphtheritic matter was performed subcutaneously and in the mucous membrane of the mouth, the animals died in only six. The question naturally arises as to whether the few animals in which the inoculation was followed by death died of diphtheria or some other disease. Only in one case were there any exudations present in any organ which could give rise to the slightest suspicion that the animal died from diphtheria. It has been asserted by Oertel that animals which have been inoculated with diphtheritic material die with their internal organs infested with micrococci, and that the presence of these is characteristic of diphtheria. Wood and Formad have carefully examined the internal organs of the rabbits which died, as well as the blood of those which survived, and found no micrococci. In this their results are in complete accord with the very careful labors of Curtis and Satterthwaite.

The utmost care is necessary to prevent the entrance into the blood of bacteria from without. Thus they have cut the jugular veins of a rabbit and examining the blood at once, found it entirely free from bacteria. When, however, after the lapse of a few minutes the post-mortem was concluded and the heart opened, the blood therein contained possessed an abundance of these low organisms.

If the animals did not die of diphtheria, of what did they die ? In every case the internal organs were tubercular.

vi PREFACE.

But this condition was not due to inoculation with diphtheritic material only. Nine experiments were made with small masses of innocuous foreign material which was put under the skin. In five out of nine of these experiments tubercle was found after death ; this large proportion apparently demonstrates that a simple local inflammation may in the rabbit act as a source of tubercular infection. Where diphtheritic matter was inoculated, inflammation was almost always induced at the seat of the lesion, with the formation of large lumps containing cheesy matter. These facts being so, it is a fair deduction that the tubercles were secondary to these inflammatory foci, and were therefore an indirect and not a direct result of the inoculation. Thus, diphtheritic membrane placed under the skin or in the muscles of rabbits may cause death in a few hours by the production of a blood poisoning which is not accompanied by any specific symptoms or lesions ; or, after many days, by the development of a secondary tuberculosis.

Experiments prove that a pseudo-membranous tracheitis can be produced by placing the exudation matter in the trachea. Other experiments show that ammonia is able to produce in the cat and dog, as well as in the rabbit, a pseudo-membranous tracheitis. Prof. Oertel states that the membrane produced by cauterization of the trachea differs from diphtheritic membrane in containing no bacteria. What has led him to such an assertion cannot be comprehended. When the death occurred very quickly

PREFACE. Vll

bacteria and micrococci may have been less abundant in the traumatic membrane than in that taken from the throat of patients, but when the animal survived some days, and the bacteria had sufficient time to develop themselves, when, in other words, they were afforded as good opportunity of growth as in the natural disease, they were immensely abundant, in some cases seeming to make up a large part of the bulk of the membrane.

If it be possible to produce a fatal pseudo-membranous tracheitis by placing the diphtheritic membrane in the trachea, and not possible to cause septicaemia by inoculating other portions of the body with the same material, it would appear as though diphtheria might be originally a local disease with a subsequent septic poisoning. Experiments were therefore performed to determine whether any products of disease other than diphtheritic exudations are capable of causing pseudo-membranous tracheitis. In two of the ten experiments it was caused by the introduction of organic matter into the trachea. In both of the cases in which false membrane was produced, the injected material was pus ; only four such experiments were made, so that the proportion of successful results is very large ; much larger indeed than with true diphtheritic exudation in the experiments of Drs. Wood and Formad.

Trendelenburg found that not only ammonia, but also various other chemical irritants are capable of causing the formation of false membrane in the trachea ; many years ago it was proven that tincture of cantharides will do the

Vlll PREFACE.

same thing. It would seem, therefore, that in the trachea the formation of a pseudo-membrane is not the result of any peculiar or specific process, but simply of an intense inflammation, which may be produced by any irritant of sufficient power. This fact, certainly, is very suggestive in regard to the pathology of diphtheria.

A general view of the anatomical and clinical facts seems to indicate that the contagious material of diphtheria is really of the nature of a septic poison which is also locally very irritant to the mucous membrane ; so that when brought in contact with the mucous membrane of the mouth and nose it produces an intense inflammation without absorption by a local action. Whilst absorption is not necessary for the production of the angina, it is very possible that the poison may act locally after absorption by being carried in the blood to the mucous membrane. Further, under this theory it is possible that the poison of diphtheria may cause an angina which will remain a purely local disorder, no absorption occurring, or a simply local tracheitis produced by exposure to cold or some other non-specific cause may produce the septic material when absorption will cause blood poisoning, the case ending as one of adynamic diphtheria. Some such an explanation as these here offered seems to reconcile the antagonistic opinions concerning the value of local treatment in diphtheria ; because it is plain that the value of such treatment must largely depend upon whether the angina has or has not been preceded by absorption.

PREFACE. IX

From the exanthemata diphtheria differs from the fact that one attack in no way protects against a second. It ranks rather with septic diseases which may recur indefinitely.

At present it seems altogether improbable that bacteria have any direct function in diphtheria, i. e., that they enter the system as bacteria and develop as such in the system, and cause the symptoms. It is, however, possible that they may act upon the exudations of the trachea as the yeast plant acts upon sugar, and cause the production of a septic poison which differs from that of ordinary putrefaction, and bears such relations to the system as to, when absorbed, cause the systemic symptoms of diphtheria. Now, these bacteria may be always in the air, but not in sufficient quantities to cause tracheitis, but enough when lodged in the membrane to set up the peculiar fermentation ; whilst during an epidemic they may be sufficiently numerous to incite an inflammation in a previously healthy throat.

The above extracts are reprinted almost literally from the remarkable paper of Drs. Wood and Formad, which is as conclusive as it is brief. Nothing equally excellent has been contributed to the literature of diphtheria for a long time. It appears to me that the mooted question of the essentiality of bacteria in regard to the nature and definition of diphtheria, to which many a page of this book had to be given up, is finally settled by them. While I regret the impossibility of quoting them at the proper

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place and at proper length, I must not refrain from giving the greatest possible publicity to their conclusions, and expressing my satisfaction at being capable of sustaining my own position by their experiments, the skilful performance of which is surpassed only by their happy results.

A. JACOBI.

Chapter I. History

Diphtheria is a specific, infectious, and contagious disease characterized principally by epithelial changes in, and the exudation of fibrin on and into mucous membranes, the surface of wounds, and the rete Malpighii, thereby constituting the so-called pseudo-membrane. Under the names: ulcus syriacum, ulcus asgyptiacum, garotillo, morbus suffocans, morbus suffocatorius, affectus suffocatorius, pestilentis gutturis affectio, pedancho maligna, angina maligna, angina passio, mal de gorge gangreneux, ulcere gangreneux, angina polyposa, angine couenneuse, synanche, croup, diphtheritis, and diphtheria, the disease has been known and described at different periods by the writers of different nations. Aretseus, of Cappadocia, is notably the first of whom we have authentic proofs, if we except Asclepiades only, who is said to have performed laryngotomy. The description of the pharyngeal and laryngeal manifestations furnished us by the former, however, can leave no doubt in our minds that he knew diphtheria and recognized it. Galen tells us that the pseudo-membrane was gotten rid of by coughing when the respiratory passages were affected by the disease, and by hawking when the disease was in the pharynx. Cselius Aurelianus recognized diphtheria of the pharynx and larynx, as well i as the diphtheritic paralysis of the soft palate ; it is to him we are indebted for the information that Asclepiades resorted to scarification of the tonsils, and even to laryngotomy. Aetius, in the fifth century, advised against energetic local treatment and the forcible removal of the deposits before they were in a condition to fall off spontaneously.

In the literature of the middle ages, there are no proofs of the occurrence of diphtheria ; still, some reports of gangrenous diseases, probably, have reference to it. Petrus Fosterus has given a fair description of an epidemic in Holland in the year 1557. Antonio Soglia, quoted by Chomel, describes an epidemic in Naples and Sicily (1563) which spread, in the following year, as far as Constantinople ; Joannes Wierus, epidemics in Dantzic, Cologne, and Augsburg (1565); Ballonius (Baillou), in Paris (1576). In Spain, epidemics raged in the years 1583, 1587, 1 59ir 1596, 1 600- 1 605, and 161 3. Mercado (1608) tells of a child that had communicated the disease to its father by biting his finger. Cascalez advised gargles of solutions of alum and of sulphate of copper. Herrera (1 5 1 5) described diphtheria of the skin and of wounds, and looked upon the pseudo-membrane he found after death as the essential characteristic of the disease. Heredia, in 1690, recognized the suffocative and asthenic forms, as well as the paralysis of the soft palate, of the pharynx, and of the limbs ; he also called attention to the occurrence of relapses, which he attributed to the absorption of the morbid products, and endeavored to prevent by cauterization. In Portugal, too, there have been epidemics in early times. Barbosa, with whose work the world has become acquainted mainly through the meritorious labors of J. B. Ullersperger, describes one which occurred in 1626. Among the older writers on the subject we may mention Juan de Villareal, 161 1, and' Francesco de Figueiras in Lima, 1616. In Italy the first epidemic raged in 1618; Rene, Moreau, and Bartholinus detail a large number of literary proofs in support thereof ;

it was characterized by its marked contagiousness and its depression of the vital powers, together with the weakness of the mental faculties left after an attack of the disease. The only autopsy, made in 1642, from a report by M. A. Severino, revealed the presence of pseudo-membrane in the larynx.* In Germany the disease was described by Wedel, in 1718. The epidemics observed by him were not very instructive, yet they sufficed to teach the importance of isolating the sick.

In the New England States diphtheria has appeared in the seventeenth century. Samuel Danforth, graduate of Harvard University, in 1643, had twelve children. The first died at the age of six months. The " next three being attacked by the ' malady of bladders in the windpipe,' in December, 1659, it pleased God to take them all away at once, even in one fortnight's time." This happened at Roxbury, Mass. (Biographical sketches of graduates of Harvard University, etc. By John Langdon Sibley, vol. I., Cambridge, 1873, p. 91. f)

John Josselyn, Gent., in " an account of two voyages to New England, made during the years 1638, 1663 " (Boston, Wm. Veazie, 1865)4 writes as follows (p. 141): "also they " (the English in New England) " are troubled with a disease in the mouth or throat, which hath proved mortal to some in a very short time, quinsies and impostumatjons of the almonds, with great distempers of cold." As Josselyn on his second voyage spent eight years in New England (principally in Maine), the foregoing must point to an epoch not later than 1671, and the manner in which he expresses himself shows that he does not speak of a recent invasion, but of a disease which had been common for

* See literature in Sanne, Diphth., 1877, and Hirsch, Hist. Ge,ogr. Path., II.

f This important historial reference I owe to the watchfulness of Dr. Elsworth Eliot, New York.

X This book was published in 1674, and reprinted in 1833, by the Massachusetts Historical Society, and may be found in the third volume of the third series of their collections.

some time. I have no proofs of epidemics during the following decades, but the year 1735 marks the recurrence of epidemics. In a " Compendious History of New Eng land " by Dr. Jedediah Morse, D.D., and Rev. Elijah Parish, Charlestown, 1804, we read with reference to the epidemic of 1735, that the throat became swollen and coated with white and ash-gray spots, an eruption appeared on the skin; great debility overcame the entire body, with a marked tendency to putridity. The disease first appeared in 1735, at Kingston, N. H. Wm. Douglass (The Practical History of anew epidemical Eruptive Miliary Fever with an angina ulcusculosa, which prevailed in Boston, New England, in the }'ears 1735 and 1736) says of this epidemic : " It was first noticed in Kingston township, on the 20th of March, 1735, about fifty miles eastward of Boston. As this was an inland place of no considerable trade or importance, it was thought (incorrectly perhaps) to be of indigenous origin, and not' of foreign importation. The first victim was a child who died in three days ; and about a week after, three children were seized in another family four miles distant ; and they also died on the third day. It continued spreading gradually, seizing here and there particular families, with that degree of violence that of the first forty cases none recovered. Some of the patients died of a sudden acute necrosis, or mortification ; but most of them were carried off by a sympathetic affection of the fauces, neck, or air-passages ; or, by an infiltration and tumefaction of the chops, and forepart of the neck which became so enlarged and turgid, as to bring upon a level all parts lying between the chin and sternum, occasioning a strangulation of the patient in a very short time.

After a few weeks it spread from Kingston to the neighboring townships, but in a milder form. No reasons could be given for this greater malignity in Kingston, except, perhaps, the prevalence of damp places near large ponds, and fresh water, but sluggish streams, like in those localities which produce the rot in sheep. There may also have been bad medical treatment. Its first recognized appearance in Boston was on the 20th of August, 1735, in a child . . . who had white specks in the throat, and a cutaneous efflorescence. A few more . . . were seized in like manner. Towards the end of September it appeared in several parts of the town of Boston, with more decided complaint of soreness of the throat. The tonsils were swelled and specked ; the uvula was relaxed ; there was slight fever, and an erysipelas or scarlet fever like efflorescence on the neck, chest, and extremities. The first alarming case was in the beginning of October, in a young man. He had lately arrived from Exeter, to the eastward of Boston, where his brother had died of the same illness. His symptoms were great prostration of strength, a single speck on one of his tonsils, and colliquative sweats. . . . It increased during the winter up to the second week in March, 1736; when it was at its height, there being twenty-four burials in all, during the week (instead of nine or ten). . . . The disease was so much milder in Boston than in some of the townships where it first prevailed that many could not be persuaded that it was the same disorder. . . . To the eastward of Boston, at times, one in three died, in other places one in four, and in scarce any towns, less than one in six; whereas in Boston not above one in thirty-five succumbed."

The disease cannot have remained so mild for any length of time in Boston, for on August 5th, 1740, the preface to the letter of I. Dickinson, A.M., dated at Cambridge, speaks of the " most malignant disease which had raged for a long time in the place where he lives, and which had commenced its fatal progress in these parts," and of the " fresh alarm by a return of that astonishing distemper among us." The letter was written in 1738, and published two years afterward, under the title of : " Observations on that terrible disease, vulgarly called the Throat Distemper, with advices as to the method of cure, in a letter to a friend. By I. Dickinson, A.M. Boston. Printed and sold by S.

Kneeland and T. Green, in Queen Street, over against the Prison. 1740."*

The clergyman to whose observations and industry we owe this short letter appears to have seen most of the forms of diphtheria. He describes cases which

1. " Begin with a shivering, a chill, or with stretching, or yawning, which is quickly succeeded with a sore throat, a tumefaction of the tonsils, uvula and epiglottis, and sometimes of the jaws, and even of the whole throat and neck. From the second to the fourth day there may be a miliary eruption, in some exactly resembling the measles, in others more like the scarlet fever, in others like the confluent small-pox." This form proved fatal but seldom.

2. " It frequently begins with a slight indisposition, much resembling an ordinary cold, with a listless habit, a slow and scarce discernible fever, some soreness of the throat and tumefaction of the tonsils ; and perhaps a running of the nose, the countenance pale, and the eyes dull and heavy. Sometimes vehement sickness of the stomach, a perpetual vomiting ; and sometimes by ejecting of black or rusty and fetid matter, having scales like bran mixed with it, which is a certain index of a fatal mortification. . . . When the lungs are thus affected, the patient is first afflicted with a dry, hollow cough, which is quickly -succeeded with an extraordinary hoarseness and total loss of the voice, with the most distressing asthmatic symptoms and difficulty of breathing, under which the poor miserable creature struggles, until released by a perfect suffocation, or stoppage of the breath. . . . Comparatively few recovered. . . . Some expectorated incredible quantities of a tough whitish slough from their lungs. ... I have seen large pieces of this crust, several inches long and near an inch broad, torn from the lungs by the vehemence of the cough."

* Reprinted by Stephen Wickes, A.M., M.D., on p. 87 to 99 of his excellent " History of Medicine in New Jersey, and of its Medical Men, from the settlement of the Province to a.d. 1800. Newark, N. J., 1879."

3. It sometimes appears in the form of an erysipelas, in some with all the terrible symptoms above described, in some with none of them.

4. In external ulcers all over the body.

5. In glandular swelling's with favorable result only when they undergo suppuration, and lastly as sudden orthopncea, which proves fatal in from one to three days. It shows its peculiar character by the presence of the " crustula in the throat, which determines it to be a sprout from the same root with the symptoms described above."

The treatment of the Reverend is a singularly rational one ; moderate temperature, disinfectant applications, warm poultices to swollen glands, but moderate purgation, and mild stimulants, all of them in the compound mixtures of his time, form his armamentarium. He adds that there is no security against a second attack ; he has seen it four times in a patient in one year, the last proving fatal, and known numbers that have passed through it in the eruptive form in the summer season, " that have died with it the succeeding fall or winter, though I have never seen any upon whom the eruptions could be brought out more than once."

According to Dr. CadwaladerColden, in a letter written 1753 to Dr. Fothergill (printed in vol. 1st of the London Med. Observations and Inquiries, pp. 21 1-225), the " throat distemper " spread from Kingston gradually westward, so that it did not reach the Hudson river till near two years afterwards. It continued some time on the east side of the river, before it passed to the west, and appeared first in those places to which the people of New England chiefly resorted for trade, and in places through which they travelled. It continued to move westerly, till it probably spread over all the British Colonies on the continent. Dr. Colden's description resembles that of Dr. Douglas. A few of the points emphasized by him are the following. Though the disease was evidently propagated by infection, yet children and young people were only subject to it, with the exception of a few. A very few aged people who were taken died. It did not spread equally to all places that were proportionately exposed to the infection. The poorer sort of people were more liable to it, and they who lived on low and wet grounds and on poor scorbutic diet. In some places, only a few persons or families were seized; while in others, all escaped. In some families it passed like a plague through all their children ; in others, only one or two were seized. Some were attacked at great distances. Some had it mildly, while others in the same place and at the same time had it most violently. . . . "Many have not been confined to their beds, but have walked about the room, till within an hour or two of their death. And the complaint has often appeared no way dangerous, at first, to the attendants, till the sick were almost in the last agonies, though the patients themselves are generally dejected and apprehensive. . . . When the surfaces of the tonsils, after the sloughs were cast off, appeared of a very fiery-red color, there was some, or even great danger ; but when they were covered with a black crust it was often a fatal omen, as also where hemorrhages followed any slight scratch. . . . When the disease first appeared, it was treated in the usual way for a common angina, and no plague was more destructive. . . . The orifices made by the lancet in bleeding, and the adjacent parts were apt to become diseased. So likewise the places where blisters were applied. The ichor which issued from them corroded the parts upon which it flowed, and even slight scratches became as it were mortified. ... A girl about ten years of age, while the throat distemper was prevailing, had sores on her private parts like those on the tonsils of others, but no symptom of the disorder appeared in her throat."

The epidemic does not appear to have abated much after this time. For, in his first letter to Mr. Hugh Gaine, of New York, dated Jamaica (Long Island), Oct. 28th, 1769 (reprinted in the " Medical Repository," Vol. V.,

New York, 1802, p. 97), Dr. Jacob Ogden refers to the " distressed condition of the people in Boston and Oxford, occasioned by the fatal effects of the malignant sore-throat distemper." He also refers to the prevalence of the disease in his neighborhood. The symptomatology contained in his second letter, dated Jamaica, Sept. 14th, 1774, contains, briefly, a recapitulation of the excellent description, mainly of the milder forms, as given by Douglas, while the first is given up to treatment alone. Calomel and a compound mixture containing Seneka (Polygala s.) are highly recommended. Seneka was, credit not being given, claimed as the sufficient remedy in diphtheria " without any other medicine — the use of mercury may, however, sometimes, as in the symptomatic kind, be necessary " — by John Archer, Jr., in " an inaugural dissertation on cynanche trachealis, commonly called croup or hives," Philadelphia, 1798, p. 46, and " on the use of the Radix Seneka in the cure of croup. Letter to B. S. Barton, M.D." Med. Repos., I., p. 120, 1798 ; and II., 1799, p. 27. In connection with the above, a few sentences will be of interest as showing the tendency to disinfecting treatment on the part of the old practitioner. " Detergent gargarisms, or injections, are of service when the patient is of an age capable of using them. The air of the room where the sick lie might also with advantage be continually impregnated with the steam of vinegar. Sea-coal might be burnt in the winter instead of other fuel; and, in the summer, the room might be fumigated with myrrh, rosin, and sulphur, strewed on burning coal often in a day. These fumes, if diligently persisted in, would, it is more than probable, not only much benefit the sick, but be the best means of preventing the infection from spreading in the family " (Med. Repos., V., 1802, p. 103).

If we disregard the dubious reports of Le Cat concerning epidemics in Rouen in 1736 and 1737, we must consider them to have first occurred in France in 1745, having begun in Paris (Astruc, Malouin, Bouillaud, Chomel, du Hamel, Boucher, Navier), and later invaded the provinces (Rolin, Grandvilliers). Chomel has given us an accurate description of paralysis of the soft palate, and reports a case of diphtheritic strabismus. The English epidemic, described by Starr, occurred in the years 1744 to 1748; that by Huxham, in Plymouth, in 175 1 to 1753. The first Swiss epidemic happened in 1752, the Dutch in 1747 (Zaff), the Swedish in 1755 (Berg).

During the subsequent part of the eighteenth century, but two writers are worthy of especial notice, Home, a Scotchman, 1765 ; and Samuel Bard, an American, 1771.

Home deserves credit for having distinctly drawn the line between the pseudo-membranous and the gangrenous affections, and also for having endeavored, to his utmost, to convince his colleagues that croup and angina maligna were two distinct diseases/ notwithstanding all that had been uttered since the time of Aretasus to prove their identity. No matter in what way he tried to explain the false membranes — he looked upon it as an aggregation of mucus — he found it, and gave an accurate description thereof. He sought for it exclusively in the respiratory tract, and disregarded any connection between it and the false membrane found in the pharynx.