Part 109

Panum, Bergmann, and Schmiedeberg have isolated poisons that contained no bacteria. Rawitsch and many others prove that septic infection is not dependent on the existence of bacteria. Davaine has shown that an infinitely small amount of a chemical poison, free from bacteria, can kill quickly.

The presence of cocco-bacteria (Billroth) in the blood during life has not once been proven, not even in pyæmia or septicæmia. Yet their being swept into the lungs with the atmospheric air is indisputable. It would therefore seem as though living blood had a greater tendency to destroy bacteria than to allow itself to be decomposed by them. Not only, however, would it seem so, but P. Grawitz (Virch. Arch., vol. lxx., p. 546) proves that sporules do not grow in the (tissue and) blood, but that they are in part dissolved, in part eliminated through the kidneys, and that this result is accomplished through the combination of the following four factors--viz. the elasticity of the blood, its constant motion, the absence of oxygen in sufficient quantity in the circulating blood, and the presence of living animal cells. All of these factors appear to be of great importance. Thus it is that, where the constant motion of the blood and the animal living cells are not present (as in the anterior chamber of the eye or in the humor vitreous) a rapid proliferation and accumulation of bacteria can take place. They are also known to increase rapidly and emigrate into the liver when deposited in the abdominal cavity.

The destruction of bacteria in the circulating blood, into which they may have penetrated, accounts for some microscopical facts in connection with (actually or apparently morbid) blood. Their remnants are probably the pale and dark particles which are discovered in the blood alongside the red and white blood-corpuscles. They could not be identified as micrococci, while in the tissue they are more recognizable. In autopsies they have been found in the urinary tubules, pressing forward and piercing the walls, not occupying a nidus of inflammation, however, and probably are even here a post-mortem phenomenon. A direct necrosis or inflammation by the inoculation of diphtheritic elements can only be produced in the cornea, as was shown by Recklinghausen, and particularly Eberth. Besides, there is nothing characteristic in the cocco-bacteria of {665} diphtheria, with the exception, perhaps, of their browner color, to justify their being looked upon as a distinct variety, certainly not as another species. It is more likely that a difference of action is not so much to be sought for in a different parasite as in the peculiarity of the corneal tissue. When fluid containing cocco-bacteria was injected into the eye of a rabbit, in twenty-four hours the eye was destroyed. If injected into the eye of a dog or guinea-pig, only a slight inflammation resulted (Billroth and Ehrlich). If these experiments were continued on a larger scale, we might eventually, by analogy, infer, and even prove, that the immunity against certain diseases enjoyed by some animals is owing to peculiarities in the very structure of their own tissues. In a similar manner I shall prove hereafter that even peculiarities and variations in the tissue and epithelium of the human body give rise to different shades and variable clinical symptoms in the diphtheritic processes.

The views of Curtis, Satterthwaite, and Charlton Bastian fully agree with those of the above observers. The latter is rather inclined to look upon bacteria as an effect of the disease than as a cause. Similar views were expressed by Burdon Sanderson.

Nor are the researches of Weissgerber and Terls, Lukomsky, Weigert, Lücke, any more conclusive; and, finally, Fürbringer, in his most recent and careful studies of diphtheritic nephritis, insists upon this, that it is not caused by immigration of fungi into the kidneys, that the very best methods employed for the finding of parasites result in the absence of micrococci from the inflamed organ, and that the renal inflammation following diphtheria is the result of a chemical process.

H. C. Wood and Henry F. Formad, in Supplement 7 of the National Board of Health Bulletin (1880), declare it 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 same authors publish a number of other experiments and conclusions in Suppl. 17 (Jan., 1882): "There is no proof as yet that the micrococci are the cause of the disease. Their presence in the exposed dead tissue is no evidence, for the membrane represents but the necrotic mucous lining.... Indeed, when the healthy mucous membrane of the mouth or trachea is destroyed by caustics--for instance, ammonia--the eschar into which it is converted--really a pseudo-membrane--contains the same micrococci as are found in true diphtheria, as Wood and Formad have learned. Moreover, in the scrapings of the healthy tongue the same micrococci can be seen. Of more significance is the detection of the same or similar micrococci in the blood of the living patients during severe attacks. But since these parasites were found only in the more severe cases, and not in all instances of the disease, were seen also {666} in the blood of other septic disorders, and since no cultures have been made with the fresh blood, there is not yet enough evidence for any decision. In the internal organs bacteria are not found with any regularity in diphtheria."

O. Heubner, while studying both the local affection and the general infection of diphtheria, availed himself of the methods of Cohnheim and Litten, who produced diphtheritic deposits by cutting off the circulation of the blood. He ligated the neck of the bladder in rabbits for two hours. On the first day he noticed a hemorrhagic oedema of the mucous membrane, with loosened and tumefied epithelium; on the second a firm and coagulated exudation took the place of the normal tissue; on the third there were genuine diphtheritic spots in the mucous membrane. The newly-formed pseudo-membrane exhibited all the morphological elements of human diphtheria (genuine or scarlatinous) and epidemic dysentery. Thus Heubner's results agree with the definition of diphtheria as the compound of severe inflammation and necrosis. The inoculation of his diphtheritic artefacts he found sterile. Animals, however, which were inoculated with diphtheritic masses taken from the diseased human patient fell sick with tumor of the spleen, hemorrhages, and general sepsis, besides a local diphtheritic affection. Scarlatinal diphtheria used for the same purpose had the same effect. Bacilli were developed, but they were not found in the blood-vessels (differing in that respect from the bacilli of anthrax), in spite of continued examination. Thus, Heubner refuses to accept the bacilli as the diphtheritic poison; they are, in his opinion, the result of the morbid process, and not its cause. Thus, though he believes the diphtheria poison to be organic, he concludes that its nature is not yet explained; contrary to the assertions of many prolific prophets of the bacteria literature, who now and then claim for this year's microscopic revelations the same infallibility which was claimed for last year's opposite views.

E. Rindfleisch expresses himself as follows: "The microphytes of diphtheria, septicæmia, and pyæmia have not been isolated and cultivated as yet. But experimenters are convinced that there are a great many species of microphytes underlying genuine putrefaction. In producing septicæmic conditions in animals their efficacy differs. Not every animal is influenced by the same microphyte. Thus it becomes probable that the human organism is endangered by a certain number of the putrefaction microphytes. Some one may have a particular predilection for granulating wounds and mucous membranes, and thereby produce a diphtheritic inflammation. Another may enter the blood from a recent wound and give rise to a septicæmic fever with rapidly fatal termination. The third may invade the body by means of a phlegmonous inflammation, purulent infiltration, thrombosis, embolism, and metastatic abscesses, accompanied with a pyæmic fever of a remittent type."

After all, it does not appear to me that the bacteria question has come {667} any nearer its solution in the last few years, in spite of the most eager researches and the fact that some of the best medical names in the world of medicine take the parasitic nature of diphtheria for granted. For instance, in the second Congress for Internal Medicine (Wiesbaden, 1883) C. Gerhardt rises in its favor. He makes the statement, or rather admits, that several parasites have been found by different men, that every one considers his the genuine one, that several writers assume that there are several diphtheria parasites, and suggests that, in his opinion, the disease may be produced by different varieties of bacteria. At the same time, he contends that the essence of the disease consists in the erosion (and change) of the epithelium and the emigration of leucocytes. If that be the case, I understand less than ever why diphtheria is, or is to be called, a parasitic disease.

Panum's words seem still to be the soundest expression of all our knowledge on the subject when he says: "It is a matter of rejoicing that physicians have come to the conclusion that certain microscopic organisms, be they considered vegetable or animal, and designated as bacteria, fungi, monads, micrococci, or vibriones, do not exist merely in the minds of theorists as causes of disease, but are in reality enemies that must be combated with all the known efficient weapons in our possession. But, while thus rejoicing, it must be borne in mind that we have but a feeble insight into the relation between these organisms and diseases, and in order to effect that much-desired advance in scientific knowledge--a matter of considerable importance in the practice of medicine--it is necessary not only to grasp at isolated data, but carefully and deliberately to observe and study all the facts before us, and even to devote some attention to those which would tend to prove that there are bacteria and fungi which, under certain circumstances, are perfectly harmless, and that even some of the malignant ones among them do not commit all those outrages with which they are charged, directly and personally."

SYMPTOMS.--In the majority of cases the disease has a prodromal stage, which usually lasts a day or two, and may run a similar course to that of a catarrhal pharyngitis. The patient feels somewhat indisposed, has slight fever, is dejected, complains of painful deglutition, more marked when swallowing fluids than solids or semi-solids, has headache and occasionally vomiting. The occurrence of the latter, however, is very much less frequent than in the outbreak of scarlatina. In very severe cases convulsions have been observed, chills very rarely; elevations of temperature of from 102.5° to 104° F. are frequent; higher ones, from 105° to 107°, rare. At this time it is often difficult or impossible to distinguish a catarrhal angina from a diphtheritic by the subjective symptoms. Slight glandular swellings under the jaw may occur in either. The characteristic objective symptom of the latter disease is the presence of membrane on the reddened mucous membrane of the fauces, which, usually, is markedly injected over all or part of the surface. The arches of the palate and the tonsils, less frequently the posterior wall of the pharynx, are so affected. A distinctly localized redness cannot be but either traumatic or diphtheritic. Larger or smaller deposits are found thereon, lying loose on the surface or deeply imbedded according to the locality. At times the first examination reveals their presence in large numbers; at other times but a single one can be {668} detected, which is soon followed by others, however. Within a certain period of time, as a rule twenty to twenty-four hours, the single deposits coalesce and form a membrane of greater or less extent. Mostly in the same proportion to its increase in size it increases in thickness. On the uvula, soft palate, and the posterior wall of the pharynx the membrane is located superficially, and at times can be easily removed; on the tonsils it has a firmer hold, and is usually amalgamated with their uppermost tissues. On the other hand, there are cases in which no actual membranous formation is observed; in such cases the tissues are more or less swollen, the surrounding portions more or less reddened, and the grayish-white discoloration is the result of an infiltration of the tissues themselves, and cannot be removed.

There are still other cases in which deposits of membrane and tissue infiltration are found at the same time, and where both history and evidence indicate that these two phenomena are the result of one and the same process. When the uvula takes part in the process the swelling is, as a rule, more marked than when the remaining parts of the fauces only are implicated. Its circumference is very considerable, and amounts sometimes to the treble or quadruple of the normal, in consequence of the oedematous condition of the entire tissue.

We have to deal, then, with three different manifestations of the diphtheritic process: first, with a membrane lying on the mucous membrane, and removable without causing much injury to the epithelium or any to the basement membrane; such membranes were given by some the name of croupous deposits; secondly, with a membrane implicating the epithelium and upper layers of the mucous membrane; to this the title of diphtheritic membrane has been given by preference; thirdly, with a whitish or grayish infiltration of the surface and the deeper tissue, which, if abundant, may give rise to a necrotic destruction of the tissue.

The severity of the disease does not always depend on the predominance of one of these three forms, for any of them may accompany a mild or a severe attack. By a severe attack we understand one attended with chills, temperatures as high as 105° and 107° F., and marked nervous symptoms, such as vomiting and convulsions. It is characteristic of such cases that when the membrane is accidentally or forcibly removed it is speedily reproduced; the lymphatic system, in addition, takes an active part in the process. The neighboring glands become swollen; the periglandular tissue does likewise, so that the circumference of the neck becomes enormous, and the space between the lower jaw and the clavicle appears one immense tumefaction. These are the cases in which, as a rule, loss of strength and general debility speedily ensue, and death occurs from exhaustion. The membrane in cases of this description frequently undergoes changes in appearance; under the influence of the atmosphere and of foreign substances, and by admixture of blood, its color becomes yellowish or brownish. The odor of the membrane and surrounding parts becomes sweetish and musty, and occasionally so fetid that it contaminates the atmosphere of the room, and the air in its transit through the nose and over the pharynx becomes by inhalation dangerous to the patient. His throat becomes more swollen, his respiration loud; he keeps his mouth open constantly, has an indifferent expression; the saliva dribbles continually, the color of the skin is sallow and livid, the {669} appetite very poor, and pulse both frequent and small. When the symptoms are of long duration, and a deep infiltration of the affected parts occurs, hemorrhages not infrequently make their appearance. These may be slight although frequent; occasionally, however, larger blood-vessels are encroached upon in the process of destruction, and dangerous, nay even fatal, hemorrhages may be the result. The septic forms which I have here described are more dangerous than the mild ones previously mentioned. Still, even in the latter bad results may ensue from a direct absorption into the blood of putrid substances and by the penetration of fetid gases to the lungs.

Occasionally, where the infiltration has been extensive, we meet with a condition that can only be considered as gangrene. In such cases we see collections of a grayish pulpy mass, which on falling off leaves a considerable loss of tissue, the further course of the disease being either favorable, or dangerous through absorption of septic material, or accompanied by local hemorrhages. When, after a time, health is completely restored, marked cicatrices are left behind. Such loss of tissue is generally seen in the tonsils only, but it may also be encountered in the soft palate. Its cicatrices on the soft palate are always a source of inconvenience, partly in swallowing, partly in speaking. Actual local perforation of the soft palate I have seen but five times in twenty-five years, sloughing without perforation very often.

The diphtheritic membrane not infrequently spreads from the pharynx to the neighboring organs. From the posterior aspect of the soft palate or pharynx the disease gradually ascends to the nasal cavities; this is particularly apt to occur when the uvula is the seat of extensive deposits, and by forced inspiration and deglutition its posterior surface becomes affected. In such cases the membrane which extends thence to the nasal cavities is very dense, and capable of narrowing the capacity of the nasal cavities anteriorly, and occasionally even to close them entirely; as a rule, however, several days elapse before the membrane assumes such a condition. Usually, when this form of nasal diphtheria is in its incipient stage, it is impossible to diagnosticate it; the most important sign thereof, besides a more nasal articulation and sometimes greater difficulty in deglutition, and the result of close ocular examination while the uvula is turned sideways or drawn forward, is a swelling of the deep facial glands at the angle of the lower jaw; when these swell rapidly it can be asserted positively that the nasal cavities have been invaded. There is little or no discharge from the nostrils under these circumstances.

The picture is a very different one, however, when the nose becomes primarily affected. This usually occurs only where an acute catarrh with but little secretion, not so often where a chronic catarrh, has preceded infection. When the secretion is thin and serous, the diphtheritic infection renders it no thicker, but makes it slightly flocculent, and it may become very profuse. This form is frequently attended with a disagreeable odor, equally unpleasant to the patient and to those around him. During the prevalence of an epidemic one must always be prepared to see an acute nasal catarrh or an influenza, or even a chronic nasal catarrh, become complicated with diphtheria or pass into it. Schuller reports the case of a five-weeks-old male child who, having had a nasal catarrh since birth, became affected with diphtheria of the nose. The glandular {670} swelling of which I spoke above is a very important diagnostic, and likewise a decidedly unpleasant symptom, which becomes very marked inside of twenty-four hours; frequently a partial swelling remains long after the disappearance of the diphtheritic membrane. Such glands rarely suppurate or undergo a necrotic degeneration; sometimes they become permanently indurated. This induration and a chronic pharyngeal and nasal catarrh are very serious matters in many instances. Both of these conditions are starting-points for a number of acute or subacute attacks of diphtheria in the same person. It is they which constitute the liability of persons once affected to be taken sick again. Not only are they liable to be affected themselves, but they are a constant danger to all around them. Diphtheria, in a large family of children living in one of the best houses of the city, after having returned half a dozen times in the course of a year, disappeared instantaneously, not to return, when a seamstress living in an infected neighborhood and suffering from occasional sore throats was relieved of her daily work in the house. Oedematous swelling of the mucous membrane and submucous tissue is often observed for a long period to come; elongated uvulæ, enlarged tonsils, often date back to such an acute attack. Thus it is with the upper portion of the larynx about the posterior insertion of the vocal cords (see below); its large amount of loose submucous tissue is liable to swell considerably in acute attacks. Frequent spells of croupy cough and a certain degree of dyspnoea are often observed for years afterward. Though the cases of genuine cicatrization between the arytenoid cartilages, as described by Michael, be rare, with their result of permanent paresis of the thyroarytenoid interni muscles, when they do occur they are either obstinate or altogether incurable.

Diphtheritic conjunctivitis occurs either primarily or as a complication of pharyngeal or nasal diphtheria. Fortunately, it is not of frequent occurrence; the cornea may become destroyed either by pressure through the considerable swelling of the eyelid or by diphtheritic keratitis. Usually the upper eyelid is the first to suffer; it is red, rigid, swollen. In the beginning the conjunctiva palpebræ is smooth, dry and pale, while that of the eye is chemosed; afterward diphtheritic deposits take place either in floccules or in solid masses. Knapp distinguishes between croup and diphtheria of the eyelid according to the facility or impossibility of removing the deposit. In favorable cases the membranes begin to macerate and the eyelids to soften after a few days. In those less favorable perforation of the cornea, prolapse of the iris, or total destruction of the eye take place.

The ear is but rarely the primary seat of diphtheria. A girl of three years died of laryngeal diphtheria on Sept. 6, 1882, after an illness of four days. A girl of seven years was removed from the house on Sept. 6th and returned on Sept. 8th. On the afternoon of the 10th an earring taken from the corpse was attached to the left ear of the sister, after having been washed with soap and water only. About noon on the 11th the lobe of the left ear reddened, on the 12th it exhibited a membrane and became swollen, and some glands enlarged in the neighborhood. On the right mastoid process the skin was not quite healthy, a vesicatory having been applied three weeks previously. This surface became {671} diphtheritic on the 12th, without consecutive glandular swelling. On the 13th the membranes grew thicker; on the 14th the pharynx was also affected, and the physician called in.

Most diphtheritic affections of the ear, however, are secondary. In pharyngeal and nasal diphtheria the narrow orifice of the Eustachian tube is easily obstructed by either catarrhal swelling or diphtheritic deposit. The disease may invade the middle ear and the drum membrane with perforation, caries, and deafness following.

The descent of the diphtheritic process into the respiratory organs may give rise to various conditions. The membrane is not always found to pass uninterruptedly from the mucous membrane of the fauces into the larynx; not infrequently isolated diphtheritic spots are found in the pouches on either side of the attached extremity of the epiglottis, or on the epiglottis, or in the larynx. At such times the epiglottis is moderately swollen, its margins hard and reddened. Occasionally the redness is interrupted by small diphtheritic deposits, which may remain isolated for a considerable time, but generally coalesce so as to coat the edges of the epiglottis with a continuous membrane. As a rule, the upper surface of the epiglottis is not completely covered by membrane, while only now and then diphtheritic deposits are found on its under surface.

The subjective symptoms accompanying the affection of the epiglottis are not always in direct proportion to the extent of the membranes. Dyspnoea and hoarseness occasionally occur where the only abnormal condition is a marked oedema at the entrance of the larynx, particularly of the posterior wall near the arytenoid cartilages and the attachment of the vocal cords. The oedematous condition causes a functional paralysis of the vocal cords, together with marked dyspnoea on inspiration. The difficulty of breathing may become so excessive that the clinical diagnosis of croup is unquestionable, and tracheotomy resorted to, while expiration is comparatively free and the voice not markedly affected. Furthermore, cases occur in which there is no marked oedema, but merely a general catarrh of the epiglottis and larynx; here, too, the subjective symptoms of hoarseness and dyspnoea may become severe and necessitate the performance of tracheotomy. Still, bearing this in mind, I have on several occasions refrained from performing this operation where I judged that, aside from the diphtheria of the pharynx, I had to deal with a moderate oedema of the glottis or a laryngeal catarrh.

Frequently, however, membranes form in the larynx in the same way as in the pharynx or nose; then inspiration and expiration are equally interfered with, and hoarseness is a more constant symptom than in the above-mentioned cases. Fever and pain are not necessarily prominent symptoms; in fact, they are frequently unimportant, but in proportion as the degree of narrowing of the larynx increases the respiration becomes more difficult, long-drawn, and loud.

It may happen that the trachea and bronchi may become affected, although diphtheria of the fauces does not exist. This does not occur as rarely as Henoch and Oertel seem to believe. They think that diphtheritic tracheo-bronchitis is mistaken for the primary condition, because the throat is not examined early enough.

Oertel is of the opinion that the membrane in the fauces is {672} overlooked in such cases. Steiner, too, asserts that "the tendency of the times is to question, nay, rather to deny, the existence of croup extending from below upward." Now, on the contrary, repeated experience enables me to assert with positiveness that diphtheritic tracheo-bronchitis may occur without an affection of the pharynx at the same time. I do not deny that it may last for days without giving rise to dangerous symptoms. I know it does. But when the process reaches the larynx, the symptoms of suffocation become so urgent that tracheotomy may be absolutely required at once, and, in spite of the operation, death soon after occurs.

Of course these cases are exceptions; as a rule, laryngeal and tracheal diphtheria result from a descent of the disease from the fauces. More or less uncomplicated cases of primary laryngeal diphtheria, or so-called sporadic membranous croup, were, however, observed before the end of the sixth decade of this century. They were then almost the only cases of diphtheria, and linked former epidemics and the present one together.

Inflammatory affections of the lungs may occur at various times and in various forms during an attack of diphtheria. That which appears after tracheotomy is usually a broncho-pneumonia, and results from rarefaction of the air in the respiratory passages during the period of impeded respiration, with consequent collapse of pulmonary tissue and dilatation of the blood-vessels, and hence a disturbance of the circulation. It may not fully develop until after tracheotomy, and is a frequent cause of death on the second or third day after the operation. Now and then a case of lobular pneumonia will result from the aspiration of pieces of membranes into the smallest bronchi. It can be easily recognized when the trachea is opened, but previous to the operation the auscultatory signs are of little or no value, being masked by the laryngeal râles. Percussion is equally useless, for a dulness may just as well indicate collapse of the lung as infiltration. The second form of pneumonia associated with diphtheria is from the beginning fibrinous in character. Here, too, auscultation and percussion are of little assistance in establishing a diagnosis when there is a laryngeal diphtheria at the same time, for the above reasons. Where, however, the dulness on percussion is accompanied by high fever, and the long-drawn inspiration is replaced by rapid respiratory movements, the diagnosis of pneumonic complication is justified.