Part 111

On the other hand, while the above reasons go to prove that diphtheria attacks children by preference, there is again an anatomical and physiological condition--to wit, the free slightly acid secretion of the mouth, beginning with the third month--that acts as a hindrance to the frequent occurrence of diphtheria after the third month. A poison or poisonous product of whatever nature can less readily find a hiding-place so long as it can be readily--we might always say must surely be--washed away. During these months of eruptive secretion from the mouth diphtheria, therefore, is not very frequent; thus teething, in the case of diphtheria, cannot be held responsible by mothers fond of diagnosticating dental diseases. In this connection the remark of Krieger ought not to be overlooked, who explains the relative scarcity of the disease in the first year of life by the fact that cumulative influences will produce a great number of cases, and cumulation requires time. Undoubtedly, however, an important etiological consideration is the fact of having had the disease previously. We can cite a host of zymotic diseases the occurrence of which once serves as a protection against future attacks. Not only can no such security be expected after one attack of diphtheria, but, cæteris paribus, the disease shows a preference for those who have survived a previous attack. The statement that only the mild cases, with but slight elevation of temperature and freedom from severe constitutional symptoms, are likely to suffer a relapse is founded on error. True, I have more frequently seen relapses after mild cases--which, fortunately, are in the majority--but the disease has also recurred where originally high fever and an extensive lymphadenitis proved it to be a severe case. Besides, second attacks of membranous croup are also recorded (Guersant, N. F. Gill, Quincke).

As there are individuals, so there are families, which have a predisposition to diseases, as there are others in whom, notwithstanding ample exposure, infection does not easily take place. Yet in the families in which diphtheria is of frequent occurrence it cannot always be attributed to enlarged tonsils and a tendency to pharyngeal or nasal catarrh.

{682} Still, catarrh and the vulnerability of mucous membranes must be considered as a frequent source of diphtheria; children will get numerous relapses often after a nasal or pharyngeal catarrh. Sudden changes in the temperature of the atmosphere or of the surface of the body are therefore dangerous in predisposed persons. And thus it is that while severe epidemics have spared no climate or land known to us, the majority of cases have occurred in winter and spring; in other words, at a time when catarrhal disorders are of most frequent occurrence. In my experience at New York, the first quarter of the year yielded more cases than any other. Still, they are frequent enough in warm seasons. Krieger insists upon the injurious influence of hot summers and dry hot rooms. I do not doubt the correctness of his views, which cannot but be strengthened by the damaging results of our furnace-heating. But the influence of season on the invasion and course of diphtheria is but indirect and conditional, and may be, perhaps, after all, compared with that exerted by filth--a term which is lately used to express all sorts and forms of nastiness, from filthy bodies of men to their clothes, their habits, their food, and the air they breathe, whether polluted by carbonic acid, by excrementitious gases, or by exhalations of sewers.

Cases of diphtheria which are traced to exhalations from sewers (or even to filthy habits of life) are very frequent. Yet typhoid is attributed to the same causes. So is dysentery. Can, then, foul exhalations produce alike diphtheria, typhoid, and dysentery? Do these diseases arise from a common poison? Or is the poison of a treble character, so that a part may give origin to diphtheria, another part to typhoid, a third to dysentery? Have we to deal, in such occurrences, with specific influences, or only with a lowering of the standard of health, thereby affording other morbid influences an opportunity to exercise their power? These questions are still involved in darkness, and constitute problems the solution of which still engages the minds of both individual writers and authorities. A report of the Board of Health of Massachusetts, closely adhering to the results of exact observations, leaves them doubtful, and the affirmative reports of some modern writers do not bear scrutiny.

Air polluted by bad drainage or leaky sewers has been considered responsible for diphtheria as well as for typhoid fever and dysentery. Not only the impairment of general health, but the direct and unmistakable disease, has been attributed to it. Thus Bayley refers, in the endemic of Bromley, the first cases to unventilated sewers and cesspools. School-children multiplied the disease. Thursfield attributes the diphtheria at Ellesmere to the accumulation of excrements under the school-room, and to deficient supply of water, which, moreover, was of bad quality. Tripe (like Railton, Bailey, Russell, Bell) accuses sewer gas; others polluted waters or bad drainage. I have not been convinced, however, that diphtheria can be considered a sewer-gas disease, in the same way as typhoid fever. The deterioration of the general health resulting from the inhalation of foul air is sufficient to explain the outbreak of the individual attack during a prevailing epidemic.

{683} In regard to polluted water, I do not think that pathologists who attribute infectious diseases to bacteria only are justified in condemning it. It may not be so guilty, after all, for the admixtures, inorganic and organic, minerals, admixtures of wood and plants, also lower fungi and their products--algæ, infusoria--would render water rather disagreeable, but not exactly unhealthy. The latter effect can be accomplished--always assuming the bacteria theory correct, for the sake of argument--by bacteria only. But when they arrive in the stomach, their doom is sealed; they are decomposed. The only places where, possibly, they could take root would be diseased or ulcerated places in either the oral cavity or the upper portion of the oesophagus.

Not only water, but the milk of animals also, has been accused of being the direct cause of diphtheria. Powers concludes, though a connection between diphtheria and the consumption of milk have not been proven as yet, that it is very probable indeed. His careful investigations into the causes of some local epidemics in North London exclude any other source from which the people could have been affected. Perhaps one of the forms of garget, cow mammitis, is of an infectious character. His reasoning, however, is not accepted by A. Dowrus, who still believes that the milk which gave rise to diphtheria at a distance may have been soiled and infected. For though the connection between milk and scarlatina and typhoid fever had been known for years and variously studied, no observation of the kind had yet been made in regard to diphtheria. Besides, where the young, in England, drink much milk--viz. in the cities--diphtheria was very much less frequent than where little or no milk was taken--viz. in the country. Even in the country the well-to-do classes, who drink milk, had but little diphtheria, while the children of the poor, who obtained none, suffered a great deal from it.

In regard to this transmission of diphtheria by means of milk O. Bollinger hesitates to express any opinion, except that the matter is very doubtful indeed. Probably the possibility of contracting diphtheria directly from animals is very much greater than the danger from water or milk. On a Pomeranian farm, during the winter 1875-76, every newly-born calf died of diphtheria. The superintendent of the farm and the woman who attended to the calves were taken with diphtheritic angina. Similar occurrences have been recorded. Bollinger reports a mycotic disease of the trachea and lungs in birds.

Friedberger's report, presented to the Veterinary Society of Munich, on croup and diphtheria of domestic fowls, leaves no doubt as to its frequency, particularly amongst the nobler varieties.

Nicati studied an epidemic diphtheria amongst hens which had similar symptoms and a course very much like that in man; it could be inoculated into other animals, and was contemporaneous with the outbreak of the epidemic amongst the human population of Marseilles. Trasbot succeeded in inoculating a healthy hen from a diphtheritic one, but the {684} attempts at transmission to dog, pig, and man were unsuccessful. The Med. and Surg. Journal contains the following: In a house at Ogdensburg, N.Y., five children were ill with diphtheria. Three kittens who had been playing with them from time to time took the disease and died. Post-mortem examination showed diphtheritic membranes in their throats.

Gerhardt reports the following: 2600 hens were imported from Verona, Italy, into a village, Messelhausen, in Baden. Some of these hens were affected with diphtheria when they arrived. Within six weeks 600 of their number died of diphtheria, and 800 more soon after. In the following summer 1000 chickens were raised by artificial breeding, all of which died of diphtheria within six weeks. Five cats kept in the place also died of diphtheria; a parrot fell sick with it, but recovered. An Italian cook, suffering from diphtheria, in the month of November, 1881, while being subjected to local treatment with carbolic acid, bit the head-nurse's left foot and hand. Both these wounds became diphtheritic, the man falling sick with high fever, and requiring three weeks for his gradual recovery. Besides, four of the six workingmen employed in taking care of the hens of the establishment were taken with diphtheria. Not a single case, however, occurred in the neighboring village. Thus, it is safe to assume that the diphtheritic disease of hens can be transmitted to man.

Diphtheria may be also produced by outside influences. In this regard the attempts at generating pseudo-membranes by artificial means are very interesting indeed. As early as 1826, Bretonneau, by the introduction of tincture of cantharides and olive oil into the trachea, succeeded in producing a "dense, elastic, reed-like membranous concretion." Delafond called croup into existence by the use of ammonia, oxygen, chlorine, corrosive sublimate, arsenic, and sulphuric acid. On the other hand, H. Mayer asserts that it is impossible, by means of ammonia, to produce a croup in the windpipes of animals which in the slightest degree resembles that occurring in human beings. Trendelenburg, however, after producing membranes in the trachea by the use of a solution of corrosive sublimate (1:120), succeeded in hardening the entire mass with bichromate of potassium, which it was impossible to do with the most tenacious mucus.

Rey observed croup in horses that inhaled smoke in a burning stable. In the collection of the veterinary school of Zurich there is a croup membrane from a heifer which had been exposed to a fire; at Munich, one from the trachea of a horse, produced by forcibly injecting medicines into the nose. Hahn made an observation on cows, W. Ammon on horses, of long croup membranes after the animals had been exposed to smoke and fire; and Oertel constantly insists on there being "no actual difference between croup as it ordinarily occurs and that excited in the windpipe of a rabbit by means of ammonia. The color and texture, the physical, chemical, and histological characteristics, are identical."

{685} MORBID ANATOMY.--Either the membrane or the granular infiltration is characteristic of diphtheria. The statement that the former occurs only when atmospheric air can gain access thereto, as A. d'Espine and C. Picot still hold, is plainly contradicted by its appearance on the mucous membrane of the lower intestines. The condition of the membrane is not unalterable, any more than the clinical symptoms of the disease, for, according to different circumstances, epithelium, mucus, blood, and vegetable parasites are added thereto. The membrane can either be lifted from the mucous membrane on which it lies or is imbedded into and underneath it. In the first instance, it consists to a great extent of fibrin, the result either of epithelial changes or derived directly from the exuded blood-serum. E. Wagner, who makes no anatomical distinction between croup and diphtheria, considers epithelial changes the principal source. The pavement epithelium becomes altered in a peculiar manner. It becomes turbid, larger, dentated, and dissolves into a network; it is at first uninhabited, but serves later as the vehicle of newly-formed cells; there also occurs a considerable infiltration of the mucous membrane pus-cells and granules; besides, the cellular tissue is studded with granules, the granular degeneration resulting sometimes in necrotic destruction, which is looked upon by Virchow as the most important element in severe forms of diphtheria. The several conditions or degrees may occur independent of each other, associated or in succession. Classen shares Wagner's views, but, according to Boldygrew, the pseudo-membrane consists of successive coagulations of a fibrinous fluid which exudes from the diseased surface. Steudener also opposes the views of Wagner. He does not believe in the probability of an exclusively endogenous origin of the cellular elements of croup membrane; in fact, he doubts the occurrence of an endogenous formation of pus-globules in epithelium. Croupous membrane, according to him, is formed by the migration of numerous white blood-globules through the walls of the vessels in the mucous membrane, and by a direct formation of fibrin from the transuded plasma. In addition to this, the mucous membrane is stripped of its epithelium (except at the mouths of the acinous glands) and infiltrated with migrating cells. Fresh croupous membrane consists of a delicate network of homogeneous structure and shining appearance, in which numerous cells and the epithelium of the various layers of the trachea are imbedded. In old membranes the cells are destroyed by granular degeneration and general maceration. Tenacious mucus with pus-cells and detritus are then found. C. Weigert looks upon the deposits as analogous to those on serous membranes. Every inflammation yields an exudation which may coagulate when the coagulating ferment is added. This latter is probably produced by the white blood-cells when in disintegration. But he does not say why it is that there is no such coagulation in suppurative processes, where the leucocytes are more numerous. He believes himself justified in establishing pathological differences of croup, pseudo-diphtheria, and diphtheria. A croupous inflammation means destruction of epithelium, which gives rise to a fibrinous exudation upon the surface, while the cellular tissue remains intact. The only difference between it and the pseudo-diphtheritic inflammation is looked for in the larger number of emigrated white {686} blood-cells. The superficial deposit consists, to a great part, of them and the fibrinous exudation. When there are but few leucocytes the deposit is a network of fibrillæ (croup). When there are many, the masses are more solid and voluminous (pseudo-diphtheritis). When, however, the tissue is changed into a hard substance resembling coagulated fibrin, when the exudation does not exist on the surface, but takes place into the mucous membrane, the process is diphtheria. Zahn also establishes three varieties--viz. 1st, such as result from a peculiar degeneration of pavement epithelium; 2d, such as originate in the solidification of a muco-fibrinous, and, 3d, of a fibrino-purulent, exudation. Each of these varieties may contain colonies of micrococci, but these organisms are neither essential nor are they constantly found.

The diphtheritic process does not merely consist of the membranous changes in the pharynx and air-passages. Its fatal cases have afforded marked evidence of the implication of most of the organs. Reimer's 17 cases give the following post-mortem results: the lungs were hyperæmic in 8 cases, twice the seat of pneumonia, and three times of embolic infarctions; in addition, emphysema in 12, oedema in 6, atelectasis in 7, subpleural ecchymoses in 7, pericardial ones in 4. The heart-muscle had undergone fatty degeneration in 6, and was the seat of ecchymoses of the size of a pin's head in 3. In addition to frequent hyperæmic conditions of the abdominal viscera, emboli of the liver in 3 (with capillary hemorrhages of the peritoneal covering in 1), emboli of the spleen in 5, desquamative nephritis in 7 (in 6 of which there were colonies of micrococci in the uriniferous tubules), cellular hyperplasia of the cervical and mediastinal glands in 14 (complicated in 6 with capillary hemorrhages in the glandular tissue). The blood was frequently normal, very often watery and dark, at times leucocythæmic. Thus the disease exerts its influence everywhere.

Rindfleisch defines diphtheritic inflammation as that form of inflammation which produces a coagulating necrosis in the tissues by the immigration of schizomycetæ. The coagulating necrosis differs from the usual form of necrosis in this, that the change from life to death is accompanied with the coagulation of fluid albuminoids. This process takes place mainly in the interior of cells and other parts of tissues, and therein differs from the coagulation of fibrin. In the cells there is taking place a peculiar homogenization of protoplasm; at the same time the nuclei disappear, and are changed into irregular masses liable to cohere and form membranous conglomerates, which owe their peculiar wax color to the invasion of a solid albuminoid endowed with a strong tendency to refract the light. Coagulating necrosis is found in circumscribed localities, and gives rise, in the neighborhood, to a marked amount of inflammation and suppuration, which leads to the expulsion of the necrotic part, with more or less loss of substance--either mild or phagedenic ulceration.

Leyden describes a gray degeneration of the muscular tissue which he believes to be truly inflammatory, and Unruh has lately published an account of some cases in which myocarditis occurred. In Leyden's cases, the muscular nuclei were increased, became atrophied, and underwent fatty degeneration, giving rise thereby to extravasations, softening, dilatation and debility of the heart, with general debility, collapse, {687} and--probably by reflex action on other branches of the pneumogastric--vomiting. Micrococci he found neither in the heart nor in the kidneys.

In the heart, particularly on the right side, numerous thrombi are frequently found in various stages of development; its muscular tissue is often in a state of fatty degeneration or the seat of parenchymatous inflammation and hemorrhages. Bridges first called attention to the occurrence of endocarditis in diphtheria. This complication, which, however, occurs more frequently with rheumatism, puerperal fever, diphtheria of wounds, pyæmia, and old valvular affections than in the course of an acute diphtheria, does not, as found in the latter affection, consist simply of a fatty degeneration and subsequent ulceration, but is considered a genuine diphtheritic process (Virchow), affecting the mitral valve more frequently than the tricuspid or pulmonary valves. It begins with hyperæmia and the exudation of plasma in the cellular elements, so that they appear larger and darker. The granulations which form are frail and easily destroyed, so that ulcers form on which fibrin is deposited, and whence it is conveyed as emboli into the terminal arteries (Cohnheim) of the spleen, nerves, brain, and eye. Infarctions may also occur in the valveless veins of these organs, giving rise rather to small multiple abscesses than to large purulent collections. Suppuration but rarely takes place in the heart; the granular mass found there resists the action of æther and alcohol, and spreads throughout the cardiac parenchyma, so that perforation of the septum and of the right auricle and aorta has been observed.

Bouchut and Labadie-Lagrave, out of 15 cases of diphtheria, met in 14 with a plastic endocarditis, which became the source of emboli. Thus, there were infarctions of the lungs, at times in their centre colorless, at other times in a state of purulent degeneration; superficial thrombi of the small veins of the heart, subcutaneous connective tissue, pia mater, brain, and liver; and in addition, moderate leucocytosis.

The lungs exhibit (post-mortem) all sorts of inflammatory and congestive conditions, with their consequences, as oedema, catarrh, broncho-pneumonia, atelectasis, emphysema, ecchymoses, and large infarctions.

The spleen (and occasionally the liver) is frequently large, congested, and friable, and studded with infarctions to a greater or less extent.

The kidneys are either simply congested or the seat of nephritis or infarctions. The same forms of inflammation which accompany scarlatina--to wit, the desquamative and the diffuse--are here observed. The diffuse form is not of so frequent occurrence as in scarlatina, but is sometimes extensive and dangerous.

The muscles occasionally exhibit ecchymoses, and are at times the seat of parenchymatous inflammation, gray degeneration, and atrophy.

The lymphatic glands are frequently inflamed and swollen, either hard or doughy, oedematous or congested. Large abscesses are rare. It is more especially the gland tissue, and less the connective tissue of the glands, which takes part in the pathological process. The periglandular tissue very soon becomes involved, however. Necrotic foci have been described by Bizzozero. When the entire surface of the mucous membrane of the mouth and of the air-passages, from the nose to the trachea, is the seat of the disease, there is an impregnation of the mucous membrane, from the epithelial surface to the submucous tissue, of the entire {688} tongue, borders of the lips, and frequently of the lips and cheeks, as well as of the tonsils, the lower portion of the nasal cavities and the upper, and especially the anterior, portion of the larynx. The fossæ Morgagni and the posterior aspect of the soft palate are more frequently affected in the same way than the anterior aspect. Small isolated spots are found on the tonsils and occasionally on the posterior wall of the pharynx. The so-called croupous form--that is to say, the one in which the membranes deposited may either be removed in large patches or lie macerated in the profuse secretion of subjacent mucous glands--is found partly in the nasal cavities, on the posterior surface of the soft palate, and also in the trachea and its subdivisions.

The character of the mucous membrane varies with the locality. Its different elements, as the epithelium, the basement membrane, the connective tissue mingled with elastic fibres, the blood-vessels, the nerves from the cerebro-spinal and sympathetic systems, and the papillæ and ducts of numberless glands, all influence the pathological process going on upon the surface. Their distribution in the oral cavity and the respiratory organs is a very interesting study, and in a table already published, I have exhibited it in a condensed tabular form.

Where elastic tissue predominates, diphtheritic impregnation is slow to take place, and recovery is also slow when the tissue has finally submitted. Pavement epithelium yields the easiest foothold to diphtheritic membrane. Thus it is that the tonsils, not from their prominent situation alone, favor the reception and development of the infection. But the elastic and connective fibres when once affected are apt to harbor the disease a long time. Still, there is another reason why the diphtheritic process should favor the tonsils. For Th. Höhr has demonstrated that their epithelium exhibits interruptions in its continuity. Through them round cells may emigrate. Wherever the epithelial covering of the integuments (skin or mucous membrane) is intact and unbroken, diphtheria takes hold with difficulty. But where a defect is established, large or small, diphtheritic formations will be apt to take place according to the size of the abrasion. This is one of the modes of the formation of small diphtheritic deposits on the tonsils, which it has been the tendency of many, both practitioners and authors, to honor with special names.

Ciliated epithelium is not so liable to be affected. It occupies a higher rank in the scale of animal formations, has a more complex function and a greater power of resistance. The presence of a large number of mucous glands impedes, as a rule, by the presence of the normal secretion, an extensive destructive action upon the tissues. The secreted mucus assists in removing epithelial masses, and even fibrinous exudations, from the surface. Thus it is that the deposits in the respiratory portion of the nasal cavities are frequently cast off through the nostrils, and in a similar manner the membranes that have formed in the trachea are ejected in a semi-solid condition through the opening made by tracheotomy. The large number of mucous glands in the larynx and trachea is unquestionably the reason why the lymphatic vessels of the mucous membrane are not influenced by the overlying loosened masses, and will not absorb; hence laryngeal and tracheal diphtheria, when not complicated, have decidedly a local character, and are usually devoid of constitutional symptoms. For the {689} same reason the usual form of tonsillar diphtheria is a mild disease. On the other hand, the large number and size of the lymphatic ducts of the Schneiderian mucous membrane, as well as their direct communication with the lymphatic glands of the neck, accounts for the dangerous character of nasal diphtheria.

Diphtheria of the intestinal canal is characterized by fibrinous deposits on the surface and in the tissues of the intestine, with subsequent granular degeneration. It is mostly preceded by a catarrhal process. The same condition is found in the urinary organs.