Synonyms.—Diphtheritis; Angina Maligna; Membranous Croup.

Definition.—An acute infectious disease characterized by a grayish-white, fibrinous exudate, usually located upon the tonsils or neighboring tissues, though it may occur upon any abraded surface; the frequent involvement of the upper air-passages, and a toxemia that is attended by severe prostration; paralysis of certain organs and muscles, together with cardiac weakness.

History.—Diphtheria is one of the most greatly feared, most fatal, and most common diseases of childhood. Its history antedates the Christian Era by more than a hundred years; for Asclepiades performed laryngotomy for respiratory obstruction, and it is therefore probable that he treated croup and diphtheria; while Aretseus, a Greek physician of Cappadocia, whose writings are still extant, accurately describes diphtheria when he says, "The tonsils are covered with a white, livid, or black concrete product," and adds, if it invades the chest by the trachea, it causes suffocation the same day.

Galen, during the second century, undoubtedly referred to diphtheria when he described a "fatal disease then prevailing, where the patient expelled a membranous tunic by coughing- or spitting." Aetius, in the fifth century, describes a disease of the throat where the ulceration had a peculiar white, ashy, or rusty color. This undoubtedly was the same dread disease.

From the fifth to the sixteenth century there is no record of the disease; but it is not at all likely that the disease had disappeared from the world, but that the medical writings of the Dark Ages suffered the same as general literature, and the disease most likely appeared during these centuries the same as before and since, numbering its victims by the thousands.

During the sixteenth century epidemics prevailed in various parts of Europe, and the disease has steadily kept pace with the intervening centuries, so that we enter the twentieth century with the dread scourge more thoroughly intrenched in all large cities than it has ever been. This is a sad confession for the medical world to make, when we remember that, during the last twenty-five years, this disease has been studied more, discussed in medical societies more frequently, and has formed a topic for innumerable journal articles; and yet, notwithstanding these facts, and the great advance made in sanitary methods, there are more deaths recorded to-day from diphtheria than from any other contagious disease. The disease has prevailed in this country ever since its first appearance in Boston, 1638.

Etiology.—The disease usually prevails epidemically, though in all large cities it is endemic. The force of the contagion varies in different epidemics; but, taken as a whole, I am inclined to believe that it is less contagious than scarlet fever. The last thirty years has witnessed greater search for the causal agent than all previous years combined.

Dr. Pruden and others, after careful investigation in a series of cases, came to the conclusion that a streptococcus, which is always present in the membranous exudate, was the causal agent. Dr. W. W. Taylor presented to the London Epidemiological Society the history of a number of cases, to prove that common mold was the causal agent. Others have tried to prove that sewer-gas was a prime factor in producing the disease. Each investigator showed an array of cases to prove his position, yet each and all fail to prove that every case can be traced to the causal agent.

Since 1868, when Oertel discovered micrococci in the pseudo-membrane, bacteriologists have been trying to separate the special bacillus which will invariably produce the disease. While it might be interesting to some to trace the work of such investigators as Oertel, Cohn, Klebs, Loemer, Roux, Yersin, and a host of others, space forbids. Suffice it to say that from out of the great mass of investigations there has been evolved the Klebs-Loeffler bacillus as the causal agent. This is the generally accepted micro-organism which is responsible for diphtheria.

Yet there is ground for much difference of opinion as to the reliability of this germ as the causal agent. First, it is found in other diseases of the mouth and pharynx. Again, it is sometimes found in the healthy mouth and the mucous surfaces of the throat and nose, and finally it is sometimes absent in well-known cases of diphtheria; but in order to prove that this special bacillus is the cause, all cases showing an absence of this germ are denominated false diphtheria, or diphtheroid angina. Hence we divide the bacilli into two classes,—the Klebs-Loeffler bacillus of true diphtheria, and Hoffman's bacillus, or the pseudo diphtheria bacillus, or bacillus xerosis. (See frontispiece.)

We are inclined to believe that the specific cause has not yet been determined. That it is a specific poison is undoubtedly true, and whether it resides in sewer-gas, common mold, or in whatever form or place, all that is necessary is for the poison to come in contact with the individual.

The toxin may so influence the blood that we see the systemic affect first, and the local lesion follows, or, as Dr. Scudder said in 1861: "I hold diphtheria to be a general as well as a local disease, as is proven by the languor, listlessness, torpor of the nervous system, and derangement of the excretory organs, which, as a general rule, precede all local disease; all being symptoms of perversion of the blood, and almost invariably indicating the establishment of febrile reaction. We also find the evidence of the perversion of the blood in the heavily coated tongue, which is always more or less discolored at the commencement of the disease, and always, in severe cases, exhibiting the brownish tinge, with more or less sordes upon the teeth as the disease progresses; in the diphtheritic deposit, which is markedly different from the exudations from highly vitalized blood; in the secretions, the urine in severe cases being abundant, in all cases discolored, frothy, more or less clouded, with a peculiar, somewhat cadaverous odor—what the ancients would have termed illy concocted; in the evacuations from the bowels, obtained by cathartics, which are frequently large, dark, and almost invariably fetid; and especially in the condition of the blood itself, when the disease has attained its maximum, which is dark, is not changed by exposure to air, forms a loose and easily broken coagulum, or does not coagulate at all.

"Post-mortem examination in those cases that have run a regular course—i. e., that have not been terminated by an extension of the disease to the larynx—shows us the blood broken down to a considerable extent, more or less discoloration of tissues from extravasation of the coloring matter, and softening of the tissues. These facts, it appears to me, prove conclusively the opinion given above."

Diphtheria in the Lower Animals.—It is now generally admitted that the lower animals may become infected, and they, in turn, communicate the same to others. Especially is this true of fowls and the common domestic animals, cats and rabbits; pigeons and domestic fowls are perhaps more frequently affected than all others.

In Keating's Encyclopedia of the Diseases of Children, Dr. Lewis Smith gives an account of an epidemic of diphtheria communicated from diseased turkeys, which would seem quite convincing. The author says: "On the Island of Skiathos, off the northeast coast of Greece, no diphtheria had occurred during at least thirty years previous to 1884, according to Dr. Bild, the medical practitioner of the island. In that year a dozen turkeys were introduced from Salonica. Two of them were sick at the time, and died soon afterwards. The others became affected subsequently, and of the whole number seven died, three recovered, and two were sick at the time of the inquiry. The two had a pseudo-membrane upon the larynx, difficult breathing, and swelling of the glands of the neck. As further evidence that the disease was true diphtheria, one of the turkeys, which had survived, had paralysis of the feet. The turkeys were in a garden on the north side of the town, and the prevailing winds on the island are from the north. While this sickness was occurring among the turkeys, an epidemic of diphtheria commenced in the houses in proximity to the garden, and spread through the town. It lasted five months, and of one hundred and twenty-five cases in a population of four thousand, thirty-six died. Diphtheria from this time was established upon the island, and frequent epidemics of it have occurred since."

Predisposing Factors are age, season, climate, and unhygienic conditions.

Age.—Diphtheria is essentially a disease of childhood, though no age is exempt. The ages most susceptible are those between two and eight years, the receptivity diminishing each year thereafter. During the first year of life it is also infrequent, most likely owing to lack of exposure in the very young. One attack does not render the patient immune.

While elderly people are not so liable to the disease, physicians and nurses should be very careful while examining or treating the throat; for in the struggle of the child a portion of the membrane may be forcibly thrown into the face and eyes of the attendant during a fit of coughing.

Season.—It prevails more extensively during the winter and spring month's.

Climate.—The disease occurs more frequently in cold and temperate climates than in the tropics. Moisture favors the propagation of all germs; hence damp cellars, where mold collects, favors the spread of the disease.

Unhygienic Conditions.—Poor sanitary conditions lower the vitality and resisting power of the individual; hence render one more susceptible to the poison. Germs of all kinds thrive in filth; therefore decaying organic material, defective drainage and sewage, cesspools, etc., favor not only the propagation of diphtheritic germs, but those likewise of all the infectious fevers. It is true that persons living with the most perfect sanitary conditions are victims of infectious diseases, but this is due to the non-resisting power of the individual to the germ or poison.

Pathology.—Diphtheria being a general as well as local disease, presents pathological features of each.

Local.—The peculiar characteristic pathological feature of diphtheria is the formation of a fibrinous exudate, varying in size and consistency, and locating generally in the throat and near neighborhood. Usually the tonsils and uvula are covered with this exudate, but it may extend in every direction, the entire fauces, the cheeks, the nares, and, passing deeper, the Eustachian tube and middle ear on the one hand, or the nasal duct and conjunctiva on the other, while the respiratory tract may receive the brunt of the attack, and a complete cast of the larynx follow.

In one of my cases, after expelling the membrane from the larynx, the napping of the loosened membrane could be distinctly heard in the bronchi upon auscultation. Others have reported the extension of this exudate through the entire digestive tract, while Smith records the passing of a false membrane from the lower bowel, a foot in length. In the female it may involve the vagina and even the uterus; in the male it has formed on the prepuce. Thus we see that any mucous surface, upon injury or severe irritation, may show the characteristic exudate.

In mild cases this exudate may be thin and superficial, and easily removed, involving only the epithelial layer and superficial mucous surfaces, the neighboring tissues showing a swollen and hyperemic condition; within forty-eight hours the. membrane slips off, leaving a slight ulcerative surface. In this case the external appearance is more cleanly looking, being of a whitish gray color.

In the severer cases, the exudate is thicker, more dense, and is firmly adherent in the tissues, like the glass in a watch-case. It is ashy gray in color at first, soon changing to a dirty brownish color as necrosis proceeds. Beneath and around the membrane there is hyperemia, and the inflamed condition of the tissues results in the discharge of a purulent material. The deeper tissues are infiltrated, and frequently extensive sloughing follows the removal of the exudate.

The pseudo-membrane is composed of fibrin, necrosed epithelium, pus, broken-down leukocytes, blood-disks, and bacilli of various kinds, of which the Klebs-Loemer predominate. The blood-vessels beneath the membrane are congested, and the lymph channels are dilated and filled with fibrous fluid.

The necrosis may be confined to the epithelium, in which case there is but little tissue change: but if the deeper connective tissues are involved, there may be extensive destruction of tissue, including blood-vessels. When the membrane in the larynx and bronchi is thick and tenacious, complete casts may be expelled.

Heart.—Among the most important lesions in severe diphtheria are those that affect the heart. There may be parenchymatous degeneration in the less severe form, while fatty degeneration occurs in the severe case. One or both ventricles may be dilated. The walls of the heart are often flabby, while interstitial myocarditis is not uncommon; a rarer lesion is endocarditis and pericarditis.

Kidneys.—In the severer cases of diphtheria there is nearly always more or less acute nephritis, and a cut surface reveals the process of degeneration. The kidneys are usually enlarged. The urine is generally rich in albumen, casts, epithelium, and leukocytes.

Spleen.—In most diseases where there is toxemia, we find enlargement of the spleen, and this disease is no exception. There is also degeneration of its tissues. The lymphatic glands of the neck are frequently swollen and more rarely hemorrhagic, while suppuration may take place, though not common.

Nervous System.—J. G. Thomas reported in the Boston Medical Journal, February, 1898, the lesions produced by diphtheritic toxin, as follows: 1. A parenchymatous degeneration of the peripheral nerves, and at times an interstitial process is added to the degenerative one, accompanied by hyperemia and hemorrhages. 2. Acute parenchymatous and interstitial degeneration in the muscles, especially the heart muscles. 3. Only slight changes in the nerve cells. 4. In rare cases a hyperemia, infiltration or hemorrhage into the brain or cord sufficient to produce permanent troubles, as hemiplegia and multiple sclerosis.

Blood.—The blood is more or less broken down, the fibrin is deficient, and the tissues are usually stained by extravasation of blood. Leukocytosis is generally pronounced, the increase of leukocytes beginning a few hours after infection.

Symptoms.—The symptoms will depend upon the character of the epidemic, the parts affected, and the complications. We shall not attempt, however, to classify and describe, as separate forms, nasal, pharyngeal, tonsillar, laryngeal, etc., believing that, when these different parts are involved, they are simply extensions of the general disease, and do not need a special classification and description, but will treat them as they occur.

Incubation.—This stage varies from two days to two weeks, depending largely upon the character of the infection and the manner of receiving the same. If by inoculation, from twelve to twenty-four hours may constitute the incubating period, and when the infectious material is very intense, as in the malignant form, the period is also short, from two to four days. The symptoms during this period are not characteristic nor constant, but might be taken for the forming stage of any of the infectious fevers.

Generally the patient is listless and languid, complains of feeling tired, and is not interested in his play; is fretful and restless at night; eats but little, but calls for water frequently, being thirsty; the breath is usually offensive, and the tongue is coated with a moist, dirty fur; the patient may complain of being chilly and of pain in head, back, and limbs. These prodromal symptoms may culminate in a chill,' to be followed by fever of varying intensity.

In some the thermometer alone reveals the increase in temperature, while in others the fever is active throughout the course of the disease. The secretions from the skin, kidneys, and bowels are more or less arrested, while albumen is generally found in the urine. As the disease progresses, the fever assumes an asthenic form, and the blood shows the presence of the septic poison by the dirty tongue, fetor, and condition of the mucous surfaces.

The local phase of the disease is shown very early by pain in deglutition, though, in rare cases, the patient experiences no pain, although inspection reveals an alarming condition. There is usually dryness, the patient swallowing frequently to moisten the throat. On inspection we note that the mucous surface of the fauces, tonsils, and pharynx are reddened and swollen, upon which the characteristic ashen gray exudate appears. Sometimes the throat presents a livid appearance, revealing the malignant character of the attack.

The exudate first appears in small patches about the size of a wheat kernel, but soon coalesces into one or more large patches or mass. The exudate, at first superficial, soon dips into the deeper tissues, and presents a characteristic appearance, embedded like the crystal in a watch; the exudate can not be wiped off like an ulcerated surface, but firmly adheres, and, when forcibly removed, leaves a raw and bleeding surface.

"For two or three days, in the majority of cases, the throat is dry; sometimes, indeed, during the entire progress of the disease. Then secretion is established from the mucous follicles, and, some patches of exudation being removed, there is a free secretion from the denuded surface. The salivary glands also become more active, and the saliva is thick, tenacious, and ropy; and altogether the secretion is large, and requires frequent efforts at removal. Occasionally cases present themselves in which this seems to be the most unpleasant symptom.

"In the latter stages of the disease we may distinguish two classes of cases. In the first the dryness continues, and the parts become stiff and immobile, so that, after a time, deglutition becomes almost impossible, and respiration is rendered very difficult and labored. Extending upward to the posterior nares and nasal cavities, these are closed by the swelling; and descending to the inferior portion of the pharynx and epiglottis, these and associated parts are swollen and rendered incapable of motion, and the patient dies, partly from want of food and drink, and partly from imperfect aeration of the blood.

"In the second class of cases, secretion commences about the second or third day. By the fifth day it is quite free, some portions of the exudation are being detached, and the exposed surface secretes pus. In very severe cases this ulceration progresses in every direction, but is mostly superficial. The tissues seem to have lost their vitality, and the muscles their power of contraction, and they hang feeble and pendulous, and infiltrated with serum where the connective tissue is loose. Thus we have paralysis of the throat in the second as well as the first case."

Malignant Diphtheria.—Some seasons the diphtheritic virus possesses a virulence entirely unaccountable. The patient seems stricken with such force that the resisting power of the system is unable to cope with its unequal foe. The patient is dull and listless; the face is a dusky hue; the tongue thick, flabby, and covered with a dirty, pasty coating, or it is dry, brown, and parched; the fever is quite active, the temperature reaching 103° to 104°, or even 105°. The pulse, however, is small, though rapid, showing marked enfeeblement of the heart. In nervous children, vomiting, followed by convulsions, may usher in the disease. The urine is scanty and often loaded with albumen.

The local affection is seen very early; the tissues of the throat are dusky and swollen; the tonsils enlarge, and, with the swollen and edematous condition of the uvula, the throat is so occluded that swallowing is exceedingly difficult, painful, and often impossible, the fluid returning through the nose. To add to the gravity, a cellulitis develops, and the deeper tissues of the neck are involved. The lymphatics of the neck become hard and swollen, the nares become almost closed, causing difficult respiration. The exudate soon appears on fauces, tonsils, and uvula, frequently passing to the nares.

If the child lives long enough, the necrotic exudate gives way, leaving a ragged and foul-looking ulcer. The odor is peculiarly offensive. From the nares a bloody, sanious, excoriating discharge takes place. The extremities become cold, the child becomes drowsy, the face becomes more dusky, the heart beats feebly, and finally death relieves the sufferings of the little patient. If convalescence takes place, recovery is slow, the heart showing the effects of the poison in the feeble frequent pulse.

Nasal Diphtheria.—While in a severe case of pharyngeal diphtheria the membrane may extend to the nares, we are not to overlook the cases where the exudate is primarily in the nares. In these cases we have all the general symptoms of diphtheria, but the throat remains clear for the first few days, though the exudate may ultimately extend to the pharynx and neighboring structures.

The exudate is usually not so firm, though sufficient to obstruct the nasal passage, and causes the child to breathe with the mouth open. An offensive sanious discharge excoriates the end of the nose and lips, and the child fights all efforts to relieve it.

When the child sleeps, the mouth remains open, and a bubbling, distressing respiration is heard. The exudate may extend to the conjunctiva, causing the eyelids to become swollen and discharge pus, or the inflammation may extend along the Eustachian tube, affecting seriously the middle ear.

Laryngeal Diphtheria.—This form is the most alarming, and causes more suffering than all other forms. The presence of the membrane is first made known by the hoarse, croupal cough, soon to be followed by the ringing, metallic cough and whistling respiration, which, once heard, can never be forgotten. The fever is not usually high, in fact may be normal, and in fatal cases may be subnormal. Inspiration and expiration are difficult, the epigastrium and lower intercostal muscles being forcibly retracted with each inspiration.

The child now labors for breath, is restless and tosses about; the respiration is sibilous or whistling, the cry shrill and piping; the face now shows the effects of the impaired respiration and imperfect aeration of the blood, in the bluish color of lips and nose. The voice sinks to a whisper, the child becomes more quiet, dull, and drowsy, the pulse small and feeble, the extremities cold, and death ends the struggle.

Where recovery takes place, the membrane becomes softened, and small bits of it are expelled with each paroxysm of coughing, till finally the larynx becomes free, and the voice and respiration are restored to the normal condition. In the severer forms the membrane extends to the trachea and bronchi, which still further obstructs the respiration and adds to the gravity of the disease.

Sequelae.—The most serious and also the most important sequela is paralysis. This is a neuritis due to the toxic poison. It most frequently affects the throat, and comes on two or three weeks after convalescence. When the patient attempts to swallow, especially liquids, they are returned through the nose. There is also a peculiar nasal twang to the voice which is characteristic. The lower limbs are also frequently the seat of the trouble, and the knees suddenly give way while walking.

The most serious sequela of all is paralysis of the heart, which is the cause of the sudden death that occurs after the patient has recovered from the severer forms of the disease. The prognosis is generally favorable in the forms of paralysis save that of the heart.

Chronic naso-pharyngeal catarrh is also quite a common result of diphtheria.

Diagnosis.—The diagnosis of diphtheria is usually not very difficult, and since the Klebs-Loeffler bacillus is found in some healthy throats, and may be absent in severe angina diphtheria, we will have to depend on clinical evidence for our diagnosis.

The history of the case, the prostration, the small, feeble pulse, the dirty tongue, the peculiar odor, and albumen in urine, and especially the characteristic ashen gray membrane, covering the tonsils and in most cases the uvula; the membrane not easily removed being embedded in the tissues,—are symptoms that can not readily be overlooked. Even in mild cases the exudate is distinct and the diagnosis readily made.

If the physician be called in late in the disease, and the exudate has disappeared, the diagnosis is not so easily made; yet the prostration, feeble pulse, and presence of albumen, even though we failed to get a history of the presence of the membrane, would be very suggestive of diphtheria.

Just here we desire to say a word as to the identity of diphtheria and membranous croup. We take the ground that they are distinct and separate diseases, though we have laryngeal diphtheria. Membranous croup comes on more or less suddenly, does not prostrate the patient as does diphtheria, there is but little evidence of sepsis, no fetor, and the patient succumbs, not to systemic poisoning, but from asphyxia.

Prognosis.—The prognosis depends upon several conditions, such as the character of the epidemic, the complications, and the age of the patient. Some years the disease appears in a mild form, and nearly all cases yield to treatment, while at other times such a malignancy attends the disease that but few recover. In 1883 I received a letter from a physician in Dakota, asking for help in the treatment of diphtheria. He wrote, "Nearly every one that contracts the disease dies, no matter what school treats them."

When the local disease extends from tonsils to uvula, to the nares and to the larynx, these are always serious, and the prognosis should be guarded. Age also figures in the prognosis; for the younger the patient, the more likely to a fatal termination. If there is broncho-pneumonia, the danger is increased. Then the tendency to paralysis after the grave symptoms disappear makes this one of the most treacherous of all diseases, and therefore, unless of a mild type, we should be guarded in our prognosis.

Treatment.—As soon as the diagnosis is made, the patient should at once be isolated, the preparation of the room being the same as for any infectious disease; viz., the removal of all unnecessary furnishings, such as carpet, draperies, etc. Where possible, the room selected should be large, with exposure to the sun, and well ventilated. All discharges from nose and mouth should be received on cloths and burned.

Where possible, a nurse should be employed and kept away from the other members of the family. The physician should be especially careful, when inspecting the throat, not to receive any of the discharges from the mouth of the patient during a paroxysm of coughing, which often occurs when the tongue is depressed and the doctor is making his examination. As soon as the patient is convalescent, the room should be thoroughly disinfected.

The medical treatment will consist of both local and systemic measures. Internally, if the temperature is high, with small, quick pulse, give aconite five drops to water four ounces. I am aware that there is an idea prevalent among a great many that aconite should not be given in diphtheria, it being a depressant, but an experience of twenty-five years in the use of this remedy does not justify the impression. If the small dose be used, I am satisfied that it is beneficial. To this we add phytolacca, fifteen to twenty drops, when the glands of the neck are swollen or when there is congestion of the tonsils.

If there be a foul odor, alternate baptisia with the former remedies. If the tissues are full and bluish, give echinacea one drachm to water four ounces. This is one of our best remedies, a good antiseptic and sedative combined. Where the breath is bad, that peculiar stench so often found, I find nothing equal to potassium chlorate and phosphate of hydrastine. This is another agent which is given credit for giving rise to nephritis, but years of experience in its use does not bear this out; perhaps the hydrastine overcomes this tendency. I am sure that the following is one of our best combinations: potassium chlorate, one drachm; hydrastine, five grains; water, four ounces; a teaspoonful every one or two hours. If the patient is old enough, have him gargle with a solution of the same strength. If the tongue and mouth become dry and brown, give hydrochloric acid ten to twenty drops, simple syrup, and water, of each two ounces; a teaspoonful every one, two, or three hours.

To keep the throat as clear as possible use a gargle of potassium chlorate and hydrastine or salicylic acid and borax; of the latter each ten grains, to water four ounces, or a spray of three per cent solution of pyrozone. In malignant cases, threatened with heart-failure, Dr. Webster speaks highly of lachesis. Where the nose is obstructed by the exudate, and a sanious discharge is excoriating the lip, the nasal toilet is especially beneficial. Unfortunately these cases are found mostly in children, and it is impossible to spray or cleanse the nose.

Where the larynx is involved, the use of inhalations will give the best results. With the first croupal symptom place a quart of boiling water in a vessel, and add a cup of cider-vinegar and a handful of hops; place this over a burner near the bed, and, by means of a tube, convey the steam directly to the child's face, so that the inhalation may be constant. This will soften and loosen the membrane. Now give nitrate of sanguinary 2x or 3x every hour, and the membrane will be expectorated in small particles or in long shreds. Inhalations of steam from boiling water is highly recommended. A cold pack to the throat may give some relief when the patient is suffering pain.

Serum Therapy.—The last few years have found many advocating the use of antitoxin. Statistics, both pro and con, have been offered to prove both its usefulness and also its danger. That harm has followed its use, none will deny; yet many able men claim good results for the serum treatment. Personally, I have not been successful in its use, and believe that the treatment above outlined will give by far the best results.

The diet should be fluid in character, milk being preferable. The child should be carefully watched during the convalescence for signs of heart-failure, and with the first evidence, put the child to bed and give cactus, digitalis, or kindred remedies.

The Eclectic Practice of Medicine, 1907, was written by Rolla L. Thomas, M. S., M. D.