Guersant and Blache (1844) describe the stomatite couenneuse (noma,
stomacace, according to them, the rarest kind of gangrenous angina) as
a form of Bretonneau's diphtheritis, and Landsberg raises the question
whether a nerve-inflammation, present in a certain case, was to be
looked upon as an accidental or an essential feature of the disease,
and finally comes to the conclusion, with Schönlein, that it was a
neurophlogosis dependent on the disease. Bouisson (1847) reports a
case of diphtheritic conjunctivitis resulting in loss of the eye.
Robert publishes his observations on diphtheria of the skin and of
wounds, which he attributes to an atmospheric contamination in crowded
wards of hospitals, and looks upon it, with Delpech and Eisenmann, as
a form of hospital gangrene. Virchow, in the same year, distinguished
the catarrhal, croupous, and diphtheritic varieties of the disease.
Meanwhile, reports of paralysis of the soft palate after diphtheria
came from Morisseau, from Trousseau and Lasegue, and lastly (1854-59)
from Maingault. The subject of diphtheritic conjunctivitis was studied
by A. v. Graefe (1854), who encountered the disease as a complication
of diphtheria of the pharynx, nose, and skin, and hence considered it
a part of the general disease rather than an independent local
affection. Diphtheria, in its effects on the system, had at the same
time been investigated by Trousseau, who sums up with the statement
that the principal source of danger lies in the invasion of the
larynx, and that the large majority of cases of croup began as a
diphtheria of the pharynx, but that, even without the occurrence of a
laryngeal localization, many cases terminate fatally owing to
adynamia.
Outside of France, too, the subject had attracted attention. West, who
had never seen the disease occur primarily, describes diphtheria as a
{662} complication of measles. Bamberger (1855) divides the
inflammations of the mouth and pharynx into the catarrhal and croupous
forms, and considers croup and diphtheria to be subdivisions of the
latter form, differing only in degree. The paralysis of the muscles of
deglutition is discussed by Dehænne (1857) who had contracted the
disease, and the paralysis of other muscles by Faure. A case of
diphtheria of the tonsils, nipples, and vagina in a woman recently
confined, followed by infection of the new-born and the death of both,
is reported by Mathieux; and cases of diphtheritic conjunctivitis by
Grichard, Warlomont, and Testelin. The same year Isambert published a
work in which he divided the diphtheritic affections into three
forms--viz. angine couenneuse, scarlatinous angina, and diphtheritic
angina. The last-mentioned is further subdivided into a
croupous-diphtheritic angina, in which croup of the larynx plays an
important part, and into that form in which death results from
adynamia; in the latter form there is a marked swelling of the
lymphatic glands. Apparently, at this time the epidemic in Paris
underwent a considerable change, for the croupous form does not occur
by far so frequently as Bretonneau had asserted, and croup of the
larynx without a preceding diphtheria of the pharynx was observed more
frequently than he would lead us to believe.
The various changes in the symptoms of the epidemics of diphtheria
which were observed in different places and countries, and at
different times, explain many of the differences of opinions in regard
to the nature of the disease. The literature of that subject is in the
last twenty-five years simply stupendous, and a few more notes must
suffice for the elucidation of the drift of theories and observations.
Beale was the first to look for organic beings as the cause of the
disease, without finding any. Laycock sees it in the bacilli and
spores of oidium albicans; Wilks, however, found the same parasite in
other affections. Cammack declares the diphtheritic membrane to be
herpetic. Feron also calls Bretonneau's mild form of the disease a
herpetic angina with pseudo-membrane; so does Gubler. Bouchut writes
against the identity of diphtheria, croup, and gangrene. Condie
describes the disease as occurring with scarlatina. Litchfield claims
that it is a concealed scarlatina, and Hillier that it has some
connection with it. Millard cites one case in the course of which
gangrene occurred, and another in which skin, mouth, pharynx,
respiratory passages, oesophagus, and vulva were affected at the same
time. Harley vainly endeavored to inoculate the disease in animals.
Stephens declares the disease to be infectious. Sanderson looks upon
it as identical with the angina maligna of the aged. Farr considered
the exhalations from sewers an important etiological factor.
Sellerier, Kingsford, and Harley (1859) report paralyses as sequelæ.
Maugin speaks of a specific eruption; Ward, of an accompanying
purpura. Bouchut and Empis remarked the frequent presence of and
danger from albuminuria; so did Wade. Maugin calls attention to the
fact that, when present in diphtheria, it occurs early, whereas in
scarlatina it is seen during the period of desquamation, and is not of
frequent occurrence even then. Gull gives an account of cases in which
death resulted from asthenia, and speaks of a nerve-lesion which he
attributes to the severity of the local inflammation. Hildige
describes diphtheritic conjunctivitis as seen in Graefe's practice,
and looks upon it as contagious. Magne denies its contagious or {663}
infectious character. Mackenzie, while probably having seen false
membrane appear on the conjunctiva when in a state of inflammation,
yet refuses to recognize diphtheritic conjunctivitis as a distinct
disease.
In the same degree that observations of cases and epidemics increased
in number, the nature of the disease and its cause commenced to be
studied. The assumption that the latter was a chemical poison was soon
doubted, and the parasitic nature of diphtheria considered by many as
proven.
After Henle had (1840) expressed his belief in the existence of a
contagium animatum, and morbid processes had for some time been
compared with the phenomena of fermentation, Schwann demonstrated the
presence of lower organisms in fermentation and putrefaction. The
discovery of the cause of the silk-worm disease by Bassis, of the
achorion by Schönlein, of the acarus by Simon, of bacteria in
malignant pustule by Pollender, Brauell, and, above all, by Davaine,
in relapsing fever by Obermeier, the teachings of Pasteur concerning
the conditions under which putrefaction occurs,--all tended to explain
the various infectious and contagious diseases by analogy also, and to
stimulate the search for a vegetable organism in diphtheria. Buhl was
the first to discover schizomycetæ in diphtheritic membrane, but
expressed no opinion as to the part they played in the process. Hüter
found them in the gray diphtheritic covering of wounds, in the
surrounding apparently healthy tissues, and in the blood. Hüter and
Tomasi found them in the diphtheritic membranes of the pharynx and
larynx, inoculated them on the mucous membranes of animals, and
described them as small, round or oval, dark-colored, active little
bodies. The latter observers look upon these organisms as a part of
the infectious element. Oertel found them in diphtheritic membrane and
in inflamed mucous membranes in the lymphatic vessels, lymphatic
glands, kidneys, and other organs; he considers them as the contagious
element of diphtheria. Nassiloff, too, after inoculations in the
cornea resulted in an enormous multiplication of the microscopic
organisms and their appearance with pus-cells in the lacteals and in
the lymphatics of the palate, and even in the bones and cartilages,
asserts that the development of organisms is the primary step in the
diphtheritic process. Eberth made successful inoculations in living
tissues; the micro-organisms, introduced into the cornea, proliferated
actively and caused an inflammation of irritative character in the
surrounding tissue. He asserts, with the positiveness of an
evangelist, that diphtheria cannot occur without bacteria. Klebs
inoculated the micrococci in pigeons and dogs, and found them in the
blood of the animals after death. Orth found them in the pleura,
lungs, kidneys, and urinary bladder. But what their action is, whether
they are directly pernicious, or deprive the body of certain elements
(as of oxygen in malignant pustule, according to Bollinger), or injure
mechanically by acting on the coats of the blood-vessels (either
directly or by means of altering the blood), thus depriving whole
territories of their blood-vessels, is a question upon which the
principal advocates of the parasitic theory have not yet agreed. Even
Oertel acknowledges the impossibility of explaining the manner in
which bacteria act (Ziemssen, _Handbuch_, ii., 1, p. 581, 2d ed.).
This much is positive, at any rate: that no one has yet proven that
the vegetable organisms alone, and not other, free or fixed, parts of
the {664} diphtheritic membrane, are the vehicles of the infecting
elements (Steudener); and even now the question has not been decided
whether the bacteria met with in diphtheria constitute the cause of
the disease, or are a part of the process, or co-effects of the
poisonous action--whether they are the carriers of the poison or
entirely indifferent entities.
The most important observations made by those who deny a direct
etiological connection between micro-organisms and septic diseases in
general, and diphtheria in particular, are those of Hiller and
Billroth. The latter has proven the morphological identity of the
various kinds of bacteria, although it cannot be denied that the
apparent similarity may mask a yet unknown difference. Hiller calls
attention to the fact that large numbers of micrococci have been found
in the cadaver where death has not been the result of septic disease,
and also that septic infection is not always severest where the
bacteria most abound, but where an extensive chemical decomposition or
a mass of putrefying tissue is found. This would indicate that the
septic process is rather dependent on chemical decomposition than on
the presence of bacteria.
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."[6]
[Footnote 6: H. Gradle, _Bacteria and the Germ Theory of Disease_,
Chicago, 1883, p. 186.]
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.[7] 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.[8]
[Footnote 7: _Die Experimentelle Diphtherie_, Leipzig, 1883.]
[Footnote 8: L. Letzerich recognized in former years the specific
parasites of diphtheria, whooping cough, and typhoid fever as if they
were labelled. Then, again (_Arch. f. Experim. Pathol. u.
Pharmacol._), he admitted the great difficulty in discriminating the
specific schizomycetæ of diphtheria, croupous pneumonia, epidemic
influenza, and typhoid fever.]
E. Rindfleisch[9] 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."
[Footnote 9: _Die Elemente der Pathologie_, Leipzig, 1883, p. 301.]
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.