KERATOSIS FOLLICULARIS 
(PSOROSPERMOSE FOLLICULAIRE 
VEGETANTE). 
A SECOND CASE. 
BY 
JAMES C. WHITE, M. D., 
Professor of Dermatology in Harvard University. 
REPRINTED FROM THE JOURNAL OF 
CUTANEOUS AND GENITO-URINARY DISEASES 
FOR JANUARY, 1890. Reprinted from the '■'■Journal of Cutaneous and Genito-Urinary Diseases'" 
for January, 1890. 
KERATOSIS FOLLICULARIS 
(PSOROSPERMOSE FOLLICULAIRE VEGETANTE) 
A SECOND CASE. 
By JAMES C. WHITE, M. D„ 
Professor of Dermatology in Harvard University. 
IN the Journal of Cutaneous and Genito-urinary Diseases 
for June, 1889,1 published the account of a remarkable case of cuta- 
neous disease, such as I had never seen before, and of which I could 
find no description in literature. It was characterized by concretions of 
epithelial cells, varying in size from the head of a pin to horn-like masses 
of half an inch in height, which had their origin within the mouth of the 
sebaceous glands, and occupied nearly the whole surface of the body. I 
called the disease, therefore, keratosis follicularis. 
At the International Congress of Dermatology, held at Paris in August, 
a patient was shown as an example of an affection described by Darier, 
chef die laboratoire de la Faculte a Vhopital Saint-Louis, in the “ Annales 
de dermatologie et de syphiligraphie,” July 25,1889, under the title psoro- 
spermose folliculaire vegetante. The same affection had formed the sub- 
ject of a “ These de Paris ” by Dr. A. Thibault, May 8, 1889. M. Darier 
had previously made a communication upon the subject before the Societe 
de biologic on March 25, 1889. The observations of these gentlemen, un- 
known to me before the meeting of the congress, were based upon two 
cases of the affection which had been seen at the Saint Louis Hospital 
during the preceding year. One of these was the patient exhibited to the 
congress, and the appearances he presented were identical with those of 
my patient, although the lesions in the former were far less developed in 
diversity and magnitude, as the duration of the disease was only eight 
years. I had no hesitation in pronouncing the affection to be the same 
as that described by myself under the name keratosis follicularis, and 
stated further that, although I was not prepared to deny the correctness 
of M. Darier’s conclusions as to the parasitic nature of the peculiar cells 
found in the epidermal concretions, neither Dr. Bowen, who had made the 
microscopic studies in my case, nor myself had recognized them as of such 
a character. 
The conclusions of M. Darier may be briefly stated as follows: There 
exists in man a group of cutaneous diseases, which deserve the name of 
psorospermoses, due to the presence in the epidermis of parasites of the 
order of sporozoaires. This class includes the gregarinae, the oval psoro- 
spermae or coccidise, the sarcosporidise, the psorosperms of fishes or myxo- 
sporidise, and the psorosperms of the articulates or microsporidiae. All 
these organisms live as parasites upon other animals, and give rise, in certain 2 
Original Communications. 
cases, to fatal diseases. The coccidise, to which the forms in question are 
claimed to belong, inhabit almost exclusively the epithelial tissues of ver- 
tebrates. They are distinguished from the sporozoaires, especially the 
gregarinse, by absence of movements at any period of their development, 
their intracellular habitat, their solitary encystment, and by the limited 
number of spores which develop in the cysts. Among the best known is 
the oviform coccidia of the biliary ducts of the rabbit, where it produces 
cysts. In the affection iisorospermose folliculaire vegetante coccidise of a 
Fig. 1.—Epidermal Plug, Neighborhood of a Hair 
Follicle invaded by Psorosperms. 
a, stratum corneum; b, stratum granulosum; c, stratum 
Malpighii; e, e,f, encysted psorosperms. 
Fig. 2.—Two Cells from the 
Deeper Portion of a Follic- 
ular Plug, each containing 
an Encysted Coccidia. 
Reproduction, in part, of the il- 
lustrations of M. Darier’s paper. 
particular kind invade the follicular orifices under the form of round 
bodies, generally encysted and contained within the epithelial cells, or of 
refracting granules, the accumulation of which forms a plug, which pro- 
jects from the mouths of the follicles. The presence of these parasites 
establishes the diagnosis of this disease, inasmuch as they are not met 
with in any clinically analogous affection. The neck of the follicles thus 
attacked becomes secondarily the seat of papillomatous affections, which 
may become enormously developed and be converted into real tumors. 
This affection, in its setiological relations, should be placed with Paget’s 
disease,* and probably with molluscum contagiosum. 
* In a paper presented to the congress by Dr. Louis Wickham, interne de I'hopital 
Saint-Louis, on “ The Pathological Anatomy of Paget’s Disease,” he describes the micro- 
scopic appearances as follows: “ In accordance with Darier, he was able to affirm that 
the peculiar cellular alterations.of the epidermis and of its prolongations, formerly 
considered, in order to explain the difficulty away, either as consisting of degenerated 
cells, or as of cells in process of endogenous transformation, are no other than parasites 
belonging to the class of sporozoa, of the order of psorospermoses. These parasites 
were seen in different stages of their evolution. At the commencement they consisted Keratosis Follicularrs. 
3 
Early after my return from the congress there presented herself at my 
clinic at the Massachusetts General Hospital a case sent by Dr. Everett, 
of Worcester, for diagnosis, under whose observation it had been for 
eighteen months. The forehead and posterior portions of the cheeks, as 
low as the angles of the jaw, were thickly occupied by discrete, dry, firm, 
brownish papular elevations, semi-globular in shape, and varying in size 
from a small to a large pin’s head. The same lesions were more sparsely 
distributed on the sides of the nose and on the chin, where they had more 
recently appeared. They were also present on the neck and upper front 
chest. The backs of the hands presented also many minute, flattened, and 
smooth papules, which had the color of the normal skin. All these ap- 
pearances might not, perhaps, have excited particular attention if seen 
before acquaintance with those of my first case, especially as the face at 
this visit was in a state of active inflammation, resulting from the action 
of applications then in use. An examination of the lower abdomen, hips, 
and upper thighs showed, however, the presence of much larger and 
more striking lesions, which confirmed the correctness of the suspicions 
aroused by the appearances upon the exposed parts of the skin. These 
surfaces presented numerous firm hemispherical and conical prominences, 
of a dark-brown color, two or three times as large as those above described, 
and more horn-like in consistence. They were all seated above the mouths 
of the sebaceous glands; over the pubes they were the most abundant and 
largest. They resembled in all particulars the lesions of the same grade 
of development in the case reported by me'in the Journal of Cuta- 
neous and Genito-urinary Diseases in June, and in that exhibited 
at the Paris Congress, above referred to. The disease was recognized by 
Dr. Bowen and myself as unmistakably identical with the former. 
The patient was a girl twenty-one years old, and her history, as given by 
Dr. Everett and herself, was as follows : At the age of five or six there were 
dry and brown patches on the sides of her forehead, so that her playmates 
used to tell her that she had a dirty face. When she was fifteen this condi- 
tion nearly covered her forehead. It appeared on her wrists, lower body, 
and thighs, also in early childhood; but she feels sure that it is less abundant 
upon the latter parts now than some years ago. The lesions upon the hands, 
of amoeboid masses, very difficult to distinguish from cellular protoplasm. The cell- 
which contained the parasite increased considerably in size, and presented a more irreg- 
ular form. At a given time the parasite became encysted, and its capsule, at first not 
clearly defined, became perfectly round, thickened, and brilliant. A distinct, enor- 
mously developed nucleus was then visible in the cell, having a round body and brilliant 
double contour, and in the central protoplasmic contents were to be seen two or several 
nuclear forms, which are no other than the pseudo-navicellae. These distinct, well- 
developed bodies are coccidiae, or psorospermia, in their adult condition. He believed 
that the presence of the parasites explained the pathological lesions.’’—From “ Report 
of Congress,” by Wickham,in “British Journal of Dermatology,” October, 1889. 4 
Original Communications. 
too, have become less distinct under the various treatments employed. The 
disease has extended upon the lower face within the last six months. The 
patient’s left leg was amputated at mid-thigh, at the age of sixteen, for “ white 
swelling” of the knee, which lasted nine years; and her general condition is 
not good. 
After the examination of the patient had been completed the surpris- 
ing discovery was made that the person described in my former article, 
whom she then accidentally met in the waiting-room, was her own father. 
This astonishing coincidence of so rare an affection in two members of 
one family naturally suggested the question of its possible bearings upon 
its aetiology, for, if we accept the views of M. Darier as to its parasitic 
nature, might not this concurrence be regarded as important evidence in 
favor of its communication from father to daughter by contagion? It 
was found on inquiry, however, that the daughter had been adopted by 
another family in infancy, and that her father had not seen her since she 
was a year old. This circumstance, although not absolutely excluding the 
possibility of the transference of the disease to her in this way, reduces 
the chance of such an occurrence to a minimum. There had been another 
child in the family, but it had died at the age of five, with a fair skin. 
The question of heredity naturally suggests itself as furnishing a pos- 
sible explanation of the appearance of the disease in Case II, an aetiologi- 
cal factor, as we know, of more potent influence in affections of the 
epidermal layers than in those of the other cutaneous structures. 
Specimens of the concretions were removed from various parts by the 
cutaneous punch, and examined by Dr. Bowen. It may be briefly stated 
in advance that the structure of the lesions was shown to be identical with 
those of a corresponding degree of development in the first case, and that 
the modified epithelial masses contained the same peculiar cells or bodies 
as were found in the latter and in the French cases. 
Dear Dr. White: I have made a further examination, as you requested, 
of the lesions of Case I, in the light of M. Darier’s researches, and have also 
studied those removed from Case II. 
The lesions removed from the thigh in Case II showed the same appear- 
ances found in Case I—namely, a dilatation of the mouths of the follicles, 
this enlarged space being filled up with a horny mass. The same prolonga- 
tion of the rete into the corium was also observed. In the lesions examined 
there was, too, no implication of the glandular structures. In a word, there 
can be no question of the anatomical identity of the lesions of the two cases. 
Examination of some newly excised pieces from Case I demonstrates une- 
quivocally the fact that Darier’s cases represent the same pathological process 
as these two. The cells which he considers to be animal parasites belonging 
to the sporozoa are to be found in both Case I and Case II—namely, round 
bodies possessing a highly refractive membrane, usually containing a nucleus, 
and often appearing to be encysted. I find that their characteristics agree Keratosis Follrcularis. 
5 
in so many respects with the description of Darier that I shall confine my- 
self to a few particulars in which I am unable to record the same results as 
this author. 
1. Their intra-epithelial situation was not so clearly shown in my speci- 
mens. After softening the horny plug that filled the follicular orifice in a 
little dilute ammonia and staining with haematoxylon, the microscope gave 
the picture of numbers of round bodies with a highly refractive contour, 
usually less deeply stained than the more central portion, where a nucleus 
could often be observed, and, together with these, the ordinary epithelial cells 
and shreds. After looking over a large number of specimens with the great- 
est care, I could find but one or two places which suggested the appearances 
pictured by Darier in his Plate IV, Fig. 3, and Plate V, Fig. 7—namely, an 
epithelial cell containing the psorosperm-like body, with the appearance of 
a nucleus pushed to one side. In the few instances where I was able to find 
these appearances I could not definitely satisfy myself or others that the 
round bodies were not simply closely adherent to the underlying cell rather 
than contained in its protoplasm. Possibly the difference in results was due 
to an imperfect application of Darier’s method, as he speaks of these appear- 
ances as very readily seen. Certainly their importance in considering the 
nature of these bodies can not be questioned. 
2. Darier makes no mention of a process of cornification, but it seems very 
difficult to believe that there is not a hyperkeratosis taking place in these 
lesions, whether or not these bodies be coccidiae. In the first place, the 
stratum granulosum in the dilated follicular mouths is greatly increased in 
width and in many places in the size of the granules, as is constantly shown 
in sections stained with haematoxylon and afterward treated with a one-per- 
cent. solution of hydrochloric acid. Moreover, it can be readily seen, in sec- 
tions so treated, that the round, psorosperm-like bodies at the level of the 
stratum granulosum are affected in the same way by the reagents as the 
neighboring tissue cells, for they contain the deeply stained granules of elei- 
dine. Above this layer these bodies are found to be scarcely or not at all 
stained, like the cells of the stratum corneum about them, and their outlines 
can be made out only in the lower portion of this layer. In Case I the horny 
plugs projected from the follicles to the extent of half an inch in some places, 
and the outer portion of the plug had precisely the appearance and consist- 
ency of a firm horn. Microscopically, sections cut parallel with the long 
axis of the horny plug showed the round, psorosperm-like cells at the base of 
the concretion, and they could be traced upward for some distance, gradually 
becoming flattened and fused together, until in the firm, hard, upper portion 
the mass is composed almost entirely of lamellae, having much the appear- 
ance of broad bands of fibrous tissue, arranged in bundles running vertically 
and obliquely, and containing small elongated nuclei. Between these fibrous- 
like bands picrocarmine staining differentiates in some places aggregations 
of round, loosely connected, highly refractive cells ; but the lamellas make 
up the greater part of the outer portion of this horny projection. Now, if, as 
Darier asserts, these horny masses that project, in the advanced stages of the 
disease, half an inch above the level of the skin, are almost entirely made 
up of psorosperms, and if these bodies, when situated in the stratum granulo- 
VOL. VIII.—3 6 
Original Communications. 
sum, contain granules similar to those characteristic of this layer, and, when 
in the stratum corneum, show the same reaction to staining agents as do the 
tissue cells—we are forced to the conclusion that they undergo at least a par- 
tial keratosis, or, in other words, are subject to much the same changes that 
affect the tissue cells proper—a phenomenon for which, so far as I am aware, 
we have no analogy in the history of animal parasites. In reply, it may be 
urged that the coccidise are so closely incorporated in the epithelial cells of 
the stratum granulosum that the eleidine granules, which have every appear- 
ance of filling the psorosperm-like body, are in reality situated in the cell 
which envelops it; but even if this be granted, the fact that we have, in addi- 
tion, a hyperkeratosis, can not, it seems to me, be denied. An analogy, too, 
may be found in the recent able article of Neisser on “ Epithelioma conta- 
giosum.”* This author, wdiile recognizing the molluscum bodies to be made 
up largely of gregarinas, another variety of the sporozoa, states emphatically 
that there occurs at the same time an exaggerated keratosis of the epithelial 
structures. Leloir and Vidal f also conclude that there is a hyperkeratosis 
in these lesions, although they express themselves with rather more reserve 
as to the parasitic nature of the molluscum cells. In any event, with regard 
to these two cases, it seems to me impossible to escape from the conclusion 
that there is present and continually active a hyperkeratosis in the cuta- 
neous lesions. 
These bodies strongly suggest, as Darier has observed, certain peculiar cell 
elements found in cancer. A number of specimens of flat-celled epithelioma, 
examined for purposes of comparison, offer appearances very similar to the 
psorosperm-like cells of these cases. Moreover, I have found in a specimen 
of verruca vulgaris round cells in the rete Malpighii, considerably larger 
than those surrounding them, containing a nucleus more or less well defined, 
of a glistening appearance, and with an apparent retraction of the proto- 
plasm from the periphery, so that nucleus and protoplasm appear as if sur- 
rounded by a clear space. In the hypertrophied horny layei’ above, the out- 
line of these bodies, unstained by the alum carmine, could occasionally be 
seen. These bodies presented many points of analogy with those found in 
the two cases, as was readily acknowledged by all to whom I showed these 
specimens. Are we to regard these also as a species of psorosperms ? 
Attempts were made to obtain some further light by cultures on agar 
plates, in water, and in bouillon, but with no result. Inoculation experiments 
were also made on animals, but these too have been entirely negative up to 
the present time. Lastly, I have to record my failure to produce a differen- 
tia] or distinctive staining of these bodies. 
It can not be denied that many good reasons have been offered by the ad- 
mirable paper of Darier for considering it not improbable that these bodies 
may be proved to be coccidiae. So little, however, is known by zoologists of 
this class of parasite, and its organism is so low in the scale (differing as it 
does so slightly from a tissue cell), that we are justified in demanding strong 
proof before fully admitting that the peculiar cell-forms in question are to 
* “ Vierteljahresschrift fur Derm, und Syph.,” 1888, 4. Heft, 
f “ Traite deseriptif des maladies de la peau,” Paris, 1889. Keratosis Follicularis. 
7 
be placed here. We can not, therefore, accept their parasitic nature as be- 
yond all doubt until some positive proof is offered by culture or inoculation, 
or at least until some further analogy with the sporozoa can be shown. 
Very truly yours, John T. Bowen. 
The following questions naturally suggest themselves in our study of 
these cases in attempting to form a positive conclusion as to their true 
nature: 
1. Have the bodies in question been found in every case of this rare 
affection ? 
As they have occurred in all four instances—the two cases reported in 
Paris and the two described by myself, which have been observed since 
attention has been especially called to their presence by Darier—it would 
be fair to assume that they will be found in all future cases. 
2. Do they occur in every affected follicle—that is, in all the lesions of 
the disease ? 
This is a question of most important bearing upon their setiological re- 
lations. Of course, a positive answer can not be given to it in such a case 
as my first one, because it presented myriads of lesions; but, inasmuch as 
they were found in every one of the many examined and in every phase 
of their development, as well as in those of the other patients, it may be 
assumed, perhaps fairly, that they are uniformly present. 
3. Are these bodies parasites ? 
This question must be settled by the histologist and zoologist. Several 
distinguished dermatologists at the Paris Congress—men like Unna, for 
example, who are thoroughly familiar with the minute anatomy of the 
cutaneous tissues in health and disease—told me that they must so regard 
them; but their opinions were based upon a mere inspection of the micro- 
scopic sections on view. My colleagues in the anatomical and pathologi- 
cal departments of Harvard University, also well acquainted with the mi- 
nute appearances of human structures, hesitate to pronounce them of 
extraneous character. Prof. Joseph Leidy, of Philadelphia, than whom 
no one is more competent to express an opinion upon their nature as a 
zoologist, has very kindly examined specimens of the lesions from both my 
cases. He writes: “ I have examined your preparations of the skin and 
have observed the large, nucleated cell-bodies in the epidermal layers, but 
feel uncertain as to their true character. They may, perhaps, be of the 
nature of psorosperms, to which they bear a resemblance, but I am not 
satisfied that they are such.” It seems to me that Dr. Bowen very fairly 
states the uncertainties which surround the positive settlement of this ques- 
tion. No definite inference upon this point can be drawn, I think, from 
the action of parasiticides thus far used in the treatment of these cases. 
4. Do these bodies cause the tissue changes in the disease in which 
they are found ? 8 
Original Communications. 
If we look upon them as parasites and not the product of the disease, 
there is no improbability in regarding them as its cause, in view of the 
much more serious and complicated modifications -of cutaneous tissues 
which foreign organisms of much less magnitude and simplicity of struct- 
ure are capable of exciting—the bacilli of leprosy and tuberculosis, for ex- 
ample. On the other hand, we should not forget that animal parasites of 
relatively high organization—the demodex foUiculorum—may inhabit the 
orifices of the sebaceous glands indefinitely without producing any recog- 
nizable tissue change. 
5. Are these bodies communicable from one person to another ? Is the 
affection contagious ? 
Our evidence upon these points is wholly of a negative character. The 
experiments made by Darier to establish new colonies of the bodies upon 
other animal tissues failed uniformly, as did those of Dr. Bowen in this 
direction. That they might readily be transferred from an affected fol- 
licle to adjoining follicles in the processes of washing the skin, scratching, 
or by the clothing, may be easily understood; so that, in time, animal para- 
sites without power of motion, like the mycoses, could affect the whole 
surface, as in my first case. We have no clinical proof of the transference 
of the disease from one person to another, although two of the four cases 
under consideration were affected husbands living with their wives. Such 
negative data are of little value, however, upon the point under considera- 
tion. It is well known that tinea versicolor may affect one of a married 
couple for many years without being communicated to the other. 
6. Are these bodies found in other dermatoses ? 
If it can be shown that they are found in other diseased conditions of 
the skin in which the characteristic tissue changes are wholly unlike those 
of the affection under consideration, or that their occurrence in healthy 
follicles shall be found to be by no means rare, then grave doubts might 
well arise as to their pathognomonic relation to our cases. It has been above 
noted that the peculiar bodies found in molluscum epitheliale or contagio- 
sum, as to the nature of which much diversity of opinion has long prevailed, 
are regarded by Darier and others as coccidise also, and that Dr. Wickham 
claims that similar bodies are found in and are the cause of Paget’s disease. 
The cutaneous lesions in these three affections are certainly wholly unlike 
in a most significant degree. Dr. Bowen calls attention to the occurrence 
of cells, strongly resembling the bodies in question, in other diseased con- 
ditions of the skin. A too universal discovery of their association with 
dermal pathology should throw grave suspicion upon them as an aetiologi- 
cal factor m any single dermatosis. 
The real nature of these rare instances of disease can not be regarded 
as definitely settled, in my opinion, or all the conclusions of M. Darier be 
accepted, until we have obtained more satisfactory information than we 
now possess upon the questions above raised.