A Contribution to the Histology 
and Pathology of Herpeti- 
form Hydroa. 
BY 
GEORGE T. ELLIOT, M.D., 
ASSISTANT VISITING PHYSICIAN TO BK SKIN 
AND CANCER HOSPITAL, VISITING DERMATOLOGIST 
TO DfiMILT DISPENSARY, ETC. 
REPRINTED PROM 
Me Neto York jfUetiical Journal 
for April 23, 1887. Reprinted from the New York Medical Journal 
for April 23, 1887. 
A CONTRIBUTION TO 
THE HISTOLOGY AND PATHOLOGY OF 
HERPETIFORM HYDROA.* 
By GEORGE T. ELLIOT, M. D., 
ASSISTANT VISITING PHYSICIAN TO THE NEW YORK SKIN AND CANCER 
HOSPITAL, VISITING DERMATOLOGIST TO DEMILT DISPENSARY, ETC. 
The subject of hydroa is one around which there is so 
much confusion and uncertainty that a short retrospective 
view of the origin of the term, of the widely varying use 
to which it has been put, and of the opinions regarding it 
held by some of the more prominent writers on derma- 
tology, will be excusable before reporting the history and 
microscopical examination of the case which forms the basis 
of this article. 
The name hydroa was first given by Bazin f to certain 
forms of vesicular and small bullous eruptions which he 
was not able to class together with other affections charac- 
terized by similar lesions. He made three divisions-hy- 
droa vesiculeux, hydroa bulleux, and hydroa vacciniforme ; 
but, though he demonstrated the existence of a distinct dis- 
ease, yet, as was shown subsequently, he included under the 
* Read before the New York Dermatological Society, February 22, 
1887. 
f "Lemons theoriques sur les maladies de la peau," Paris, 1862. 2 
HISTOLOGY AND PATHOLOGY OF 
designation eruptions which had no connection whatever 
with it. 
Bazin's description does not seem to have been received 
with great favor by the French dermatologists. With a few 
exceptions, they only refer to it in their writings, while in 
the latest work of one of them, Hardy,* we do not even find 
hydroa mentioned. It can not be said to be accepted by 
the Germans as yet, since they give no description of the 
affection, but dispose of it with the bare statement that 
Bazin applied the name to a form of vesicating erythema, 
and that Tilbury Fox afterward described it, and divided it 
into three forms, f 
The literature of hydroa is at best meager. Nothing of 
importance appeared in regard to it during the few years 
subsequent to the publication of Bazin's book, and only 
from 1870 on did any interest seem to be displayed in it. 
The attention of the English had been directed toward the 
disease, and they had begun to study it, but their views 
were decidedly against it, and not until a number of years 
later were any of them inclined to accept hydroa as a dis- 
tinct and separate affection of the skin. In the mean time 
the Americans had entered the field, and within certain 
limits had accepted the hydroa given by Bazin; but yet it 
must be said that the credit of establishing it upon a satis- 
factory basis is due especially to the English. 
The first serious consideration of the subject was made 
by Hutchinson,| who devoted considerable editorial space to 
it in the "British Medical Journal." He reported six cases 
which be considered were examples of Bazin's hydroa, and 
thought that it had a close connection with erythema and 
urticaria. He concluded, however, that it was only a vesi- 
* Hardy, "Traite des maladies de la peau," Paris, 1886. 
f Weyl, von Ziemssen, " Hautkrankheiten," Th. ii, p. 541. 
| Hutchinson, " Brit. Med. Jour.," May 14, 1870. HERPETIFORM HYDROA. 
3 
eating form of erythema papulatum. A few years later * he 
again modified his opinion, and was in favor of regarding 
iodide of potassium as an important causal factor in the 
production of the disease. 
Tilbury Fox,f in 1873, described the various forms given 
by Bazin under the head of " Anomalous Forms of Bullous 
Eruptions ; Hydroa," but objected entirely to the use of the 
term. According to him, these eruptions were in reality 
unusual manifestations of herpes iris and of pemphigus 
prurigi nosus. 
In 1876, G. H. Fox J gave the clinical history of a case 
which he considered to be hydroa, but he advanced no 
opinion in regard to its nature. The discussion on this 
case, at a meeting of the New York Dermatological Society, 
was also inconclusive, only the mention of similar eruptions 
having been seen by the various members being brought 
out. 
In 1877, L. D. Bulkley # reported two cases, and was 
the first in America to state his belief in the entity of hy- 
droa. He held that it was entirely distinct from herpes and 
pemphigus, and also expressed the opinion that the erup- 
tion was closely connected with, if not dependent upon, the 
nervous system. 
In 1878, Saundby || described a case under the name of 
purpuric hydroa, but, after the patient had had a second 
attack, concluded that the eruption was a bullous urticaria. 
About the same time G. II. FoxA reported another case 
seen by him, and maintained that some vesiculo-bullous 
* Hutchinson, "Brit. Med. Jour.," 1873. 
f Tilbury Fox, " Skin Diseases," etc., London, 1873. 
I G. H. Fox, "Arch, of Dermatology," New York, vol. iii, No. 1. 
* L. D. Bulkley, " Arch, of Dermatology," New York, vol. iii, No. 3. 
|| Saundby, " Brit. Med. Jour.," 1878. 
A G. H. Fox, "Arch, of Dermatology," New York, 1878, No. 3. 4 
HISTOLOGY AND PATHOLOGY OF 
eruptions could justly be classed under the name hydroa, 
since they were neither herpes nor pemphigus. In this he 
agreed with L. D. Bulkley (Joe. citj, only he expressed his 
convictions much more forcibly and decisively. 
We next find, however, Sangster and Malcolm Morris* 
objecting absolutely to the existence of such a disease as 
hydroa, and, in addition, maintaining that the term was 
both illogical and misleading, while Finny * applied it to an 
iodide-of-potassium eruption. 
In 1880 a new stimulus to the study of the disease was 
given by Tilbury Fox.f The opinions previously expressed 
by him seemed to have undergone a great change, for, tak- 
ing up the subject again, he states his belief, within certain 
bounds, in Bazin's hydroa as a distinct and separate disease. 
He divides it into three forms-simple hydroa, herpetiform 
hydroa, and bullous or pruriginous hydroa. His descrip- 
tion is unquestionably the most comprehensive and the best 
which has yet been given, and stamps the affection with an 
individuality which is nothing less than convincing. 
More lately cases have been reported by A. R. Robin- 
son, J who agrees with Tilbury Fox ; by R. W. Taylor,* who 
gives the clinical history of an eruption which he considers 
identical with the hydroa bulleux of Bazin ; and also by H. 
Radcliffe Crocker, || while Duhring A maintains that many 
cases of so-called hydroa belong to his dermatitis herpeti- 
formis. 
These are possibly only a few of the opinions which 
exist in regard to the disease, but they are sufficient to illus- 
* Sangster, Malcolm Morris, Finny, " Trans, of the Brit. Med. 
Assoc.," reported in "Arch, of Dermat.," New York, 1879. 
f Tilbury Fox, "Arch, of Dermatology," 1880, No. 1. 
£ A. R. Robinson, " Journ. of Cut. and Ven. Dis.," 1885. 
* R. W. Taylor, "Journ. of Cut. and Ven. Dis.," 1886. 
|| Radcliffe Crocker, "Brit. Med. Jour.," May, 1886. 
A Duhring, "Med. News," October, 1885. HERPETIFORM HYDROA. 
5 
trate the history of this obscure affection which, though 
first described by Bazin in 1862, yet required so many years 
before receiving even a moderate amount of acceptance at 
the hands of the dermatologists of the world. That this 
acceptation is due in great part to the late Tilbury Fox 
seems to me unquestionable, since he first definitely de- 
scribed and categorized the disease and pointed out its 
salient characteristics and also Bazin's errors, though it 
must be acknowledged that, previous to him, Bulkley and 
Fox in America had begun to lay the foundations which 
led to its recognition as a separate and distinct affection. 
Turning to the clinical symptoms which characterize 
hydroa, I would state that I have followed those given by 
the late Tilbury Fox, and it is upon them that the diagnosis 
of the case reported in this article is based. According to 
him, the lesion is a small vesicle or bulla developing from 
a red itchy papule or patch. In hydroa simplex the vesi- 
cles are found single and discrete, more or less localized 
upon the face, arms, and shoulders. It appears at times as 
an acute eruption, running a course of from ten to twenty 
days without disturbance of the general health, or a<jain, 
breaking out in successive crops, it becomes chronic. When 
acute, the basic infiltration is not very marked and the 
amount of itchiness is slight, but they both increase pro- 
gressively as the affection becomes chronic. There is no 
sharp division between simple and herpetiform hydroa, 
the two forms being always more or less co-existent, only 
the preponderance in the arrangement of the vesicles in 
groups upon a reddened elevated base or patch constitutes 
the division to which the additional characteristic of her- 
petiform is given. In the acute outbreaks the tendency to 
the formation of erythematous circular patches, bounded 
peripherally by vesicles, is not marked, though they are the 
rule in the chronic forms, as mentioned by Crocker and 6 
HISTOLOGY AND PATHOLOGY OF 
others. This brief resume of the clinical symptoms will suf- 
ficiently introduce the following case : 
W. S., aged twenty-three, a native of the United States, a 
wood-turner by trade, presented himself, October 1, 1886, at the 
New York Skin and Cancer Hospital in Dr. Bulkley's service. 
He was of wiry build, medium size; had always been and was 
then in perfect health. His bowels were regular, he had no 
drinking habits, his work was hard, and he always felt very 
tired at the end of the day. His appetite had not been very 
good for some weeks, but be bad had no subjective gastric dis- 
turbances. He had never before had any eruptions on the skin. 
He stated that on the Saturday preceding the appearance of 
the eruption he had been at a picnic and had passed much of 
the time lying on the ground, feeling afterward a little chilly. 
On the following Monday, September 27th, he noticed the 
presence of a number of small blisters along the margin of the 
pinna of the left ear. They were small, separate from each 
other, and somewhat itchy. On the following day, September 
28th, the eruption showed itself upon the left hand and fore- 
arm, and on September 29th on the right hand and forearm. 
The backs of the hands and the wrists were first affected. On 
these parts small red, itchy papules and erythematous blotches 
of variable size appeared, and their presence was also quickly 
noted on the arms. The eruption increasing, on the blotches 
papules developed, which in turn became small vesicles, while 
new patches, vesicles, and papules continued appearing. 
Status prawns.-The lesions which had first shown them- 
selves on the ear had disappeared, and only a few small crusts 
were found there. The eruption was now situated entirely on 
the forearms and hands, but to a greater extent upon the left 
side. Upon this extremity, more especially on its extensor and 
ulnar surface, but also on the flexor aspect and upon the backs 
of the hands, a large number of lesions were seen. They were 
single and also aggregated into groups, and consisted of hard 
papules, small vesicles, and bullae of the size of a pea. A group- 
ing of the lesions largely predominated, and they were found 
by twos, and even up to twenty and thirty, standing together HERPETIFORM I1YDR0A. 
7 
upon one base. The zone of redness around the larger groups 
was narrow, but quite broad around the single vesicles and the 
small groups. At the wrist, more especially upon its ulnar side, 
there was a very extensive group of bullte of about the size of a 
large pea. It extended from the joint a distance of three inches 
upward, and laterally about an inch over the anterior and pos- 
terior surface of the arm. The bullaa forming this group had 
become confluent, yet its puckered appearance pointed out the 
various septa which had originally divided the lesions one from 
the other. Over the flexor surface of the arm there were also 
some single vesicles and groups of three and four, but the erup- 
tion was much less here than upon the extensor side. Above, 
the outbreak of the lesions did not occur beyond the elbow, but 
converged more especially toward the uluar notch. Their epi- 
dermal wall was strong and tense, and did not rupture easily. 
On the back of the hand and on the fingers there was quite a 
large number of papules and vesicles, grouped and single. One 
very large group was situated on the surface lying between the 
metacarpal bones of the index-finger and of the thumb, and it 
presented the same appearances which accompanied the one at 
the wrist. As already mentioned, the eruption began to appear 
on the right hand and forearm on September 29th. The lesions 
here, when I saw the patient, were the same in nature and pre- 
sented the same characteristics as those on the left upper ex- 
tremity, only they were more discrete and not so abundant. 
They also were situated especially over the course of the ulnar 
nerve and upon the extensor surface of the forearm. On the 
backs of the hands and on the fingers there were likewise pap- 
ules and vesicles, single and grouped. On both the upper ex- 
tremities the various single lesions and groups were separated 
from one another by areas of normal skin. The contents of the 
vesicles and bullae were of a light straw-color, and only in a few 
was slight cloudiness of the fluid noted. Here and there were 
a few small crusts and marks of scratching. On the left side 
the eruption had not been very pruritic, but on the right hand 
and arm the itching was very much more intense and was com- 
plained of by the patient. 
The patient was given four doses of Fowler's solution, and 8 
HISTOLOGY AND PATHOLOGY OF 
unguentum zinci oxidi was applied over* the arms and hands. 
The fluid was removed from the large patch near the left wrist 
and was found to be of neutral reaction. 
October 6th.-The patient being seen again, it was found that 
the major part of the eruption present at the time of his first visit 
had disappeared. In place of the large groups and many of the 
single lesions, only small crusts and the flakes of epidermis which 
had formed their covering were found. The redness surround- 
ing the lesions had diminished to a great extent, but new single 
vesicles and small groups of three or more had cropped out here 
and there over the arms and hands. He felt, however, in every 
way well, though still troubled by the itching, which had become 
more intense. The treatment was continued, but the patient 
unfortunately did not return. 
From this clinical history it can be seen that, so far as 
its localization, its course, its objective symptoms, and its 
termination went, the case agreed substantially with an acute 
outbreak of herpetiform hydroa as given by Tilbury Fox. 
It was peculiar, however, in its following so closely and espe- 
cially the course of the ulnar nerve, and also in having cer- 
tain symptoms which might cause it to be confounded with 
some other grouped affections. I specify grouped affections 
because the majority of the lesions were in groups of two or 
more, and for that reason those eruptions which have or 
might have the same localization as in this case, but are 
never grouped, would be excluded from a comparison with 
it. Among these come erythema multiforme, eczema vesi- 
culosum artificiale, and pemphigus. The eruption to which 
it bore the greatest resemblance was zoster, but from this it 
differed in important particulars. It was symmetrical, a 
very rare occurrence in zona. It was neither preceded, nor 
accompanied, nor followed, by any subjective sensation of 
pain, the absence of which is exceptional in herpes of the 
type under consideration. Besides, in this latter, the lesions 
which appear are slow in development, are always grouped, HERPETIFORM HYDROA. 
9 
and do not exist as single papules and vesicles more or less 
plentifully distributed between the characteristic patches. 
The course of the lesions is also much slower than in hydroa, 
and they almost invariably become pustular and leave be- 
hind a slight or great amount of scarring and pigmentation. 
Finally, zoster always follows closely the course of one or 
more nerves, whereas in this case of hydroa, though most of 
the lesions were situated in the line of distribution of the 
ulnar, yet they were also irregularly distributed over the rest 
of the forearm, the backs of the hands, and the fingers. 
There were no lesions which bore any resemblance to an 
herpetic one, and their being arranged in groups was their 
only point of agreement. 
From dermatitis herpetiformis it could be easily differ- 
entiated, though it had a few facts in common with it, such 
as grouped vesicles and some itchiness. But in the acute- 
ness of the outbreak, the localization, the short duration, and 
the rapid course, the hydroa differed entirely from the clini- 
cal symptoms which have been described as accompanying 
dermatitis herpetiformis. 
I do not think it necessary to continue further the com- 
parison of this case with others which might resemble it, 
since it agreed so accurately with Tilbury Fox's description 
of hydroa that the correctness of the diagnosis seems to me 
unquestionable, and I will preferably turn to a considera- 
tion of the anatomical features presented by it. Before do- 
ing this, however, let me add that I have searched diligent- 
ly through the literature on hydroa, but have been unable 
to find any recorded microscopical examination previously 
made, and that I consequently am obliged to give only the 
results of my own work. 
At the time of his first visit the patient allowed me to ex- 
cise a portion of skin from the extensor surface of the left fore- 
arm, upon which a group of vesicles was situated. They had 10 
HISTOLOGY AND PATHOLOGY OF 
appeared only a few hours before I saw him, each was some- 
what larger than the head of a pin, and their contents were of 
a clear straw-color. The specimen was put into 90-per-cent. 
alcohol for a few hours, then into absolute alcohol, and, when 
hardened, it was mounted in celloidin and cut with the sliding 
microtome. The sections were stained with borax-carmine and 
potash-alum carmine, cleared in oil of cloves, and mounted in 
damar balsam. They were examined with both low and high 
powers. 
The stratum corneum was broad and well defined, but much 
of it showed a loosening and a separation of its layers. In some 
portions near the vesicles, nuclei, which stained moderately well, 
extended almost up to the external surface. The loosening of 
the layers of this stratum was principally in the vicinity of the 
vesicles, but it was also very decidedly marked around that por- 
tion of the ducts of the sweat-glands which passed through it, 
and over some of these latter it was raised up to such an extent 
as to form cavities of variable size, containing a small amount of 
granular matter. The stratum lucidum was scarcely demonstra- 
ble. The stratum granulosum was seen only to a limited extent, 
and then consisted of a single layer of cells. The rete Malpighii 
proper, beyond the immediate vicinity of the vesicles, was not 
increased in depth, neither were the interpapillary prolonga- 
tions lengthened. Its cells stained well and appeared unchanged. 
As we approached the vesicles the rete was seen to be much 
deeper-double, and even more. Its cells became long and nar- 
row, with their long axes directed perpendicularly tothecorium. 
They had a slightly granular appearance, and were somewhat 
loosened from one another. Their nuclei were for the most part 
well stained, but occasionally some were absent, though the 
shape of the cell was unchanged. In all the sections only two 
vacuoles were found, and they were situated in the outer wall of 
the vesicles. The characteristics of the stratum spinosum were 
only faintly demonstrable, while the basic layer of the rete was 
proliferating, the cells having long processes extending into the 
corium. The line of demarkation between these two latter was 
rather indistinct; the papillae were flattened and the interpapil- 
Jary prolongations were only slightly marked. The lesions HERPETIFORM HYDROA. 
11 
themselves were multilocular. The loculi were situated in the 
interpapillary prolongations of the rete, occupying the place of 
the epithelial cells, which had been destroyed. The external wall 
was composed of the strata, corneum, lucidum, and granulosum, 
and more or less of the rete. The amount of this latter which 
entered into the formation of this wall was variable. In some 
loculi only a few pale, granular, degenerated epithelial cells with 
pale nuclei, or even without these, were found along their upper 
border adherent to the stratum corneum, while in others the 
rete was quite deep and its cells were for the most part entirely 
healthy. The point where the wall was thinnest was not con- 
stant in all the vesicles, but varied-an important fact, which will 
be referred to further on and more fully brought out. The lat- 
eral walls of the vesicles were also formed by the same layers as 
mentioned above, and were for the most part sharply defined, 
but in them were likewise found masses of pale, degenerated 
epithelial cells. The base of the lesions was constituted by a 
single layer or by several layers of rete cells, which were com- 
pressed. and formed a narrow boundary between the contents 
of the loculi and the tissue of the corium. In some places it 
was, however, entirely wanting, having succumbed to the degen- 
erative process. 
The septa separating the various loculi consisted of long, 
spindle-shaped epithelial cells. These columns were of variable 
size and the cells composing many of them were unchanged, 
but, as may be seen in Fig. 1, the healthy portions were for the 
most part situated in the centers, while those next to and nearest 
to the contents of the loculi were in all stages of degeneration ; 
in fact, in some places their former presence was only shown by 
a well-defined, moderately broad zone of granular matter, while 
in others, in addition to this, nucleated cells and cells which 
had lost their nuclei were still distinguishable. 
It can also be seen from Fig. 1 that the loculi were situated 
in the interpapillary prolongations of the rete. As evidence of 
this we see the blood-vessels proceeding upward almost to the 
base of the septa, and a slight prominence of the corium at 
these points marking the papillae. And, besides, one other fac- 
tor, to be mentioned shortly, removes this question entirely from 12 
HISTOLOGY AND PATHOLOGY OF 
the realm of doubt. The contents of the vesicles consisted of 
granular matter, a few pns-cells, and free nuclei. 
The corium, immediately below the lesions, was slightly 
oedematous, and along the bases of these latter a more or less 
dense infiltration of small round and wandering cells was ob- 
served. The infiltration was also sprinkled throughout the sub- 
capillary layer, but more especially around the blood-vessels, 
and it gradually decreased until at a short distance from the 
vesicles it was localized entirely around the vessels. The re- 
mainder of the corium was normal, except in the immediate 
vicinity of the vessels, the nuclei of which were multiplied and 
which throughout their entire extent were surrounded by a 
broad zone of small round cells. At a distance from the lesion, 
however, these characteristics were necessarily much dimin- 
ished, and the changes seen were only slight. The hair-follicles 
and the sebaceous glands were normal. 
Important and decided deviations from the normal were ob- 
served in the sweat-glands and their ducts. Certain changes 
which were found connected with the horny epidermis have 
already been mentioned, but there were others in the rete and 
corium which demanded careful examination. These were not 
limited to one or two of the ducts, but nearly every one in the 
sections showed more or less degeneration, it might be only at 
its exit or throughout its entire extent. The rete portion of 
certain of them was somewhat dilated, and the cells in their 
immediate vicinity were pale, granular, and not staining well; 
in others the cells were a little swollen, their protoplasma being 
slightly clearer and broader than normal. In no place, however, 
was any vacuole formation seen. Around one of the ducts, dis- 
tant from the vesicles, these features were especially marked. 
At its upper portion, contiguous to the horny epidermis and 
extending through almost one half of the rete, but more on one 
side than on the other, a mass of cells was seen presenting the 
same degenerated appearances as were found in the walls of the 
vesicles. Those forming and those nearest to the canal of the duct 
had lost their nuclei, and were unstained and slightly granular, 
but still retained their contour. Those situated between these 
and healthy epithelium contained their nuclei, but were pale, HERPETIIORM HYDROA. 
13 
granular, and only very slightly stained. The line of demarka- 
tion separating the healthy and degenerated cells was not 
sharply defined, but there was a gradual transition from one to 
the other. In examining the vesicles, it was found that in many 
of the sections the duct opened directly into a loculus at its 
base. This occurred sometimes in the central one, or again in 
one on the side (Fig. 2). At the point of entrance the duct was 
surrounded by the intiltration at the base of the lesions, and 
throughout its entire extent it and the capillaries accompany- 
ing it, the nuclei of which were multiplied, were surrounded 
by more or fewer small round and wmndering cells. The 
epithelium of the duct itself was pale, in places more or less 
destroyed, its nuclei stained only faintly, and infiltration and 
wandering cells had passed through its walls and were dis- 
tributed throughout it. These appearances diminished some- 
what in proportion as the ducts penetrated more deeply into 
the cutis, but owing, unfortunately, to the fact that the specimen 
was not cut deeply enough, the condition of the glands them- 
selves could only be partially determined. A portion of one 
coil was found, however, and in it the epithelium was seen to 
. be somewhat detached and pale, some of the cells having lost 
their nuclei, while surrounding it was the same cellular intiltra- 
tion which accompanied the ducts. 
It only remains to describe the changes found in the nerves. 
The preparation of the specimen and of the sections after they 
were cut was not such that the nerves were brought into any 
particular prominence. Nevertheless, the degenerative features 
in some were so patent that special preparation could not have 
demonstrated them more clearly. In Fig. 3 are shown three 
nerve-fibers, which were situated just below the rete in the 
papillary layer of the corium. They were all enormously swollen, 
grayish in color, and granular, w'hile here and there small 
clumps of pigment were seen. In fiber A only at one end small 
segments of the axis-cylinder were found, it having entirely 
disappeared from the remainder. The portions present were 
stained slightly, but the nuclei of the sheath of Schwann still 
stained -well, being also somewhat increased in number. In 
fiber C the same condition was present, but there was no trace 14 
HISTOLOGY AND PATHOLOGY OF 
of any axis-cylinder. In fiber B the axis was present to a 
greater extent than in the other two, but was also in segments 
and only lightly stained. The larger trunks seen in cross-sec- 
tion would probably have shown decided changes if they had 
been properly treated, but I should at present prefer to leave 
these for future investigation, notwithstanding that they were 
not normal. The features accompanying the degeneration en- 
title the process, it seems to me, to be regarded as a parenchy- 
matous neuritis. 
As far as the corium and blood-vessels are concerned, 
the microscopical features are, as a whole, only those found 
in inflammation in general. There is nothing peculiar in 
regard to the cellular infiltration of the tissue, nor are there 
any changes in the vessels which can be regarded as be- 
longing entirely to this affection. We may, consequently, 
omit any further consideration of them and turn preferably 
to the vesicular lesions, the connection of the sweat ducts 
and glands with them, and the relation which the changes 
in the nerves bear to both of these. 
According to Touton,* who has summarized our knowl- 
edge in regard to the formation of vesicles, etc., in the skin, 
there are two ways in which those associated with inflamma- 
tion originate : by vacuole formation, or, as he termed it, by 
dropsical degeneration of the epithelial cells, and by a sort 
of coagulative destruction first described by Weigert, f and 
to which Cohnheim gave the name of coagulation necrosis. 
As 1 have already mentioned, in this case of herpetiform 
hydroa there was an entire absence of vacuoles, with the 
exception of two. Their absence would thus exclude their 
being considered as causal factors in the formation of the 
lesion, and a legitimate conclusion would be that the epithe- 
* Touton, " Vergleicli. Unters. u. d. Entwick. d. Blasen in d. Epi- 
dermis," Tubingen, 1882. 
f Weigert, Virchow's "Arch.," vol. Ixxix. HERPETIFORM HYDROA. 
15 
lial destruction was not due to dropsical degeneration. On 
the contrary, instead of vacuole formation, we find, not only 
in the periphery of the vesicles and in their septa, but also 
in and around the ducts of the sweat-glands, those appear- 
ances which accompany coagulation necrosis. The cells are 
not swollen, but are pale, and lose their nuclei, though 
preserving for a time their natural contour. In a mass of 
the epithelium undergoing this degeneration, cells were 
found in every stage of the process, and it could be seen 
how they became finely granular, and, finally succumbing 
to the degenerative process, disappeared entirely, to be re- 
placed by fluid. These features throw the lesions into Tou- 
ton's (Zoe. cit.) second division, and we have consequently to 
regard their formation as being due to coagulation necrosis 
of the epithelium. 
Having established this much, let us seek for the point 
of origin of the vesicles. This seems to me to offer little 
difficulty. There are many facts in favor of locating it in 
and around the sweat-ducts. In the first place, we find them 
opening directly into one or another of the loculi, and it is 
also in the loculus into which they empty that we find the 
external wall the thinnest. In fact, as may be seen in Fig. 
1, a reasonable presumption existing that the sweat-duct 
shown enters the loculus just above it, we find that the ex- 
ternal wall at that point consists only of the horny epider- 
mis and a few degenerated cells, while in all the remaining 
loculi a considerable amount of the rete intervenes between 
their cavities and the stratum corneum. This is again ap- 
parent in Fig. 2, in which there is no question about the 
entrance of the duct into the loculus, and, besides, this same 
condition of things was distinct in every section in which 
there was found a direct connection between the vesicle and 
the sweat-duct. In addition, there were those changes 
which have been described as being present in the cells of 16 
HISTOLOGY AND PATHOLOGY OF 
the duct and in those immediately around it, in the upper- 
most portion of the rete, and it will be remembered that 
one of them especially showed extensive epithelial degener- 
ation beginning in and about it, its own cells having suf- 
fered to the greatest degree. When the definite localization 
of these changes is taken into consideration, and also the 
additional fact that epithelial necrosis is not found else- 
where in the rete, there is, it seems to me, every reason for 
placing the inception of the process in and around the 
sweat-duct, in that portion of the rete just below the horny 
epidermis. I would not, however, give the impression that 
a vesicle develops around and is connected with only one 
sweat-duct. On the contrary, from the number of impli- 
cated ducts found in the sections and connected with the 
lesions, I hold that the process originated simultaneously in 
several contiguous ducts. It must be remembered that each 
section showed different portions of the vesicles, and, con- 
sequently, this mode of origin would allow the formation of 
multilocular lesions to be understood, and also why a duct 
was found entering a central loculus and another one next to 
the lateral wall of the vesicle. 
It may seem, perhaps, to be a rather daring conclusion 
to draw in view of what has previously been written on 
hydroa, but this latter was entirely from a clinical and 
symptomatic standpoint. We find, for instance, Tilbury 
Fox (Zoc. cz'Z.) objecting to the term as suggesting sweat, 
and, besides, none of the writers whom I have been able to 
consult either mention or consider any possible connection 
between the sweat-producing glands and hydroa. Never- 
theless, a study of the history of the disease and of the 
cases which have been reported does not seem to exclude 
this. The affection occurs especially in the spring and in 
the autumn-seasons during which the skin is most exposed 
to sudden variations of temperature and the functions HERPETIFORM HYDROA. 
17 
of the sweat-glands are most apt to be interfered with. 
Bazin (Zoe. czL) himself spoke of the effect that changes of 
temperature had on the disease, and several observers men- 
tion the diminution in the amount of perspiration in pro- 
portion as the eruption decreases. Moreover, in the case 
reported in this article a strong suspicion is warrantable 
that the patient lay on the ground when in a state of per- 
spiration. He was at a picnic, and it is scarcely a usual 
thing at such affairs to remain quiet, so that my surmise 
may not be very incorrect that a sudden shock was com- 
municated to the sweat apparatus. It is true, however, 
that these facts may be regarded only as presumptions, but 
yet, when taken in connection with the histological features 
present, they gain in weight, and would seem to point to 
an undoubted connection between hydroa and the sweat- 
glands. 
What causal factor or factors were active in producing 
the lesions is a much more difficult question to answer, but 
I am inclined to regard the nerve degeneration as the impor- 
tant agent. Schwimmer,* Leloir, f Jarisch, J and countless 
others have contributed valuable observations, both ana- 
tomical and pathological, which point clearly and unques- 
tionably to the association of cutaneous lesions with morbid 
processes in the central and peripheral nervous systems, 
and, in the light of so many recorded facts, it would be 
curious should a neuritis be present in this case of hydroa 
and yet not be related in any way to the eruption. It has 
been said, it is true, that there, are always, even in health, 
certain degenerative changes present in the peripheral 
* Schwimmer, " Die neuropathischen Dermatonosen," Wien u. Leip- 
zig, 1883. 
f Leloir, " Recherehes chir. et anat.-path. s. 1. affections cutanees 
d'origine nerveuse," Paris, 1882. 
J Jarisch, " Vierteljhschft. f. Derm. u. Syph.," H. 2 u. 3, 1880. 18 
HISTOLOGY AND PATHOLOGY OF 
nerves; but Leloir (loc. cit.) and others assert that they 
have been unable to find any evidences pointing to that fact, 
notwithstanding that they have repeatedly examined the 
skin of persons who had died without having bad any cuta- 
neous disease. It has likewise been advanced that the alter- 
ations found in the nerves in the neighborhood of a lesion 
are secondary in origin, and due to it. The testimony of 
Leloir (loc. cit.}, Chambard,* Vulpian,f Cornil and Ran- 
vier, J Weir Mitchell,* and many others does not, however, 
bear this out, but establishes entirely the contrary. 
When we proceed to connect together the nerve degen- 
eration found in this case with the cutaneous manifestations 
an a posteriori conclusion is not immediately possible, yet 
we obtain a clew when we refer to the anatomy and the 
physiology of the nerve-supply of the skin and of the sweat- 
glands. According to Landois,|| the sweat-glands have spe- 
cial nerves of secretion, which for the anterior extremities 
(in cats) run in the ulnar and median nerves and enter into 
the ganglion stellatum of the sympathetic, or, according to 
others, go directly to the cord through the spinal roots. 
For the head, these special nerves arise from the thoracic 
sympathetic and also pass through the ganglion stellatum. 
That this special supply exists in man was shown by Adam- 
kiewitz,A while Heidenhain,0 who eliminated the vaso- 
motor influences, asserts that the changes in the cells are 
due to trophic action-in other words, to trophic nerves. 
* Chambard, "Des gommes cutanees," Soo. anatomique, 1878. 
f Vulpian, "Lemons s. le systeme nerveux professees au museum," 
Paris, 1866. 
| Cornil et Ranvier, " Manuel d'histologie pathologique," Paris, 
1881. 
* Weir Mitchell, quoted by Leloir (loc. nt.}. 
|| Landois, " Lehrbuch der Physiologic," etc., Wien u. Leipzig, 1886. 
A Adamklewitz, "Die Secretion d. Schweisses," etc., Berlin, 1878. 
Q Heidenhain, "Studien d. physiolog. Instituts zu Breslau," 1868, HERPETIFORM HYDROA. 
19 
This view has been more and more favorably accepted, and 
we find very lately, among others championing it, Schwim- 
mer (loc. cit.) and Kopp,* who regard the sweat production 
as unquestionably due to trophic nerves. 
To enter here into the theories in regard to these nerves 
is naturally out of the question ; they are fully dealt with 
by the authors referred to, and also by many others, and it 
is only their conclusions which are of interest to us. The 
functions of trophic nerves are considered to be those of 
guarding and regulating the nutrition of the tissues. The 
view held at the present day, though not yet fully demon- 
strated, is that trophic nerves are supplied to every part of 
the body. We must, therefore, regard the rete and the 
epithelium of the sweat-ducts, and other constituent por- 
tions of the skin, as all possessing these special nerves, 
which, like those which go to the sweat-glands, are probably 
to be found in the ulnar and median, in those portions of 
the skin to which these two are distributed. From the 
nature of their functions, the nutrition of tissue must suffer 
should any of those supplying it be destroyed or become 
diseased, and the morbid change resulting, owing to the 
more or less intimate connection between the vaso-motor 
and the trophic nerves, may be accompanied, as in zoster, 
mal perforant, etc., by manifestations of inflammation. 
When we now turn to this case of hydroa, we find that it 
presents features which allow us to connect the nerve 
changes in a causal manner with the cutaneous lesions, and 
to regard these latter as the result of disturbed trophic re- 
lations. Microscopically, so far as the nerves themselves 
are concerned, we receive no aid, since it is impossible to 
determine in that way which are trophic nerves and which 
are not. 
Clinically, we know that the lesions which were exam- 
*Kopp, "Die Trophoneurosen d. Haut," Wien u. Leipzig, 1886. 20 
HISTOLOGY AND PATHOLOGY OF 
ined had been present only a few hours, and that the erup- 
tion followed to a striking degree the distribution of the 
ulnar nerve, being also to a lesser extent situated over the 
median, only a few being over the radial; that is, it was 
especially over those nerves-the ulnar and the median- 
supplying the affected skin, and in which the trophic nerves 
for the sweat-glands, etc., run. We find microscopically, 
in connection with the cutaneous manifestations, a diseased 
state of the nerves, and we have the highest authority for 
concluding that it is primary and not secondary. Besides, 
as already mentioned, the pathological changes are found 
entirely in and around the sweat-ducts and glands, the other 
appendages of the skin being unaffected. We thus have in 
this case three prominent factors: the localization over the 
nerves, the degeneration of the nerves, the morbid changes 
situated in a constant manner in a certain cutaneous organ ; 
and when we compare these factors with those found in 
other diseases of the skin which are recognized as being 
dependent directly upon nerve lesions, the conclusion that 
the nerve changes stand in a causal relation to the cutaneous 
eruption in herpetiform hydroa seems to me unavoidable 
arfd unquestionable. 
Is this, however, the result of trophic disturbances? It 
can not be absolutely proved, but yet is most probable. As 
already mentioned, the primary steps leading to the forma- 
tion of the vesicle were situated in the epithelial cells of 
that portion of the sweat-duct lying in the rete, and con- 
sisted in death of the nucleus and cell. This could not 
have been due to the direct influence of the accompanying 
inflammation, since the ducts in which this primary stage 
was seen were not in its immediate vicinity, but at a dis- 
tance from it, and there were besides no inflammatory evi- 
dences surrounding them. On the contrary, they must have 
been caused by the nerve changes, since we have shown HERPETIFORM HYDROA. 
21 
that a causal connection existed between these and the 
cutaneous lesions. Now, when we consider that of the 
three theories-functional inactivity, propagation of inflam- 
mation along the nerve-fibers to their peripheral endings, 
and trophic disturbances-which have been advanced in 
explanation of the influence of nerve lesions upon cutaneous 
and other diseases, the two former have been cast out (Vul- 
pian,* Charcot,f Leloir \loc. cit.J, etc.), and only the last 
one has been found tenable, we can not be in error if we 
conclude that, in a case presenting the neurotic features and 
the nerve lesions described in this article, the cutaneous 
manifestations are the result of trophic disturbances, and 
are dependent upon the degeneration of the trophic nerves 
distributed to the affected part. 
From these histological and pathological features my 
conception of the genesis of the lesions of herpetiform 
hydroa would be as follows: A primary degeneration of 
certain special nerve-fibers having occurred, this being pe- 
ripheral or even possibly central in origin, a disturbance in 
the nutrition results, with consequent death of the cells of 
the sweat-ducts in the rete. The destruction of the con- 
tiguous cells of the mucous layer ensues, and inflammation 
is lighted up secondarily and implicates the coils of the 
sweat-glands and the ducts, already the seat of degenerative 
changes. Effusion of serum fills the cavities formed by the 
epithelial destruction, and with this there is also the sweat 
still produced by the glands. In the lesions, death of the 
epithelium forming the septa between the loculi progresses, 
until instead of multilocular we have unilocular vesicles or 
bullae, which when grouped may all communicate one with 
another. These steps in the histogenesis of the disease 
have, I think, been fully brought out by the facts given. 
* Vulpian, " Vaso-moteurs," tome ii. 
f Charcot, " Lemons s. 1. maladies du systeme nerveux," vol. i. 22 
HISTOLOGY AND PATHOLOGY OF 
In order to demonstrate the individuality of the his- 
tology presented by this case of herpetiform hydroa, allow 
me to compare it with that of some lesions which have or 
might have the same clinical localization, and with that of 
one which has the same anatomical situation. Any one 
familiar with the anatomy of zoster will immediately per- 
ceive the entire want of similarity between it and hydroa. 
The herpetic vesicles belong to that class formed by a drop- 
sical degeneration of the epithelial cells of the rete (Touton, 
loc. cit.), while in hydroa, as has been shown, they are pro- 
duced by means of a coagulative necrosis of these same 
cells. The result in both is the same-a vesicle-but the 
process by which they are produced is not the same. The 
lesions in zoster have no particular localization as in hydroa; 
they originate over the papillae, and the infiltration is not 
limited to the blood-vessels, but it is diffuse throughout the 
entire cutis, extending even into the fatty layer. 
Still greater are the differences between the anatomy of 
hydroa and that of erythema multiforme. Leloir* has made 
the latest examinations of the bullae and vesicles occurring 
in this latter affection. He found that in all the lesions the 
horny epidermis was lifted up en masse by the exudation, 
and, together with some portions of the stratum lucidum, 
formed the external wall of the lesion. The remaining 
portions of the stratum lucidum, together with the stratum 
granulosum, constituted the base. He also found the epi- 
dermis in some places raised up in its entirety, but only to 
a very slight extent. We thus see that there is not a sin- 
gle factor in common between hydroa and erythema multi- 
forme. Dermatitis herpetiformis I shall pass over in this 
article, since my studies on its histology are shortly to 
* Leloir, " Lesions d. 1'epiderme dans I'eryth&me polymorphe. Ery- 
theme bulleux ou pemphigoide. Erytheme vesiculeux." "Progres 
med.," 1885. HERPETIFORM HYDROA. 
23 
appear elsewhere, but 1 will compare hydroa with one other 
affection, the dysidrosis of Tilbury Fox, also called pompho- 
lyx and cheiro-pompholyx. It might be omitted, since clin- 
ically there is no resemblance between the two diseases, but 
yet anatomically they both have one feature in common- 
their localization around and about the sweat-ducts. This 
would seem, however, to be their only point of similarity, 
for, according to G. and F. E. Hoggan,* who have reviewed 
the whole subject and have carefully studied a large num- 
ber of sections, the lesions in dysidrosis originate by vacuole 
formation in the stratum granulosum, the sweat-duct being 
only secondarily implicated. There is, consequently, the 
important distinction between the two that in hydroa the 
mode of origin is different and begins primarily in the 
sweat-duct, while in dysidrosis this latter, though it plays 
in the end an important part in the process, is yet only a 
secondary factor. 
The histological and pathological features which this 
case of herpetiform hydroa presented, and the facts which 
have been brought forward and as far as possible connected 
together upon warrantable and reasonable bases, allow the 
following conclusions to be made : 
1. That in herpetiform hydroa we have an affection 
which owes its origin to a degenerative process situated in 
the nerves supplying the affected skin, and that there is 
every reason to consider it as being trophoneurotic in its 
nature. 
2. That as a result we have the formation of more or 
less grouped vesicles and small bullae, which are directly 
connected with the sweat-ducts, and through them with the 
sweat-glands. 
3. That the point of origin of these lesions is primarily 
in the epithelium of the sweat-ducts just below the horny 
* G. and F. E. Hoggan, "Monatsh. f. prakt. Dermatologic," 1883. 24 
HERPETIFORM I1YDR0A. 
layer of the epidermis, extending from there to the cells of 
the rete Malpighii. 
4. That the affection is accompanied by the ordinary 
symptoms of inflammation, which, however, are secondary 
and situated especially in the papillary layer of the corium. 
5. That its histogenetic and pathogenetic characteristics 
are sufficiently distinctive to entitle it to be considered as a 
disease which is separate from all others. A REASONS WHY 
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Fxg. 1. 
Vertical section through a vesicle of hydroa herpetiforme. a, epidermis; 6, rete Malpighii; c, several loculi of vesicle-between each loculus 
are columns of rete, the cells of which are some normal, others more or less degenerated; «?, blood-vessels; e, duct of sweat-gland. 
Fig. 2. 
Fig. 3. 
Three nerve-fibres situated in papillary layer of corium and enlarged. 
Duct of sweat-gland opening into cavity of vesi- 
cle-only one loculus of vesicle shown.