A CONTRIBUTION TO THE STUDY OF THE BUL- 
LOUS ERUPTION INDUCED BY THE INGESTION 
OE THE IODIDE OF POTASSIUM.* 
BY JAMES NEVINS HYDE, A.M., M.D., 
Professor of Dermatology and Venereal Diseases, Rush Medical College, Chicago 
[Reprinted from Archives of Dermatology, October, i8jq.~\ 
ON the 23d of June, 1879, I was visited by a female patient 
with an infant at her breast, who delivered a note from a 
physician of Chicago, in which the latter requested me to give an 
opinion as to the skin disorder with which the child was affected. 
From the statements made by this mother, and from the information 
subsequently given by her attending physician, the following history 
was obtained : 
The father was and had always been an entirely healthy man. The 
mother had occasionally suffered from head-and back-ache, and from 
an affection of the skin which had at times troubled her since child- 
hood, but which had not manifested itself since her marriage. At 
one time, however, since that date, she had suffered from a small 
abscess on the inner face of the thigh, which, after discharging, had 
healed without untoward symptoms. Upon examination, this woman 
was found to be free from all evidences of syphilitic infection. She 
was well developed, had an abundant supply of milk for her infant, 
and only exhibited a moderate pallor of the exposed mucous sur- 
faces. The cicatrix left by the abscess described above had no sus- 
picious features. 
Soon after her marriage she had been delivered of an infant which 
speedily displayed an eruption upon the surface of its skin. This 
was, according to the diagnosis of her physician, a simple eczema 
of the face and scalp, which, though somewhat rebellious, yielded 
to appropriate treatment. When convalescing from this attack the 
child was seized with cholera infantum, and died in its ninth month. 
The second pregnancy terminated in the birth of the present fe- 
* Read at the third annual meeting of the American Dermatological Associa- 
tion, New York, August 26, 1879. 2 
BULLOUS LODLDE OF POTASSLUM ERUPTLON. 
male infant, Amanda Gabrielle, now eight months old. As in the 
case of the child which was lost, she had, soon after birth, exhibited 
over the skin of the face and scalp an eruption which was recognized 
by the physician to be a typical eczema capitis. This cutaneous 
disease had also proved persistent under the treatment employed, but 
had gradually improved until about one month prior to the present 
examination, when an abundant crop of boils had appeared over 
the scalp. These increased in number until the physician estimated 
that he had opened hundreds with the lancet in the region described. 
They gave exit to an abundant, creamy, and laudable pus, when the 
process of repair speedily followed. During that time the eczema- 
tous condition had gradually ameliorated. In spite of these acci- 
dents the case was progressing fairly well, when the complication 
ensued with regard to which my opinion was asked. This complica- 
tion was the development of certain cutaneous lesions, of formidable 
aspect, greatly different from those previously observed. 
Upon examination the little patient was seen to be a fat and well- 
nourished baby, with the eruption of six teeth accomplished. It 
was exceedingly fretful and irritable, no doubt partly in consequence 
of the extent of the cutaneous disease with which it was affected, 
and which was pretty surely the source of disagreeable, if not pain- 
ful, sensations. 
The entire scalp was covered with an extensive yellowish crust 
of moderate thickness, evidently composed of the dried exudation of 
a preceding inflammation of pustular type, together with the seba- 
ceous secretion usually seen in such cases. Sparse and light-colored 
hair-filaments were embedded in the crust. Similar, less bulky, and 
slightly-reddened crusts covered also the temples and the upper por- 
tions of the cheeks. Here it was evident that the surfaces had been 
irritated by scratching, as the marks of the fingers and nails were to 
be distinguished. No pus was confined beneath the crusts either of 
the scalp or face. The acuteness of the inflammatory process had 
evidently subsided. Here and there could be seen the sites of the 
abscesses whose history has been given. In short, the external ap- 
pearances of the portions of the body described were those of an 
ordinary eczema capitis in the phase of retrogression. 
But over the extremities and nates an eruption of a distinctly 
different type was visible. It consisted of variously-sized vesicles 
and bullae, displayed upon the arms, forearms, hands, palms, inter- 
digital spaces, backs of the hands, wrists, nates, thighs, legs, ankles, 
dorsum of the feet, and the spaces between the toes. The smaller 
lesions were dispersed between the others, but the larger were 
grouped about the wrists and ankles. They were displayed upon both 
sides of the body, and were limited to similar localities on each side, 
so that a certain degree of symmetry was thus demonstrable. Pro- 
ceeding upward and downward from a circlet surrounding the wrists 
and ankles, where, as has been stated, was the region of most plenti- 
ful development for the upper and lower extremities, the bullae be- 
came progressively fewer and smaller. Thus there were but a few BULLOUS IODIDE OF POTASSIUM ERUPTION. 
3 
small, imperfectly-developed vesicles upon the extremities of the 
fingers and toes, and above the elbows and knees. Those upon the 
nates were not only ill developed, but surrounded by hyperaemic 
patches and sparse, delicate crusts, suggesting that in this locality 
the two disorders of the skin had coexisted and their phenomena 
become intermingled. 
The vesicular and bullous lesions varied in size from that of a 
large pin-head to a pigeon’s egg, those fully developed far outnum- 
bering all others. Though they were for the most part discrete, it 
was clear that some of the largest had resulted from coalescence, the 
partition-septa showing after rupture. Some were elevated above 
the general surface of the integument to the extent of from 8 to io 
millimetres. The smaller were roundish in shape : the larger were 
either globoid or—and this was not rarely to be noted—elliptical in 
contour. Often they showed as merely irregular and bulging pro- 
jections from the general surface. 
These lesions had no disposition to rupture, but were remarkably 
firm and persistent. According to the statement made by the physi- 
cian, they had originally contained a serous and in some cases a semi- 
purulent fluid, but at the time of the observation now detailed there 
were very few which could be made to exude a fluid sufficiently thin 
to drop from between the fingers after rupture of the wall of the bleb. 
Each contained a semi-gelatinous mass, suggesting the appearance 
of boiled sago. The smaller bodies*contained a thickened serum of 
high specific gravity. Here and there among these smaller bodies 
were slightly larger lesions resembling pustules and containing in- 
spissated pus. 
The color of the skin affected with this eruption was unchanged, 
nor was the peripheral integument altered by inflammation-exudates 
or oedema. The bullae were of a dark purplish shade when fully 
developed, this hue being most distinct about the sides of each. 
There was no areola of redness about the base of any. The smaller 
lesions were yellowish and reddish-yellow in color. 
In many of the larger and a few of the smaller lesions, there was 
an appearance which suggested umbilication. This in some instances 
amounted merely to an apical flattening, and was without question 
in all cases due to the collapse of the roof-wall upon the shrunken 
contents of the enclosing chamber. This feature, especially when 
distinguishable in the lesions of a vesicular or pustular type, strongly 
suggested the similar eruptive symptoms of varicella and certain 
forms of variola. It was clear, however, that in the case of these 
smaller lesions they were no longer in process of development. As 
compared with those which were evidently more mature, all seemed 
alike to have been arrested in their course after each had attained 
its greater or less size. 
On the 7th of July I enjoyed a final opportunity of examining 
this patient. At that date the lesions had naturally much changed in 
appearance. The eruption as a whole was much less prominent and its 
earlier characters much less pronounced. Still, here and there over 4 
BULLOUS LODLDE OF POTASSIUM ERUPTION. 
the originally affected surfaces were to be seen relics of large-sized 
bullae, distinct in outline, though otherwise changed. For the most 
part the lesions remaining evident were dark brownish-colored 
scabs, made up of the desiccated roof-wall of the pre-existing pem- 
phigoid lesions, without traces of desiccated or otherwise altered 
exudation. These crusts were firmly adherent to the surface beneath, 
which seemed to be a base constituted of a more or less solid tissue 
resembling the flattened syphilitic condyloma. When removed, they 
disclosed a granulating surface beneath, without the interposition of 
a purulent or other pathological fluid. The general condition of 
the little patient had also in the mean time greatly improved. There 
had been but little loss of flesh, which was the more noticeable as 
the temperature was unusually high, and the child, while dentition 
was in progress, had an extensive eczematous trouble upon the scalp. 
At the conclusion of my first examination of this patient I recorded 
the case as one of eczema of the face and scalp, for the relief of 
which the iodide of potassium had probably been administered, with 
the result of producing a pemphigoid rash. In the present state of 
our knowledge, and especially since the publication of Dr. Duhring’s 
similar case, I feel confident that such would have been the prompt 
diagnosis of all who have studied the literature of the subject. To 
this source only could I refer, as I had never before enjoyed the 
opportunity of studying this particular one of the several rashes 
which the potassium iodide is» capable of producing. Soon after 
this date, in an interview with the attending physician, he admitted, 
in response to my questions, that for four weeks prior to the ap- 
pearance of the intercurrent skin disease the child had taken daily 
0.30 gm. of the iodide of potassium, which had been intended for 
the relief, not of the eczema, but of the numerous boils which suc- 
ceeded to the former trouble. The remedy had been suspended at 
the time of the appearance of the bullae, though the doctor had not 
suspected that the two stood in the relation of cause to effect. 
The number of recorded cases in which this accident has occurred 
is sufficient to establish the origin and identity of this eruption, and 
to justify certain deductions respecting its natural history. 
As far as known to me, the literature of the subject consists of 
papers by Bumstead, of New York (Amer. Journ. of the Medical 
Sciences, July, 1871, p. 99); the Boinet-Cazenave cases, cited by 
Bumstead (.Iodotherapie, 2d, 1865, p. 68); a paper by Dr. Til- 
bury Fox, of London (reprint from “The Clinical Society’s Trans- 
actions,” vol. xi., 1877) > the observations of an anonymous reviewer 
in the Edinburgh Med. Journ. for August, 1873, cited by Dr. Fox; 
reports from the practice of Mr. .Hutchinson, of London (vid. “ Clin- 
ical Society’s Transactions,” 1875, v°l- and also “Report of 
the Medical and Surgical Registrars of the London Hospital” for 
1875); with a clinical lecture by Dr. Duhring, of Philadelphia 
(The Med. and Surg. Reporter, August 4, 1877, p. 89) ; a report of 
cases treated by Dr. R. W. Taylor, of New York (Arch, of Derma- 
tology, April, 1877, p. 227); a case recorded in the service of Dr. BULLOUS IODIDE OF POTASSIUM ERUPTION. 
5 
F. N. Otis, at the Charity Hospital, New York (N. Y. Med. Record, 
March 8, 1879, P- 225) '* and a PaPer by Dr. J. M. Finny, of 
Dublin, read before the Dermatological Subsection of the British 
Medical Association (Brit. Med. Jour., Aug. 23, 1879, P- 29I-)t 
Respecting the rarity of this eruption, it may be remarked that 
Dr. Fox, at the date of writing his paper, was in position to say 
that Mr. Lane, Mr. Berkely Hill, Mr. Alfred Cooper, Mr. Coulson, 
and Profs. Hardy, Bazin, Guibout, and Fournier had never seen a 
bullous or pemphigoid eruption which could be attributed to the 
drug. And Dr. Bumstead relates that, in the article written by H. 
E. Fischer, of Vienna (vid. L'Union Medicale, January 31, i860, 
from the Wien. Med. Wochensch.), devoted especially to the erup- 
tions produced by the iodide of potassium, no mention is made of 
the rash here considered.! 
A chromo-lithograph of about the size of an octavo page accom- 
panies Dr. Fox’s paper, and represents well in outline the lesion 
observed by me. Had a few more stones been used in the produc- 
tion of this plate, giving the purplish shades seen by me, more 
especially at the sides of the bullae, the portrait would fairly repre- 
sent also the colors of the larger lesions I have described. Plate 
numbered 33, in the Sydenham Society’s series, entitled “ Hydroa 
from the Iodide of Potassium,” in no way suggests either the erup- 
tion figured by Dr. Fox or that described by me. 
In the following table I have plaoed side by side (for the purpose 
of comparison) the salient features of the various cases detailed by 
the authors named above : 
* I am indebted for my record of this case to the kindness of Dr. P. B. Porter, 
of New York. 
f See Archives of Dermatology, Oct. 1879, page 404. 
j In a note from Prof. White, of Boston, received since these lines were written, 
I am informed that he has never seen the eruption here described. 6 
BULLOUS IODIDE OF POTASSIUM ERUPTION. 
M 
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M M M M 
On 
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Total Amount of Iodide 
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Interval between Admin- 
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s, interdigital spaces, 
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, thighs, legs, ankles, 
and between the 
ad, backs of hands, 
r lip, side of nose, 
s of arms, elbows. 
of hands, backs and 
of fingers, one 
(inner surface), 
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of forearms, groins, 
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forehead, arms, 
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al region. 
of neck, forehead, 
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Locality of Lesions. BULLOUS IODIDE OF POTASSIUM ERUPTION. 
7 
Color of Lesion. 
Contents of Lesion. 
Size of Lesion. 
General Condition of 
Patient and Concomi- 
tant Symptoms. 
Interval after Discontin- 
uance of Drug to Dis- 
appearance of Lesions. 
<U 
a 
CJ 
Is 
rt 
fe 
Remarks. 
Reddish or 
Clear to tur- 
Very large. 
Cachexia. 
A few 
Skin about lesions red 
purplish. 
bid serum, 
days. 
and oedematous. 
blood. 
blood. 
swollen, fever. 
Alarming symptoms, 
swelling of face, 
mouth, and pharynx. 
Large. 
ing of the skin. 
days. 
been produced by 
burn. 
Pale, yel- 
Clear serum, 
Pin - point 
Good. 
4 or 5 
Septa, boiled sago- 
lowish- 
no pus. 
to large 
. 
days. 
grain appearance. 
while, 
pea. 
No oedema. One 
and glist- 
lesion in centre of 
ening. 
palm. 
thin pus, 
feebleness. 
days. 
inodorous. 
Yellowish 
l'urbid se- 
Three- 
Pleurisy, peri- 
5 to 6 
t. Chro- 
Painful. 
scab. 
rum, gray- 
penny 
carditis, sore 
days. 
nic 
ish pus. 
piece. 
mouth. 
Bright’s 
Disease. 
Sanguinolent 
Large. 
Sore mouth. 
6 to 8 
and puru- 
days. 
lent. 
Dark - pur- 
Serum, sero 
Pin - head 
Fair general con- 
A few 
Quasi-umbilication. 
pie. 
pus, gelati- 
to pig- 
dition; eczema. 
days. 
nous mass. 
eon's 
egg. 
Purple and 
Thin, yel- 
Vi, to lA in. 
18 days. 
I 
Inflamed areola. 
red. 
low, often- 
high. 
sive. 
cherry. 
pressed centre. 
Lesions readily torn. 
blood. 
Large. 
i week. 
Some HlStinCt 
ia; extensive 
ly umbilicated. 
superficial ul- 
cerations of 
surface of ex- 
tremities. 
6 days. 
to split 
pea. 
• 8 
BULLOUS IODIDE OF POTASSIUM ERUPTION. 
A study of the cases tabulated above suffices to establish the fol- 
lowing facts: 
The eruption has been recorded by the authors named as occur- 
ring eighteen times in fourteen individuals. Of nine patients, 
whose sex is stated, four were males and five females. The young- 
est patient is she whose case I have described,—one which, for that 
reason, has an especial interest in this connection,—an infant at 
the breast, 8 months old. The age of the eldest of those whose 
age is given was 39 years. In two cases, the eruption recurred in 
each individual; once in a second, and once in a fourth attack. 
The quantity of the drug recorded to have been ingested, varied 
from 0.30 gramme to 12 grammes. In a few instances the medi- 
cament was continued after the production of its toxic effects, in 
consequence of a failure to recognize their import. Four times the 
remedy was administered for the relief of syphilis; twice in the 
treatment of eczema. The period which elapsed between the ad- 
ministration of the last dose and the explosion of the cutaneous 
symptoms varied between four hours and five days. 
By ten writers the lesions are described as “ bullous,” five add- 
ing the term “vesicle;” two adding the word “pustule;” in one 
case only is the eruption said to be constituted only of “ large 
vesicles;” once, of “vesico-pustules.” 
As regards the localities affected by the eruption, we find that it 
was observed twenty-one times upon the different portions of the 
head and neck; twenty times upon the upper extremities; twelve 
upon the lower; and but six times over the surface of the trunk. 
To enumerate these localities more precisely, we find six observa- 
tions of the disease on the forehead; five on the face ; two on the 
sides of the nose ; two on the tongue ; one on the cheeks ; one on 
the eyelids; one on the under lip; and three on the back of the 
neck. Eight times it was noticed on the arms and forearms; once 
on the hands; six times on the backs of the hands; twice on the 
backs and sides of the fingers; twice over the wrists; and once only 
over the elbows. Twice the bullae appeared over the general surface 
of the body; twice over the nates; and once over the groins and 
pubis. Four times the legs were affected, and twice each the thighs, 
ankles, feet, and toes. 
The lesions, which were generally described as bullae, began 
either as, from the first, pin-point-sized vesicles, or as shot-like 
papules, at the apices of which vesiculation subsequently occurred. 
These in color were pale yellowish-white, and glistening. In some 
instances, where only a small dose of the drug had been adminis- 
tered, or where it had been promptly discontinued on the appear- 
ance of toxic effects, the subsequent evolution of symptoms was not 
decided. Where, however, the dose had been large, or persistently 
continued, and especially when there had been coincident cachexia, 
subsequent changes were noticed in the eruptive phenomena. In 
color the bullae became successively red, dark-red, purple, and dark- 
purple. Containing at first merely a clear and limpid serum, the BULLOUS IODIDE OF POTASSIUM ERUPTION. 
9 
contents of the lesions changed to a thin sero-pus, inodorous, and 
sometimes almost creamy. To this succeeded a pure yellowish 
pus, which, in cases, degenerated to a sanguinolent ichor, of foul 
odor. In a few instances blood only was found in the pemphigoid 
lesions at an early stage. 
The existence of the toxic phenomena is in cases compatible with 
the enjoyment of fair health. This, at least, was noted in two in- 
stances. In four there was a record of cachexia and prostration ; 
in one the patient suffered from chills. Two fatal cases are re- 
corded ; one from chronic Bright’s disease, with pleuritic and peri- 
cardial complications. In the case of the other patient the history 
is indefinite. It seems clear, however, that the result was due 
rather to the depraved general condition of the patient than to 
either the remedy or the eruption produced by it. It should be re- 
membered in this connection that the greater number of patients 
displaying this form of cutaneous disease will always be those in 
whom the effects produced by the drug are partially masked by the 
disorder for which the drug is prescribed. There is no reason to 
believe that in those depressed states of the system where the bullae 
have been noted, for example, upon the mucous surfaces of the roof 
of the mouth and the tongue, the cachexia is immediately and 
solely due to the action of the iodide of potassium. 
Upon one point all the authors are agreed, viz., that in a few 
days after the drug is discontinued, the eruption disappears, even in 
cases where there is great cachexia. Eight days at the longest have 
sufficed to greatly improve the cutaneous symptoms, the patient in 
one case dying over two weeks after the eruption first appeared. 
Upon two points there is a discrepancy between those who have 
reported cases. One of these concerns the inflammatory areola, 
which, in certain patients, has been seen surrounding the individual 
lesions, and in others has been absent. The other relates to the 
umbilication of the bullae. This has not been observed by the 
greater number of authors ; and I am inclined to believe that in 
those cases where it has been seen, the phenomenon was due to the 
shrinkage of the roof-wall of the lesion upon its contents. 
The late lamented Dr. Tilbury Fox, from the observations to 
which he had access at the time his paper on this subject was read 
before the Clinical Society of London, draws some conclusions 
which can only be accepted with reserve in the light we can command 
at the present time. He states, for example, that the pemphigoid 
rash is excited only “under the influence of small and few doses,” 
a conclusion certainly not warranted if the history of my case be 
accepted as typical of the infantile symptoms. He also declares that 
“ the action of the drug in these cases is not limited to the skin, but 
produces great depression, with or without pyrexia, ulcerations of the 
mucous membranes, etc.,” a deduction which is manifestly incor- 
rect as applicable to all cases, and one which, as I have attempted 
to show, may be doubted in all those cases where a depressing dis- 
ease has existed, for the relief of which the remedy was prescribed. 10 
B ULL O US IODIDE OF PO TASSIUM ER UPTION. 
Lastly, Dr. Fox is of opinion that the eruption is one which 
originates in the sebaceous glands, and that the contents of the 
bullae are altered secretions of the sebaceous glands. Investigation, 
chemical and microscopical, will of course be necessary to set at 
rest the problem which he thus presents, but the clinical reasons for 
dissenting from his opinion seem to me to be worthy of considera- 
tion. If the sebaceous glands were the seat of the disease, it would 
be reasonable to look for its most abundant development in those 
localities where we are accustomed to find the sites of election of 
such other sebaceous-gland disorders as milium, comedo, sebor- 
rhoea, acne, etc. These sites of election, it need not be said, are 
the face, the scalp, the back of the neck, the back of the trunk, and 
the genital region. But it has been pointed out above that the 
pemphigoid rash under discussion, though occurring most often 
upon the head, has never been reported upon the scalp, and that 
the region of next preference is the upper extremity, especially over 
the wrists and forearms, localities which, as Bumstead shows, are 
exposed to the air, and which, it need not be said, are not regions 
where we are accustomed to find the sebaceous-gland disorders 
mentioned above. I desire also to call special attention to the fact 
that, both by Dr. Duhring and myself, the lesions were observed 
upon the palms of the hands, where Biesiadecki and others have 
never been able to demonstrate the presence of either sebaceous 
glands or lanugo follicles. 
Two other clinical considerations should be here mentioned. One 
is the chronicity which usually characterizes sebaceous-gland dis- 
orders, such as acne, comedo, etc., as opposed to the circumstance 
that the bullse produced by the iodide of potassium have been 
seen within five hours after the administration of the drug. The 
other is the recorded occurrence of blood-contents in the lesions. 
The transformation of the secretion of a sebaceous gland into a thin 
odorless or offensively-smelling sero-pus cannot be viewed as beyond 
the possibility of occurrence; but a sanguineous seborrhcea could be 
regarded only as the symptom of a formidable constitutional dys- 
crasia. These and possibly other considerations which might be 
suggested lead me to the conclusion that, for the present, at least, we 
are not justified in accepting without reserve the statements relative 
to the sebaceous origin of the rash which we have been studying. 
The most valuable of the practical conclusions to which such a 
study leads would seem to be: (a), that, in eczema, where a dis- 
tinctively vesicular or bullous eruption becomes suddenly apparent, 
the lesions intermingled with those characteristic of the disorder 
named, in the person of patients who have been under the charge 
of inexperienced practitioners, the possibility that the iodide of 
potassium has been previously administered should be carefully esti- 
mated ; {&), that it is not only possible but quite probable that the 
rare vesicular and bullous lesions recorded as occurring in acquired 
syphilis may be rashes induced by the administration of the iodide 
of potassium for the relief of the disease.