ERYTHEMA MULTIFORME BULLOSUM FOLLOWING THE USE OF
SULFADIAZINE
BY V. J. DARDINSKI, M.D., F.A.C.P.
Georgetown University Hospital, Washington, D. C.
Since the advent of sulfonamide drugs, many reports
have appeared in the literature, calling attention to the
various complications which have resulted from their
use. The majority of these complications have been
in the nature of a depression of some particular element
of the hematopoietic system.
A summary of these effects, by Kracke, appeared
recently 1 . Greenberg and Messer recently reported a
fatal case of bullous dermatitis following the use of
sulfadiazine 2 .
Many aspects of the clinical picture presented by
their patient, were also present in the case I wish to
present here.
M. J. white, female, age 17 years, was admitted to
Georgetown University Hospital March 29, 1942 with
a diagnosis of toxic erythrodermia. Her present illness, began two weeks prior to admission, with chills,
fever and a pain in the chest. The findings were
typical of bronchopneumonia. The following day
sulfadiazine therapy was instituted and continued as
follows: two tablets every four hours until 32 tablets
had been taken. Then one tablet every four hours for
20 more tablets. Because of insufficient improvement
the dosage of two tablets every four hours, for thirtysix more hours, was again instituted.
Following this last course, all medication was stopped
because a generalized red rash appeared, resembling
"sunburn".
The day after the appearance of the rash, watery
"blisters" of various sizes, began to appear. The condition became worse on the following day, at which time
she was admitted to the hospital. On the day of
admission, she had a temperature of 104.5°, pulse 100
and respirations 22. The face was slightly swollen and
diffusely erythematous. Large bullae were present
under both eyes. There was diffuse erythema with
multiple varioliform scaly macules and papules over
the entire body. Numerous large bullae, arising from a
erythematous base, were also present over the entire
body. Similar bullous lesions were found involving
the vagina and anus.
The mucous membrane of the nose was diffusely
reddened. The oral mucous membrane was red and
angry. The posterior pharynx was acutely inflamed
and covered with several small detachable pieces of
white membrane. The conjunctivas were markedly
injected and severe photophobia was present. Several
small peanut sized glands were present in the posterior
cervical region.
Blood examination showed a hemoglobin of 69 per
cent, leucocytes 23,800, with 84 polymorphonuclears,
3 juveniles, 13 lymphocytes. Nonprotein nitrogen
was 23 mg. per 100 cc. of blood. The total protein was
4.39 grams, with 2.93 grams of albumen and 1.46
grams of globulin per 100 cc. of serum. The blood
sulfadiazine level was 2.8 mg. per cent. Urinalysis
at this time was essentially negative.
On March 31, large bullae were present over the
entire body, which were fusing and involving extensive
areas of body surface. Many of these were breaking,
liberating clear, light yellow fluid and leaving raw
denuded surface areas. Similar large watery bullae
were present in the external auditory canals, which
when ruptured, liberated a similar watery fluid. The
tympanic membranes, however, were red but not bulging. There was no fluid behind the membranes.
Urinalysis on that day showed specific gravity of
1.020; albumin 3 plus, acetone 2 plus, red blood cells
1 plus, white blood cells 2 plus, and bacteria 2 plus.
No crystals were present. The sulfadiazine level on
fluid from the bullae was too low to be determined.
On April 3, blood hemoglobin was 66 per cent; red
blood cells 3,210,000; white blood cells 4,000.
During the six days in the hospital the temperature
ranged from 103° to 105°, the pulse from 110 to 150
per minute, the respirations from 22 to 38 per min.
The skin condition, and general condition, became
progressively worse throughout this period, with ruptured large bullae over the entire body. In the region
where these ruptures occurred, most extensive over the
back, large sheets of epidermis were rubbed off, leaving
a red, beefy raw surface which continually oozed a light
yellow, watery fluid.
The fluid intake and urinary output are rather significant because they apparently parallel the fluid loss
through the surface, on the other hand the possibility
of anuria developing must also be considered.
Intake
1590
4900
5020
4060
5750
Output
1170 3/29/42 day of admission
1400 3/30
2440 3/31
1260 4/1
830 4/2'
On April 3, the patient gradually became stuporous
and incontinent. Coma gradually developed and the
patient expired on April 4, in spite of all treatment,
including whole blood and plasma transfusions.
28
ERYTHEMA MULTIFORME AFTER SULFADIAZINE
At necropsy the external examination of the body
showed essentially the same findings as described above.
The liver, spleen and kidneys were congested. Numerous petechial hemorrhages were present throughout
the gastro-intestinal tract but were more numerous in
the duodenum. The brain was markedly congested
and edematous, and the convolutions were moderately
flattened. No other gross lesions of significance were
found.
The microscopic examination of the tissues was
rather disappointing, because nothing remarkable was
found. The picture in all the tissues was quite similar
to that seen in any severe cardiac decompensation. Sections of several lymph nodes showed almost complete
destruction, by an acute necrosis, resembling a caseous
type of necrosis. However, no evidence of giant cell
formation was seen. The remainder of the organs
showed nothing significant.
Sections of the skin (fig. 1) showed all the usual
changes seen in bullous lesions. Splitting of the epithelium by accumulation of non-cellular fluid; congestion of the blood vessels in the papillary layer, with
a moderate number of round cells infiltrating throughout the dermis, appears to be the only finding. The
29
usual eosinophilic cell, so characteristic in other skin
conditions, was not found in this case.
COMMENT
T h e histologic picture in this case is compatible
with t h a t seen in erythema multiforme bullosum.
T h e only difference, if one can call it t h a t , is t h a t
the degree of cellular reaction in the involved areas
was very moderate and did not seem to be in
proportion to the severity of the condition.
SUMMARY
A case of fatal E r y t h e m a Multiforme Bullosum,
involving the entire external surface of the body,
oral cavity, conjunctiva, external auditory canal
and vagina occurred, apparently following sulfadiazine therapy.
REFERENCES
(1) KRACKE, R.: A review of Hematology in 1942,
South. M. J., 38: 429, 1943.
(2) GREENBERG, S. T.
AND MESSER, A. L.:
Fatal
Bullous dermatitis following administration of
sulfadiazine, J. A. M. A., 122: 944, 1943.