Erythema multiforme exudativum

Erythema multiforme exudativum

ERYTtIEMA MULTIFORME EXUDATIVUM LYDIA WRIGHT, M.D., AND SAMUEL JENKINS, M.D. NEW YORK, N. Y. i f o r m e exudatiFjRrYu mT H EhasM A beenm u l tdescrib...

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ERYTtIEMA MULTIFORME EXUDATIVUM LYDIA WRIGHT, M.D., AND SAMUEL JENKINS, M.D. NEW YORK, N. Y. i f o r m e exudatiFjRrYu mT H EhasM A beenm u l tdescribed as an acute i n f l a m m a t o r y disease of the skin with constitutional s y m p t o m s compatible with an acute infection. The eruption m a y be e r y t h e m a t o p a p u l a r , vesiculobullous, or both. Lesions usually start as maeules or papules on the dorsa of the hands and spread along the forearms and neck, eventually, involving the forehead and face. Spread is similar over the lower extremities. A t the height of fever the lesions are generalized. Vesicles and bullae f o r m when sufficient exudate occurs in the original lesions. Pustules are secondary to superimposed infection. L e v e r 1 has stated t h a t when there is involvement of the mucous membranes, it is most common in the vesiculobullous t y p e of eruption, and it usually dominates the clinical picture. I t s incidence has been estimated by KeiF at f r o m 25 to 60 p e r cent. A n y or all of the mucous membranes m a y be involved. Oral lesions are bullous f r o m the onset and erosion develops quickly. There is extensive swelling of the lips, gmns, and tongue. Lesions of the glans penis m a y produce adhesions. D y s p n e a results f r o m edema of the larynx. I n v o l v e m e n t of the tracheobronchial mucosa m a y lead to bronchopneumonia. D u k e - E l d e r 3 has described three types of conjunctivitis that m a y occur: a catarrhal type that hems in a few weeks; a p u r u l e n t type t h a t m a y cause a panophthalmitis resuiting in blindness; and a pseudoF r o m t h e P e d i a t r i c D e p a I : t m e n t of H a r l e m Hospital, Dr. Morris Gleich, Director.

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membranous type with corneal involvement and symblepharon. Usually lesions on the mucous membranes continue to f o r m f o r several months and heal without scarring. Conjunctiva] lesions represent an exception where there m a y be persistence for m a n y years. Mucosal lesions are responsible f o r the acute emergencies t h a t m a y arise in this disease. The course o2 the disease m a y be mild with only the skin eruption and pruritus, or severe with prostration and t e m p e r a t u r e as high as 105 ~ F. The disease m a y be accompanied by arthralgia, vomiting, albuminuria, and salivation. Constitutional symptoms are absent or mild unless the mucous membranes are involved. Extensive bacteriological, serological, pathological, and virus studies have failed to identify a causative organism. To f u r t h e r confuse the etiology, there m a y be a history of contact by way of mouth or externally with drugs or chemicals either in therapeutic or toxic doses. Cases have been reported following the use of sulfadiazinc ( D a r d i n s k P ) , phenytoin sodium (Ellish), and exposure to sick dogs (Bradlow and Schless~ Kove 7 reported a case t h a t developed during convalescence f r o m mumps. Evidence suggesting a possible infection with a psittacosis-like virus was reported by Finland, Jolliffe, and Parker. s Wetsberg and Rosen 9 suggested avitaminosis B as a causation and reported three patients successfully treated with nicotinic acid.

WRIGHT

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JENKINS:

ERYTHEIV[A

Most cases last f r o m two to five weeks, but there m a y be recurrences at frec]uent intervals. There is no evidence that this is a contagious disease. However, Keil 2 states t h a t one case of this sort in the c o m m u n i t y generally means that more will be seen shortly. Most cases occur in the spring and autumn. There seems to be a predilection f o r y o u n g males. The prognosis depends on the extent and severity of the mucous m e m b r a n e involvement. Deaths are due to atypical pneumonia and, to a lesser degree, to extensive secondary infection. There is no specific therapy. D u r i n g the past y e a r both the severe and the mild types of e r y t h e m a multiforme exudativum have been seen on the Pediatric Service of H a r l e m Hospital. The two cases t h a t are being presented showed m a r k e d differences in clinical course and response to therapy. They are being reported in supp o r t of the arguments of Kove 7 and M u r p h y 1~ who feel t h a t severe cases with mueosal involvement should be classed as a separate entity. CASE REPORTS

CAsE 1.--C. P. was admitted to H a r lem Hospital on Sept. 25, 1949, for lethargy, fever, and vomiting of three d a y s ' duration, and for what the mother described as " f e v e r b l i s t e r s " of two d a y s ' duration. No history of a n y previous illness other than measles was obtainable. The p a t i e n t was delivered normally and h a d a birth weight of 6 pounds, 5 ounces. H e sat up at 7 months of age, and walked and talked at 18 months. The mother and f a t h e r were both living and well. Of possible significance was t h a t the f a t h e r was p a i n t i n g the a p a r t m e n t in which they lived on the same d a y t h a t the p a t i e n t ' s illness began. Physical examination revealed a well-developed, well-nourished, 3:year-

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old Negro male who was acutely ill and lethargic. The temperature was 103 ~ F. The skin was hot and dry and there were herpetic lesions on tile lips. Tearing and a small amount of purulent exudate were present in both eyes. The lids were edematous and the conjunctivae were hyperemic. A mucoid discharge was present in both nostrils. The p h a r y n x was injected, and the tonsils were benign. Several white patches were present over the tongue and mucous membranes of the mouth. Coarse rgles and rhonchi were present in both lung fields. The heart rate was rapid; no m u r m u r s were h e a r d and the heart was not enlarged. The abdomen was soft, flat, and nontender. Within t w e n t y - f o u r hours a f t e r admission, an erythematous m a e u l a r and vesicular eruption appeared and quickly became bullous. The lesions spread r a p i d l y f r o m their origin on the face to involve the neck, torso, and extremities, and the patient developed a urethritis. A diagnosis of StevensJ o h n s o n ' s syndrome with bronchopneumonia was established. On the second hospital day, the pat i e n t ' s condition was critical. L a r g e denuded areas a p p e a r e d as r a p i d l y as the bullae r u p t u r e d . The patient continned lethargic. He had been treated with boric acid irrigations f o r the eyes and 300,000 units of penicillin each day since admission. P e t r o l a t u m gauze dressings were applied to the skin lesions. I n addition, the patient received 200 c.c. of whole blood. Because the skin lesions were worse, penicillin t h e r a p y was replaced by aureomycin in a dosage of 50 rag. per kilogram of body weight. B y the sixth hospital day, the t e m p e r a t u r e was 98.6 ~ F., and the skin lesions had begun to dry. The patient was rational for the first time since admission. Blood and spinal fluid cultures were consistently sterile. Blood chemistries and blood counts were within normal limits. A l p h a streptococcus was cult u r e d f r o m the throat; Staph~]lococcus aure~s was cultured f r o m the eyes. No new lesions were noted after the fifth hospital day. Aureomycin was

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discontinued on the sixteenth hospital day, and the patient was discharged seven weeks after admission. At that time he had several large areas of hyperpigmentation over the face, and dime-sized hypopigmented areas were present over the neck, torso, and extremities. The nails were hypertrophic and loosened f r o m the base. The general condition was good. CASE 2.--J. B., a 51/2-year-old Negro male, was admitted to this hospital on Jan. 21, 1950, for severe pruritis. He had been in a state of good health until J a n u a r y 12, when his mother noticed a large blister on his right knee. This lesion was aspirated and dressed in the Emergency Unit, and the patient was sent home. Subsequently, bullous lesions appeared on the buttocks, back, and lower extremities. There was no history of any previous illness other than chicken pox three years ago. There was no history of chemotherapy. Physical examination revealed a well-developed, alert, cooperative patient complaining of itching. The temperature was 100 ~ F., the pulse was 88, and the respirations were 18. Numerous bullae varying in size from 1 to 3 em. were present over the occipital region of the head, buttocks, knees, and elbows. Several bullae had coalesced and a few had ruptured, leaving large denuded areas. In other places the lesions had crusted. No lesions were present on the mucous membranes, but there were two small vesicles on the vermilion border of the lower lip. The lungs were clear to auseultatiori and percussion. There was a soft systolic m u r m u r at the apex; there was no cardiac enlargement. The abdomen was soft, flat, and nontender. The axillary, cervical, and inguinal lymph nodes were palpable. The admitting diagnosis was bullous eruption of unknown origin. On the second hospital day, the dermatologist made a diagnosis of erythema multiforme bullosum. L a b o r a t o r y work-up revealed a normal urine, total blood protein 5.03, albumin 3.02, globulin 1.97, hemoglobin

75 per cent, white blood count 12,000, and red blood count 3,200,000. Bact e r i u m coli and gamma streptococcus were cultured from the skin lesions. The patient was treated with 50 rag. of aureomycin per kilogram of body weight per day and 50 rag. of Pyribenzamine every six hours. A heat cradle was placed over the lower extremities. New bullae continued to form over the torso and the extremities. They enlarged rapidly, coalesced, became hemorrhagic, and then ruptured. On the ninth hospital day, the lesions began to dry. However, on the eighteenth hospital day, after nine days of seemingly clinical improvement, the temperature spiked to 103 ~ F. and a new crop of bullae appeared on the face, buttocks, and around the genitalia. Aureomycin therapy was replaced by penicillin and 5 per cent sulfathiazole ointment locally. B y the next day, the lesions -'~ere again drying and the temperature was 99 ~ F. Subsequently, the patient's general condition seemed good in spite of continued low-grade fever until one month later when the temperature again rose t o 104 ~ F. At that time the patient complained of severe generalized pruritis, and another crop of bu]lae appeared on his face. This patient remained in the hospital for six months, and continued to develop vesicles and bullae at intervals of about two weeks. At no time were all the lesions in the crusted stage prior to his discharge. DISCUSSION

Until recently, erythema multiforme exudativum was seldom seen in hospitals or private practice. This may be attributed to the multiplicity of names by which the disease is known. Credit is given to yon Itebra 11 for the original description of this condition. Bazin 12 denied the m?ity of the disease and was the first to recognize lesions in the mouth and prodromal constitutional symptoms in the vesicu]obullous

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ERYTHEMA 1VIULTIFOI~IKE EXUDATIVUM

type. Since his time, the severe pluriorifieialis type has been reported under names other than e r y t h e m a - m u l t i forme exudativum, suggestive evidence of the feeling t h a t this is a separate disease. I n 1922, Stevens and Johnson, ~3 thinking t h a t they were describing a new disease, reported two cases of eruptive fever with stomatitis and ophthalmia. This syndrome now bears their name. I n 1937, K l a u d e r ~ reported thirty-seven cases of ectodermosis erosiva pluriorifieiaIis. Cases of Stanyon and W a r n e r ~5 were reported u n d e r the title of mueosal r e s p i r a t o r y syndrome. Fletcher, and Harris, ~8 Keil, 2 and LeveV are among those who have stressed the essential identity of these eases with erythema multiforme exudativum. Costello and Vandow ~7 have suggested the name e r y t h e m a bullosum malignans-pluriorifieialis to describe the severe type. Several factors f a v o r i n g the classification of cases with severe mucosal involvement a p a r t f r o m erythema exud a t i v u m multiforme are suggested b y the clinical courses of the reported eases. The first patient became ill suddenly. He was acutely ill and lethargic with bronehopneumonia on admission. H i s skin lesions changed rapidly f r o m one stage to another eventually becoming bullous. The mucous membranes were involved early. Adequate dosages of penicillin did not affect the bronchopneumonia, but there was a p r o m p t response to aureomycin. No new lesions a p p e a r e d a f t e r the fifth hospitaI day. This patient made a quick and uneventful recovery without sequellae. The second patient was never ill enough to w a r r a n t confinement to bed except for f e a r of secondary infection

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and when a new crop of lesions appeared. The lesions were vesieulobullous f r o m the onset. His hospitalization extends over a long period. A t no time was he entirely free of lesions. There were no constitutional symptoms, a n d no involvement of the mucous membranes. Adequate courses of penicillin and aureomycin failed to institute a cure. SU313IARY

Two cases of erythema multiforme e x u d a t i v u m with distinct clinical differences have been presented. One, representing the severe pluriorifieialis type, made a dramatic response to therapy. The other, a mild ease with only a skin eruption, responded to no therapy, and the patient remained hospitalized over a long period for frequent recurrences of vesiculobullous skin lesions. Although the causative agents in these two variants of the disease are not known, we feel that they are separate entities. However, the m a n y names now in use for describing all of the variants have confused the recognition and reporting of eases. I t is suggested that eases be reported u n d e r one name until a sound classification is made. REFERENCES 1. Lever, W. F.: Severe Erythema: Two Cases of Type Eeto~ermosis Erosive Pluriorlficlalis, With Development of Cieatricial Conjunctivitis and Keratis in One Case, Arch. Dermat. & Syph. 49: 47, 1944. 2. Nell, H.: Erythema Multiforme Exudativum ( t t e b r a ) : Clinical Entity Assod a t e d W i t k Systemic Features, Ann. rnt. Med. 14: 449, 1940. 3. Duke-Elder, W. S.: Erythema Exudativum Multiforme ( H e b r a ) , Textbook of Ophthalmology, vol. 2, St. Louis, 1938, The C. V. 3/Iosby Co., p. 1733. 4. Dardinski, V. J . : Erythema Bullosum Following Use of Sulfadiazine (Sulfonamide), Clin. Path. 15: 28, 1945.

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5. Ellis, F. A.: Ectodermosis Erosiva Pluriorificialis Following Ingestion of Phenytoin Sodium i Case, SoUth, M. J. 36: 575, 1943. 6. :Bradlow, F. A., and Schless, R. A.: Unusual Eruptive Fever Involving Skin and lYiucous l~embranes ; Relation to and Status of So-called Stevens-Johnson Disease, J. p~DIAT. 32: 293, 1948. 7. t{ove, S. : Stevens-Johnson Syndrome (Eruptive Fever With Stomatitis and Conjunctivitis), Am. J. M. Sc. 210: 611, 1945. 8. Finland, M., Jolliffe, I~. S., and Parker, F., Jr. : Paeumonia and Erythema Multiforme Exudativum; Four Cases and Three Autopsies, Am. J. Med. 4: 473, 1948. 9. Weisberg, A., aad Rosen, E. : Erythema Exudativum Multiforme, Arch. Dermat. & Syph. 53: 106~ 1946. 10. Murphy, 1~. C. : Eruptive Fever Involving 1Yloutk a a d Eyes ( S t e v e n s - J o h n s o n Disease), l~Iew England 5. ivied. 230: 69, 1944. 11. "con Hebra, F.: Diseases of the Skin, London New Sydenham Society 1: 285, 1866.

12. Bazin, E.: Lecons Theoriques et Cliniques sur les Affections Generiques de la peau, Paris, 1862, A. Delahaye. 13. Stevens, A. M., and Johnson, F. C.: A New Eruptive Fever Associated With Stomatitis, Am. J. Dis. Child. 24: 526~ 1922. 14. It:lauder, J. V.: Ectodermose Erosiva Pluriorifieialis: Its Resemblance to Human Form of Foot and Mouth Disease and I t s Relation to E r y t h e m a Exudativum Mu]tiforme, Arch. Dermat. & Syph. 36: 1067, 1937. 15. Stanyon, J. H., and Warner, W. P.: Mueosal Respiratory Syndrome, J. Canad. M. Serv. 3: 11, 1946. 16. Fletcher, IVL W. C., and tIarrls, R. C.: Erythema Exudativum multiforme (Hebra)--Bullous Type; Cases Seen in a Contagious Disease IIospital, J. PEDIA$. 27: 465, 1945. 17. Costello, ~I. J., and Yandow, J. E.: Erythema l~ultiforme, New York State J. Med. 48: 2481, 1948.