British Journal of Dermatology (1976) 95, 181.
Erythema multiforme in children RESPONSE TO TREATMENT WITH SYSTEMIC CORTICOSTEROIDS
JAMES E.RASMUSSEN Departments of Dermatology and Pediatrics, State University of New York at Buffalo, Children's Hospital of Buffalo, New York, U.S.A. Accepted for publication 7 November 1975
SUMMARY
It is generally accepted that the correct treatment for patients with severe erythema multiforme is systemic corticosteroids. This paper is a review of thirty-two paediatric patients with severe erythema multiforme (Stevens-Johnson syndrome) who were treated with either large doses of systemic corticosteroids or supportive care only. Those patients treated with steroids did not recover sooner than those treated in other fashions and the steroid treated group had a significant incidence of medical complications. This retrospective study proves nothing but it does suggest that treatment of patients with the Stevens-Johnson syndrome with systemic corticosteroids may be associated with significant side effects and prolonged recovery.
Erythema multiforme (EM) is a distinct clinical entity whose aetiology is diverse and usually remains enigmatic. Infiamed cutaneous lesions—papular, iris or target—are sharply marginated, relatively non-pruritic and located primarily on the extremities. The inciting agent, whether mediated by a primary reaction acting directly on the skin and mucous membranes or through secondary chemical mediators, produces a spectrum of responses from erythema to haemorrhage, bullae and necrosis. Any theory of pathogenesis must also explain the febrile reaction that almost always accompanies the exanthem and enanthem. A wide variety of agents have been reported to be associated with EM: infectious organisms such as bacteria (Washington, Fowler & Guarino, 1967; Meyers, 1970), mycoplasma (Gordon & Lyell, 1970), herpes (Shelley, 1967), fungi (Medeiros et al., 1966) and parasites (March, 1965); drugs such as long acting sulphonamides, oral contraceptives, dilantin (Bianchine et al., 1968); chemicals such as 9-bromofiuorene (DeFeo, 1966); and a variety of other diseases. A considerable number of patients with erythema multiforme have no such associations and it must be presumed that EM has a variety of causes working through a final common pathway. The therapy of erythema multiforme (EM) has been established by convention. The clinical features of this disease and the effectiveness of systemic corticosteroids in abolishing them have been accepted by most authors (Lyell, 1971; Domonkos, 1970; Pearson, 1972; Costello & DeFeo, 1963; Hambrick, 1965; Coursin, 1966). There is, however, little published evidence that corticosteroids control the Reprint requests to: JER, Children's Hospital of Buffalo, 219 Bryant St., Buffalo, New York 14222, U.S.A. 181
182
J.E.Rasmussen
inflammatory component of erythema multiforme or accelerate healing. This paper is an analysis of thirty-two paediatric patients with Stevens-Johnson syndrome (SJS) which focuses on their response to treatment. MATERIAL AND METHODS
The criteria for inclusion in this study were: admission to the Buffalo Children's Hospital; and a clinical description consistent with erythema multiforme of the SJS variety, i.e. 1. Severe inflammation and erosion of the oropharynx and either conjunctivitis, vaginids or balanitis. 2. Erythematous papules and plaques or bullae with darker centers that slowly expand but do not migrate. It was not necessary for a patient to have iris or target lesions to be included in this study. RESULTS
Thirty-two patients met the criteria for SJS (Tables 1-3). The 17 males and 15 females, whose age varied from 8 months to 14 years, were admitted from 1952 to 1974. Increased incidence of admissions occurred during the autumn and winter months of October to May but the disease was clinically TABLE I. Thirty-two patients
Age (mean) Sex
Duration of prodrome before hospitalization (days) (mean) Number of patients with prodrome Exposure to drugs before hospitalization Initial fever (mean) Initial WBC (mean) Other treatment (antibiotics)
Steroid treated (17)
No steroids (15)
6 yr, 4 months 8M, 9 F
5 yr, 5 months 9M, 6 F
4
3
13
10
2
3
39-6°C 12,400/mm^
39-8°C 14,200/mm^
8
5
similar regardless of when the patients were admitted. Twenty-three of the thirty-two patients had a febrile prodrome that featured pharyngitis and conjunctivitis andflvepatients in this group received antibiotics for these symptoms—penicillin (two patients), sulphonamides (two patients) and lincomycin (one patients). Four other children in this series were each exposed to one drug during the prodrome of their illness—xylocaine for a dental extraction, diphenylhydantoin, butisol and a diphtheria-pertussis-tetanus vaccination. Because of the selection of cases, extensive oral inflammation and erosion were always present and haemorrhagic labial crusts were a common accompaniment. Conjunctivitis was also frequent and severe in this group of patients (26/32) and was usually bilaterial. Erythema, haemorrhage and erosions also aflected the anal (4/32) or genital areas (9/32). Erythematous papules and bullae were a prominent component of the SJS in this group of patients. The lesions were arbitrarily called localized if conflned to the extremities and generalized if they were also present on the trunk. Seventeen of the thirty-two patients had iris lesions.
Erythema multiforme in children
183
Laboratory Cold agglutinins were found in titres less than i :8 in 11/15 patients and were never higher than 1:64 (1/15 patients). A variety of pathogenic bacteria were cultured from the oropharynx (21/32) (Table 3), but thirty-five blood cultures taken on the day of admission in seventeen patients were all sterile. Three patients subsequently developed sepsis with positive blood cultures (staphylococcus in one patient and pneumococcus in two). Treatment Seventeen patients received systemic corticosteroids. Corticosteroids were used on a basis of 40-80 mg/m^ of prednisone or equivalents per day and they were always begun on the ist or 2nd day of hospitalization. Systemic antibiotics were used in 8/17 patients in the steroid group and 5/15 in the non-steroid group. Penicillin was the most popular choice followed by ampicillin and erythromycin. TABLE 2. Severity and extent Steroid treated (17) Mouth and eyes Rectum, vagina, penis Papules—local generalized Bullae—local generalized
No steroids (15) II
12
4 4
5 4 6 3
4 4 3
I
TABLE 3. Pathogens isolated on initial throat culture
Staphylococcus Pneiunococcus fi Haemolytic streptococcus Mycoplasma H. Influenzae
Steroid treated (17)
No steroids (15)
4 2 3 i 2
3 4 i i o
Recovery and complications Nine patients had a complicated course before recovery. These patients were all in the corticosteroidtreated group. It was not possible to state with certainty when active inflammation began to subside in either the steroid- or the non-steroid-treated groups but the average length of hospitalization was significantly different. The fifteen patients in the non-steroid group were in the hospital for an average of 13 days compared to a 21 day hospitalization for those treated with steroids (P