Treatment of erythema multiforme
- David A Wetter, MD
David A Wetter, MD
- Professor of Dermatology
- Mayo Clinic, Rochester, MN
Erythema multiforme (EM) is an acute, immune-mediated condition characterized by the appearance of distinctive target-like lesions on the skin. These lesions are often accompanied by erosions or bullae involving the oral, genital, and/or ocular mucosae (picture 1A-F). Erythema multiforme major is the term used to describe EM with mucosal involvement; erythema multiforme minor refers to EM without mucosal disease. (See "Pathogenesis, clinical features, and diagnosis of erythema multiforme", section on 'Clinical manifestations'.)
A variety of factors have been implicated in the pathogenesis of EM. The disorder is most commonly induced by infection, with herpes simplex virus (HSV) being the most frequent precipitator. The clinical course of EM is usually self-limited, resolving within weeks without significant sequelae. However, in a minority of cases, the disease recurs frequently over the course of years.
Similarities in clinical and histopathologic findings have led to controversy over the distinction between EM and Stevens-Johnson syndrome (SJS), an often drug-induced disorder that may present with cutaneous targetoid lesions and mucosal erosions. However, there is suggestive evidence that EM with mucous membrane involvement and SJS are different diseases with distinct causes . The term erythema multiforme major should not be used to refer to SJS. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis".)
The treatment and prognosis of acute and recurrent EM will be reviewed here. The epidemiology, pathogenesis, clinical features, evaluation, and diagnosis of this disorder are discussed separately. (See "Pathogenesis, clinical features, and diagnosis of erythema multiforme".)
TREATMENT OF ACUTE EM
The treatment of acute erythema multiforme (EM) varies according to disease severity. The clinical course of an episode of EM is self-limited, although the disease may recur. (See 'Prevention of recurrent EM' below.)
Subscribers log in hereLiterature review current through: Nov 2017. | This topic last updated: Jul 20, 2017.References
- Assier H, Bastuji-Garin S, Revuz J, Roujeau JC. Erythema multiforme with mucous membrane involvement and Stevens-Johnson syndrome are clinically different disorders with distinct causes. Arch Dermatol 1995; 131:539.
- Schofield JK, Tatnall FM, Leigh IM. Recurrent erythema multiforme: clinical features and treatment in a large series of patients. Br J Dermatol 1993; 128:542.
- Weston WL, Morelli JG. Herpes simplex virus-associated erythema multiforme in prepubertal children. Arch Pediatr Adolesc Med 1997; 151:1014.
- Bean SF, Quezada RK. Recurrent oral erythema multiforme. Clinical experience with 11 patients. JAMA 1983; 249:2810.
- Farthing PM, Maragou P, Coates M, et al. Characteristics of the oral lesions in patients with cutaneous recurrent erythema multiforme. J Oral Pathol Med 1995; 24:9.
- Tatnall FM, Schofield JK, Leigh IM. A double-blind, placebo-controlled trial of continuous acyclovir therapy in recurrent erythema multiforme. Br J Dermatol 1995; 132:267.
- Creamer D, Walsh SA, Dziewulski P, et al. U.K. guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016. Br J Dermatol 2016; 174:1194.
- Wetter DA, Davis MD. Recurrent erythema multiforme: clinical characteristics, etiologic associations, and treatment in a series of 48 patients at Mayo Clinic, 2000 to 2007. J Am Acad Dermatol 2010; 62:45.
- Kerob D, Assier-Bonnet H, Esnault-Gelly P, et al. Recurrent erythema multiforme unresponsive to acyclovir prophylaxis and responsive to valacyclovir continuous therapy. Arch Dermatol 1998; 134:876.
- Routt E, Levitt J. Famciclovir for recurrent herpes-associated erythema multiforme: a series of three cases. J Am Acad Dermatol 2014; 71:e146.
- Fawcett HA, Wansbrough-Jones MH, Clark AE, Leigh IM. Prophylactic topical acyclovir for frequent recurrent herpes simplex infection with and without erythema multiforme. Br Med J (Clin Res Ed) 1983; 287:798.
- Sen P, Chua SH. A case of recurrent erythema multiforme and its therapeutic complications. Ann Acad Med Singapore 2004; 33:793.
- Jones RR. Azathioprine therapy in the management of persistent erythema multiforme. Br J Dermatol 1981; 105:465.
- Davis MD, Rogers RS 3rd, Pittelkow MR. Recurrent erythema multiforme/Stevens-Johnson syndrome: response to mycophenolate mofetil. Arch Dermatol 2002; 138:1547.
- Oak AS, Seminario-Vidal L, Sami N. Treatment of antiviral-resistant recurrent erythema multiforme with dapsone. Dermatol Ther 2017; 30.
- Leigh IM, Mowbray JF, Levene GM, Sutherland S. Recurrent and continuous erythema multiforme--a clinical and immunological study. Clin Exp Dermatol 1985; 10:58.
- Bakis S, Zagarella S. Intermittent oral cyclosporin for recurrent herpes simplex-associated erythema multiforme. Australas J Dermatol 2005; 46:18.
- Moisson YF, Janier M, Civatte J. Thalidomide for recurrent erythema multiforme. Br J Dermatol 1992; 126:92.
- Cherouati K, Claudy A, Souteyrand P, et al. [Treatment by thalidomide of chronic multiforme erythema: its recurrent and continuous variants. A retrospective study of 26 patients]. Ann Dermatol Venereol 1996; 123:375.
- Dumas V, Thieulent N, Souillet AL, et al. Recurrent erythema multiforme and chronic hepatitis C: efficacy of interferon alpha. Br J Dermatol 2000; 142:1248.
- Geraminejad P, Walling HW, Voigt MD, Stone MS. Severe erythema multiforme responding to interferon alfa. J Am Acad Dermatol 2006; 54:S18.
- Kieny A, Lipsker D. Efficacy of interferon in recurrent valaciclovir-refractory erythema multiforme in a patient not infected with hepatitis C virus. Clin Exp Dermatol 2016; 41:648.
- Chen T, Levitt J, Geller L. Apremilast for treatment of recurrent erythema multiforme. Dermatol Online J 2017; 23.
- Baillis B, Maize JC Sr. Treatment of recurrent erythema multiforme with adalimumab as monotherapy. JAAD Case Rep 2017; 3:95.
- Damsky W, King BA. Idiopathic erythema multiforme: Evidence of underlying Janus kinase-signal transducer and activator of transcription activation and successful treatment with tofacitinib. JAAD Case Rep 2016; 2:502.
- Kürkçüoğlu N, Alli N. Cimetidine prevents recurrent erythema multiforme major resulting from herpes simplex virus infection. J Am Acad Dermatol 1989; 21:814.
- Hirsch G, Ingen-Housz-Oro S, Fite C, et al. Rituximab, a new treatment for difficult-to-treat chronic erythema multiforme major? Five cases. J Eur Acad Dermatol Venereol 2016; 30:1140.
- TREATMENT OF ACUTE EM
- Inciting agents
- Mild disease
- Severe oral mucosal involvement
- Ocular involvement
- PREVENTION OF RECURRENT EM
- Antiviral therapy
- - Continuous antiviral therapy
- Choice of antiviral agent
- - Intermittent antiviral therapy
- - Topical acyclovir
- Second-line systemic therapies
- - Azathioprine
- - Mycophenolate mofetil
- - Dapsone
- - Other therapies
- - Adverse prognostic features
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS