Erythema Multiforme

Grading & Level of Importance: A


W. Burgdorf, Munich; A. Salam, J. McGrath, London
Revised by RM. Pujol, A. Gimenez-Arnau, Barcelona




Erythema exsudativum multiforme.


Acute, self-limited disease with typical target or iris like lesions and frequent mucosal blisters and erosions.

Aetiology & Pathogenesis

Many causes, most important are infections: mainly herpes simplex (HSV), but also Mycoplasma pneumoniae, streptococci; less common are medications (antibiotics, anti-epileptics, protease inhibitors, pyrazolone), connective tissue diseases (systemic lupus erythematosus); often (>50%) no cause found. A skin-directed immune reaction appears to play a pathogenetic role.

Signs & Symptoms

Frequently observed in young adults. Acral exanthem with formation of typical target lesions with multiple concentric rings of varying color tones occasionally with a central bulla. Mucosal involvement (lips, mouth, genitalia) with erosions and crusts.


Symmetrically distributed on the distal extremities: backs of the hands and palms, forearms as well as on knees, elbows, nape; on mucosae: vesiculo-bullous lesions leading to erosions involve the lips, mouth, eyes, nose, trachea and genitalia.


Divided into minor (80%) and major forms (depending on the absence or presence of mucosal involvement and systemic symptoms).


Strong lymphocytic epidermotropism followed by vacuolar alteration of the basal layer, apoptosis of individual keratinocytes. Edema of papillary dermis sometimes with blistering. Prominent superficial polymorphous inflammatory infiltrate with mononuclear cells and neutrophils. 


Abrupt onset (24-72 hours). Resolution in 2-3 weeks. In cases associated with HSV infection and certain drugs recurrences are frequent.  


No sequelae, except in cases with ocular involvement. 


Clinical features. In atypical lesions, histopathological examination may be useful.

Differential diagnosis

Typical target lesions are diagnostic. The differential diagnostic possibilities include acute urticaria, subacute cutaneous lupus erythematosus, urticarial vasculitis, erythema annulare centrifugum. For the mucosal lesions: Stevens-Johnson syndrome, erosive lichen planus, autoimmune bullous diseases, viral diseases (especially herpes simplex).

Prevention & Therapy

Elimination and treatment of underlying causes. Corticosteroids topically and in severe cases systemically. In cases with mucosal disease, topical corticosteroids in appropriate vehicle along with antimicrobial solutions to prevent superinfection. If eye involvement ophthalmologic consultation is mandatory (risk of permanent scarring and visual impairment). Prophylactic oral antiviral treatment in cases of HSV-association with frequent recurrences.

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