What are the key clinical features that differentiate erythema multiforme from other similar skin conditions?

Erythema multiforme (EM) is primarily differentiated from other similar skin conditions by its characteristic target lesions, acute onset, and typical distribution. The hallmark clinical feature is the presence of target or iris lesions—well-defined, round lesions with three concentric zones: a central dusky or necrotic area, a paler edematous zone, and an erythematous outer ring.

These lesions commonly appear symmetrically on the extensor surfaces of the extremities, especially the hands and feet, and may involve the face and mucous membranes, particularly in EM major.

Unlike other dermatoses such as pityriasis rosea or urticaria, EM lesions evolve rapidly over days and often follow a prodrome of infection, most notably herpes simplex virus (HSV).

Oral mucosal involvement, when present, is typically painful with erosions and ulcerations, distinguishing EM from other conditions like aphthous stomatitis or Stevens-Johnson syndrome (SJS), which has more extensive mucosal and systemic involvement.

EM lesions are usually self-limiting and less severe than SJS or toxic epidermal necrolysis (TEN), which show widespread epidermal detachment and systemic symptoms.

In contrast to other targetoid lesions seen in fixed drug eruptions, EM lesions are more widespread and symmetric, and the history often includes preceding infection rather than drug exposure.

Thus, the key differentiators are the classic target lesions with three zones, acral and symmetric distribution, association with HSV infection, and limited mucosal involvement in EM minor, which help distinguish it from other similar skin conditions.

¹ (Sokumbi and Wetter, 2012) (Brice et al., 1991) (Ayangco and Rogers RS 3rd, 2003)