QHow can I avoid the overdiagnosis of erythema multiforme (EM)?

Nicholas Brownstone, MD

Nicholas Brownstone, MD

Dermatology Resident
Temple University Hospital
Philadelphia, PA

Erythema multiforme (EM) is an acute, self-limited skin disease characterized by the rapid onset of symmetric fixed red papules. Some of these papules evolve into typical and/or occasional “atypical” papular target lesions. A typical target is usually <3 cm in diameter, has a regular round shape and a well-defined border, and consists of at least 3 distinct zones with a dusky center; an “atypical target” is defined as round, edematous, palpable, and reminiscent of EM but with only 2 zones and/or a poorly defined border. In most cases, lesions of EM develop mostly on the extremities and the face; target lesions favor the upper extremities. The etiology of EM is thought to likely be a mucocutaneous immune reaction to an infection in predisposed individuals, with herpes simplex virus (HSV) having the highest association.

EM is often misdiagnosed and overdiagnosed by medical students, dermatology residents, nondermatologist physicians, and even practicing dermatologists. This is because many other diseases in dermatology may manifest as targetoid lesions, and many clinicians still automatically associate any “targetoid” lesion with the diagnosis of EM. Differentiating EM from other target-shaped lesions requires a thorough physical exam and history of present illness. In patients with EM secondary to HSV infection, EM lesions appear about 1 to 2 weeks after manifestation of HSV. To correctly diagnosis EM, the eruption should meet one or both of the following conditions: correct morphological appearance and/or correct distribution. In reality, distribution of lesions is much more important (acral/elbows/knees). Atypical EM morphology in an acral and elbows/knees distribution could still be EM, while correct morphology in an atypical location is still possible but very rare.

Target-shaped lesions are classically associated with EM, but similar lesions are found in a variety of other dermatologic conditions such as bullous fixed drug eruption, urticaria multiforme, Rowell syndrome (an EM-like presentation of cutaneous lupus erythematosus), paraneoplastic pemphigus, and acute febrile neutrophilic dermatosis (aka Sweet syndrome). A complete physical exam, history of present illness, and review of systems is necessary in helping to correctly diagnosis EM, with a special focus on the distribution and morphology of the rash. Prodromal manifestations or history of HSV infection (and other infectious causes) should also be investigated.


  1. Markeson CD, Brownstone ND, Sun CW, Hsu S. Targetoid lesions, but the diagnosis is not erythema multiforme. Skinmed. 2023;21(2):107-109.
  2. Bolognia JL, Schaffer JV, Cerroni L, eds. Dermatology. 4th ed. Elsevier; 2018.