Dermatology · Hypersensitivity Reactions
The facts most likely to be tested
Erythema multiforme is a Type IV hypersensitivity reaction most commonly triggered by Herpes Simplex Virus (HSV) infection.
The hallmark clinical presentation is target lesions (or iris lesions) characterized by a dusky central area, a surrounding pale edematous ring, and a peripheral erythematous halo.
Lesions are typically fixed and distributed symmetrically on the extensor surfaces of the extremities, palms, and soles.
Erythema multiforme minor is localized to the skin, whereas Erythema multiforme major involves one or more mucous membranes.
The condition is distinguished from Stevens-Johnson Syndrome (SJS) by the absence of extensive epidermal detachment and the lack of systemic drug-induced etiology.
Diagnosis is primarily clinical, and skin biopsy is reserved for cases with atypical presentations to rule out other vesiculobullous disorders.
Management of recurrent cases associated with HSV involves prophylactic oral antiviral therapy such as acyclovir or valacyclovir.
Vignette unlocked
A 24-year-old male presents to the urgent care clinic with a rash that appeared three days ago. He reports a history of recurrent cold sores. Physical examination reveals multiple target-shaped lesions with a dusky center and peripheral erythema distributed symmetrically on his dorsal forearms and palms. There is no evidence of mucosal involvement, fever, or skin sloughing. The patient is otherwise hemodynamically stable.
What is the most likely diagnosis?
Erythema multiforme
The patient's presentation of classic target lesions on the extremities following a history of HSV infection is pathognomonic for erythema multiforme, which is a Type IV hypersensitivity reaction.
Full handout
High yield triage
Etiology / Epidemiology
Triggered primarily by Herpes Simplex Virus (HSV); also associated with Mycoplasma pneumoniae and sulfonamides.
Clinical Manifestations
Acute, self-limiting hypersensitivity reaction characterized by target lesions; acral distribution is classic.
Diagnosis
Primarily a clinical diagnosis; skin biopsy is reserved for atypical cases to rule out SJS/TEN.
Treatment
Supportive care; oral acyclovir for HSV-associated cases; avoid systemic corticosteroids in early stages.
Prognosis
Generally self-limiting within 2-4 weeks; recurrence is common if HSV is the underlying trigger.
Full handout
Epidemiology & Etiology
Most common in young adults, often following an HSV outbreak. Infections account for 90% of cases, while drug-induced cases are significantly less common than previously thought. Mycoplasma pneumoniae is the leading non-viral trigger, particularly in children.
Pertinent Anatomy
Lesions typically favor the extensor surfaces of the extremities, palms, and soles. Involvement of the mucous membranes occurs in the severe form (EM Major) but is usually limited to one site.
Pathophysiology
A cell-mediated immune response (Type IV hypersensitivity) targets keratinocytes expressing viral antigens. This leads to epidermal necrosis and the formation of the characteristic target lesion. The process is typically self-limiting as the immune system clears the inciting antigen.
Clinical Manifestations
Presents with sudden onset of target lesions (dusky central area, pale edematous ring, and peripheral erythematous halo). Lesions are fixed and often pruritic or painful. Red flags include extensive mucosal involvement or skin sloughing, which suggest SJS/TEN rather than EM.
Diagnosis
Diagnosis is clinical based on the morphology and distribution of lesions. If the diagnosis is uncertain, a skin biopsy is the gold standard to differentiate from other bullous diseases. No specific laboratory values are diagnostic.
Treatment
Management is primarily supportive with topical corticosteroids and antihistamines for pruritus. For HSV-associated cases, oral acyclovir may shorten the duration of the outbreak. Systemic corticosteroids are generally discouraged as they may prolong the disease course.
Prognosis
Most cases resolve spontaneously within 2-4 weeks without scarring. Recurrent episodes are common, often requiring prophylactic antiviral therapy if HSV is the confirmed trigger.
Differential Diagnosis
Stevens-Johnson Syndrome: >10% body surface area involvement and significant mucosal sloughing
Urticaria: lesions are transient and migratory, lasting <24 hours
Fixed Drug Eruption: solitary, recurrent lesions at the same site after drug exposure
Bullous Pemphigoid: tense bullae in elderly patients with positive anti-BP180 antibodies
Secondary Syphilis: palm/sole involvement but typically associated with systemic lymphadenopathy