Erythema Multiforme

Introduction And Classification

Subtype	Clinical Characteristics	Mucosal Involvement
Erythema Multiforme Minor	Affects < 10% body surface area.	Absent or limited (often single site like mouth).
Erythema Multiforme Major	Affects < 10% body surface area. Constitutional symptoms present.	Conspicuous involvement of $\geq$ 2 mucosal sites. Includes severe buccal erosions and hemorrhagic crusts of lips.

Factor Category	Specific Triggers And Mechanisms
Viral Infections	Herpes simplex virus represents most common trigger. Herpes simplex virus labialis or genitalis implicated in 60-70% of episodes. Recurrent episodes frequently associated with sun exposure.
Bacterial Infections	Mycoplasma pneumoniae produces similar lesions, particularly in children and young adults.
Pharmacologic	Accounts for < 10% of cases. Associated agents include nonsteroidal anti-inflammatory drugs, sulfonamides, and antibiotics.
Genetic Predisposition	Human leukocyte antigens A33, B62, B35, DQw3, and DR53 associated with increased risk of herpes simplex virus-induced recurrent disease.
Pathophysiology	Host-specific, cell-mediated immune response to antigenic stimulus causes keratinocyte damage. Herpes simplex virus Pol1 gene upregulates transcription factor SP1 and inflammatory cytokines. Cytokine release contributes to epidermal cell death.

Peak incidence occurs between 10 and 40 years, highest in males during second decade.
Eruption appears abruptly and symmetrically.
Predilection for acral parts, especially extensor upper extremities, palms, and soles.
Face, trunk, and legs relatively spared.
Initial morphology features red macules or urticarial plaques expanding centrifugally.
Pathognomonic targetoid (iris or bull’s-eye) papules develop within 72 hours.
Target lesions consist of three distinct concentric rings: central dusky erythema or vesicle/bulla, intermediate pale edematous ring, and peripheral erythematous halo.
Lesions remain fixed in place for average duration of 7 days.
Fades within approximately 2 weeks without sequelae, though postinflammatory dyspigmentation occurs in darker skin.
Usually asymptomatic, occasionally accompanied by burning sensation or pruritus.

Cleavage site occurs at subepidermal level.
Early lesions demonstrate slight intercellular edema, rare dyskeratotic keratinocytes, and epidermal basal vacuolation.
Upper dermis exhibits edema and perivascular lymphohistiocytic infiltrate.
Mature lesions show lymphocytic exocytosis, intense interstitial mononuclear infiltrate, and potential full-thickness epidermal necrosis.

Stevens-Johnson syndrome: Distinguished by erythematous or purpuric macules (lacking papules) starting primarily on trunk.
Urticaria: Individual lesions fade within 24 hours, unlike fixed erythema multiforme lesions.
Reactive infectious mucocutaneous eruption.
Bullous pemphigoid and pemphigus vulgaris.
Kawasaki disease.
Cefaclor-induced serum sickness-like reaction (pruritic, transient, migratory).

Primary therapy remains entirely supportive.
Treat underlying primary infections concurrently.
Provide symptomatic relief using topical emollients, systemic antihistamines, and nonsteroidal anti-inflammatory drugs.
Utilize opioids and diligent oral hygiene for severe mucosal pain management.
Systemic corticosteroids lack controlled prospective evidence supporting routine use.

Initiate prophylactic oral acyclovir for 6 months for recurrent herpes simplex virus-associated disease.
Tapering acyclovir may prompt disease recurrence, albeit milder.
Refractory cases necessitate steroid-sparing agents including azathioprine, mycophenolate mofetil, or dapsone.