Symptoms of Erythema Multiforme
Erythema multiforme presents with characteristic target or "iris" lesions consisting of a dark red center surrounded by a pink ring in a well-defined circular pattern, distributed symmetrically on the extremities (particularly ankles, wrists, forearms, palms, and soles), with or without mucous membrane involvement. 1
Cutaneous Manifestations
Primary Lesion Characteristics
- Target lesions with three-zone configuration: central dark papule or vesicle, surrounded by a pale zone, with an outer erythematous halo 1
- Lesions are fixed and remain in place for a minimum of 7 days (unlike urticaria which resolves within 24 hours) 1
- Symmetrical distribution predominantly on acral surfaces: extremities, hands, feet, palms, and soles 2, 3
- Lesions may be targetoid with dusky red and white concentric rings 1
Lesion Evolution and Distribution
- Initial appearance typically on ankles, wrists, or forearms, then spreading to palms, soles, arms, legs, and trunk 4
- Lesions usually spare the face 4
- May progress from erythematous macules to maculopapular lesions, sometimes with central vesicles or bullae 2, 5
Mucosal Involvement
Oral and Mucosal Symptoms
- Tender superficial erythematous plaques to painful deep hemorrhagic bullae and erosions in the mouth 6
- Involvement of multiple mucosal surfaces: oral cavity, lips, ocular, nasal, pharyngeal, and anogenital areas 6, 7
- EM minor typically affects no more than one mucosa 7
- EM major involves two or more mucous membranes 7
Special Presentation in Mycoplasma-Associated Cases
- Predominantly mucous membrane involvement with little or no cutaneous lesions (termed "Mycoplasma pneumoniae-associated mucositis"), particularly common in children 1
Systemic Symptoms
Prodromal and Associated Features
- Acute onset with self-limiting course 3, 5
- May have preceding infection (typically herpes simplex virus appearing 10 days before rash) 1, 2
- Generally minimal systemic symptoms in EM minor 7
- EM major may have systemic symptoms and internal organ involvement 7
Critical Differentiation from Stevens-Johnson Syndrome/TEN
Key Distinguishing Features
- EM has typical target lesions or raised atypical targets predominantly on limbs and extremities 1
- SJS/TEN features flat atypical targets or purpuric macules with epidermal detachment and positive Nikolsky sign 1
- EM is mostly related to HSV infection with lower mortality and better prognosis 1
- SJS/TEN is usually triggered by drugs with higher mortality (5-30%) 4, 1
Clinical Variants
EM Minor vs. Major
- EM minor: isolated cutaneous involvement or single mucosal surface involvement with symmetrical target lesions on extremities 7, 5
- EM major: more severe with two or more mucous membranes involved, more variable skin involvement 7
Common Pitfalls to Avoid
- Do not exclude EM based on absence of target lesions early in disease course, as lesions evolve over time 5
- Do not confuse with urticaria: EM lesions are fixed for ≥7 days while urticaria resolves within 24 hours 1
- Do not misdiagnose as SJS/TEN: look for raised typical targets on extremities (EM) versus flat atypical targets with epidermal detachment (SJS/TEN) 1
- Document lesion morphology precisely by photographing and marking borders to track progression 1