Erythema Multiforme Characteristics
Erythema multiforme is characterized by distinctive target or "iris" lesions consisting of three concentric zones (dark red center, pale middle ring, erythematous outer halo), symmetrically distributed primarily on the extremities, most commonly triggered by herpes simplex virus infection. 1, 2
Pathognomonic Lesion Morphology
- Target lesions display a characteristic three-zone configuration: central dark papule or vesicle, surrounded by a pale edematous zone, with an outer erythematous halo creating the classic "iris" appearance 1, 2
- The targetoid morphology features dusky red and white concentric rings that are well-defined and circular 1
- Lesions remain fixed in location for a minimum of 7 days, distinguishing them from urticaria which resolves within 24 hours 1, 3
Distribution Pattern
- Lesions are symmetrically distributed, predominantly affecting the extremities (particularly hands, feet, elbows, knees) and extending to the trunk 4, 5
- The palms and soles are frequently involved 6, 4
- Acral distribution (hands and feet) is particularly characteristic 6
Clinical Variants Based on Severity
EM Minor (most common form):
- Affects no more than one mucosal surface 5
- Typical target lesions on extremities with minimal or no mucosal involvement 5
- Self-limited course with better prognosis 1
EM Major (more severe):
- Involves two or more mucous membranes 5
- More extensive cutaneous involvement with target lesions 5
- Oral manifestations range from tender erythematous plaques to painful hemorrhagic bullae and erosions 7
Primary Etiologic Triggers
- Herpes simplex virus (HSV) is the most frequently implicated infectious agent, with lesions resulting from cell-mediated immune reaction triggered by HSV-DNA 4, 5
- Mycoplasma pneumoniae is another significant trigger, particularly common in children, and may present with predominantly mucous membrane involvement with minimal cutaneous lesions (Mycoplasma pneumoniae-associated mucositis) 1
- Drug-induced cases occur but are less common than infectious triggers 6, 5
Pathophysiology
- EM represents a type IV hypersensitivity reaction with cytotoxic T lymphocytes inducing keratinocyte apoptosis 1, 4
- Lesions typically appear approximately 10 days after viral infection 1
- The immune attack targets keratinocytes expressing non-self antigens (primarily viral or drug-related) 7
Critical Differentiation from Stevens-Johnson Syndrome/TEN
Key distinguishing features (this differentiation is clinically essential):
- EM presents with typical raised target lesions or raised atypical targets, predominantly on limbs and extremities 1, 2
- SJS/TEN features flat atypical targets or purpuric macules with widespread epidermal detachment and positive Nikolsky sign 8, 1, 2
- EM is mostly HSV-related with lower mortality and better prognosis, while SJS/TEN is usually drug-triggered with mortality rates of <10% for SJS and up to 30% for TEN 8, 1
- SJS/TEN presents with a prodrome of fever, malaise, and upper respiratory symptoms, with cutaneous pain as a prominent early feature 8
Histopathologic Features
- Variable epidermal damage ranging from individual keratinocyte apoptosis to confluent epidermal necrosis 1
- Massive edema of dermal papillae may lead to subepidermal vesicle formation 9
- Dense perivascular inflammatory infiltrate in the dermis 9
- Satellite-cell necrosis or more widespread epithelial necrosis is characteristic 7
Common Pitfalls to Avoid
- Do not confuse with urticaria: EM lesions are fixed for ≥7 days, while urticarial lesions migrate and resolve within 24 hours 1
- Do not misdiagnose as tinea corporis: fungal infections have a raised leading edge with satellite lesions and scale, lacking the three-zone target configuration 3
- Always examine all mucosal surfaces (oral, ocular, genital) as mucosal involvement determines disease severity classification 2, 7
- Perform direct immunofluorescence when diagnosis is uncertain to exclude immunobullous disorders (pemphigus, pemphigoid) that can mimic EM 2, 7