Erythema multiforme (EM) is an acute, immune-mediated eruption characterized by target lesions, commonly triggered by herpes simplex virus (HSV). Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe, life-threatening mucocutaneous reactions—usually drug-induced—marked by epidermal necrosis and detachment. EM is clinically and etiologically distinct from SJS/TEN. Management of EM centers on treating triggers and symptomatic relief; SJS/TEN requires urgent hospitalization, ideally in burn/ICU units, with immediate withdrawal of the culprit drug and multidisciplinary supportive care, plus consideration of systemic immunomodulatory therapies.
Definitions and Epidemiology
- EM minor: typical target lesions with minimal or no mucosal involvement; often HSV-associated.
- EM major: target lesions with prominent mucosal involvement; still distinguished from SJS.
- SJS/TEN: spectrum based on body surface area detachment: SJS <10%, SJS/TEN overlap 10–30%, TEN >30%. Incidence of SJS/TEN ~1–2 per million/year.
Etiology and Triggers
- EM: HSV-1/2 most common; Mycoplasma pneumoniae, other infections; occasional drugs.
- SJS/TEN: high-risk drugs within 1–3 weeks of initiation—sulfonamides, allopurinol, aromatic anticonvulsants (carbamazepine, lamotrigine, phenytoin), oxicam NSAIDs, nevirapine; HLA associations in specific populations (e.g., HLA-B15:02 and carbamazepine in Han Chinese/SE Asian; HLA-B58:01 and allopurinol).
Clinical Features
- EM: fixed “target” lesions with three zones (central dusky area, pale edematous ring, outer erythematous halo) on acral sites; may have mild mucosal erosions, minimal systemic symptoms.
- SJS/TEN: prodrome (fever, malaise), rapidly progressive painful erythematous macules evolving to blisters and epidermal detachment; positive Nikolsky sign; severe mucosal involvement (oral, ocular, genital). Multisystem complications: sepsis, fluid/electrolyte imbalance, ocular sequelae.
Differential Diagnosis
- Fixed drug eruption (localized recurrent plaques), acute generalized exanthematous pustulosis (AGEP), DRESS, staphylococcal scalded skin syndrome, bullous pemphigoid, EM vs early SJS confusion—morphology and distribution aid distinction.
Diagnostic Workup
- EM: clinical; swab/serology for HSV if needed; consider Mycoplasma testing in children with respiratory symptoms.
- SJS/TEN: urgent clinical diagnosis; skin biopsy shows full-thickness epidermal necrosis; labs for severity scoring and complications.
- SCORTEN on admission and day 3 for mortality risk (age, cancer, HR, BUN, detached BSA, bicarbonate, glucose).
Management
- Erythema multiforme
- Treat trigger: HSV suppression with oral antivirals (acyclovir/valacyclovir) for recurrent EM.
- Symptomatic: topical corticosteroids for lesions, oral antihistamines, pain control; mucosal care (mouth rinses).
- Severe recurrent EM may require prolonged antiviral prophylaxis and, rarely, immunomodulators (dapsone, azathioprine) under specialist care.
- SJS/TEN
- Immediate cessation of suspected culprit drug(s); use causality tools (e.g., ALDEN) to prioritize.
- Admit to burn/ICU-capable unit; supportive care:
- Fluid/electrolyte resuscitation, thermoregulation, nutritional support.
- Wound care with nonadherent dressings; avoid debridement of intact epidermis.
- Infection prevention; early cultures if sepsis suspected; antibiotics only for documented infections.
- Ophthalmology evaluation within 24 hours; genital/urogynecology and ENT as needed.
- Systemic therapies (evidence evolving; institutional protocols vary):
- Early high-dose IVIG, systemic corticosteroids (short course), cyclosporine, TNF-α inhibitors (etanercept), or combination regimens have shown benefit in some studies; cyclosporine and etanercept have growing supportive data.
- DVT prophylaxis and pain management are standard.
Prevention and Long-term Care
- Pharmacogenetic screening in high-risk populations: HLA-B15:02 before carbamazepine in SE Asian ancestry; HLA-B58:01 before allopurinol in certain ethnicities.
- Comprehensive drug allergy documentation; patient counseling and medical alert identification.
- Long-term sequelae after SJS/TEN: ocular sicca and symblepharon, dyspigmentation, nail dystrophy, psychosocial impact—arrange specialty follow-up.
References (recent guidelines and key reviews)
- International consensus differentiating EM vs SJS/TEN, 2022–2024.
- European/US guidelines for SJS/TEN acute management and supportive care, 2022–2024.
- Studies on cyclosporine and TNF inhibitors in SJS/TEN, 2020–2024.
- HSV-associated EM management reviews, 2021–2024.