Management of Erythema Multiforme
Erythema multiforme is primarily managed with supportive care including topical corticosteroids and antihistamines for symptomatic relief, combined with treatment of the underlying trigger—most importantly, antiviral prophylaxis for herpes simplex virus-associated cases and antibiotics for Mycoplasma pneumoniae infection. 1, 2
Immediate Assessment and Trigger Identification
When evaluating a patient with suspected erythema multiforme, immediately:
- Identify and discontinue any potential causative medications including allopurinol, phenobarbital, phenytoin, antibacterial sulfonamides, penicillins, erythromycin, tetracyclines, NSAIDs, statins, and TNF-α inhibitors 3
- Test for infectious triggers, particularly herpes simplex virus (most common) and Mycoplasma pneumoniae (especially in children with respiratory symptoms) 3, 1, 2
- Document lesion characteristics: typical target lesions with acral distribution on extensor surfaces, fixed for minimum 7 days (unlike urticaria which resolves within 24 hours) 1
- Assess mucosal involvement (oral, ocular, genital) to determine if this is isolated cutaneous or mucocutaneous disease 1, 2
Symptomatic Treatment
Mild Cutaneous Disease
- Topical corticosteroids (e.g., hydrocortisone 1% cream or prednicarbate cream) applied to affected areas 4, 1
- Oral antihistamines (cetirizine, loratadine, fexofenadine, or diphenhydramine) for pruritus 4, 1
- Emollients and moisturizers to prevent skin dryness 4
Moderate to Severe Mucosal Involvement
- Hospitalization may be required for severe mucosal disease with inability to maintain oral intake 1, 2
- Intravenous fluids and electrolyte repletion for patients unable to eat or drink adequately 1
- Systemic corticosteroids (prednisone) for severe cases, particularly with extensive mucosal involvement 5, 6
- Oral care: gentle mouth rinses, topical anesthetics (lidocaine solutions), and soft diet 2
Etiologic Treatment
Herpes Simplex Virus-Associated EM
- For acute episodes: Treat active HSV infection if present 3, 2
- For recurrent EM (≥6 episodes/year): Prophylactic antiviral therapy is the cornerstone of management 3, 1, 2
Mycoplasma pneumoniae-Associated EM
- Immediate antibiotic therapy is critical when M. pneumoniae is suspected or confirmed 2, 6
- Macrolides (azithromycin) are first-line, but note that azithromycin itself can rarely trigger EM 6
- If drug-induced EM is suspected with azithromycin, switch to alternative antibiotic and avoid re-exposure 6
Drug-Induced EM
- Rapid identification and permanent discontinuation of the causative drug 3, 6
- Avoid re-exposure to the same drug or chemically similar agents 6
- Document the reaction clearly in the medical record 6
Important Caveats
Distinguish EM from Stevens-Johnson Syndrome (SJS): SJS presents with widespread erythematous or purpuric macules with blisters and more extensive epidermal detachment, requiring different management 4, 1. EM has typical raised target lesions with acral predominance, while SJS has flat atypical targets with central blistering and mucosal involvement is more severe 4.
Topical prophylactic acyclovir does not prevent EM recurrences—systemic antiviral prophylaxis is required 3.
Avoid greasy creams and occlusive preparations as they may worsen follicular involvement 4.
Monitor for secondary bacterial infection of erosions, particularly with Staphylococcus aureus, which may require systemic antibiotics 4.
Follow-Up and Prevention
- Patient education about avoiding identified triggers 6
- For recurrent disease: Consider HLA typing if drug-induced, as certain genotypes (e.g., HLA-DQB1*03:01) may confer susceptibility 6
- Reassess after 2 weeks of treatment; most cases resolve within 2-4 weeks with appropriate management 1, 2
- Long-term antiviral prophylaxis should be continued for at least 6 months in HSV-associated recurrent EM before attempting discontinuation 2