What is the treatment for drug-induced erythema multiforme?

Treatment for Drug-Induced Erythema Multiforme

Immediately discontinue the suspected causative drug and provide symptomatic treatment with topical corticosteroids and antihistamines, escalating to systemic corticosteroids for severe mucosal involvement. 1, 2

Immediate Management

Drug Discontinuation

• Stop the offending medication immediately upon suspicion of drug-induced erythema multiforme 3, 1
• Document all medications taken over the previous 2 months, including over-the-counter and complementary therapies, to identify the culprit drug 3
• Common causative agents include NSAIDs (particularly diclofenac), antibiotics (sulfonamides, penicillins, cephalexin, tetracyclines), anticonvulsants (phenobarbital, phenytoin, valproic acid), and allopurinol 2, 4

Initial Assessment

• Perform full physical examination documenting extent of skin and mucosal involvement 3
• Examine all mucosal sites (eyes, mouth, nose, genitalia) for erosions and blistering 3
• Obtain skin biopsy from lesional skin for histopathology and perilesional skin for direct immunofluorescence to exclude immunobullous disorders 3
• Order complete blood count, inflammatory markers, liver and renal function tests, and mycoplasma serology 3

Symptomatic Treatment by Severity

Mild Cases (Isolated Cutaneous Involvement)

• Topical corticosteroids: Apply hydrocortisone 1% cream or prednicarbate 0.02% cream to affected areas 3, 1
• Oral antihistamines: Cetirizine, fexofenadine, or diphenhydramine for pruritus 3
• Emollients: Regular moisturization with urea- or glycerin-based products 3
• Continue treatment for minimum 7 days as lesions remain fixed during this period 1

Moderate Cases (Mucosal Involvement)

• Systemic corticosteroids: Prednisolone 10-20 mg daily for one week, then taper to 5-10 mg daily for second week 2, 5
• Topical corticosteroids: Continue moderate-potency steroids (clobetasone butyrate 0.05%) for oral lesions 3
• Antiseptic measures: Germicidal drugs or antiseptic mouth rinses to prevent secondary infection 2, 5
• Reassess after 2 weeks; if no improvement, escalate therapy 3

Severe Cases (Extensive Mucosal Involvement)

• Hospitalization may be required for intravenous fluids and electrolyte repletion when oral intake is compromised 1
• Higher-dose systemic corticosteroids: Prednisolone 20 mg daily with gradual taper 5
• Potent topical corticosteroids: Betamethasone valerate 0.1% or mometasone furoate 0.1% for severe lesions 3
• Pain management: Topical anesthetics for oral lesions to facilitate eating and drinking 1

Differential Diagnosis Considerations

The UK guidelines emphasize actively excluding other severe blistering conditions before finalizing treatment 3:

• Stevens-Johnson syndrome/toxic epidermal necrolysis (more widespread erythematous or purpuric macules with extensive epidermal detachment) 3
• Pemphigus vulgaris and mucous membrane pemphigoid (require direct immunofluorescence to exclude) 3
• Urticaria (individual lesions resolve within 24 hours versus 7+ days for erythema multiforme) 1

Important Clinical Pitfalls

Do not confuse drug-induced erythema multiforme with Stevens-Johnson syndrome, as the latter requires more aggressive management and has significantly worse prognosis 3. The key distinguishing feature is that erythema multiforme presents with classic targetoid lesions predominantly on acral/extensor surfaces, while SJS/TEN shows widespread purpuric macules with positive Nikolsky sign and extensive epidermal detachment 3, 1.

Absence of skin lesions can lead to misdiagnosis when only oral mucosa is involved 2, 5. In these cases, detailed drug history becomes critical for diagnosis.

Follow-Up and Monitoring

• Reassess at 2-week intervals until complete resolution 3
• Healing typically evident by third week after drug discontinuation and corticosteroid therapy 5
• Document the causative drug in patient's allergy record to prevent future exposure 3
• Educate patients about avoiding over-the-counter medications without medical supervision 5

Recurrent Disease Management

For herpes simplex virus-associated erythema multiforme (not drug-induced), prophylactic antiviral therapy is indicated 1, 4. However, this does not apply to drug-induced cases, where avoidance of the causative medication is the primary prevention strategy 4.