What is the treatment for Erythema multiforme?

Treatment of Erythema Multiforme

Erythema multiforme is a self-limited condition that requires symptomatic treatment with topical corticosteroids or antihistamines for acute episodes, while recurrent cases associated with herpes simplex virus should be managed with prophylactic antiviral therapy. 1, 2

Distinguishing Erythema Multiforme from Stevens-Johnson Syndrome

Before initiating treatment, it is critical to confirm the diagnosis, as erythema multiforme is fundamentally different from Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN):

• Erythema multiforme presents with typical target lesions starting on acral surfaces and progressing proximally, with patients typically constitutionally well and making good recovery without long-term complications. 3
• Stevens-Johnson syndrome presents with widespread erythematous or purpuric macules with blisters and significant mucosal involvement, requiring immediate hospitalization. 3, 1
• Erythema multiforme major (EMM) may have mucosal erosions usually confined to the mouth, but does not progress to SJS/TEN. 3
• If diagnostic uncertainty exists, a skin biopsy will show subepidermal cleavage in SJS/TEN versus the typical histology of erythema multiforme. 3

Acute Erythema Multiforme Treatment

Identify and Remove Triggering Factors

• Stop any suspected culprit medications immediately (common offenders include antibiotics, anticonvulsants, NSAIDs, allopurinol, phenobarbital, phenytoin, valproic acid, sulfonamides, penicillins, erythromycin, and TNF-α inhibitors). 1, 4
• Treat underlying infections, particularly herpes simplex virus and Mycoplasma pneumoniae, which are the most common infectious triggers. 1, 4

Symptomatic Management

• Apply topical corticosteroids to cutaneous lesions for symptomatic relief of inflammation and pruritus. 1, 2
• Use oral antihistamines (cetirizine, loratadine, fexofenadina, or clemastine) for pruritus control. 1, 2
• For mucosal involvement, use antiseptic or anesthetic solutions to provide symptomatic relief. 2
• Severe mucosal erythema multiforme requires hospitalization for intravenous fluids and electrolyte repletion. 1

FDA-Approved Systemic Corticosteroid Therapy

• Prednisone is FDA-indicated for severe erythema multiforme (Stevens-Johnson syndrome) and can be used for controlling acute outbreaks. 5
• Systemic corticosteroids proved effective in controlling outbreaks in all patients in retrospective studies, though their use as maintenance therapy is not clearly indicated. 6

Recurrent Erythema Multiforme Treatment

First-Line Prophylactic Therapy

• For herpes simplex virus-associated recurrent erythema multiforme, initiate prophylactic antiviral therapy as the primary treatment strategy. 1, 2
• If resistance to one antiviral agent develops, switch to an alternative antiviral drug. 4
• High-potency topical corticosteroids can be used for localized recurrent lesions. 2

Second-Line Therapies for Antiviral-Resistant Cases

• Consider dapsone for patients non-responsive to antiviral agents. 4
• JAK-inhibitors or apremilast represent novel treatment options for refractory cases. 4
• Other immunosuppressive agents, antibiotics, anthelmintics, and antimalarials may be considered as second-line options. 2

Common Pitfalls and Caveats

• Do not confuse erythema multiforme with urticaria: erythema multiforme lesions remain fixed for a minimum of 7 days, whereas urticarial lesions resolve within 24 hours. 1
• Avoid misclassifying erythema multiforme as SJS/TEN, as this leads to inappropriate aggressive management; previous publications may have been biased by such misclassification. 3
• Topical prophylactic acyclovir does not appear to prevent further episodes of herpes simplex virus-associated erythema multiforme, requiring systemic prophylactic therapy instead. 4
• Perform skin biopsy in diagnostically uncertain cases, as conditions like granuloma annulare can masquerade as erythema multiforme, and misdiagnosis could lead to unnecessary medication changes. 7
• Individual erythema multiforme lesions are typically fixed for at least 7 days, helping distinguish from other conditions. 1