Table 2.

A summary of the first-line treatment for each type of EM as well as special considerations that need to be evaluated in each case. Adapted from “Clinical Features, Diagnosis, and Treatment of Erythema Multiforme: A Review for the Practicing Dermatologist” by Sokumbi et al. [1] with permission from the John Wiley and Sons Publishing on behalf of the International Journal of Dermatology, © 2021.

EM Type	First-Line Therapy	Special Considerations
Acute EM	Topical corticosteroids Topical antiseptics	Antiviral therapy in the setting of HSV-associated EM. Antibiotic therapy in the setting of M. pneumoniae associated EM.
	Oral antihistamines	Oral methylprednisolone in SARS-CoV-2 associated EM.
Mucosal Involvement	High potency corticosteroid gel	If mucosal involvement is severe, the hospitalization for fluid and electrolyte replacement should be considered in patients with poor oral intake.
	Oral antiseptic or anesthetic solutions	Systemic glucocorticoid therapy, tapered.
		If ocular involvement present, then ophthalmologic evaluation is necessary to prevent serious long-term sequelae.
Recurrent EM	Prophylactic antiviral therapy—topical, continuous oral or intermittent oral (continuous for ≥6 months) acyclovir, valacyclovir, or famciclovir	If resistant to prophylactic antivirals, systemic agents that may be used include: azathioprine, dapsone, mycophenolate mofetil, or immunoglobulin hydroxychloroquine, thalidomide, and cyclosporine.
		For non-responsive EM, another antiviral medication may be substituted, or the dose of the current antiviral doubled.