Dapsone
Dapsone has been reported as beneficial in persistent or recurrent EM.[48]Oak AS, Seminario-Vidal L, Sami N. Treatment of antiviral-resistant recurrent erythema multiforme with dapsone. Dermatol Ther. 2017 Mar;30(2):e12449.
http://www.ncbi.nlm.nih.gov/pubmed/27860166?tool=bestpractice.com
[49]Dias de Oliveira NF, Miyamoto D, Maruta CW, et al. Recurrent erythema multiforme: a therapeutic proposal for a chronic disease. J Dermatol. 2021 Oct;48(10):1569-73.
http://www.ncbi.nlm.nih.gov/pubmed/34223646?tool=bestpractice.com
In one systematic review, the overall complete response rate among patients with recurrent EM treated with dapsone was 29% (9/31).[46]de Risi-Pugliese T, Sbidian E, Ingen-Housz-Oro S, et al. Interventions for erythema multiforme: a systematic review. J Eur Acad Dermatol Venereol. 2019 May;33(5):842-9.
http://www.ncbi.nlm.nih.gov/pubmed/30680804?tool=bestpractice.com
Further studies are required.
Rituximab
Rituximab has been tried in 5 patients with refractory EM with between 9 and 20 years of disease activity.[50]Hirsch G, Ingen-Housz-Oro S, Fite C, et al. Rituximab, a new treatment for difficult-to-treat chronic erythema multiforme major? Five cases. J Eur Acad Dermatol Venereol. 2016 Jul;30(7):1140-3.
http://www.ncbi.nlm.nih.gov/pubmed/26369288?tool=bestpractice.com
Four of these patients had antidesmoplakin antibodies. Four of the patients experienced complete or quasi-complete remission, and one patient experienced partial remission, for 3 to 11 months.
Adalimumab
Adalimumab is a recombinant human IgG1 monoclonal antibody against human tumor necrosis factor. It has been successfully used to treat recurrent EM secondary to herpes simplex virus.[51]Baillis B, Maize JC Sr. Treatment of recurrent erythema multiforme with adalimumab as monotherapy. JAAD Case Rep. 2017 Mar 2;3(2):95-7.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334521
http://www.ncbi.nlm.nih.gov/pubmed/28280768?tool=bestpractice.com
Caution must be used because adalimumab can trigger hypersensitivity reactions, including EM and Stevens-Johnson syndrome.
Apremilast
Apremilast is a phosphodiesterase-4 inhibitor. It has been successfully used to treat recurrent oral EM.[52]Chen T, Levitt J, Geller L. Apremilast for treatment of recurrent erythema multiforme. Dermatol Online J. 2017 Jan 15;23(1):13030/qt15s432gx.
https://escholarship.org/uc/item/15s432gx
http://www.ncbi.nlm.nih.gov/pubmed/28329479?tool=bestpractice.com
In one case series, three patients with oral EM refractory to corticosteroid and antiviral treatment experienced complete remission without recurrences for up to 6 months after treatment with apremilast.[52]Chen T, Levitt J, Geller L. Apremilast for treatment of recurrent erythema multiforme. Dermatol Online J. 2017 Jan 15;23(1):13030/qt15s432gx.
https://escholarship.org/uc/item/15s432gx
http://www.ncbi.nlm.nih.gov/pubmed/28329479?tool=bestpractice.com
Immunosuppressive therapy and phototherapy
A few isolated case reports and case series describe use of phototherapy (oral psoralens plus ultraviolet A) or immunosuppressive therapy with mycophenolate, azathioprine, or cyclosporine.[36]Wetter DA, Davis MD. Recurrent erythema multiforme: clinical characteristics, etiologic associations, and treatment in a series of 48 patients at Mayo Clinic, 2000 to 2007. J Am Acad Dermatol. 2010 Jan;62(1):45-53.
http://www.jaad.org/article/S0190-9622(09)00778-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/19665257?tool=bestpractice.com
[53]Davis MD, Rogers RS, Pittelkow MR. Recurrent erythema multiforme/Stevens-Johnson syndrome: response to mycophenolate mofetil. Arch Dermatol. 2002 Dec;138(12):1547-50.
http://archderm.ama-assn.org/cgi/content/full/138/12/1547
http://www.ncbi.nlm.nih.gov/pubmed/12472339?tool=bestpractice.com
[54]Morison WL, Anhalt GJ. Therapy with oral psoralen plus UV-A for erythema multiforme. Arch Dermatol. 1997 Nov;133(11):1465-6.
http://www.ncbi.nlm.nih.gov/pubmed/9371042?tool=bestpractice.com
In one systematic review, 80% (12/15) of patients completely responded to treatment with azathioprine and 37% (3/8) complete responded to mycophenolate, but risk of bias in the included studies was high.[46]de Risi-Pugliese T, Sbidian E, Ingen-Housz-Oro S, et al. Interventions for erythema multiforme: a systematic review. J Eur Acad Dermatol Venereol. 2019 May;33(5):842-9.
http://www.ncbi.nlm.nih.gov/pubmed/30680804?tool=bestpractice.com