By Gary M. White, MD

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Recurrent erythema multiforme (EM) is defined as typical erythema multiforme that recurs with episodes of normal skin in-between. This is in contrast to persistent EM in which the lesions persist without interruption.


The patient classically develops the pain/tingling of the herpes infection and 24 hours to several days later develops erythematous lesions. The HS may be labial intranasal (felt as pain), facial or elsewhere. The EM most commonly occur on the dorsal hands. The lesions may be targetoid or the skin may just be erythematous. The EM may be photodistributed (with or without blisters) or diffuse or occur on the oral mucous membranes.

Some patients without herpes involvement have a chronic disease and exhibit antidesmoplakin autoantibodies, but whether these antibodies are the cause or consequence of the disease flares is unknown.


Any EM should be treated with prednisone, e.g., 1 mg/kg/day x 10-14 days given along with an oral antiviral agent if HSV is present.

If there is recurrent HSV that is precipitating the EM, it is best suppressed with an oral antiviral agent e.g., acyclovir 400 BID or valaciclovir 1 gram daily. If one antiviral fails to suppress, another should be tried. Resistant cases may respond well to azathioprine.

For recurrent EM seemingly unassociated with HSV, continuous suppression with acyclovir or valaciclovir should be tried anyway. If this fails, mycophenolate mofetil can be very effective. Other options include azathioprine (e.g., 100-150 mg/d), dapsone (e.g., 100-150 mg/d), hydroxychloroquine or thalidomide (e.g., 100 mg/day) [BJD 1992;126;92].

Apremilast kept 3 patients with recurrent EM clear [Dermatology Online Journal 33;1]. One patient completely cleared on adalimumab [JAAD CR 2017;3;95].


Rituximab was very effective in 5 patients with severe, chronic relapsing EM [JEADV 2016;30;1140].

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JAAD January 2010 Volume 62, Issue 1, Pages 45–5


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