Famciclovir for recurrent herpes-associated erythema multiforme: A series of three cases
Authors: Ethan Routt, Jacob Levitt
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: Patient 1 is a 50-year-old Caucasian woman with serologically proven herpes simplex virus (HSV) 2 (negative for HSV 1) who presented in September 2012 with herpes-associated erythema multiforme (HAEM) of 15 years' duration. Mycophenolate mofetil, cyclosporine, methotrexate, adalimumab, intravenous immunoglobulin (IVIg), valacyclovir, acyclovir, doxycycline, hydroxychloroquine, oxycodone, hydroxyzine, and long-term prednisone (which induced osteoporosis) were tried by multiple academic dermatologists but were unsuccessful. Examination revealed red, targetoid, confluent plaques, some eroded, on her face, trunk, and extremities without mucosal involvement. Serology was positive for Mycoplasma pneumoniae IgG. The patient partially responded to methylprednisolone 125 mg intravenously followed by prednisone 60 mg. Biopsy confirmed HAEM. Complete prednisone taper was accomplished after famciclovir 500 mg was given 3 times daily.1Wetter D.A. Davis M.D. 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; 62: 45-53Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar The patient remains clear at 19 months on oral famciclovir 500 mg daily.Patient 2 is a 65-year-old Caucasian woman who was seen 1 year earlier by a dermatologist for erythematous targetoid lesions on her right lower extremity, which was treated with doxycycline 100 mg twice daily for 2 weeks without effect. Lyme titer was negative. She presented in July 2013 with an erythematous targetoid macule of her left calf with a central bulla of 5 days' duration. Biopsy showed erythema multiforme. Five weeks of valacyclovir 1 g daily and desoximetasone 0.25% ointment twice daily failed. Confirmatory HSV 1 and 2 and M. pneumoniae titers were positive. Since switching to famciclovir 500 mg daily, the patient has been free of HAEM lesions for 7 months.Patient 3 is a 27-year-old Latina woman with serologically proven HSV 1 and 2 who presented several years ago to a dermatologist with targetoid macules and bullae of her hands and elbows and erosions of her hard palate. After valacyclovir treatment failed, she saw a rheumatologist, who diagnosed pemphigus vulgaris, reportedly by biopsy (no anti-desmoglein titers were drawn), and initiated prednisone at varying doses as high as 80 mg, a regimen she has been on since. Her course waxed and waned, prompting a trial of IVIg and rituximab, which resulted in 5 months of improvement. Ultimately, her lesions recurred. On presentation to us in February 2014, she was Cushingoid with erythematous targetoid lesions with central bullae on her fingers and erosions on her hard palate. Biopsy and positive titers of HSV 1 and 2 confirmed HAEM. Bone densitometry predictably revealed osteopenia. Following treatment with famciclovir 500 mg orally twice daily, her palatal and cutaneous erosions resolved completely. Upon prednisone taper, some lesions recurred, prompting increase of famciclovir to 3 times daily. At 75 days since beginning treatment, she is stable on this dose and off prednisone.Our patients failed valacyclovir, then multiple immunosuppressive medications, yet responded dramatically to famciclovir. Patients 1 and 3 suffered significant morbidity from long-term corticosteroid therapy and were exposed fruitlessly to numerous immunosuppressive medications. We have found famciclovir 500 mg orally 2 to 3 times daily to be effective initial treatment for refractory cases of HAEM with maintenance therapy at 500 mg daily. A failed trial of valacyclovir should not preclude a trial of famciclovir. All safe antiviral medications should be trialed in cases of chronic HAEM before moving to long-term immunosuppressive therapy. To the Editor: Patient 1 is a 50-year-old Caucasian woman with serologically proven herpes simplex virus (HSV) 2 (negative for HSV 1) who presented in September 2012 with herpes-associated erythema multiforme (HAEM) of 15 years' duration. Mycophenolate mofetil, cyclosporine, methotrexate, adalimumab, intravenous immunoglobulin (IVIg), valacyclovir, acyclovir, doxycycline, hydroxychloroquine, oxycodone, hydroxyzine, and long-term prednisone (which induced osteoporosis) were tried by multiple academic dermatologists but were unsuccessful. Examination revealed red, targetoid, confluent plaques, some eroded, on her face, trunk, and extremities without mucosal involvement. Serology was positive for Mycoplasma pneumoniae IgG. The patient partially responded to methylprednisolone 125 mg intravenously followed by prednisone 60 mg. Biopsy confirmed HAEM. Complete prednisone taper was accomplished after famciclovir 500 mg was given 3 times daily.1Wetter D.A. Davis M.D. 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; 62: 45-53Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar The patient remains clear at 19 months on oral famciclovir 500 mg daily. Patient 2 is a 65-year-old Caucasian woman who was seen 1 year earlier by a dermatologist for erythematous targetoid lesions on her right lower extremity, which was treated with doxycycline 100 mg twice daily for 2 weeks without effect. Lyme titer was negative. She presented in July 2013 with an erythematous targetoid macule of her left calf with a central bulla of 5 days' duration. Biopsy showed erythema multiforme. Five weeks of valacyclovir 1 g daily and desoximetasone 0.25% ointment twice daily failed. Confirmatory HSV 1 and 2 and M. pneumoniae titers were positive. Since switching to famciclovir 500 mg daily, the patient has been free of HAEM lesions for 7 months. Patient 3 is a 27-year-old Latina woman with serologically proven HSV 1 and 2 who presented several years ago to a dermatologist with targetoid macules and bullae of her hands and elbows and erosions of her hard palate. After valacyclovir treatment failed, she saw a rheumatologist, who diagnosed pemphigus vulgaris, reportedly by biopsy (no anti-desmoglein titers were drawn), and initiated prednisone at varying doses as high as 80 mg, a regimen she has been on since. Her course waxed and waned, prompting a trial of IVIg and rituximab, which resulted in 5 months of improvement. Ultimately, her lesions recurred. On presentation to us in February 2014, she was Cushingoid with erythematous targetoid lesions with central bullae on her fingers and erosions on her hard palate. Biopsy and positive titers of HSV 1 and 2 confirmed HAEM. Bone densitometry predictably revealed osteopenia. Following treatment with famciclovir 500 mg orally twice daily, her palatal and cutaneous erosions resolved completely. Upon prednisone taper, some lesions recurred, prompting increase of famciclovir to 3 times daily. At 75 days since beginning treatment, she is stable on this dose and off prednisone. Our patients failed valacyclovir, then multiple immunosuppressive medications, yet responded dramatically to famciclovir. Patients 1 and 3 suffered significant morbidity from long-term corticosteroid therapy and were exposed fruitlessly to numerous immunosuppressive medications. We have found famciclovir 500 mg orally 2 to 3 times daily to be effective initial treatment for refractory cases of HAEM with maintenance therapy at 500 mg daily. A failed trial of valacyclovir should not preclude a trial of famciclovir. All safe antiviral medications should be trialed in cases of chronic HAEM before moving to long-term immunosuppressive therapy.