Highlights & Basics
- Erythema multiforme is typically a mild, self-limited, potentially recurring mucocutaneous inflammatory condition.
- Characterized by target lesions that resemble a bull's eye. These usually erupt over 24-48 hours and last for 1-2 weeks.
- Typically presents in a symmetrical distribution of lesions over the dorsal surfaces of the extensor extremities with minimal mucous membrane involvement.
- Generally related to infectious diseases and not drug exposure. The most commonly associated infections are herpes simplex virus and Mycoplasma pneumoniae. Other less commonly associated infections include hepatitis B, hepatitis C, influenza, Epstein-Barr virus, cytomegalovirus, histoplasmosis (with concomitant erythema nodosum), orf, coccidioidomycosis, Kawasaki disease, herpes zoster, syphilis, HIV, gardnerella, and SARS-CoV-2.
- Certain drugs have been associated with erythema multiforme. Vaccines and allergic response to contact allergens have also been known to elicit the disorder.
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Citations
Lerch M, Mainetti C, Terziroli Beretta-Piccoli B, Harr T. Current perspectives on erythema multiforme. Clin Rev Allergy Immunol. 2018 Feb;54(1):177-84.[Abstract]
Grünwald P, Mockenhaupt M, Panzer R, et al. Erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis - diagnosis and treatment. J Dtsch Dermatol Ges. 2020 Jun;18(6):547-53.[Abstract]
Soares A, Sokumbi O. Recent updates in the treatment of erythema multiforme. Medicina (Kaunas). 2021 Sep 1;57(9):921.[Abstract][Full Text]
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.[Abstract]
1. Lerch M, Mainetti C, Terziroli Beretta-Piccoli B, Harr T. Current perspectives on erythema multiforme. Clin Rev Allergy Immunol. 2018 Feb;54(1):177-84.[Abstract]
2. Sokumbi O, Wetter DA. Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist. Int J Dermatol. 2012 Aug;51(8):889-902.[Abstract][Full Text]
3. Grünwald P, Mockenhaupt M, Panzer R, et al. Erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis - diagnosis and treatment. J Dtsch Dermatol Ges. 2020 Jun;18(6):547-53.[Abstract]
4. Bastuji-Garin S, Rzany B, Stern RS, et al. Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol. 1993 Jan;129(1):92-6.[Abstract]
5. Assier H, Bastuji-Garin S, Revuz J, et al. Erythema multiforme with mucous membrane involvement and Stevens-Johnson syndrome are clinically different disorders with distinct causes. Arch Dermatol. 1995 May;131(5):539-43.[Abstract]
6. Xia Y, Yang Z, Chen S, et al. Extranodal NK/T-cell lymphoma mimicking erythema multiforme. Indian J Dermatol. May-Jun 2015;60(3):322.[Abstract][Full Text]
7. Ma JH, Smith S, Gordon LA. Acute HIV infection presenting as erythema multiforme in a 45-year-old heterosexual man. Med J Aust. 2015 Mar 16;202(5):273-5.[Full Text]
8. Ghosh I, Pahwa P, Dinda AK, et al. Erythema multiforme associated with metastatic breast cancer. Indian J Dermatol. 2013;58:485-486.[Abstract][Full Text]
9. Auquier-Dunant A, Mockenhaupt M, Maldi L, et al. Correlations between clinical patterns and causes of erythema multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis: results of an international prospective study. Arch Dermatol. 2002 Aug;138(8):1019-24.[Abstract][Full Text]
10. Rossi L, Tiecco G, Venturini M, et al. Human orf with immune-mediated reactions: a systematic review. Microorganisms. 2023 Apr 27;11(5):1138.[Abstract][Full Text]
11. Kishore BN, Ankadavar NS, Kamath GH, et al. Varicella zoster with erythema multiforme in a young girl: a rare association. Indian J Dermatol. 2014 May;59(3):299-301.[Abstract][Full Text]
12. Kasuya A, Sakabe J, Kageyama R, et al. Successful differentiation of herpes zoster-associated erythema multiforme from generalized extension of herpes by rapid polymerase chain reaction analysis. J Dermatol. 2014 Jun;41(6):542-4.[Abstract]
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14. Saleh W, Alharbi H, Cha S. Increased prevalence of erythema multiforme in patients with COVID-19 infection or vaccination. Sci Rep. 2024 Feb 2;14(1):2801.[Abstract][Full Text]
15. Joseph RH, Haddad FA, Matthews AL, et al. Erythema multiforme after orf virus infection: a report of two cases and literature review. Epidemiol Infect. 2015 Jan;143(2):385-90.[Abstract][Full Text]
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17. Eun LY, Go JW, Kang WH, et al. Erythema multiforme associated with kawasaki disease in a Korean child. Eur J Dermatol. Jul-Aug 2010;20(4):524-5.
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20. Ballester I, Guijarro J, Silvestre JF, et al. Erythema multiforme induced by imiquimod 5% cream. Int J Dermatol. 2014 Jul;53(7):e347-8.[Abstract]
21. Sai Keerthana PC, Anila KN, Reshma R. Naproxen induced erythema multiforme - a rare case report. Int J Pharm and Pharmaceutical Sci. 2017;9:294-5.[Full Text]
22. Rodríguez-Pazos L, Sánchez-Aguilar D, Rodríguez-Granados MT, et al. Erythema multiforme photoinduced by statins. Photodermatol Photoimmunol Photomed. 2010 Aug;26(4):216-8.[Abstract]
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24. Utsunomiya A, Oyama N, Iino S, et al. A case of erythema multiforme major developed after sequential use of two immune checkpoint inhibitors, nivolumab and ipilimumab, for advanced melanoma: possible implication of synergistic and/or complementary immunomodulatory effects. Case Rep Dermatol. 2018 Jan 18;10(1):1-6.[Abstract][Full Text]
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26. Abou Assalie N, Durcan R, Durcan L, et al. Hydroxychloroquine-induced erythema multiforme. J Clin Rheumatol. 2017 Mar;23(2):127-8.[Full Text]
27. Mantovani A, Álvares-Da-Silva MR. Anaphylaxis preceded by erythema multiforme with sorafenib: first case report. Ann Hepatol. 2019 Sep-Oct;18(5):777-9.[Abstract][Full Text]
28. Chahal D, Aleshin M, Turegano M, et al. Vaccine-induced toxic epidermal necrolysis: a case and systematic review. Dermatol Online J. 2018 Jan 15;24(1):13030/qt7qn5268s.[Full Text]
29. Allione A, Dutto L, Castagna E, et al. Erythema multiforme caused by tattoo: a further case. Intern Emerg Med. 2011 Jun;6(3):263-5.[Full Text]
30. Gantala R, Devaraju RR, G SG, et al. Condiments costing high. . . ! A case report of erythema multiforme. J Clin Diagn Res. 2015 Jul;9(7):ZD22-4.[Abstract][Full Text]
31. Kumar MS, Kumar MH, Kumar VS, et al. Herpes-associated erythema multiforme worsened by a Siddha drug, Alpinia galanga, in an 18-year-old man. BMJ Case Rep. 2015 Sep 21;2015:bcr2015212303.[Abstract][Full Text]
32. Sundram U. A review of important skin disorders occurring in the posttransplantation patient. Adv Anat Pathol. 2014 Sep;21(5):321-9.[Abstract]
33. Ng PP, Sun YJ, Tan HH, et al. Detection of HSV genomic DNA in various subsets of Erythema multiforme by polymerase chain reaction. Dermatology. 2003;207(4):349-53.[Abstract]
34. Ono F, Sharma BK, Smith CC, et al. CD34+ cells in the peripheral blood transport HSV DNA fragments to the skin of patients with erythema multiforme (HAEM). J Invest Dermatol. 2005 Jun;124(6):1215-24.[Abstract][Full Text]
35. Kokuba H, Aurelian L, Burnett J. Herpes simplex virus associated erythema multiforme (HAEM) is mechanistically distinct from drug-induced erythema multiforme: interferon-gamma is expressed in HAEM lesions and tumor necrosis factor-alpha in drug-induced erythema multiforme lesions. J Invest Dermatol. 1999 Nov;113(5):808-15.[Abstract][Full Text]
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.[Abstract][Full Text]
37. Bitterman R, Oren I, Geffen Y, et al. Prolonged fever and splinter hemorrhages in an immunocompetent traveler with disseminated histoplasmosis. J Travel Med. 2013 Jan-Feb;20(1):57-9.[Abstract][Full Text]
38. Bennardo L, Nisticò SP, Dastoli S, et al. Erythema multiforme and COVID-19: what do we know? Medicina (Kaunas). 2021 Aug 16;57(8):828.[Abstract][Full Text]
39. Amode R, Ingen-Housz-Oro S, Ortonne N, et al. Clinical and histologic features of mycoplasma pneumoniae-related erythema multiforme: a single-center series of 33 cases compared with 100 cases induced by other causes. J Am Acad Dermatol. 2018 Jul;79(1):110-7.[Abstract]
40. Yousefian M, Khadivi A. Occurrence of erythema multiforme following COVID-19 vaccination: a review. Clin Exp Vaccine Res. 2023 Apr;12(2):87-96.[Abstract][Full Text]
41. Soares A, Sokumbi O. Recent updates in the treatment of erythema multiforme. Medicina (Kaunas). 2021 Sep 1;57(9):921.[Abstract][Full Text]
42. Cote B, Wechsler J, Bastuji-Garin S. Clinicopathologic correlation in erythema multiforme and Stevens-Johnson syndrome. Arch Dermatol. 1995 Nov;131(11):1268-72.[Abstract]
43. Yachoui R, Cronin PM. Systemic lupus erythematosus associated with erythema multiforme-like lesions. Case Rep Rheumatol. 2013;2013:212145.[Abstract][Full Text]
44. Lee HJ, Kwon JA, Kim JW. Erythema multiforme-like molluscum dermatitis. Acta Derm Venereol. 2002;82(3):217-8.[Abstract]
45. Primary Care Dermatology Society. Erythema multiforme. Nov 2021 [internet publication].[Full Text]
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.[Abstract]
47. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.[Abstract][Full Text]
48. Oak AS, Seminario-Vidal L, Sami N. Treatment of antiviral-resistant recurrent erythema multiforme with dapsone. Dermatol Ther. 2017 Mar;30(2):e12449.[Abstract]
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.[Abstract]
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.[Abstract]
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.[Abstract][Full Text]
52. Chen T, Levitt J, Geller L. Apremilast for treatment of recurrent erythema multiforme. Dermatol Online J. 2017 Jan 15;23(1):13030/qt15s432gx.[Abstract][Full Text]
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.[Abstract][Full Text]
54. Morison WL, Anhalt GJ. Therapy with oral psoralen plus UV-A for erythema multiforme. Arch Dermatol. 1997 Nov;133(11):1465-6.[Abstract]
55. de Castro Rodrigues CM, dos Reis DCS, Jaime Paiva LG, et al. Microstomy after erythema multiforme: surgical treatment and results. Ann Pediatr Child Health 2020;8(7):1198.[Full Text]
56. Oluwadaisi AM, A. Adewale A, Mogaji IK, et al. Erythema multiforme: a retrospective study of the clinical manifestations of patients attending an oral medicine clinic in Nigeria. Int J Res Rep Dent. 2020 Jan 25;3(1):6-14.[Full Text]
