Highlights & Basics
- Erythema multiforme is a mild, self-limited, potentially recurring mucocutaneous inflammatory condition.
- Characterized by target lesions that resemble a bull's eye. These usually erupt over 24 to 48 hours and last for 1 to 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, Epstein-Barr virus, cytomegalovirus, histoplasmosis (with concomitant erythema nodosum), orf (parapox virus that can be transmitted from sheep or goats to humans), coccidioidomycosis, Kawasaki disease, herpes zoster, and gardnerella.
- Associated drugs include aminopenicillins, docetaxel, tumor necrosis factor-alpha inhibitors, antimalarials, anticonvulsants, and lidocaine injections. Phenylbutazone, triclocarban, paclitaxel, and statin medications have been associated with photo-induced lesions. Vaccines such as hepatitis B, smallpox, varicella, meningococcal, human papillomavirus, and hantavirus, 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]
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]
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;131:539-543.[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. Trayes KP, Love G, Studdiford JS. Erythema multiforme: recognition and management. Am Fam Physician. 2019 Jul 15;100(2):82-8.[Abstract][Full Text]
5. 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]
6. 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]
7. Xia Y, Yang Z, Chen S, et al. Extranodal NK/T-cell lymphoma mimicking erythema multiforme. Indian J Dermatol. 2015;60:322.[Abstract][Full Text]
8. Ma JH, Smith S, Gordon LA. Acute HIV infection presenting as erythema multiforme in a 45-year-old heterosexual man. Med J Aust. 2015;202:273-275.[Abstract][Full Text]
9. 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]
10. 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]
11. 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.[Abstract]
12. 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]
13. 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]
14. Borrás-Blasco J, Navarro-Ruiz A, Borrás C, et al. Adverse cutaneous reactions induced by TNF-alpha antagonist therapy. South Med J. 2009 Nov;102(11):1133-40.[Abstract]
15. Lenalidomide: Stevens-Johnson syndrome. Prescrire Int. 2010 Jun;19(107):125.[Abstract]
16. 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]
17. 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.[Abstract][Full Text]
18. 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.[Abstract][Full Text]
19. 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]
20. 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]
21. Rodríguez-Pazos L, Gómez-Bernal S, Rodríguez-Granados MT, et al. Photodistributed erythema multiforme. Actas Dermosifiliogr. 2013 Oct;104(8):645-53.[Abstract][Full Text]
22. Lamoreux MR, Stern MR, Hsu WT. Erythema multiforme. Am Fam Physician. 2006 Dec 1;74(11):1883-8.[Abstract][Full Text]
23. 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]
24. 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]
25. Sundram U. A review of important skin disorders occurring in the posttransplantation patient. Adv Anat Pathol. 2014 Sep;21(5):321-9.[Abstract]
26. 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]
27. 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]
28. 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]
29. 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]
30. 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]
31. Olut AI, Erkek E, Ozunlu H, et al. Erythema multiforme associated with acute hepatitis B virus infection. Clin Exp Dermatol. 2006 Jan;31(1):137-8.[Abstract]
32. Hafsi W, Badri T. Erythema multiforme. In: StatPearls [internet]. Treasure Island, FL: StatPearls Publishing; 2020.[Abstract][Full Text]
33. 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.[Abstract][Full Text]
34. 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]
35. 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]
36. 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]
37. de Arruda JA, Silva P, Amaral MB, et al. Erythema multiforme induced by alendronate sodium in a geriatric patient: a case report and review of the literature. J Clin Exp Dent. 2017 Jul;9(7):e929-33.[Abstract][Full Text]
38. Abou Assalie N, Durcan R, Durcan L, et al. Hydroxychloroquine-induced erythema multiforme. J Clin Rheumatol. 2017 Mar;23(2):127-8.[Abstract][Full Text]
39. 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]
40. Wine E, Ballin A, Dalal I. Infantile erythema multiforme following hepatitis B vaccine. Acta Paediatr. 2006 Jul;95(7):890-1.[Abstract]
41. Loche F, Schwarze HP, Thedenat B, et al. Erythema multiforme associated with hepatitis B immunization. Clin Exp Dermatol. 2000 Mar;25(2):167-8.[Abstract]
42. Chiang MC, Chiang FC, Chang YT, et al. Erythema multiforme caused by Treponema pallidum in a young patient with human immunodeficiency virus infection. J Clin Microbiol. 2010 Jul;48(7):2640-2.[Abstract][Full Text]
43. 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]
44. Yachoui R, Cronin PM. Systemic lupus erythematosus associated with erythema multiforme-like lesions. Case Rep Rheumatol. 2013;2013:212145.[Abstract][Full Text]
45. Lee HJ, Kwon JA, Kim JW. Erythema multiforme-like molluscum dermatitis. Acta Derm Venereol. 2002;82(3):217-8.[Abstract]
46. Tirado-Sánchez A, Bonifaz A. Paraneoplastic pemphigus. A life-threatening autoimmune blistering disease [in Spanish]. Actas Dermosifiliogr. 2017 Dec;108(10):902-10.[Abstract][Full Text]
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. 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]
50. 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]
51. 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]
52. Jones RR. Azathioprine therapy in the management of persistent erythema multiforme. Br J Dermatol. 1981 Oct;105(4):465-7.[Abstract]
53. Bakis S, Zagarella S. Intermittent oral cyclosporin for recurrent herpes simplex-associated erythema multiforme. Australas J Dermatol. 2005 Feb;46(1):18-20.[Abstract]
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]
57. Sokumbi O, Wetter DA. Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist. Int J Dermatol. 2012;51:889-902.[Abstract][Full Text]
58. French LE, Prins C. Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis. In: Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology. 2nd ed. London, UK: Mosby-Elsevier; 2008:287-300.
59. 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;129:92-6.[Abstract]
60. 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;131:539-543.[Abstract]
61. 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;138:1019-1024.[Abstract]
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