- Daniela Kroshinsky, MD
Daniela Kroshinsky, MD
- Assistant Professor of Dermatology
- Harvard Medical School
- Section Editor
- Jeffrey Callen, MD, FACP, FAAD
Jeffrey Callen, MD, FACP, FAAD
- Editor-in-Chief — Dermatology
- Section Editor — Skin and Systemic Disease
- Professor of Medicine
- University of Louisville School of Medicine
Erythema nodosum (EN) is a delayed-type hypersensitivity reaction that most often presents as erythematous, tender nodules on the shins (picture 1A-D). Common triggers for EN include infection, drugs, pregnancy, malignancy, and inflammatory conditions, such as sarcoidosis or gastrointestinal diseases; however, many cases are idiopathic (table 1). The characteristic histologic finding in EN is a septal panniculitis without vasculitis.
EN usually resolves spontaneously within several weeks. When necessary, treatment can be given to reduce symptoms or hasten resolution.
The etiologies, diagnosis, and management of EN will be reviewed here. Other forms of panniculitis and erythema nodosum leprosum (a complication of leprosy that is also known as a type 2 reaction) are reviewed separately. (See "Panniculitis: Recognition and diagnosis" and "Epidemiology, microbiology, clinical manifestations, and diagnosis of leprosy", section on 'Type 2 reaction'.)
EN occurs in all ages, sexes, and racial groups but is most common in women in their second to fourth decades . Women are affected three to six times more often than men. The specific incidence of EN varies based upon the local prevalence of the associated triggering diseases . (See 'Etiology' below.)
EN is considered a delayed-type hypersensitivity reaction resulting from exposure to various antigens; however, the pathogenesis is not fully understood. The pathogenic mechanism may involve immune complex deposition in the septal venules of the subcutaneous fat, neutrophil recruitment with resulting reactive oxygen species formation, tumor necrosis factor (TNF)-alpha production, and granuloma formation [3-5].To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Requena L, Requena C. Erythema nodosum. Dermatol Online J 2002; 8:4.
- Bondi EE, Margolis DJ, Lazarus GS. Panniculitis. In: Fitzpatrick’s Dermatology in General Medicine, 5th ed, Freedberg IM, Eisen AZ, Wolff K, et al (Eds), McGraw-Hill, New York 1999. p.1284.
- Cox NH, Jorizzo JL, Bourke JF, Savage COS. Vasculitis, neutrophilic dermatoses and related disorders. In: Rook’s Textbook of Dermatology, 8th ed, Burns T, Breathnach S, Cox N, Griffiths C (Eds), Wiley-Blackwell, Hoboken 2010. Vol 3, p.50.1.
- Patterson JW. Panniculitis. In: Dermatology, 3rd ed, Bolognia JL, Jorizzo JL, Schaffer JV (Eds), Elsevier Saunders, Philadelphia 2012. p.1641.
- Kunz M, Beutel S, Bröcker E. Leucocyte activation in erythema nodosum. Clin Exp Dermatol 1999; 24:396.
- Elkayam O, Caspi D, Segal R, et al. Familial erythema nodosum. Arthritis Rheum 1991; 34:1177.
- Labunski S, Posern G, Ludwig S, et al. Tumour necrosis factor-alpha promoter polymorphism in erythema nodosum. Acta Derm Venereol 2001; 81:18.
- Weizman A, Huang B, Berel D, et al. Clinical, serologic, and genetic factors associated with pyoderma gangrenosum and erythema nodosum in inflammatory bowel disease patients. Inflamm Bowel Dis 2014; 20:525.
- García-Porrúa C, González-Gay MA, Vázquez-Caruncho M, et al. Erythema nodosum: etiologic and predictive factors in a defined population. Arthritis Rheum 2000; 43:584.
- Mert A, Kumbasar H, Ozaras R, et al. Erythema nodosum: an evaluation of 100 cases. Clin Exp Rheumatol 2007; 25:563.
- Braverman IM. Protective effects of erythema nodosum in coccidioidomycosis. Lancet 1999; 353:168.
- Hanauer SB. How do I treat erythema nodosum, aphthous ulcerations, and pyoderma gangrenosum? Inflamm Bowel Dis 1998; 4:70; discussion 73.
- White WL, Hitchcock MG. Diagnosis: erythema nodosum or not? Semin Cutan Med Surg 1999; 18:47.
- Cribier B, Caille A, Heid E, Grosshans E. Erythema nodosum and associated diseases. A study of 129 cases. Int J Dermatol 1998; 37:667.
- Fine RM, Meltzer HD. Chronic erythema nodosum. Arch Dermatol 1969; 100:33.
- Thurber S, Kohler S. Histopathologic spectrum of erythema nodosum. J Cutan Pathol 2006; 33:18.
- Sentürk T, Aydintuğ O, Kuzu I, et al. Adhesion molecule expression in erythema nodosum-like lesions in Behçet's disease. A histopathological and immunohistochemical study. Rheumatol Int 1998; 18:51.
- Honma T, Bang D, Lee S, Saito T. Ultrastructure of endothelial cell necrosis in classical erythema nodosum. Hum Pathol 1993; 24:384.
- Winkelmann RK, Frigas E. Eosinophilic panniculitis: a clinicopathologic study. J Cutan Pathol 1986; 13:1.
- www.upsher-smith.com/wp-content/uploads/SSKI_PI.pdf (Accessed on October 31, 2016).
- Potassium iodide and streptomycin for tuberculosis. N Engl J Med 1949; 240:664.
- Ubogy Z, Persellin RH. Suppression of erythema nodosum by indomethacin. Acta Derm Venereol 1982; 62:265.
- Schulz EJ, Whiting DA. Treatment of erythema nodosum and nodular vasculitis with potassium iodide. Br J Dermatol 1976; 94:75.
- Horio T, Imamura S, Danno K, Ofuji S. Potassium iodide in the treatment of erythema nodosum and nodular vasculitis. Arch Dermatol 1981; 117:29.
- Sterling JB, Heymann WR. Potassium iodide in dermatology: a 19th century drug for the 21st century-uses, pharmacology, adverse effects, and contraindications. J Am Acad Dermatol 2000; 43:691.
- Honma K, Saga K, Onodera H, Takahashi M. Potassium iodide inhibits neutrophil chemotaxis. Acta Derm Venereol 1990; 70:247.
- Miyachi Y, Niwa Y. Effects of potassium iodide, colchicine and dapsone on the generation of polymorphonuclear leukocyte-derived oxygen intermediates. Br J Dermatol 1982; 107:209.
- Winter HS. Treatment of pyoderma gangrenosum, erythema nodosum, and aphthous ulcerations. Inflamm Bowel Dis 1998; 4:71.
- Tremaine WJ. Treatment of erythema nodosum, aphthous stomatitis, and pyoderma gangrenosum in patients with IBD. Inflamm Bowel Dis 1998; 4:68.
- Blake T, Manahan M, Rodins K. Erythema nodosum - a review of an uncommon panniculitis. Dermatol Online J 2014; 20:22376.
- Song JS, Halim K, Vleugels RA, Merola JF. Dapsone for treatment of erythema nodosum. Dermatol Online J 2016; 22.
- Wallace SI, Bernstein D, Diamond H. Diagnostic value of the colchicine therapeutic trial. JAMA 1967; 199:525.
- De Coninck P, Baclet JL, Di Bernardo C, et al. [Treatment of erythema nodosum with colchicine]. Presse Med 1984; 13:680.
- Wozniacka A, Carter A, McCauliffe DP. Antimalarials in cutaneous lupus erythematosus: mechanisms of therapeutic benefit. Lupus 2002; 11:71.
- Alloway JA, Franks LK. Hydroxychloroquine in the treatment of chronic erythema nodosum. Br J Dermatol 1995; 132:661.
- Jarrett P, Goodfield MJ. Hydroxychloroquine and chronic erythema nodosum. Br J Dermatol 1996; 134:373.
- Marmor MF, Kellner U, Lai TY, et al. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology 2016; 123:1386.
- Boyd AS. Etanercept treatment of erythema nodosum. Skinmed 2007; 6:197.
- Quin A, Kane S, Ulitsky O. A case of fistulizing Crohn's disease and erythema nodosum managed with adalimumab. Nat Clin Pract Gastroenterol Hepatol 2008; 5:278.
- Ortego-Centeno N, Callejas-Rubio JL, Sanchez-Cano D, Caballero-Morales T. Refractory chronic erythema nodosum successfully treated with adalimumab. J Eur Acad Dermatol Venereol 2007; 21:408.
- Kugathasan S, Miranda A, Nocton J, et al. Dermatologic manifestations of Crohn disease in children: response to infliximab. J Pediatr Gastroenterol Nutr 2003; 37:150.
- Vanbiervliet G, Anty R, Schneider S, et al. [Sweet's syndrome and erythema nodosum associated with Crohn's disease treated by infliximab]. Gastroenterol Clin Biol 2002; 26:295.
- Clayton TH, Walker BP, Stables GI. Treatment of chronic erythema nodosum with infliximab. Clin Exp Dermatol 2006; 31:823.
- Acosta KA, Haver MC, Kelly B. Etiology and therapeutic management of erythema nodosum during pregnancy: an update. Am J Clin Dermatol 2013; 14:215.
- CLINICAL MANIFESTATIONS
- EVALUATION FOR UNDERLYING DISEASE
- DIFFERENTIAL DIAGNOSIS
- General measures
- Treatment of associated conditions
- First-line therapy
- - Nonsteroidal anti-inflammatory drugs
- - Potassium iodide
- Second-line therapy
- - Systemic glucocorticoids
- - Intralesional corticosteroid injections
- Recalcitrant, chronic, or recurring disease
- - Dapsone
- - Colchicine
- - Hydroxychloroquine
- Other therapies
- In pregnancy
- INDICATIONS FOR REFERRAL
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS