Erythema nodosum

Erythema nodosum

Erythema nodosum
Erythema nodosum in a person who had recently had streptococcal pharyngitis
Classification and external resources
Specialty Dermatology, rheumatology
ICD-10 L52
ICD-9-CM 695.2, 017.1
DiseasesDB 4462
MedlinePlus 000881
eMedicine derm/138
MeSH D004893

Erythema nodosum (EN) is an inflammatory condition characterised by inflammation of the fat cells under the skin, resulting in tender red nodules or lumps that are usually seen on both shins. It can be caused by a variety of conditions, and typically resolves spontaneously within 3–6 weeks. It is common in young people between 12–20 years of age.


  • Signs and symptoms 1
    • Pre-eruptive phase 1.1
    • Eruptive stage 1.2
  • Causes 2
  • Pathophysiology 3
  • Diagnosis 4
  • Treatment 5
  • Epidemiology 6
  • References 7

Signs and symptoms

Erythema nodosum lesion in a person with tuberculosis.
A single lesion of erythema nodosum

Pre-eruptive phase

The first sign of erythema nodosum is often flu-like symptoms.[1] It may involve a pyrexia, weakness and arthralgia.

Eruptive stage

It is characterized by the appearance of dermo-hypodermic rounded nodules which may be bright red or purplish, bilaterally symmetrical, located on the extensor surface of the legs. They are movable relative to the deep plane and skin. They generally disappear in 1–6 weeks without sequelae.

Erythema nodosum is characterised by red nodules that are tender and warm.[2] Nodules occur under the skin, classically in front of the shins. Nodules may occur anywhere there is fat under the skin, including the thighs, arms, trunk, face, and neck.[2]

Erythema nodosum may occur concurrently with fever, malaise, and joint pain and inflammation.[2] Nodules vary from 1–10 cm in diameter, and may coalesce to form large areas of hardened skin.[3]

As the nodules age, they become bluish purple, brownish, yellowish, and finally green, similar to the color changes that occur in a resolving bruise. The nodules usually subside over a period of 2–6 weeks without ulceration or scarring.[4]

Less common variants of erythema nodosum include:

  • Ulcerating forms, seen in Crohn's disease [2]
  • Erythema contusiforme, an erythema nodosum lesion with subcutaneous haemorrhage [2]
  • Chronic erythema nodosum, more likely to be unilateral and migratory.[2]
  • Erythema nodosum migrans, (also known as subacute nodular migratory panniculitis of Vilanova and Piñol), a form of erythema nodosum with lesions that spread centrifugally with central clearing,[2] and a form of chronic erythema nodosum.[5]) is a form of septal panniculitis that is much less common than acute erythema nodosum.[6]:488
  • Lofgren's syndrome, a form of acute sarcoidosis with erythema nodosum, bilateral hilar adenopathy and fever, often accompanied by joint symptoms.


EN is associated with a wide variety of conditions, including:


In about 30-50% of cases, the cause of EN is unknown.[7]

Autoimmune disorders, including[2]
Medications, including[2][7][8]
  • Sulfonamides
  • Penicillins
  • Oral contraceptives
  • Bromides
  • Hepatitis B vaccination[9]
Cancer, including[2]

EN may also be due to excessive antibody production in lepromatous leprosy leading to deposition of immune complexes.[10]

There is an association with the HLA-B27 histocompatibility antigen, which is present in 65% of patients with erythema nodosum.[11]

A useful mnemonic for causes is SORE SHINS (Streptococci, OCP, Rickettsia, Eponymous (Behçet), Sulfonamides, Hansen's Disease (Leprosy), IBD, NHL, Sarcoidosis.[12]


Erythema nodosum is probably a delayed hypersensitivity reaction to a variety of antigens. Although circulating immune complexes have been demonstrated in patients with inflammatory bowel disease, they have not been found in idiopathic or uncomplicated.[13]


Erythema nodosum is diagnosed clinically. A biopsy can be taken and examined microscopically to confirm an uncertain diagnosis.[4]:148 Microscopic examination usually reveals a neutrophilic infiltrate surrounding capillaries that results in septal thickening, with fibrotic changes in the fat around blood vessels. A characteristic microscopic finding is radial granulomas, well-defined nodular aggregates of histiocytes surrounding a stellate cleft.[3]

Additional evaluation should be performed to determine the underlying cause of erythema nodosum. This may include a full blood count, erythrocyte sedimentation rate (ESR), antistreptolysin-O (ASO) titer and throat culture, urinalysis, intradermal tuberculin test, and a chest x-ray.[14] The ESR is typically high, the C-reactive protein elevated, and the blood showing an increase in white blood cells.[4]:148

The ESR is initially very high, and falls as the nodules of erythema nodosum. The ASO titer is high in cases associated with a streptococcal throat infection. A chest X-ray should be performed to rule out pulmonary diseases, in particular sarcoidosis and Löfgren syndrome.[4]:148


Erythema nodosum is self-limiting and usually resolves itself within 3–6 weeks. A recurring form does exist, and in children it is attributed to repeated infections with streptococcus.[10] Treatment should focus on the underlying cause. Symptoms can be treated with bedrest, leg elevation, compressive bandages, wet dressings, and nonsteroidal anti-inflammatory agents (NSAIDs).[3] NSAIDs are usually more effective at the onset of EN versus with chronic disease.

Potassium iodide can be used for persistent lesions whose cause remains unknown. Corticosteroids and colchicine can be used in severe refractory cases.[15][16] Thalidomide has been used successfully in the treatment of Erythema nodosum leprosum,[17] and it was approved by the U.S. FDA for this use in July 1998.[18]


Erythema nodosum is the most common form of panniculitis. It is most common in the ages of 20–30, and affects women 3–6 times more than men.[4]:148

About 15 percent of patients with inflammatory bowel disease develop erythema nodosum.[19]


  1. ^ Erythema nodosum information
  2. ^ a b c d e f g h i j k Gilchrist, H; Patterson, JW (Jul–Aug 2010). "Erythema nodosum and erythema induratum (nodular vasculitis): diagnosis and management". Dermatologic therapy 23 (4): 320–7.  
  3. ^ a b c d Schwartz, RA; Nervi, SJ (Mar 1, 2007). "Erythema nodosum: a sign of systemic disease". American family physician 75 (5): 695–700.  
  4. ^ a b c d e Fitzpatrick, Thomas B. (2005). Fitzpatrick's color atlas and synopsis of clinical dermatology (5th ed.). New York: McGraw-Hill Medical Pub. Division.  
  5. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby.  
  6. ^ a b Berger, William D. James, Dirk M. Elston, Timothy G. Andrews' Diseases of the skin : clinical dermatology. (11th ed.). [London]: Saunders/ Elsevier.  
  7. ^ a b Mert, A; Ozaras, R; Tabak, F; Pekmezci, S; Demirkesen, C; Ozturk, R (2004). "Erythema nodosum: an experience of 10 years". Scandinavian journal of infectious diseases 36 (6–7): 424–7.  
  8. ^ Bohn S, Buchner S, Itin P; Büchner; Itin (1997). "Erythema nodosum: 112 cases. Epidemiology, clinical aspects and histopathology". Schweiz Med Wochenschr 127 (27–28): 1168–76.  
  9. ^ Rogerson SJ, Nye FJ; Nye (1990-08-11). "Hepatitis B vaccine associated with erythema nodosum and polyarthritis" (PDF). BMJ 301 (6747): 345.  
  10. ^ a b Kumar V, Abbas A (2009). Robbins and Coltran Pathological Basis of Disease. pp. 372–373.  
  11. ^ Cunha, Burke A. (1999). Infectious disease pearls. Philadelphia: Hanley & Belfus. p. 105.  
  12. ^ Dr Kevin McCarthy, Cork, Ireland or DIPOUT: Drugs (e.g. sulfonamides), Infections (e.g. strep), Pregnancy, OCP, Ulcerative colitis, TB
  13. ^ Nguyen, GC; Torres, EA; Regueiro, M; Bromfield, G; Bitton, A; Stempak, J; Dassopoulos, T; Schumm, P; Gregory, FJ; Griffiths, AM; Hanauer, SB; Hanson, J; Harris, ML; Kane, SV; Orkwis, HK; Lahaie, R; Oliva-Hemker, M; Pare, P; Wild, GE; Rioux, JD; Yang, H; Duerr, RH; Cho, JH; Steinhart, AH; Brant, SR; Silverberg, MS (May 2006). "Inflammatory bowel disease characteristics among African Americans, Hispanics, and non-Hispanic Whites: characterization of a large North American cohort". The American journal of gastroenterology 101 (5): 1012–23.  
  14. ^ García-Porrúa, C; González-Gay, MA; Vázquez-Caruncho, M; López-Lazaro, L; Lueiro, M; Fernández, ML; Alvarez-Ferreira, J; Pujol, RM (March 2000). "Erythema nodosum: etiologic and predictive factors in a defined population". Arthritis and rheumatism 43 (3): 584–92.  
  15. ^ Mat C, Yurdakul S, Uysal S, Gogus F, Ozyazgan Y, Uysal O, Fresko I, Yazici H; Yurdakul; Uysal; Gogus; Ozyazgan; Uysal; Fresko; Yazici (2005). "A double-blind trial of depot corticosteroids in Behcet's syndrome". Rheumatology (Oxford) 45 (3): 348–52.  
  16. ^ Yurdakul S, Mat C, Tuzun Y, Ozyazgan Y, Hamuryudan V, Uysal O, Senocak M, Yazici H; Mat; Tüzün; Ozyazgan; Hamuryudan; Uysal; Senocak; Yazici (2001). "A double-blind trial of colchicine in Behcet's syndrome". Arthritis Rheum 44 (11): 2686–92.  
  17. ^ Silverman WA (August 2002). "The schizophrenic career of a "monster drug"". Pediatrics 110 (2 Pt 1): 404–6.  
  18. ^ Rouhi, Maureen. "Thalidomide". Chemical & Engineering News.  
  19. ^ Goldman, Lee. Goldman's Cecil Medicine (24th ed.). Philadelphia: Elsevier Saunders. p. 915.