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Erythema Nodosum (EN)

Erythema nodosum (EN) is an inflammation of the subcutaneous fat  characterized by  painful, red swellings over the shins. The eruption may also involve the extensor aspects of the thighs and forearms. The condition is believed to be a delayed hypersensitivity reaction and occurs most often in women during their reproductive years [2, 3].  Erythema nodosum migrans, subacute nodular migratory panniculitis, and chronic erythema nodosum, are considered to be variants of the same disease [1].

Excisional biopsy of the lesions in the early stages of EN shows a perivascular infiltrate of neutrophils   in the interlobular septa that is sub-sequently replaced by lymphocytes, and a granulomatous infiltrate with giant cells. Small histiocytes, radially placed around a central cleft, Miescher's radial granulomas, are a characteristic finding. 

EN may be associated with a  variety of systemic diseases or medications. However, an identifiable cause is not found in about 50% of patients.  The most common identifiable causes of EN are streptococcal infection and sarcoidosis [1-5].

Conditions Associated with Erythema Nodosum

Common [1 -16]

  • Streptococcal phyaryngitis    
  • Tuberculosis  
  • Coccidioidomycosis
  • Yersinia
  • Histoplasmosis
  • Sarcoidosis
  • Sulfa drugs
  • Oral contraceptives
  • Amoxicillin
  • Inflammatory bowel disease
    Behçet disease
    (most often during the first half of pregnancy [12])

    Less Common [1-4,16]

  • Campylobacter
  • Rickettsiae
  • Salmonella
  • Psittacosis
  • Syphilis
  • Amoebiasis
  • Giardiasis
  • Herpes simplex virus
  • Mycoplasma
  • Epstein-Barr virus
  • Hepatitis B and C viruses
  • Human immunodeficiency virus
  • Toxoplasmois
  • Cat scratch disease (Bartonella)
  • Malignancies
  • Leukemia
  • Hodgkin’s disease


    Initial evaluation shouldincludes:

    • Throat culture>
    • Antistreptolysin-O (ASO) titer
    • CBC
    • Erythrocyte sedimentation rate , ESR
    • Intradermal skin tests for tuberculosis and coccidioidomycosis
    • Chest film to evaluate for hilar adenopathy.
    • In patients with GI symptoms obtain stool culture to include Yersinia enterocolitica (consider serological testing also).
    • Consultation with a dermatologist and/or internist for evaluation of underlying cause of EN may be helpful.

    If a biopsy is necessary to confirm the diagnosis , deep skin incisional biopsies are required to sample the subcutaneous tissue adequately.

    Other conditions to consider in the differential diagnosis include alpha-1 antitrypsin deficiency panniculitis, lupus panniculitis, cutaneous polyarteritis nodosa, superficial thrombophlebitis , and erythema induratum.

    Clinical Course

    EN typically presents as multiple, tender, bright red, 1 to 20 cm in diameter,  poorly demarcated nodules on the shins (usually bilateral). The eruption may also involve the extensor aspects of the thighs and forearms. Over the course of 2 weeks the the lesions  change in color to a bluish hue, and then fade to resemble a bruise. Ulceration and scarring does not normally occur. Ankle swelling and joint pain are common and usually resolve within a few weeks. However,  joint pain has been reported to persist for up to 2 years [4]. Pulmonary hilar adenopathy may also develop.

    Prodromal symptoms of fatigue and malaise or upper respiratory tract infection often precede the eruption by 1 to 3 weeks. In a study by Metz and coworkers patients with fever, leukocytosis, elevated CRP level ( 6 X upper limits), accelerated ESR, presence of cough, sore throat, diarrhea, arthritis, and pulmonary pathology  were more likely to have EN secondary to an identifiable cause [2].

    EN is characteristically self limited and resolves on its own in 3 to 6 weeks. Adverse effects upon the course of pregnancy or fetal outcome would not be expected in idiopathic cases [8]. Underlying causes of EN that might result in increased morbidity or mortality in the mother or fetus should be excluded.

    Treatment [1,12,17,18]

    Treatment of EN is aimed at the underlying disease or removal of the offending drug when identified. Otherwise treatment during pregnancy is supportive and includes cool wet compresses, elevation, and rest.  Acetaminophen may be used for pain relief, but nonsteroidal anti-inflammatory drugs (NSAIDs) are avoided because of their potential to cause oligohydramnios and constriction  of the ductus arteriosus.

    Systemic steroids at a dosage of 1 mg per kg daily may be used for more persistent complaints if underlying infection, risk of sepsis, and malignancy have been excluded. Oral prednisone at a dosage of 60 mg every morning is a typical dose.


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    Am Fam Physician. 2007 Mar 1;75(5):695-700.PMID: 17375516
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    14. Mert A, Ozaras R, Tabak F, Ozturk R. Primary tuberculosis cases presenting with erythema nodosum. J Dermatol. Jan 2004;31(1):66-8.PMID: 14739509
    15. Farhi D, Cosnes J, Zizi N, et al. Significance of erythema nodosum and pyoderma gangrenosum in inflammatory bowel diseases: a cohort study of 2402 patients. Medicine (Baltimore). Sep 2008;87(5):281-93. PMID: 18794711
    16. Sullivan R, Clowers-Webb H, Davis MD. Erythema nodosum: a presenting sign of acute myelogenous leukemia. Cutis. Aug 2005;76(2):114-6PMID:16209157
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