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Erythema nodosum

Original article (1997) updated by: Ardalan Akbari, Medical Student, Faculty of Medicine, University of British Columbia, Vancouver, Canada. DermNet NZ Editor in Chief: Adjunct Assoc. Prof. Amanda Oakley, Dermatologist, Hamilton, New Zealand. October 2019.


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What is erythema nodosum?

Erythema nodosum is a type of panniculitis, an inflammatory disorder affecting subcutaneous fat. It presents as tender red nodules on the anterior shins. Less commonly, they affect the thighs and forearms [1–3].

Erythema nodosum

See more images of erythema nodosum.

Who gets erythema nodosum?

Erythema nodosum can occur in all ethnicities, sexes, and ages, but is most common in women between the ages of 25 and 40 [4]. It is 3–6 times more common in women than in men except before puberty when the incidence is the same in both sexes [5].

What are the causes of erythema nodosum?

Erythema nodosum is a hypersensitivity reaction of unknown cause in up to 55% of patients [6]. In other cases, it is associated with an identified infection, drug, inflammatory condition, or malignancy [7].

Other viral and bacterial diseases associated with erythema nodosum include herpes simplex, viral hepatitis, human immunodeficiency virus (HIV) infection, Campylobacter infection, and Salmonella infection.

Drugs (3–10%)

Inflammatory

Others

What are the clinical features of erythema nodosum?

Erythema nodosum presents with tender bilateral erythematous subcutaneous nodules 3–20 cm in diameter erupting over one to several weeks. They are accompanied by fever and joint pain. In 50% the ankle is swollen and painful for up to several weeks. The knees and other joints can also be affected [8].

Common clinical findings [9-12]

  • The nodules are found on the anterior lower legs, knees and arms and rarely on the face and neck.
  • They are ill-defined, warm, oval, round or arciform, and without ulceration
  • The nodules are initially bright to deep red. 
  • They spontaneously resolve within eight weeks, through a violaceous, brownish, or yellowish/green bruise-like appearance known as erythema contusiformis.

Erythema nodosum does not cause permanent scarring.

What are the complications of erythema nodosum?

Erythema nodosum has few known complications and lesions usually resolve spontaneously. A rare complication is encapsulated fat necrosis, or ‘mobile encapsulated lipoma’ [14].

How is erythema nodosum diagnosed?

Erythema nodosum is primarily a clinical diagnosis confirmed by laboratory tests and histopathology [8]. The pathology of erythema nodosum shows inflammation primarily of the septa between the subcutaneous fat lobules without vasculitis [15].

Supporting investigations [4,7]

Appropriate tests may include:

  • Complete blood count with differential, C-reactive protein levels (infectious and inflammatory causes)
  • Chest X-ray (tuberculosis and sarcoidosis)
  • Throat swab and anti-streptolysin O and streptodornase serology (streptococcal infection)
  • Viral serology (preferably two samples at four-week intervals)
  • Stool culture and evaluation for ova and parasites in patients with gastrointestinal symptoms
  • Mantoux test or QuantiFERON gold (tests for TB).
  • Deep incisional or excisional skin biopsy.

What is the differential diagnosis for erythema nodosum?

A range of causes of panniculitis should be considered in a patient with subcutaneous nodules, especially if lesions are not located on the legs, there is ulceration, or symptoms last longer than eight weeks.

Panniculitis can be predominantly septal (inflammation between lobules) or lobular (inflammatory cells within subcutaneous fat lobules) [16]. Mixed septal and lobular inflammation can occur.

Nodules due to predominantly septal panniculitis include:

Nodules due to predominantly lobular panniculitis include:

What is the treatment for erythema nodosum?

Erythema nodosum is treated based on the underlying disease. An underlying infection should be treated.

What is the outcome for erythema nodosum?

Erythema nodosum follows a relatively benign and favourable course. It is important to recognise the underlying cause, if any, and initiate symptomatic treatment [4]. Most cases resolve within days to weeks. Relapses may occur in approximately one-third of cases erythema nodosum may become a chronic or persistent disorder lasting for 6 months and occasionally for years [13].

 

References

  1. Cox NH, Jorizzo JL, Bourke JF, Savage COS. Vasculitis, neutrophilic dermatoses and related disorders. In: Rook’s Textbook of Dermatology. 8th edn. Burns T, Breathnach S, Cox N, Griffiths C (eds). Wiley-Blackwell, Hoboken 2010: Vol 3, 50.1.
  2. Patterson JW. Panniculitis. In: Dermatology. 3rd edn. Bolognia JL, Jorizzo JL, Schaffer JV (eds). Elsevier Saunders, Philadelphia 2012: 1641.
  3. Kunz, Beutel, Bröcker. Leucocyte activation in erythema nodosum. Clin Exp Dermatol 1999;24:396-401. PubMed 
  4. Hafsi W, Haseer Koya H. Erythema, Nodosum. StatPearls Publishing. Updated 12 December 2017. Available at: https://www.ncbi.nlm.nih.gov/books/NBK470369/ (accessed 27 June 2018).
  5. R.M. Söderstrom, E.A. Krull. Erythema nodosum. A review. Cutis 1978;21(6)806-10. PubMed
  6. Cribier B, Caille A, Heid E, Grosshans E. Erythema nodosum and associated diseases. A study of 129 cases. Int J Dermatol 1998;37:667–72. PubMed
  7. Schwartz RA, Nervi SJ. Erythema nodosum: a sign of systemic disease. Am Fam Physician 2007;75:695. PubMed
  8. L Requena et al, in K, Wolff et al (eds): Fitzpatrick's Color Atlas and Synopsis of Clinical Dermatology, 6th edn. New York: McGraw-Hill, 2009, 152-3.
  9. Fox MD, Schwartz RA. Erythema nodosum. Am Fam Physician 1992;46:818–22. PubMed 
  10. Kakourou T, Drosatou P, Psychou F, Aroni K, Nicolaidou P. Erythema nodosum in children: a prospective study. J Am Acad Dermatol 2001;44:17–21. PubMed 
  11. Requena L, Yus ES. Panniculitis. Part I. Mostly septal panniculitis. J Am Acad Dermatol 2001;45:163–83. PubMed
  12. Mert A, Ozaras R, Tabak F, Pekmezci S, Demirkesen C, Ozturk R. Erythema nodosum: an experience of 10 years. Scand J Infect Dis 2004;36:424–7. PubMed
  13. Patterson JW. Panniculitis. In: Dermatology, 3rd ed, Bolognia JL, Jorizzo JL, Schaffer JV (eds), Elsevier Saunders, Philadelphia 2012:1641.
  14. Weedon D. Panniculitis. In Weedon's Skin Pathology (Third Edition). Churchill Livingstone, 2010: 477. Available at: http://www.sciencedirect.com/science/article/pii/B9780702034855000188 (accessed 20 June 2018).
  15. Baldock NE, Catterall MD. Erythema nodosum from Yersinia enterocolitica. Br J Dermatol 1975;93:719–20. Journal
  16. Pink A, Barker J. Erythema nodosum. Br J Hosp Med 2012;73:C50-C52. Journal
  17. Marshall JK, Irvine EJ. Successful therapy of refractory erythema nodosum associated with Crohn's disease using potassium iodide. Can J Gastroenterol 1997;11:501–2. PubMed 

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