Erythema nodosum

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]

Overview

Erythema nodosum (EN) (red nodules) is an inflammation of the fat cells under the skin (panniculitis). It causes tender, red nodules that are usually seen on both shins. EN is an immunologic response to a variety of different causes.

Historical Perspective

Classification

Pathophysiology

Causes

In about 30-50% of cases, the cause of EN is unknown.[1] EN may be associated with a wide variety of diseases, including infections (e.g., tuberculosis, streptococcal, Mycoplasma pneumoniae, and Epstein-Barr virus), sarcoidosis, inflammatory bowel disease, autoimmune disorders (e.g., Behçet's disease), pregnancy, medications (sulfonamides, clomiphene, oral contraceptives (Desogestrel and Ethinyl Estradiol), bromides, certolizumab pegol, dapsone), and cancer.[1][2][3][4]

Differentiating Erythema nodosum from Other Diseases

Erythema nodosum is indicative of an underlying infectious disease but a cause is not found in about half the cases.

Epidemiology and Demographics

Erythema nodosum is the most common form of panniculitis (inflammation of the subcutaneous fat). The prevalence is 24 cases per 100,000 per year. The peak incidence of EN occurs between 20-30 years of age. Women are 3-6 times more commonly affected than men[5].

Age

Gender

Race

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Criteria

Diagnosis is clinical. A deep punch biopsy or an incisional biopsy may be performed in cases where the diagnosis is unclear. Microscopic examination will reveal a septal panniculitis with acute and chronic inflammation in the fat and around blood vessels[5].

Once EN is diagnosed, additional evaluation needs to be performed to determine the underlying cause. A complete blood count, erythrocyte sedimentation rate (ESR), antistreptolysin-O (ASO) titer, urinalysis, throat culture, intradermal tuberculin test, and chest x-ray is part of the initial examination.[6]

The ESR is initially very high, and falls as the nodules fade. 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. Hilar lymphadenopathy may be due to tuberculosis, sarcoidosis, or Löfgren syndrome (a form of acute sarcoidosis with erythema nodosum , parotid swelling and bilateral hilar adenopathy, often accompanied by joint symptoms).

Symptoms

Erythema nodosum occurs 3-6 weeks after an event, either internal or external to the body, that initiates a hypersensitivity reaction in subcutaneous fat [7][8]. EN is frequently associated with fever, malaise, arthralgia, and joint pain and inflammation. It presents as tender red nodules on the shins that are smooth and shiny. The nodules may occur anywhere there is fat under the skin, including the thighs, arms, trunk, face, and neck [9][10]. The nodules are 1-5 cm in diameter, and individual nodules may coalesce to form large areas of hardened skin.

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[5].

Dermatophytids are similar skin lesions that result from a fungus infection such as ringworm in another area of the body.

Physical Examination

Skin

Extremities
  • Lesions begin as red, tender nodules. The borders are poorly defined and they are 2 to 6 cms in diameter
  • In the first week the lesions become tense, hard, and painful. In the second week, they may become fluctuant, rather like an abscess, but they do not suppurate or ulcerate. Individual lesions last around 2 weeks, but occasionally, new lesions continue to appear for 3 to 6 weeks.
  • Initially, in the first week the lesions are bright red but in the second week they assume a more blue or purple hue.
  • The lesions may eventually even turn yellow like a bruise which is resolving before they disappear in a several weeks.
  • Usually the rash appears on the extremities, but most frequently they occur on the anterior aspect of the lower leg.
  • When the underlying cause is an infection, the lesions usually heal in 6 to 8 weeks.
  • If the cause is idiopathic, 30% of cases last 6 months.

Laboratory Findings

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

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).[5] NSAIDS are usually more effective at the onset of EN versus with chronic disease. Steroids can be of benefit but may be contraindicated if infection is present. In erythema nodosum associated with leprosy, thalidomide may be helpful.

Potassium iodide can be used for persistent lesions whose cause remains unknown. Corticosteroids and colchicine can be used in severe refractory cases (Yurdakul et al, 2001).[13][14][15]

Surgery

Prevention

References

  1. 1.0 1.1 Mert A, Ozaras R, Tabak F, Pekmezci S, Demirkesen C, Ozturk R (2004). "Erythema nodosum: an experience of 10 years". Scand J Infect Dis. 36 (6-7): 424–7. PMID 15307561. 
  2. Anan T, Imamura T, Yokoyama S, Fujiwara S (2004). "Erythema nodosum and granulomatous lesions preceding acute myelomonocytic leukemia". J Dermatol. 31 (9): 741–7. PMID 15628321. 
  3. Bohn S, Buchner S, Itin P (1997). "[Erythema nodosum: 112 cases. Epidemiology, clinical aspects and histopathology]". Schweiz Med Wochenschr. 127 (27-28): 1168–76. PMID 9324739. 
  4. Lin JT, Chen PM, Huang DF, Kwang WK, Lo K, Wang WS (2004). "Erythema nodosum associated with carcinoid tumour". Clin Exp Dermatol. 29 (4): 426–7. PMID 15245549. 
  5. 5.0 5.1 5.2 5.3 Wolff K, Johnson RA, Suurmond R (2005). "Section 7: Miscellaneous inflammatory disorders". Fitzpatrick's Color Atlas & Synopsis of Clinical Dermatology (5th ed. ed.). New York, NY: McGraw-Hill Professional. ISBN 0-07-144019-4. 
  6. Garcia-Porrua C, Gonzalez-Gay MA, Vazquez-Caruncho M, Lopez-Lazaro L, Lueiro M, Fernandez ML, Alvarez-Ferreira J, Pujol RM (2000). "Erythema nodosum: etiologic and predictive factors in a defined population". Arthritis Rheum. 43 (3): 584–92. PMID 10728752. 
  7. Ryan TJ (1998). "Cutaneous vasculitis". In Burns DA, Breathnach SM. Textbook of Dermatology (6th ed. ed.). London: Blackwell Science Ltd. pp. 2155–225. ISBN 0-632-05064-0. 
  8. Camilleri MJ, Su WPD (2003). "Panniculitis". In Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI. Fitzpatrick's Dermatology In General Medicine (6th ed. ed.). New York, NY: McGraw-Hill. ISBN 0-07-138076-0. 
  9. Cribier B, Caille A, Heid E, Grosshans E (1998). "Erythema nodosum and associated diseases. A study of 129 cases". Int J Dermatol. 37 (9): 667–72. PMID 9762816. 
  10. White WL, Hitchcock MG (1999). "Diagnosis: erythema nodosum or not?". Semin Cutan Med Surg. 18 (1): 47–55. PMID 10188842. 
  11. http://picasaweb.google.com/mcmumbi/USMLEIIImages
  12. 12.0 12.1 12.2 12.3 12.4 12.5 "Dermatology Atlas". 
  13. Mat C, Yurdakul S, Uysal S, Gogus F, Ozyazgan Y, Uysal O, Fresko I, Yazici H (2005). "A double-blind trial of depot corticosteroids in Behcet's syndrome". Rheumatology (Oxford). PMID 16263779. 
  14. Wallace SL (1967). "Erythema nodosum treatment with colchicine". JAMA. 202 (11): 1056. PMID 6072607. 
  15. Yurdakul S, Mat C, Tuzun Y, Ozyazgan Y, Hamuryudan V, Uysal O, Senocak M, Yazici H (2001). "A double-blind trial of colchicine in Behcet's syndrome". Arthritis Rheum. 44 (11): 2686–92. PMID 11710724. 

Additional Resource

  • Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:131-132 ISBN 1591032016

External Links

  • [3] Erythema Nodosum Support Group Website
  • [4] Erythema Nodosum Yahoo Support Group


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