Erythema nodosum

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.

Epidemiology
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.

Causes
In about 30-50% of cases, the cause of EN is unknown. 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, oral contraceptives, bromides), and cancer.

Clinical manifestations
Erythema nodosum occurs 3-6 weeks after an event, either internal or external to the body, that initiates a hypersensitivity reaction in subcutaneous fat. 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. 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.

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

Skin

 * 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.

Diagnosis
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.

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.

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).

Differential Diagnosis
E. Nodosum is indicative of an underlying infectious disease but a cause is not found in about half the cases.


 * Behcet's Syndrome
 * Brucellosis
 * Campylobacter
 * Cat-Scratch Fever
 * Chlamydia
 * Coccidioidomycosisimportant in the south-west USA
 * Corynebacterium diphtheria
 * Crohn's Disease
 * Dermatophytosis
 * Drugs such as sulphonylureas, gold and oral contraceptives
 * Francisella tularensis
 * Hepatitis
 * Herpes simplex
 * Histoplasmosis
 * Hodgkin's Lymphoma can precede the diagnosis
 * Hookworm infection
 * Infectious mononucleosis
 * Leprosymay closely resemble erythema nodosum but the histological findings are different
 * Leptospirosis
 * Leukemia
 * Milker's nodule
 * Mycobacterium
 * Mycoplasma pneumoniae
 * Neisseria Meningitidis
 * North American Blastomycosis
 * Postradiated pelvic cancer
 * Pregnancy usually in the second trimester. Often recurs during future pregnancies and may occur with oral contraceptive uses
 * Radiation therapy
 * Reiter's Disease
 * Salmonella
 * Sarcoidosis
 * Sporotrichosis
 * Streptococcal infections are one of the most common causes
 * Toxoplasmosis
 * Tuberculosis
 * Ulcerative colitis
 * Yersinia

Treatment
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). 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).

Additional Resource

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