Erythema nodosum usually resolves itself 3 to 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, 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 1-10 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 to 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. 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 , bilateral hilar adenopathy, fever and often accompanied by joint symptoms). Erythema nodosum is the most common form of panniculitis (inflammation of the subcutaneous fat). The peak incidence of EN occurs between 20 to 30 years of age. Women are 3-6 times more commonly affected than men. 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, Yersinia, and Epstein-Barr virus), coccidioides immitis, sarcoidosis, autoimmune disorders (e.g., Inflammatory bowel disease or Behçet's disease), pregnancy, medications (sulfonamides, oral contraceptives, bromides), and cancer. EN may also be due to excessive antibody production in lepromatous leprosy leading to deposition of immune complexes. There is an association with the HLA-B27 histocompatibility antigen, which is present in 65% of patients with erythma nodosum. 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. Potassium iodide can be used for persistent lesions whose cause remains unknown. Corticosteroids and colchicine can be used in severe refractory cases. Thalidomide has been used successfully in the treatment of Erythema nodosum leprosum, and it was approved by the U.S. FDA for this use in July of 1998. Source: Wiki.