Erythema nodosum (EN) is an acute inflammatory reaction of the subcutaneous fat. It is considered a delayed hypersensitivity reaction to various antigenic stimuli.

EN is three times more common in females than in males and has a peak incidence between 20 and 30 years of age.

Sarcoidosis (see below), streptococcal infections, pregnancy, and the use of oral contraceptives are the most common causes of EN in the United States.

In children, streptococcal pharyngitis is the most likely underlying cause.

Approximately 40% of cases are idiopathic.

In addition to sarcoidosis and pregnancy, EN is associated with a variety of conditions: deep fungal infections (in endemic areas), including coccidioidomycosis, histoplasmosis, and blastomycosis; tuberculosis; Yersinia enterocolitica infection; inflammatory bowel disease, including ulcerative colitis and Crohn disease; malignant disease, including lymphoma and leukemia; radiation therapy; and Behçet syndrome. Drugs such as sulfonamides, penicillin, gold, amiodarone, and opiates also have been implicated as causes of EN.

Lesions begin as bright red, deep, extremely tender nodules (Fig. 34.37).

During resolution, lesions become dark brown, violaceous, or bruiselike macules (“contusiform”) (Fig. 34.38).

EN tends to occur in a bilateral distribution on the anterior shins, thighs, knees, and arms.

Malaise, fever, arthralgias, and periarticular swelling of the knees and ankles may accompany the panniculitis.

Other symptoms may also be present, depending on the cause of EN.

Spontaneous resolution of lesions occurs in 3 to 6 weeks, regardless of the underlying cause.

Generally, EN indicates a better prognosis in patients who have sarcoidosis.

The diagnosis of EN is usually made on clinical grounds, but a biopsy may be helpful for confirmation.

Usually, a complete blood count, erythrocyte sedimentation rate, throat culture, antistreptolysin titer, purified protein derivative skin test (PPD), and chest film are all that are necessary.

If indicated, an excisional skin biopsy will show panniculitis with infiltration of lymphocytes in the septa of the fat.

Additional tests, such as gastrointestinal tract evaluation and serum angiotensin-converting enzyme determination, can be performed if suggested by the review of systems and physical examination.