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New Treatments for Erythema Nodosum 

Erythema nodosum (EN) is a nodular erythematous eruption that is usually limited to the extensor aspects of the extremities. EN represents a hypersensitivity reaction to a variety of antigenic stimuli and may be observed in association with several diseases (infections, immunopathies, malignancies) and during drug therapy (with halides, sulfonamides, oral contraceptives). Approximately 50% of cases are idiopathic. The clinical picture is that of a nonspecific systemic illness.

Clinical manifestations and course.

Prodromal symptoms of fatigue and malaise or symptoms of an upper respiratory infection precede the eruption by 1 to 3 weeks.

Arthralgia occurs in more than 50% of patients and begins during the eruptive phase or precedes the eruption by 2 to 8 weeks. Symptoms may disappear in a few weeks or persist for 2 years, but they always resolve without destructive joint changes. The rheumatoid factor is negative. Joint symptoms consist of erythema, swelling, and tenderness over the joint, sometimes with effusions; arthralgia and morning stiffness, most commonly in the knee, but any joint may be affected.

The eruptive phase begins with flulike symptoms of fever and generalized aching. The characteristic lesions begin as red, nodelike swellings over the shins; as a rule, both legs are affected. Similar lesions may appear on the extensor aspects of the forearms, thighs, and trunk. The border is poorly defined, with size varying from 2 to 6 cm. Lesions are oval.

Pathogenesis and etiology.

Erythema nodosum is probably a delayed hypersensitivity reaction to a variety of antigens; circulating immune complexes have not been found in idiopathic or uncomplicated cases. EN is a reaction pattern elicited by many different diseases. In one large series, 32.5% of cases were idiopathic. The most common cause today is streptococcal infection and tuberculosis in children and streptococcal infection and sarcoidosis in adults.

Coccidioidomycosis (San Joaquin Valley fever) is the most common cause of EN in the west and southwest United States. In approximately 4% of males and 10% of females, the primary fungal infection, which may be asymptomatic or involve symptoms of an upper respiratory infection, is followed by the development of EN. The lesions appear when the skin-test result becomes positive, 3 days to 3 weeks after the end of the fever caused by the fungal infection.

Histoplasmosis, blastomycosis, and lymphogranuloma venereum may cause EN. Leprosy is another possible inciting factor. Clinically, erythema nodosum leprosum resembles EN, but the histologic picture is that of leukocytoclastic vasculitis.

Inflammatory bowel diseases such as ulcerative colitis and regional ileitis may trigger EN, usually during active disease with symptoms of abdominal complaints and diarrhea.

Sulfonamides, bromides, and oral contraceptives have been reported to cause EN. Several other drugs, such as antibiotics, barbiturates, and salicylates, are often suspected but seldom proved causes of EN.

EN occurs in up to 39% of cases of sarcoidosis and has also been observed in pregnant women.

EN should be considered as a warning signal of impending relapse in a patient with a history of Hodgkin's disease.

Dental treatment and the possible presence of infectious dental foci should be considered in the differential diagnosis. EN is reported following dental treatment associated with gingival bleeding or due to infectious dental foci.

Sweet's syndrome (acute febrile neutrophilic dermatosis) and EN are both reactive dermatoses. There are several associated conditions that these disorders have in common. The appearance of both conditions in the same patient has been reported.