Differential diagnoses: insect bites, erysipelas, erythema induratum (nodular vasculitis), urticaria, thrombophlebitis.

In the large majority of cases, which exhibit typical EN, there is no indication to perform a skin biopsy. The dermatological diagnosis is based on clinical features. However, in very few atypical cases of unusual presentation, a skin biopsy can be performed to rule out other diagnoses. Histopathologically, erythema nodosum is a septal panniculitis (Fig. 3.2a), which is characterised by inflammation of fibrous septa between fat lobules variably spreading into the lobules, septa being thickened [2, 3]. Inflammatory cells often extend to the periseptal areas of the fat lobules. Direct immunofluorescence studies have shown deposits of immunoglobulins in the blood vessel walls of the septa of subcutaneous fat. At early stages, lymphocytes and macrophages dominate but neutrophils are often present (Fig. 3.2b). Oedema, fibrin deposition and foci of vasculitis may also be seen; at later stages, fibrosis dominates (Fig. 3.2c). In some cases, giant cells may be present, located around clefts in collagen. Miescher’s granuloma is unconstant but prototypical of EN and is formed by more or less radially arranged macrophages, often around cleft-like defects of septal collagen.

Some series have reported the characteristic of EN patients seen in rheumatology (Table 3.1). A series from Greece included 110 patients (83 % women, mean age 41.0 ± 14.0 years) [4]. Sarcoidosis was diagnosed in 28 % of the patients, infections in 17.3 % and tuberculosis in 1.5 %. Other aetiologic factors were Adamantiadis-Behçet’s syndrome (3.8 %), pregnancy (6 %), oral contraceptives (3.8 %) and other drugs (3.8 %). The aetiology of EN was not found in 35 % of the patients. Among 100 Turkish patients [2], the leading aetiology was poststreptococcal (11 %), followed by primary tuberculosis (10 %), sarcoidosis (10 %), Behçet’s syndrome (6 %), drugs (5 %), inflammatory bowel diseases (IBD) (3 %) and pregnancy (2 %), but nearly half (53 %) of the cases had undetermined aetiology. Recurrences occurred in patients having primary EN in 62 % (33/53) of patients. The outcomes were usually favourable within 7 days, patients being at bed rest and receiving nonsteroidal anti-inflammatory drugs, together with specific treatment for patients with an underlying disease.