Tumour necrosis factor-alpha promoter polymorphism in erythema nodosum

Erythema nodosum is a common skin disease characterized by erythematous, te nder subcutaneous nodules, mostly located on the lower extremities, Little is known about its pathogenesis, although a wide variety of aetiological fa ctors (e.g. bacterial and viral infections, neoplastic diseases and drugs) have been described. Sarcoidosis, a typical granulomatous disease, often oc curs in association with erythema nodosum (Loefgren syndrome). Since granul omatous diseases have been closely linked to a deregulated tumour necrosis factor (TNF)-alpha production, it was tempting to speculate whether TNF-alp ha might play a role in the pathogenesis of erythema nodosum, at least in c ases associated with sarcoidosis. A previously described nucleotide exchang e, (G -->A) at position -308 in the human TNF-alpha gene promoter, has been shown to be a major cause for enhanced TNF-alpha production. In the presen t report, we investigated the genomic TNF-alpha promoter region in patients suffering from EN with and without underlying sarcoidosis. Our results sho wed a strong correlation between the uncommon TNF A II allele and sarcoidos is-associated erythema nodosum, Patients with erythema nodosum without unde rlying sarcoidosis displayed a similar allele frequency compared with contr ols. Taken together, we provide evidence that erythema nodosum in associati on with sarcoidosis might be pathogenically linked to altered TNF-alpha pro duction due to a genetic promoter polymorphism.