Erythema nodosum leprosum (ENL) is characterized by the appearance of crops of painful, erythematous, sub-cutaneous nodules not related to former leprosy lesions. Systemic manifestations of pyrexia, malaise, lymphadenopathy, neuritis, arthralgia, and weight loss are often observed. ENL occurs in approximately 40% of multibacillary leprosy patients within the first year of chemotherapy. Thalidomide is the drug of choice for the management of ENL. We have recently suggested that the inflammatory cytokine tumor necrosis factor alpha (TNF- ) plays a significant role in the pathogenesis of ENL. We have shown that TNF- is elevated in the sera of ENL patients, and thalidomide reduces serum levels of TNF- in ENL patients, as well as TNF- production by peripheral blood mononuclear cells in vitro. Since thalidomide is a known teratogenic drug its use is limited and it can not be used safely in women of child-bearing age. Glucocorticoids are the current available treatment for ENL, in substitution of thalidomide. Its use in ENL is not very effective if compared to thalidomide, and the drug is associated with toxicities such as immunosuppression. We will test whether pentoxifylline (Trental), another known inhibitor of TNF- production, is effective in alleviating the symptoms of ENL. This will enable us to evaluate an alternative drug for the management of ENL. This protocol will also enable us to further characterize the role of TNF- in the pathophysiology of ENL.
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