Double-blind trial of the efficacy of pentoxifylline vs thalidomide for the treatment of type II reaction in leprosy

Abstract

Type II reaction in leprosy, or erythema nodosum leprosum (ENL), is often characterized by severe clinical symptoms together with nerve function impairment leading to permanent disabilities. Thalidomide has been shown to be a highly effective drug for the treatment of ENL. It is, however, contraindicated for women of childbearing age due to its teratogenicity. On the other hand, pentoxifylline, used to treat hypercoagulable states, is not teratogenic and, like thalidomide, can inhibit the synthesis of tumor necrosis factor-α and other cytokines. In the present randomized double-blind clinical study we compared the effectiveness of orally administered pentoxifylline vs thalidomide in treating type II reaction in 44 patients. Daily doses of 300 mg thalidomide or 1.2 g pentoxifylline were administered for 30 days to multibacillary leprosy patients undergoing type II reaction. Randomly chosen patients were included in the study before, during, and after specific multidrug therapy. Clinical evaluations were performed on the 1st, 7th, 14th, 21st, and 30th days of treatment and laboratory tests were carried out on the 1st and 30th days. As expected, overall, thalidomide proved to be more effective in the treatment of type II leprosy reaction. Nevertheless, continuous treatment with pentoxifylline was effective in relieving the clinical signs of ENL, especially limb edema and systemic symptoms, in 62.5% of the patients.

Comparative efficacy of thalidomide and prednisolone in the treatment of moderate to severe erythema nodosum leprosum: A randomized study

“…However, continuous treatment with pentoxifylline relieved clinical signs of ENL, particularly limb oedema and systemic symptoms, in the majority of patients. 14 The starting dose and duration of thalidomide in treating ENL have always been areas of uncertainty. We chose 300 mg as the starting dose and a slow reduction of 50 mg every 2 weeks, based on previous studies that have found that a slow reduction in the 300 mg dose over a 6-week period resulted in a significantly better response for ENL.…”

Clinical, immunological, and genetic aspects in leprosy

“…Therefore, there is a predominance of ENL in patients classified as having the lepromatous pole (LL, BL), and it is more common in patients with a high bacillary index. Although ENL tends to occur during treatment, commonly later during MDT (after the sixth month of chemotherapy), there are reports of ENL either preceding diagnosis or emerging only after the completion of MDT [Feuth et al, 2008;Kahawita and Lockwood, 2008;Sales et al, 2007;Saunderson et al, 2000;Shen et al, 2009;Teixeira et al, 2010;Walker et al, 2007]. Penna and colleagues [2008], in a study that included 1,124 leprosy patients from a state in Brazil, documented 328 (29.3%) leprosy reactions, and ENL was the most commonly observed (192 from 328 cases, 58.5%).…”

Leprosy type 1 reactions and erythema nodosum leprosum

“…48 Prospective clinical trials have shown that treatment with thalidomide has a quicker action of onset and reduces the number of skin lesions, fever and systemic symptoms better than pentoxifylline, aspirin and placebo. [49][50][51][52] Treatment with thalidomide has also been shown to reduce the prednisolone requirement of patients with chronic ENL. 53 We suggest using a starting dose of 400mg thalidomide at night in severe ENL and to reduce the dose to 300mg as soon as possible.…”

“…The pentoxifylline was also less well tolerated. 49 Colchicine and chloroquine have been evaluated in small studies and their effect was marginal. There are case reports and case series on the use azathioprine, 63 methotrexate, 64 oral zinc, 65 and the chimeric anti-TNF monoclonal antibody, infliximab, 66 for the treatment of ENL.…”