The role of thalidomide in the management of erythema nodosum leprosum.

Erythema nodosum leprosum (ENL, Type 2 reactions) complicates lepromatous and borderline lepromatous leprosy and can affect many organ systems, often with irreversible damage. The reactions commonly occur in the 2 years after starting treatment and often run a recurrent or chronic course, sometimes for many years. Even with WHO multi-drug therapy about 30% of LL patients experience ENL. We review drug management of ENL focussing on data from controlled trials and other studies. The treatment of ENL is difficult because high doses of steroids may be required for prolonged periods and do not always control the inflammation. The paradox of ENL is that it can be a life-threatening disorder and requires control with immunosuppression which may itself pose life-threatening risks for patients. Treatment with thalidomide provides an effective alternative to steroid therapy, gives better long-term control and avoids the adverse effects of prolonged steroid therapy. Controlled clinical trials have demonstrated that thalidomide rapidly controls ENL and is superior to aspirin and pentoxifylline. However, thalidomide is teratogenic when taken in early pregnancy and is unavailable in many leprosy endemic countries. We discuss the role of thalidomide in treating ENL, the complications encountered and risk reduction strategies that can be used. These include good patient selection and counselling, close supervision and adequate access to appropriate contraception. Further research is needed to improve the understanding and treatment of this severe and debilitating complication of leprosy. Topics for research include: i. The development of validated tools to measure the severity and/or activity of ENL. ii. A detailed assessment of the neurotoxic effects of thalidomide when used to treat ENL. iii. A well designed trial comparing thalidomide with prednisolone. iv. The development of a safe and effective alternative to both steroids and thalidomide.

Pentoxifylline in the treatment of erythema nodosum leprosum.

Erythema nodosum leprosum (ENL) is a well-known serious complication affecting 10% of lepromatous multibacillary leprosy patients. In the chronic form, its morbidity may be considerable. Thalidomide and systemic steroids are the two current effective drugs for the management of ENL. However, their use in endemic countries is often difficult and hazardous, and a search for new therapies is needed. We report our experience on the effects of pentoxifylline, a methylxanthine derivative, which has recently been suggested as a possible effective treatment for ENL attacks.

Pentoxifylline in the treatment of erythema nodosum leprosum

Erythema nodosum leprosum (ENL) is a well-known serious complication affecting 10 per cent of lepromatous multibacillary leprosy patients. In the chronic form, its morbidity may be considerable. Thalidomide and systemic steroids are the two current effective drugs for the management of ENL. However, their use in endemic countries is often difficult and hazardous, and a search for new therapies is needed. We report our experience on the effects of pentoxifylline, a methylxanthine derivative, which has recently been suggested as a possible effective treatment for ENL attacks.

[Pentoxifylline in the treatment of erythema nodosum leprosum: results of an open study]. / Efficacité de la pentoxifylline dans le traitement de l'érythème noueux lépreux: résultats d'une étude ouverte.

Erythema nodosum leprosum (ENL) is a well-known immunological serious complication affecting lepromatous multibacillary leprosy patients. For a long time, ENL has been regarded as an immune complex-mediated disease or Arthus phenomenon. Recently, it has been reported that ENL was associated with high serum tumor necrosis factor-alpha (TNFa) levels, suggesting that this cytokine could also play a central role in the manifestations of ENL. Thalidomide (TH) and systemic steroids (S), both TNFa production inhibitors, are the two current effective drugs for the management of ENL. However, TH is rarely available in leprosy endemic countries, and its teratogenicity and neurotoxicity strongly limit its use. Moreover, the morbidity of S and the frequent steroid-dependence of ENL also create real therapeutic problems. Recently, the efficacy of pentoxifylline (PTX), which also inhibits in vitro and in vivo production of TNFa, has been suggested for ENL treatment. We report our experience on its use for the treatment of 15 leprosy patients suffering from a first ENL. attack. (11 cases), a chronic steroid-dependent ENL (3 cases) or chronic steroid- and thalidomide-dependent ENL (1 case). PTX has been given at 800 mg t.i.d, (2 cases) or 400 mg t.i.d. (13 cases) doses. The patients received PTX at the initiating dosage until complete clinical cure. At the end of ENL attacks, PTX was either abruptly stopped or tapered down over the next 4 months. In ten of 11 patients who developed ENL for the first time, the systemic symptoms and neuritic pains disappeared within one week; at three weeks, half of the patients were cured and the other half had striking clinical improvement; complete cure was obtained within 7 to 35 days (mean: 27 days). A relapse occurred within 2-3 months in the 5 patients, in which PTX was abruptly stopped. In contrast, no relapse occurred in the patients who benefited from decreasing doses of PTX. Recurrent ENL episodes also responded well to PTX. The 3 patients who had chronic steroid-dependent ENL failed to show any improvement after 3 to 6 weeks of PTX. In contrast, steroid therapy could be stopped in the steroid- and thalidomide-dependent patient. Our results confirm the action of PTX if it is slowly tapered down (4 months seem sufficient) and not abruptly to avoid relapses. As it is safe use, PTX could constitute the first line of ENL attack treatment.

A new therapeutic approach to type II leprosy reaction.

BACKGROUND: An increase in tumor necrosis factor (TNF) has been implicated in type II leprosy reaction. Thalidomide, which inhibits TNF, is an effective drug, but has severe side-effects in pregnant women. Other therapeutic drugs are required. METHODS: Clofazimine and pentoxifylline were evaluated for their efficacy against severe type II leprosy reaction in four patients (three men and one woman). RESULTS: All four patients showed a similar fast response to treatment. CONCLUSIONS: The results obtained in this study are promising; however, clofazimine and pentoxifylline must be evaluated in a larger group of patients in order to determine their value in controlling type II leprosy reaction.