Treatment with corticosteroids of long-standing nerve function impairment in leprosy: a randomized controlled trial (TRIPOD 3). The prognostic importance of detecting mild sensory impairment in leprosy: a randomized controlled trial (TRIPOD 2). Corticosteroid treatment of childhood Bell's palsy.
Some leprosy patients with long-standing nerve function impairment (NFI) appear to have responded favourably to treatment with corticosteroids. This study investigated whether patients with untreated NFI between 6 and 24 months duration and who are given standard regimen corticosteroid therapy, will have a better treatment outcome than a placebo group. A multicentre, randomized, double-blind placebo-controlled trial was conducted in Nepal and Bangladesh. Subjects were randomised to either prednisolone treatment starting at 40 mg/day, tapered by 5 mg every 2 weeks, and completed after 16 weeks, or placebo. Outcome assessments were at 4, 6, 9, and 12 months from the start of treatment. 92 MB patients on MDT were recruited, of whom 40 (45%) received prednisolone and 52 (55%) placebo treatment. No demonstrable additional improvement in nerve function, or in preventing further leprosy reaction events was seen in the prednisolone group. Overall, improvement of nerve function at 12 months was seen in about 50% of patients in both groups. Analysis of subgroups according to nerve (ulnar and posterior tibial), duration of NFI, and sensory and motor function, also did not reveal any differences between the treatment and placebo groups. There was however, indication of less deterioration of nerve function in the prednisolone group. Finally, there was no difference in the occurrence of adverse events between both groups. The trial confirms current practice not to treat long-standing NFI with prednisolone. Spontaneous recovery of nerve function appears to be a common phenomenon in leprosy. Leprosy reactions and new NFI occurred in a third of the study group, emphasizing the need to keep patients under regular surveillance during MDT, and, where possible, after completion of MDT. This study was designed to investigate whether leprosy patients diagnosed with mild sensory impairment have a better prognosis when treated with steroids than similarly impaired patients treated with placebo. A multi-centre, randomized, double-blind, placebo-controlled trial was conducted in Nepal and Bangladesh. Patients were eligible if they had a confirmed leprosy diagnosis, were between 15 and 50 years old, had mild sensory impairment of the ulnar or posterior tibial nerve of less than 6 months duration and did not require steroids for other reasons. 'Mild impairment' was defined as 'impaired on the Semmes-Weinstein monofilament test, but testing normal on the ballpen sensory test'. Subjects were randomized to either prednisolone treatment starting at 40 mg per day, tapering over 4 months, or placebo. Nerve function was monitored monthly. Any patient who deteriorated was taken out of the trial and was put on full-dose steroid treatment. Outcome assessment was done at 4, 6, 9 and 12 months from the start of the treatment. Outcome measures were the proportion of patients needing full-dose prednisolone and the Semmes-Weinstein sum scores. Each patient contributed only one nerve to the analysis. Seventy-five patients had nerves eligible for analysis, of whom 41 (55%) and 34 (45%) were allocated to the prednisolone and placebo arms, respectively. At 4 months, three patients in the prednisolone arm (7%) and six in the placebo arm (18%) had an outcome event requiring full dose steroids. At 12 months, these proportions had almost reversed, 11 (27%) and 6 (18%) in the treatment and placebo arms, respectively. In the latter group, 75% had recovered spontaneously after 12 months. Prednisolone treatment of sensory impairment of the ulnar and posterior tibial nerves detectable with the monofilament test, but not with the ballpen test, did not improve the long-term outcome in terms of recovery of touch sensibility, not did it reduce the risk of leprosy reactions or nerve function impairment beyond the initial 4-month treatment phase. Two unexpected main findings were the strong tendency of mild sensory impairment to recover spontaneously and the fact that patients with mild sensory impairment without any other signs or symptoms of reaction or nerve function impairment are relatively rare. The therapeutic effect of corticosteroids in acute idiopathic peripheral nerve paralysis (Bell's palsy) in children is controversial. The authors evaluated the effect of steroids on the early and late outcome of children with Bell's palsy in a prospective randomized controlled setting. Forty-two patients (21 females, 21 males) with complete paralysis were enrolled in the study. Group 1 (n = 21) received methylprednisolone (1 mg/kg daily for 10 days orally); Group 2 (n = 21) did not. All patients were observed in the first 3 days of the disease and at 4, 6, and 12 months of follow-up. The mean age of Group 1 was 52.4 +/- 4.3 months, not significantly different from that of Group 2. In Group 1, 86% and 100% exhibited normal nerve function at 4 and 6 months of follow-up, respectively; in Group 2, 72% and 86% demonstrated complete recovery at 4 and 6 months, respectively, with improvement in all patients by 12 months. The improvement rates between the treated and untreated groups did not differ significantly. No side effects necessitated steroid withdrawal. The results of this study indicate that steroid therapy initiated at an early stage of childhood Bell's palsy does not significantly improve the outcome.
Corticosteroids are used for treating acute nerve damage in leprosy, but evidence from two randomised controlled trials, treating either long-standing or mild nerve function impairment, did not show a significant long-term effect. A third trial showed significant benefit of a five-month steroid regimen over a three-month regimen. Standard corticosteroid regimens are not significantly more harmful than placebo treatment, despite known adverse effects of corticosteroids. Further randomised controlled trials are needed to establish the effectiveness of corticosteroids and the optimal regimens and to examine new therapies. Future trials should pay more attention to non-clinical aspects, such as costs and impact on quality of life, because these are highly relevant indicators for both policy makers and participants.