Corticosteroids for treating nerve damage in leprosy.

BACKGROUND: Leprosy causes nerve damage that can result in nerve function impairment and disability. Corticosteroids are commonly used for treating nerve damage, although their long-term effect is uncertain. This is an update of a review first published in 2007, and previously updated in 2009 and 2011. OBJECTIVES: To assess the effects of corticosteroids on nerve damage in leprosy. SEARCH METHODS: On 16 June 2015, we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL Plus, and LILACS. We also checked clinical trials registers and contacted trial authors. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of corticosteroids for nerve damage in leprosy. The comparators were no treatment, placebo treatment, or a different corticosteroid regimen. DATA COLLECTION AND ANALYSIS: The primary outcome was improvement in nerve function after one year. Secondary outcomes were change in nerve pain, limitations in activities of daily living, limitations in participation, and adverse events. Two review authors independently extracted data and assessed trial quality. When data were lacking, we contacted trial authors for additional information. MAIN RESULTS: We included five RCTs involving 576 people. The trials were largely at low risk of bias, but we considered the quality of the evidence from these trials as moderate to low, largely due to imprecision from small sample sizes. Two out of the five trials reported on improvement in nerve function at one year. These two trials compared prednisolone with placebo. One trial, with 84 participants, treated mild sensory impairment of less than six months' duration, and the other, with 95 participants, treated nerve function impairment of 6 to 24 months' duration. There was no significant difference in nerve function improvement after 12 months between people treated with prednisolone and those treated with placebo. Adverse events were not reported significantly more often with corticosteroids than with placebo. The other three trials did not report on the primary outcome measure. One (334 participants) compared three corticosteroid regimens for severe type 1 reactions. No serious side effects of steroids were reported in any participant during the follow-up period. Another trial (21 participants) compared low-dose prednisone with high-dose prednisone for ulnar neuropathy. Two participants on the higher dose of prednisone reported adverse effects. The last (42 participants) compared intravenous methylprednisolone and oral prednisolone with intravenous normal saline and oral prednisolone. The trial found no significant differences between the groups in the occurrence of adverse events. AUTHORS' CONCLUSIONS: Corticosteroids are used for treating acute nerve damage in leprosy, but moderate-quality evidence from two RCTs treating either longstanding or mild nerve function impairment did not show corticosteroids to have a superior effect to placebo on nerve function improvement. A third trial showed significant benefit from a five-month steroid regimen over a three-month regimen in terms of response to treatment (need for additional corticosteroids). Further RCTs are needed to establish optimal corticosteroid regimens and to examine the efficacy and safety of adjuvant or new therapies for treating nerve damage in leprosy. Future trials should address non-clinical aspects, such as costs and impact on quality of life, which are highly relevant indicators for both policymakers and participants.

Decompressive surgery for treating nerve damage in leprosy.

BACKGROUND: Leprosy causes nerve damage which may result in nerve function impairment and disability. Decompressive surgery is used for treating nerve damage, although the effect is uncertain. This is an update of a review first published in 2009 and previously updated in 2010. OBJECTIVES: To assess the effects of decompressive surgery on nerve damage in leprosy. SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized Register (15 October 2012), CENTRAL (2012, Issue 9 in The Cochrane Library), MEDLINE (January 1966 to October 2012), EMBASE (January 1980 to October 2012), AMED (January 1985 to October 2012), CINAHL Plus (January 1937 to October 2012) and LILACS (from January 1982 to October 2012). We checked reference lists of the studies identified, the Current Controlled Trials Register (www.controlled-trials.com) (1 November 2012), conference proceedings and contacted trial authors. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of decompressive surgery for nerve damage in leprosy. DATA COLLECTION AND ANALYSIS: The primary outcome was improvement in sensory and motor nerve function after one year. Secondary outcomes were improvement in nerve function after two years, change in nerve pain and tenderness, and adverse events. Two authors independently extracted data and assessed trial quality. We contacted trial authors for additional information. We collected adverse effects information from the trials and non-randomised studies. MAIN RESULTS: We included two RCTs involving 88 participants. The trials were at high risk of bias. The trials examined the added benefit of surgery over prednisolone for treatment of nerve damage of less than six months duration. After two years' follow-up there was only very low quality evidence of no significant difference in nerve function improvement between participants treated with surgery plus prednisolone or with prednisolone alone. Adverse effects of decompressive surgery were not adequately described. AUTHORS' CONCLUSIONS: Decompressive surgery is used for treating nerve damage in leprosy but the available evidence from RCTs is of very low quality and does not show a significant added benefit of surgery over steroid treatment alone. Well-designed RCTs are needed to establish the effectiveness of the combination of surgery and medical treatment compared to medical treatment alone.

Decompressive surgery for treating nerve damage in leprosy.

BACKGROUND: Leprosy causes nerve damage which may result in nerve function impairment and disability. Decompressive surgery is used for treating nerve damage, although the effect is uncertain. OBJECTIVES: To assess the effects of decompressive surgery on nerve damage in leprosy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register (November 2007), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2007), MEDLINE (from January 1950 to November 2007), EMBASE (from January 1980 to November 2007), AMED (from January 1985 to November 2007), CINAHL (from January 1982 to November 2007) and LILACS (from January 1982 to November 2007) in November 2007. We checked reference lists of the studies identified, the Current Controlled Trials Register (www.controlled-trials.com), conference proceedings and contacted trial authors. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of decompressive surgery for nerve damage in leprosy. DATA COLLECTION AND ANALYSIS: The primary outcome was improvement in sensory and motor nerve function after one year. Secondary outcomes were improvement in nerve function after two years, change in nerve pain and tenderness, and adverse events. Two authors independently extracted data and assessed trial quality. We contacted trial authors for additional information. We collected adverse effects information from the trials and non-randomised studies. MAIN RESULTS: We included two randomised controlled trials involving 88 people. The trials examined the added benefit of surgery over prednisolone for treatment of nerve damage of less than six months duration. After two years follow-up there was no significant difference in nerve function improvement between people treated with surgery plus prednisolone or with prednisolone alone. Adverse effects of decompressive surgery were not adequately described. AUTHORS' CONCLUSIONS: Decompressive surgery is used for treating nerve damage in leprosy but evidence from randomised controlled trials does not show a significant added benefit of surgery over steroid treatment alone. Well-designed randomised controlled trials are needed to establish the effectiveness of the combination of surgery and medical treatment compared to medical treatment alone.

Interventions for erythema nodosum leprosum.

BACKGROUND: Erythema nodosum leprosum (ENL) is a serious immunological complication of leprosy, causing inflammation of skin, nerves, other organs, and general malaise. Many different therapies exist for ENL, but it is unclear if they work or which therapy is optimal. OBJECTIVES: To assess the effects of interventions for erythema nodosum leprosum. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 1, 2009), MEDLINE (from 2003), EMBASE (from 2005), LILACS and AMED (from inception), CINAHL (from 1981), and databases of ongoing trials, all in March 2009. We checked reference lists of articles and contacted the American Leprosy Missions in Brazil to locate studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of interventions for ENL in people with leprosy. DATA COLLECTION AND ANALYSIS: Two authors performed study selection, assessed trial quality, and extracted data. MAIN RESULTS: We included 13 studies with a total of 445 participants. The quality of the trials was generally poor and no results could be pooled due to the treatments being so heterogeneous. Treatment with thalidomide showed a significant remission of skin lesions compared to acetylsalicylic acid (aspirin) (RR 2.43; 95% CI 1.28 to 4.59) (1 trial, 92 participants). Clofazimine treatment was superior to prednisolone (more treatment successes; RR 3.67; 95% CI 1.36 to 9.91) (1 trial, 24 participants), and thalidomide (fewer recurrences; RR 0.08; 95% CI 0.01 to 0.56) (1 trial, 72 participants). We did not find any significant benefit for intravenous betamethasone compared to dextrose (1 trial, 10 participants), pentoxifylline compared to thalidomide (1 trial, 44 participants), indomethacin compared to prednisolone, aspirin or chloroquine treatments (2 trials, 80 participants), or levamisole compared to placebo (1 trial, 12 participants). Mild to moderate adverse events were significantly lower in participants taking 100 mg thalidomide compared to 300 mg thalidomide daily (RR 0.46; 95% CI 0.23 to 0.93). Significantly more minor adverse events were reported in participants taking clofazimine compared with prednisolone (RR 1.92; 95% CI 1.10 to 3.35). None of the studies assessed quality of life or economic outcomes. AUTHORS' CONCLUSIONS: There is some evidence of benefit for thalidomide and clofazimine, but generally we did not find clear evidence of benefit for interventions in the management of ENL. However, this does not mean they do not work, because the studies were small and poorly reported. Larger studies using clearly defined participants, outcome measures, and internationally recognised scales are urgently required.

Evaluation of simplified tests for the diagnosis of nerve function impairment in leprosy: the Sensory Motor Screening (SMS) study.

OBJECTIVE: Rapid and simple tests for diagnosing nerve function impairment (NFI) in leprosy are required in integrated settings. We examined whether simplified tests performed by newly trained general health workers (GHWs) have comparable diagnostic accuracy to the reference test conducted by experienced physiotherapists. DESIGN: This multi-centre study from India and Bangladesh evaluated three simplified tests named: ILEP Learning Guide Two (M2), Indian dance (M3), and a questionnaire (M4) in 408 people affected by leprosy. Sensitivity (Se) and specificity (Sp) of the three tests were calculated using the full assessment (M1) as reference. Se and Sp were calculated at both whole body and individual nerve levels: whether any NFI and if single NFI (voluntary muscle testing of lid gap, eye closure, little finger out, thumb up and foot up, sensory testing of hands and of feet) was present. RESULTS: M2 had 83% Se and 69% Sp, M3 had 76% Se and 84% Sp and M4 had 85% Se and 46% Sp in diagnosing any NFI. At the level of single NFI, M2 was most or similarly accurate in diagnosing single NFIs with highest prevalence (ST feet, ST hands, little finger out, thumb up), compared to M3 and M4. CONCLUSIONS: ILEP Learning Guide Two (M2) and Indian dance (M3) were found to be the most accurate simplified tests for diagnosing the presence of NFI compared to the reference. M2 was the most useful test, because of greatest accuracy for most of the common types of NFI and inclusion of sensory testing of the hands. M2 is considered to be a useful tool in the hands of GHWs with time constraints in integrated settings.

Decompressive surgery for treating nerve damage in leprosy. A Cochrane review.

OBJECTIVE: Decompressive surgery is used for treating nerve damage in leprosy. We assessed the effectiveness of decompressive surgery for patients with nerve damage due to leprosy. METHODS: A broad search strategy was performed to find eligible studies, selecting randomised controlled trials (RCTs) comparing decompressive surgery alone or plus corticosteroids with corticosteroids alone, placebo or no treatment. Two authors independently assessed quality and extracted data. Where it was not possible to perform a meta-analysis, the data for each trial was summarised. RESULTS: We included two randomised controlled trials involving 88 people. The trials examined the added benefit of surgery over prednisolone for treatment of nerve damage of less than 6 months duration. After 2 years follow-up there was no significant difference in nerve function improvement between people treated with surgery plus prednisolone or with prednisolone alone. Adverse effects of decompression surgery were not adequately described. CONCLUSIONS: Evidence from randomised controlled trials does not show a significant added benefit of surgery over steroid treatment alone. Well-designed randomised controlled trials are needed to establish the effectiveness of the combination of surgery and medical treatment compared to medical treatment alone.

Interventions for erythema nodosum leprosum. A Cochrane review.

INTRODUCTION: Treatment for erythema nodosum leprosum (ENL), an immunological complication of leprosy, is diverse. We undertook a systematic review as it was not clear which treatments were most beneficial. METHODS: We did a systematic search to identify randomised controlled trials (RCTs) comparing treatment with placebo, no treatment or another therapy. Two authors assessed quality and checked data. RESULTS: We included 13 studies involving 445 participants. These trials assessed: betamethasone, thalidomide, pentoxifylline, clofazimine, indomethacin and levamisole. The quality of the trials was generally poor and no results could be pooled due to the treatments being so heterogeneous. Treatment with thalidomide showed a significant benefit compared to aspirin (RR 2.43; 95% CI 1.28 to 4.59). Clofazimine treatment was superior to prednisolone (more treatment successes; RR 3.67; 95% CI 136 to 9.91) and thalidomide (fewer recurrences; RR 0.08; 95% CI 0.01, 0-56). Minor adverse events were significantly lower in participants on a low dose thalidomide regimen compared to a high dose thalidomide regimen (RR 0.46; 95% CI 0.23 to 0.93). Significantly more minor adverse events were reported in participants taking clofazimine compared with prednisolone (RR 1.92; 95% CI 1.10 to 3.35). None of the studies assessed quality of life or economic outcomes. CONCLUSION: There is some evidence of benefit for thalidomide and clofazimine, but generally we did not find clear benefits for interventions in the management of ENL. This does not mean they do not work because the studies were small and poorly reported. Larger studies using clear definitions and internationally recognised scales are urgently required.

Future prevalence of WHO grade 2 impairment in relation to incidence trends in leprosy: an exploration.

OBJECTIVES: To explore the relationship between leprosy incidence trends and the future prevalence of World Health Organization (WHO) grade 2 impairment caused by leprosy. METHODS: Three scenarios were defined to estimate incidences and prevalences of leprosy impairment beyond 2000, assuming 6%, 12% and 18% annual declines in case detection rate respectively, and 6% impairment among new patients. Case detection data from 1985 to 2000 were used for projecting leprosy incidences up to 2020. To estimate future prevalences of WHO grade 2 impairment, the survival of existing and new impaired individuals was calculated. RESULTS: In the 6% scenario, 410 000 new patients will be detected in 2010 and 250 000 in 2020. The number of people living with WHO grade 2 impairment in these years will be 1.3 and 1.1 million, respectively. The 12% scenario predicts that 210 000 new patients will be detected in 2010 and 70 000 in 2020. The grade 2 prevalences will be 1.2 and 0.9 million, respectively. In the 18% scenario, the incidence will be 110 000 in 2010 and 20 000 in 2020, and the grade 2 prevalences will be 1.1 and 0.8 million, respectively. CONCLUSIONS: Declines in numbers of people living with grade 2 impairment lag behind trends in leprosy incidence. The prevalence of people with grade 2 decreases much slower than leprosy incidence and case detection in all three scenarios. This implies that a substantial number of people will live with impairment and will need support, training in self-care and other prevention of disability interventions in the next decades.

Corticosteroids for treating nerve damage in leprosy. A Cochrane review.

OBJECTIVE: Corticosteroids are commonly used for treating nerve damage in leprosy. We assessed the effectiveness of corticosteroids for treating nerve damage due to leprosy. METHODS: A systematic search was undertaken to identify randomised controlled trials (RCTs) comparing corticosteroids with placebo or with no treatment. Two authors independently assessed quality and extracted data. Where it was not possible to perform a meta-analysis, the data for each trial was summarised. RESULTS: Three RCTs involving 513 people were found. Two trials compared prednisolone with placebo. One trial treated mild sensory impairment of less than 6 months duration and the other trial treated nerve function impairment of 6 to 24 months duration. Both trials examined nerve function improvement 12 months from the start of treatment, but found no significant difference between the two groups. The third trial compared three corticosteroid regimens for severe type 1 reactions. After 12 months, a significantly higher proportion of individuals on a 3 month course required extra corticosteroids compared to the groups with a high-dose and low-dose regimen of 5 months duration. Diabetes and peptic or infected ulcers were not significantly more often reported in the corticosteroid compared to the placebo group. CONCLUSIONS: Evidence from RCTs does not show a significant long-term effect for either long-standing nerve function impairment or mild sensory impairment. A 5 month corticosteroid regimen was significantly more beneficial than a 3 month corticosteroid regimen. Further RCTs are needed to establish the effectiveness and optimal regimens of corticosteroids and to examine new therapies.

The relationship between detection delay and impairment in leprosy control: a comparison of patient cohorts from Bangladesh and Ethiopia.

INTRODUCTION: It is acknowledged that longer delays between first symptoms and diagnosis result in increased impairment in newly detected leprosy patients. However, it is unclear whether detection delay in relation to impairment can be used as a general or absolute performance indicator of leprosy control programmes. It is unknown whether similar delays always result in similar proportions of impairment. Therefore, the present study examined the quantitative relationship between delay and impairment in two different patient populations. METHODS: Patients from two study cohorts (BANDS and AMFES) who reported voluntarily were included in the analysis. Data on detection delay, WHO impairment status, type of leprosy, age and sex were analysed using descriptive statistics and multivariate logistic regression analysis to identify significant risk factors for impairment and to quantify the relationship between detection delay and impairment status at intake. RESULTS: Detection delay was an independent risk factor for impairment at presentation in multivariate analysis. The AMFES cohort reported more impairment at detection than BANDS. In multivariate analysis, this difference was significant among PB patients (51% in AMFES versus 15% in BANDS), but not in MB patients (56% in AMFES versus 45% in BANDS). In fact, for every delay category PB patients from AMFES had much higher proportions of impairment than PB BANDS patients. Impairment rates in MB patients from AMFES were higher in every delay category, but the differences between the two cohorts were much smaller compared to PB patients. CONCLUSIONS: Our analysis confirms earlier findings that with longer delays, the risk of impairment at presentation increases. With the same reported delay, however, the proportion impaired can vary considerably between different patient populations, in particular for PB leprosy. Delay can therefore not simply be used as a general or absolute performance indicator for programme evaluation. Achieving short delays remains important in general, but understanding and addressing the underlying mechanisms of delay specific to a patient population adds substantially to the effectiveness of leprosy control.

Evaluation of activity limitation and social participation, and the effects of reconstructive surgery in people with disability due to leprosy: a prospective cohort study.

PURPOSE: To assess how activity limitation and social participation of individuals with leprosy-related disability change over time, and to quantify the effect of reconstructive surgery. METHOD: Individuals with disability due to leprosy who accepted invitations for assessment at a leprosy clinic between March and July 2007 were interviewed using the SALSA Scale (measuring activity limitation) and the Participation Scale (assessing social participation). All participants were offered reconstructive surgery. Follow-up interviews were done 1 year after the first interview or 1 year after surgery. The main outcomes were changes in SALSA score and Participation score. We used analysis of variance to identify the effects of independent factors on mean SALSA and Participation scores. RESULTS: We interviewed 222 participants, 15 of whom took up the offer of surgery and 207 who did not. Comparison of SALSA Scale scores at baseline and 1 year revealed that activity limitation did not significantly change over time in individuals who declined surgery; however, participants who had surgery showed a significant improvement at 1 year (p < 0.001). Social participation improved over time in both groups, but the difference was significant only in the non-surgery group (p < 0.001). CONCLUSIONS: The findings suggest that reconstructive surgery has beneficial effects on functioning. Evaluation of the need for, and effect of, surgery in larger studies is recommended.

Cost-effectiveness of interventions to prevent disability in leprosy: a systematic review.

BACKGROUND: Prevention of disability (POD) is one of the key objectives of leprosy programmes. Recently, coverage and access have been identified as the priority issues in POD. Assessing the cost-effectiveness of POD interventions is highly relevant to understanding the barriers and opportunities to achieving universal coverage and access with limited resources. The purpose of this study was to systematically review the quality of existing cost-effectiveness evidence and discuss implications for future research and strategies to prevent disability in leprosy and other disabling conditions. METHODOLOGY/PRINCIPAL FINDINGS: We searched electronic databases (NHS EED, MEDLINE, EMBASE, and LILACS) and databases of ongoing trials (www.controlled-trials.com/mrct/, www.who.int/trialsearch). We checked reference lists and contacted experts for further relevant studies. We included studies that reported both cost and effectiveness outcomes of two or more alternative interventions to prevent disability in leprosy. We assessed the quality of the identified studies using a standard checklist for critical appraisal of economic evaluations of health care programmes. We found 66 citations to potentially relevant studies and three met our criteria. Two were randomised controlled trials (footwear, management of neuritis) and one was a generic model-based study (cost per DALY). Generally, the studies were small in size, reported inadequately all relevant costs, uncertainties in estimates, and issues of concern and were based on limited data sources. No cost-effectiveness data on self-care, which is a key strategy in POD, was found. CONCLUSION/SIGNIFICANCE: Evidence for cost-effectiveness of POD interventions for leprosy is scarce. High quality research is needed to identify POD interventions that offer value for money where resources are very scarce, and to develop strategies aimed at available, affordable and sustainable quality POD services for leprosy. The findings are relevant for other chronically disabling conditions, such as lymphatic filariasis, Buruli ulcer and diabetes in developing countries.