WITHDRAWN: Interventions for skin changes caused by nerve damage in leprosy.

BACKGROUND: More than three million persons are disabled by leprosy worldwide. The main complication of sensory nerve damage is neuropathic ulceration, particularly of the feet. In this review we explored interventions that can prevent and treat secondary damage to skin and limbs. OBJECTIVES: To assess the effects of self-care, dressings and footwear in preventing and healing secondary damage to the skin in persons affected by leprosy. SEARCH METHODS: We searched the Cochrane Skin Group Specialised Register (April 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2008), MEDLINE (from 2003 to April 2008), EMBASE (from 2005 to April 2008), CINAHL (1982-2006) and LILACS (1982- April 2008 ) as well as online registers of ongoing trials (April 2008). SELECTION CRITERIA: Randomised controlled trials involving anyone with leprosy and damage to peripheral nerves treated with any measures designed to prevent damage with the aim of healing existing ulcers and preventing development of new ulcers. DATA COLLECTION AND ANALYSIS: Two authors assessed trial quality and extracted data. MAIN RESULTS: Eight trials with a total of 557 participants were included. The quality of the trials was generally poor. The interventions and outcome measures were diverse. Although three studies that compared zinc tape to more traditional dressings found some benefit, none of these showed a statistically significant effect. One trial indicated that topical ketanserin had a better effect on wound healing than clioquinol cream or zinc paste, RR was 6.00 (95% CI 1.45 to 24.75). We did not combine the results of the two studies that compared topical phenytoin to saline dressing, but both studies found statistically significant effects in favour of phenytoin for healing of ulcer (SMD -2.34; 95% CI -3.30 to -1.39; and SMD -0.79; 95% CI -1.20 to 0.39). Canvas shoes were not much better than PVC-boots, and double rocker shoes did not promote healing much more than below-knee plasters. AUTHORS' CONCLUSIONS: One study suggested that topical ketanserin is more effective than clioquinol cream or zinc paste. Topical phenytoin (two studies) may be more effective than saline dressing regarding ulcer healing. For the other dressings the results were equivocal. Canvas shoes were a little better than PVC-boots, but not significantly, and the effect of double rocker shoes compared to below-knee plasters was no different in promoting the healing of ulcers. No side effects were documented.There is a lack of high quality research in the field of ulcer prevention and treatment in leprosy. New trials should follow the current standards for design and reporting of randomised controlled trials.

Leprosy in a patient infected with HIV.

A 60-year-old Nigerian man, who had lived in Europe for 30 years but had returned home frequently, presented with right frontalis muscle weakness and right ulnar nerve palsy, without skin lesions. Neurophysiology showed a generalised neuropathy with demyelinating features. Blood tests were positive for HIV, with a normal CD4 count. There was nerve thickening both clinically and on MRI. Nerve biopsy showed chronic endoneuritis and perineuritis (indicating leprosy) without visible mycobacteria. His neuropathy continued to deteriorate (lepra reaction) before starting treatment with WHO multidrug therapy, highly active antiretroviral therapy and corticosteroids. There are 10 new cases of leprosy diagnosed annually in the UK. Coinfection with HIV is rare but paradoxically does not usually adversely affect the outcome of leprosy or change treatment. However, permanent nerve damage in leprosy is common despite optimal therapy. Leprosy should be considered in patients from endemic areas who present with mononeuritis multiplex.

Administración de esteroides y talidomida para el control del eritema nodoso leproso durante 17 años en el hospital para enfermedades tropicales de Londres / No disponible

Objetivos: La prednisolona y la talidomida se administran frecuentemente en el control del eritema nodoso leproso (ENL) y proporcionan alivio a los pacientes con esta condición en todo el mundo. Sin embargo, tanto el ENL como sus tratamientos causan gran morbilidad. Este trabajo describe el espectro del ENL observado en el Hospital para Enfermedades Tropicales de Londres (HTD), la utilización de esteroides y el uso de esteroides y talidomida en su control y las consiguientes complicaciones. Metodología: Se llevó a cabo una revisión retrospectiva de los pacientes diagnosticados con ENL entre 1996 y 2013. Los datos se obtuvieron de los archivos clínicos, incluyendo la severidad y duración del episodio, además del tratamiento y efectos adversos. Resultados: Entre 1996 y 2013 se diagnosticaron 30 pacientes con ENL. El índice bacteriológico (IB) promedio en el momento del diagnóstico fue > 4.65, superior al aceptado en otros estudios. La mayoría de los pacientes desarrollaron ENL durante el tratamiento (67%) y presentaron ENL crónico (57%). La duración media del ENL fue de 60 meses (rango 9-192); los pacientes con IB > 4.5 presentaron períodos de tiempo más largos. El 87% de los pacientes recibieron prednisolona durante 9 meses; 33% desarrolló efectos adversos, incluyendo diabetes e hipertensión; el 87% de los pacientes recibió talidomida durante 16 meses y el 65% presentó efectos adversos. No hubo casos de embarazo o tromboembolismo. El 77% de los pacientes dejó la prednisolona a los dos meses de iniciar la talidomida. No hubo casos de fallecimiento en nuestro grupo. Conclusión: Describimos el curso clínico del ENL en un país no endémico con acceso a la talidomida y prednisolona. El ENL puede durar mucho más que el tiempo descrito anteriormente y tiene un gran impacto sobre la salud del paciente. En el Reino Unido, la talidomida es esencial para cesar la administración de los esteroides, prevenir efectos adversos y la mortalidad por esteroides, lo cual esté documentado en otros trabajos

Objectives: Prednisolone and thalidomide are commonly used in the management of erythema nodosum leprosum (ENL) and bring relief to patients with this condition worldwide. However, both ENL and its treatments can cause significant morbidity. This study describes the spectrum of ENL seen at The Hospital for Tropical Diseases, London (HTD), the use of steroids and thalidomide in its management and the complications of their use. Study Design: We conducted a retrospective audit of patients diagnosed with ENL between 1996 and 2013. Data were obtained from hospital records including severity and length of disease, together with treatments received and adverse effects. Results: Between 1996 and 2013, 30 patients were diagnosed with ENL. The median bacillary index (BI) at diagnosis was 4.65, higher than in previous studies. Most patients developed ENL during leprosy treatment (67%) and had chronic ENL (57%). The median length of ENL was 60 months (range 9-192); patients with BI. 4.5 had significantly longer duration of disease. 87% patients received prednisolone for median nine months; 35% developed adverse effects including diabetes and hypertension. 87% patients received thalidomide for median 16 months; 65% complained of side effects. There were no pregnancies or venous thromboembolisms. 77% patients stopped prednisolone within two months of starting thalidomide. There were no deaths in our cohort. Conclusion: We describe the clinical course of ENL in a non-endemic country with access to thalidomide and prednisolone. ENL may last far longer than previously described and has significant impact on a patient’s health. In the UK, thalidomide is essential as a steroid-sparing agent, to prevent the adverse effects and mortality of longterm steroids which have been documented elsewhere

Serological responses to prednisolone treatment in leprosy reactions: study of TNF-α, antibodies to phenolic glycolipid-1, lipoarabinomanan, ceramide and S100-B.

BACKGROUND: Corticosteroids have been extensively used in the treatment of immunological reactions and neuritis in leprosy. The present study evaluates the serological response to steroid treatment in leprosy reactions and neuritis. METHODS: Seven serological markers [TNF-α, antibodies to Phenolic glycolipid-1 (PGL-1 IgM and IgG), Lipoarabinomannan (LAM IgG1 and IgG3), C2-Ceramide and S100 B] were analyzed longitudinally in 72 leprosy patients before, during and after the reaction. At the onset of reaction these patients received a standard course of prednisolone. The levels of the above markers were measured by Enzyme linked immunosorbent assay (ELISA) and compared with the individuals own value in the month prior to the reaction and presented as percentage increase. RESULTS: One month before the reaction individuals showed a varying increase in the level of different markers such as TNF-α (53%) and antibodies to Ceramide (53%), followed by to PGL-1 (51%), S100B (50%) and LAM (26%). The increase was significantly associated with clinical finding of nerve pain, tenderness and new nerve function impairment. After one month prednisolone therapy, there was a fall in the levels [TNF-α (60%), C2-Ceramide (54%), S100B (67%), PGL-1(47%) and LAM (52%)] with each marker responding differently to steroid. CONCLUSION: Reactions in leprosy are inflammatory processes wherein a rise in set of serological markers can be detected a month before the clinical onset of reaction, some of which remain elevated during their action and steroid treatment induces a variable fall in the levels, and this forms the basis for a variable individual response to steroid therapy.

Leprosy now: epidemiology, progress, challenges, and research gaps.

Leprosy continues to be a challenge to health worldwide, with about 250,000 new cases being detected every year. Despite widespread implementation of effective multidrug therapy, leprosy has not been eliminated. A third of newly diagnosed patients have nerve damage and might develop disabilities, although the proportion varies according to several factors, including level of self-care. Women who develop leprosy continue to be especially disadvantaged, with rates of late diagnosis and disability remaining high in this subgroup. Leprosy was not a specified disease in the Millennium Development Goals, but improvements in the other areas they cover, such as education and levels of poverty, will help leprosy patients and services. We review data and make recommendations for research on diagnosis, treatment, and prevention, such as further use of molecular analysis of the Mycobacterium leprae genome, implementation of BCG vaccination, and administration of chemoprophylaxis to household contacts. We also suggest development of tools for early diagnosis and detection of infection and nerve damage, and formulation of strategies to manage the chronic complications of leprosy, such as immune-mediated reactions and neuropathy.

La talidomida en el control del eritema nodosum leprosum / No disponible

El eritema nodosum leprosum (ENL, reacción tipo 2) es una complicación de la lepra lepromatosa borderline que puede afectar a muchos sistemas orgánicos causando alteraciones irreversibles. Normalmente, las reacciones se presentan durante los 2 años después de iniciar el tratamiento y frecuentemente, evoluciona de forma crónica o recurrente , a veces durante años. Con la actual MDT de la OMS experimentan ENL un 30% de pacientes lepromatosos (LL). Se revisa el control farmacológico del ENL en base a la información procedente de ensayos clínicos controlados y otros trabajos. El tratamiento del ENL es complicado por las elevadas dosis de esteroides que se necesitan durante largos períodos y que no siempre controlan la inflamación. La paradoja del ENL es que siendo un episodio que pone en riesgo la vida del paciente requiere un control con inmunosupresores que, a su vez, suponen otro riesgo grave para el afectado. El tratamiento con talidomida es una alternativa a los esteroides, proporciona un mejor control a largo plazo y evita los efectos secundarios de los tratamientos prolongados con esteroides. Ensayos clínicos controlados han demostrado que la talidomida controla rápidamente el ENL y su efecto es superior a la aspirina y a la pentoxifilina. Pero la talidomida es teratogénica si se administra durante los primeros meses del embarazo y no está disponible en muchos países endémicos. En este trabajo se revisa el papel de la talidomida controla rápidamente el ENL y su efecto es superior a la aspirina y a la pentoxifilina. Pero la talidomida es teratogénica si se administra durante los primeros meses de embarazo y no está disponible en muchos países endémicos. En este trabajo se revisa el papel de la talidomida en el tratamiento del ENL, sus complicaciones y posibles estrategias a emplear para reducir el riesgo. Estos incluyen la correcta selección de los pacientes, supervisión y disponibilidad de anticonceptivos. Se necesitan más estudios para entender mejor esta complicación grave y debilitante de la lepra. Los puntos principales a investigar son: i. El desarrollo de instrumentos validados para evaluar la gravedad y/o actividad de la ENL. Ii. Una valoración detallada de los efectos neurotóxicos de la talidomida cuando se administra para el ENL. Iii. Un ensayo clínico válido que compare talidomida con prednisolona. Iv. El desarrollo de una alternativa segura y efectiva tanto para esteroides como talidomida (AU)

Erythema nodosum leprosum (ENL, Type 2 reactions) complicates lepromatous and bordeline 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, sometime for many years. Even with WHO multi-drug therapy about 30% of LL patients experience ENL. We review drug management of ENL focusing on data form 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 teratogénica 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 counseling, 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 (AU)

Leprosy.

INTRODUCTION: The World Health Organization field leprosy classification is based on the number of skin lesions: single-lesion leprosy (1 lesion), paucibacillary leprosy (2-5 skin lesions), and multibacillary leprosy (more than 5 skin lesions). Worldwide, about 720,000 new cases of leprosy are reported each year, and about 2 million people have leprosy-related disabilities. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent leprosy? What are the effects of treatments for leprosy? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 20 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: Bacillus Calmette Guerin (BCG) plus killed Mycobacterium leprae vaccine; BCG vaccine; ICRC vaccine; multidrug treatment; multiple-dose treatment; mycobacterium w vaccine; single-dose treatment.

A pilot study of three potential vaccines for leprosy in Bombay

Three vaccines, BCG Glaxo alone (vaccine A), BCG Glaxo plus 10(7) killed Mycobacterium vaccae (vaccine B), and BCG Glaxo plus 10(7) killed M. leprae (vaccine C), were given to groups of selected children. The effects of these vaccines on subsequent quadruple skin testing 1-3 years after vaccination were compared. All three vaccines equally and significantly (p less than 0.00001) increased positivity to tuberculin, but only vaccine B was found to significantly enhance development of skin-test positivity to leprosin A (p less than 0.002). The data support the evidence previously obtained in rural Iran that the combination of BCG with killed M. vaccae is likely to be a better vaccine for leprosy than is BCG alone