Adverse effects of polychemotherapy for leprosy in 13 years of follow-up at a university hospital

Abstract Leprosy is one of the neglected diseases in the world and Brazil is the second country with more cases. A retrospective study was conducted based on the medical records of 196 leprosy patients diagnosed during the course of 13 years at a university hospital. The aim was to describe the adverse effects of polychemotherapy, as well the most prevalent and most vulnerable populations. In the study, dapsone was the most implicated drug, especially in women, and the risk increased with age. The authors conclude that with this patient profile, greater vigilance should be taken regarding possible adverse effects, especially anemia.

Shortened tuberculosis treatment regimens: what is new? / Esquemas mais curtos de tratamento da tuberculose: o que há de novo?

ABSTRACT Given the global burden of tuberculosis, shortened treatment regimens with existing or repurposed drugs are needed to contribute to tuberculosis control. The long duration of treatment of drug-susceptible tuberculosis (DS-TB) is associated with nonadherence and loss to follow up, and the treatment success rate of multidrug-resistant tuberculosis (MDR-TB) is low (approximately 50%) with longer regimens. In this review article, we report recent advances and ongoing clinical trials aimed at shortening regimens for DS-TB and MDR-TB. We discuss the role of high-dose rifampin, as well as that of clofazimine and linezolid in regimens for DS-TB. There are at least 5 ongoing clinical trials and 17 observational studies and clinical trials evaluating shorter regimens for DS-TB and MDR-TB, respectively. We also report the results of observational studies and clinical trials evaluating a standardized nine-month moxifloxacin-based regimen for MDR-TB. Further studies, especially randomized clinical trials, are needed to evaluate regimens including newer drugs, drugs proven to be or highly likely to be efficacious, and all-oral drugs in an effort to eliminate the need for injectable drugs.

RESUMO Em virtude da carga global da tuberculose, esquemas mais curtos de tratamento com medicamentos já existentes ou reaproveitados são necessários para contribuir para o controle da doença. A longa duração do tratamento da tuberculose sensível (TBS) está relacionada com não adesão e perda de seguimento, e a taxa de sucesso do tratamento da tuberculose multirresistente (TBMR) é baixa (de aproximadamente 50%) com esquemas mais longos. Neste artigo de revisão, relatamos avanços recentes e ensaios clínicos em andamento cujo objetivo é encurtar os esquemas de tratamento de TBS e TBMR. Discutimos o papel da rifampicina em altas doses, assim como o da clofazimina e linezolida em esquemas de tratamento de TBS. Relatamos também os resultados de estudos observacionais e ensaios clínicos de avaliação de um esquema padronizado de nove meses à base de moxifloxacina para o tratamento de TBMR. Mais estudos, especialmente ensaios clínicos randomizados, são necessários para avaliar esquemas que incluam medicamentos mais novos, medicamentos comprovadamente ou provavelmente eficazes e medicamentos exclusivamente orais na tentativa de dispensar o uso de medicamentos injetáveis.

Acute renal failure by rapidly progressive glomerulonephritis with IgA deposition in a patient concomitantly diagnosed with multibacillary Hansen's disease: a case report / IRA por glomerulonefrite rapidamente progressiva com depósito de IgA em uma paciente com diagnóstico concomitante de hanseníase multibacilar: relato de caso

ABSTRACT Rapidly progressive glomerulonephritis (RPGN) is a renal disease with an extensive differential diagnosis. This paper reports the case of a 55-year-old female patient diagnosed with Hansen's disease with acute progressive renal impairment after developing lower limb pyoderma. The association between Hansen's and kidney disease has been well documented, with glomerulonephritis (GN) ranked as the most common form of renal involvement. Post-infectious glomerulonephritis (PIGN) in adults has been associated with a number of pathogens occurring in diverse sites. The patient described in this case report had RPGN and biopsy findings suggestive of PIGN with C3 and IgA detected on immunofluorescence and kidney injury secondary to recent infection by Staphylococcus, a well-documented manifestation of renal impairment in patients with Hansen's disease.

RESUMO A Glomerulonefrite Rapidamente Progressiva (GNRP) é um padrão de doença renal com amplo diagnóstico diferencial. O caso reporta uma paciente de 55 anos com deterioração aguda e progressiva da função renal após quadro de piodermite em membro inferior com diagnóstico concomitante de hanseníase. Associação da hanseníase com doença renal é bem descrita, sendo a GN a forma de acometimento renal mais comum. As glomerulonefrites pós-infecciosas (GNPIs) em adultos ocorrem devido a um grande número de patógenos, nos mais diversos sítios. A paciente do caso relatado apresentava quadro de GNRP e achados de biópsia que sugerem GNPI com marcação de C3 e IgA na imunofluorescência, sugestiva de lesão renal secundária a infecção recente por Staphylococcus, uma manifestação bem descrita de doença renal em pacientes com hanseníase.

Lobomycosis: a therapeutic challenge

Abstract: Lobomycosis or lacaziosis is a chronic granulomatous fungal infection caused by Lacazia loboi. Most cases are restricted to tropical regions. Transmission is believed to occur through traumatic inoculation in the skin, mainly in exposed areas. It is characterized by keloid-like nodules. There are only a few hundred cases reported. The differential diagnoses include many skin conditions, and treatment is difficult. The reported case, initially diagnosed as keloid, proved to be refractory to surgical treatment alone. It was subsequently approached with extensive surgery, cryotherapy every three months and a combination of itraconazole and clofazimine for two years. No signs of clinical and histopathological activity were detected during follow-up.

Leprosy: current situation, clinical and laboratory aspects, treatment history and perspective of the uniform multidrug therapy for all patients

Abstract: In this review, the most relevant and current epidemiological data, the main clinical, laboratory and therapeutical aspects of leprosy are presented. Detailed discussion of the main drugs used for leprosy treatment, their most relevant adverse effects, evolution of the therapeutic regimen, from dapsone as a monotherapy to the proposed polychemotherapy by World Health Organization (WHO) can be found in this CME. We specifically highlight the drug acceptability, reduction in treatment duration and the most recent proposal of a single therapeutic regimen, with a fixed six months duration, for all clinical presentations, regardless of their classification.

Avances en el tratamiento de la tuberculosis multirresistente / Advances in the treatment of multi-drug resistant tuberculosis

Resumen El tratamiento de las tuberculosis multidrogorresistentes (TBC-MDR) se basa en esquemas de fármacos con diseños muy variables, en pacientes con patrones de resistencia heterogéneos y seguimientos no estandarizados, lo que hace dificil plantear recomendaciones con fuerte nivel de evidencia. Además, sólo una minoría de estos enfermos recibe tratamiento a nivel mundial y con los actuales esquemas menos del 50% de los que logran ser tratados curan. Afortunadamente, durante los últimos años han aparecido nuevos medicamentos, (bedaquilina, delamanid y pretomanid), que están demostrando ser de real utilidad para estos pacientes en ensayos con mejor diseño y seguimiento, donde se puede establecer con mayor precisión la eficacia, toxicidad y grado de recaídas. Además, algunos fármacos ya conocidos, (fluoroquinolonas, linezolid, clofazimina) están siendo introducidos dentro de los nuevos esquemas de tratamiento.

Abstract Therapy of multi-drug resistant tuberculosis (MDR TB) is based on trials with drugs with highly variable patterns of resistance and non-standardized follow-ups that make it difficult to provide recommendations with strong levels of evidence. Also, the vast majority of MDR-TB patients fail to receive therapy and those who receive it, only achieve around 50% of good results. Fortunately new drugs have emerged (bedaquiline, delamanid, pretomanid) that are being useful for these patients with better designed trials and monitoring, in which the efficacy, toxicity and degree of relapses can be evaluated more accurately. Some drugs already known (fluorquinolones, linezolid and clofazimine) are also being introduced in new schemes of therapy.

Ashy dermatosis with involvement of mucous membranes

Abstract: Ashy dermatosis is a rare condition, of unknown aetiology, in which mucous membranes are typically spared. The authors report the case of a 57-year-old female with a history of asymptomatic gray-bluish macules located on the trunk and oral mucosa. There were no relief changes on examination. Skin biopsies from the oral mucosa and trunk were performed and both were compatible with ashy dermatosis. The patient started treatment with oral clofazimine but due to the absence of clinical improvement the drug was discontinued three months later. This case report illustrates an atypical case of ashy dermatosis owing to the involvement of mucous membranes, which is rarely described in the literature.

Protocolo 7: manejo del paciente con lepra en atención primaria de la salud / Protocol 7: management of patients with leprosy in primary health care

Afine del 2001, nuestro país, con acción mancomunada del Ministerio de Salud Pública y Bienestar Social, la Asociación Alemana de Ayuda al enfermo de Lepra (DAHW), la Oficina Sanitaria Panamericana ( OPS ) y el Comité de iglesias Mennonitas del Paraguay, ha conseguido reducir la tasa de prevalencia país a menos de 1 caso por 10.000 habitantes.

La lepra y el testículo / Leprosy and the testis

Introducción. La afección testicular es frecuente en la lepra lepromatosa, daño que se incrementa cuando cursa con eritema nudoso leproso. Objetivo. Presentar un paciente con lepra lepromatosa y eritema nudoso leproso con grave compromiso testicular. Materiales y métodos. Se estudió un hombre de 28 años con lepra lepromatosa desde los 22, que durante la poliquimioterapia para la lepra presentó eritema nudoso leproso crónico que afectó ambos testículos y no respondió al manejo convencional. El dolor persistente obligó a practicar orquidectomía izquierda. Resultados. Este testículo presentaba atrofia tubular y fibrosis notorias, conglomerados de macrófagos espumosos, sin bacilos, hiperplasia focal de células de Leydig, endarteritis y arteritis linfocitaria y granulomatosa de vasos pequeños y medianos; estos cambios también estaban presentes en el epidídimo. Un estudio llevado a cabo dos años después de terminar su tratamiento y de la orquidectomía izquierda, demostró azoospermia, testosterona total normal, testosterona libre discretamente disminuida y hormonas lutropina (luteinizante) y folitropina (estimulante del folículo) elevadas. No había disminución de la libido ni de su actividad sexual. Se revisaron los conceptos generales sobre el eritema nudoso leproso y las alteraciones que la lepra produce en el testículo. Conclusión. La lepra lepromatosa puede conducir a hipogonadismo. Los programas de lepra deben contemplar esta complicación para corregir y evitar sus secuelas.

Introduction. Damage of testicles is frequent in lepromatous leprosy and worsened by the presence of erythema nodosum leprosum. Objective. A patient is presented who developed lepromatous leprosy and erythema nodosum leprosum with major testicular compromise. Material and methods. The 28-year-old male patient had lepromatous leprosy since age 22. During a polychemotherapy treatment for the lepromatous leprosy, he presented chronic erythema nodosum leprosum that affected both testicles; he did not respond to the conventional treatment. A left orchidectomy was performed to treat the persistent pain. Results. The extracted testis evidenced the following: tubular atrophy, extensive fibrosis, cumulus of foamy macrophages without rods, focal Leydig cell hyperplasia, linfocitary and granulomatous arteritis and endarteritis of small and medium size vessels. These changes were also observed in the epididymis. Two years after the polychemoterapy and the orchidectomy, the patient exhibited azoospermy, normal total testosterone, slightly diminished free testosterone and elevated levels of luteinizing hormone and follicle-stimulating hormone. No loss of libido or sexual activity was reported. General concepts of erythema nodosum leprosum were reviewed, as well as the pathologic changes produced by leprosy in the testis. Conclusion. Lepromatous leprosy may lead to hypogonadism. This condition is recommended for inclusion in leprosy diagnostic programs in order to detect and treat the consequences of the possible hypogonadism.

Esquema alternativo para tratamento de hanseníase multibacilar em um caso de hepatotoxicidade durante a poliquimioterapia / Alternative treatment of multibacillary leprosy in a case of hepatotoxicity during multidrug therapy

A associação da dapsona, rifampicina e clofazimina tem se mostrado eficaz do tratamento da hanseníase multibacilar,entretanto a dapsona é responsável por inúmeros efeitos colaterais. Relata-se um caso de hepatoxocidade durante a poliquimioterapia, tratado com sucesso com a introdução de esquema alternativo com rifampicina,clofazimina e ofloxacino.

The combination of dapsone, rifampicin and clofazimine has proven quite effective in the treatment of multibacillary leprosy, however dapsone is responsible for numerous side effects. We report a case of hepatoxocidade during multidrug therapy, successfully treated with the introduction of alternative treatment with rifampicin,clofazimine and ofloxacin.

Efetividade da vitamina E sobre o estresse oxidativo, em hansenianos da forma multibacilar sob tratamento / Effectiveness of vitamin E on oxidative stress in patients with leprosy, multibacillary form of under treatment

INTRODUÇÃO: A hanseníase é uma doença infecto contagiosa crônica, causada pelo Mycobacterium leprae, enão foi exterminada no Brasil, que atualmente, ocupa o segundo lugar em número absoluto de casos, perdendoapenas para a Índia. A doença hanseníase não provoca estresse oxidativo, e sim a terapêutica utilizada. Diversos trabalhos evidenciam a redução do estresse oxidativo, em diferentes patologias, pelo uso da vitamina E. Na hanseníase, no entanto, a literatura é escassa a respeito desse efeito OBJETIVO: O objetivo deste estudo foi verificar a redução, pela vitamina E, do estresse oxidativo causado pelo uso da dapsona, clofazimina e rifampicina no tratamento pacientes hansenianos, da forma multibacilar. CASUÍSTICA E MÉTODO: Foi avaliada a presença prévia de estresse oxidativo em 32 pacientes hansenianos, da forma multibacilar, por meio de exames de sangue e, posteriormente, os pacientes foram divididos em 2 grupos, aleatoriamente, com 16 pacientes em cada grupo,denominados: grupos “com vitamina E” e “controle”. Os pacientes do grupo “com vitamina E” fizeram uso de800 UI/dia, por via oral, de vitamina E e o grupo “controle” não fez uso de suplemento vitamínico. Decorridos30, 60 e 90 dias de tratamento suplementar, foram coletadasamostras de sangue dos 2 grupos para determinar a concentração de metahemoglobina e presença de corpos de Heinz. RESULTADOS: Os resultados foram submetidos ao testeestatístico Qui-quadrado (χ2). Não foi encontrada diferença entre os 2 grupos.CONCLUSÃO: Conclui-se que a vitamina E na dose e duração de tratamentos utilizados, não confere efeitoprotetor contra o estresse oxidativo causado pela dapsona, clofazimina e rifampicina utilizada pelos pacientesportadores de hanseníase da forma multibacilar.

INTRODUCTION: Leprosy is a chronic contagious infectious disease caused by Mycobacterium leprae, and has not been wiped out in Brazil, which currently ranks second in the absolute number of cases, second only to India. The disease is not leprosy causes oxidative stress, but the therapy used. Several studies show the reductionof oxidative stress in different pathology, the use of vitamin E. In leprosy, however, the literature is scarce about this effect. OBJECTIVE: The aim of this study was the reduction by vitamin E, oxidative stress caused by the use of dapsone, rifampicin and clofazimine for treating leprosy patients, the multibacillary form.PATIENTS AND METHODS: We reviewed the previous presence of oxidative stress in 32 leprosy patients, themultibacillary form, through blood tests and then the patients were divided into two groups randomly, with 16 patients in each group, namely: groups with vitamin E “and” control “. Patients in the group with vitamin E “made use of 800 IU / day orally, vitamin E and” control “group did not use vitamin supplement. After 30, 60 and 90 days of treatment, blood samples were collected from two groups to determine the concentration of methemoglobin and the presence of Heinz bodies.RESULTS: The results were subjected to statistical test Chi-square (χ2). No difference was found between thetwo groups. CONCLUSION: We conclude that vitamin E dose and durationof treatments, does not confer a protective effect against oxidative stress caused by dapsone, rifampicinand clofazimine used by patients with multibacillary leprosy.

Extensively drug resistance (XDR) tb is not always fatal.

The chance of incidence of XDR TB is on the rise due to improper use of second line anti-tubercular drugs. XDR-TB is very difficult to treat successfully and is often referred to as "virtually untreatable form of TB". We herein report a case of XDR TB confirmed by bacteriological examination in a WHO recognised laboratory who after 12 months of regular treatment improved both clinically and radiologically with sputum smear conversion. To the best of our knowledge, there has been no previous report of any similar case in literature.

Enfermedad de Hansen: Revisión a propósito de un caso / Hansen's disease: Case report and review of literature

Leprosy is a granulomatous disease affecting the skin and peripheral nerves caused by Mycobcicterium leprcie. The range of clinical forms varying from tuberculoid to lepromatous leprosy results from variations in the cellular immune response to the mycobacterium. Despite available combined drug-therapy, it continues to be a significant public health problem, carrying a strong stigma. Although recently there has been no native cases in Chile, a few imported cases have been diagnosed. We present a 56-year-old man who had lived in Paraguay for 8 years, and presented with leprosy 6 years after returning to Chile. The biology of leprosy, clinical features of the disease, current diagnostic criteria and approaches to treatment are discussed.

La lepra es una enfermedad granulomatosa causada por Mycobacterium leprae, que afecta la piel y los nervios. Su espectro clínico comprende desde lepra tuberculoidea hasta la lepromatosa, siendo el resultado de las variaciones de la respuesta inmune celular a la micobacteria. A pesar de la terapia combinada, la enfermedad sigue siendo un problema de salud pública significativo y se asocia a una fuerte estigmatización. Aunque no ha habido casos autóctonos en Chile, algunos casos contraídos en el extranjero han sido diagnosticados. Se presenta un hombre de 56 años, que vivió en Paraguay durante ocho años y debutó con lepra después de seis años viviendo en Chile. Se discute la biología de la lepra, las características clínicas de la enfermedad, los criterios diagnósticos actuales y el enfoque terapéutico.

Estudo terapêutico comparando a associação de rifampicina, ofloxacina e minociclina com a associação rifampicina, clofazimina e dapsona em pacientes com hanseníase multibacilar / Therapeutic study comparing the association rifampin, ofloxacinand minocycline, with the association rifampin, clofazimine anddapsone in multibacillary leprosy patients

Foram comparados dois esquemas terapêuticos em pacientes com hanseníase multibacilar. O grupo controle com 14 pacientes recebeu o tratamento convencional.O grupo teste com 12 pacientes recebeu a associação de rifampicina 600 mg, ofloxacina 400 mg,e minociclina 100 mg, uma vez por mês, durante dois anos. Na avaliação inicial foram realizados exames clínicos, baciloscópicos e histológicos. A baciloscopia e a biópsia foram repetidas no final do primeiro e segundo ano de tratamento. As avaliações clínicas realizadas mensalmente. Todos pacientes apresentavam lesões cutâneas, que os caracterizavam como virchovianos ou peri-virchovianos. No grupo controle, o índice baciloscópico antes do tratamento variou de 2 a 4,8 e no grupo teste de 1,6 a 4,8. Histologicamente apresentavam quadro de hanseníase virchoviana ativa, exceto um paciente do grupo teste. Ao final do primeiro ano de tratamento estavam todos clinicamente melhorados,o índice baciloscópico diminuído e quadro histológico regressivo. Essa tendência se mantinha e ao final do segundo ano todos estavam clinicamente, baciloscopicamente e histologicamente ainda melhores. Análise estatística mostrou não haver diferença significante entre os grupos, sendo os esquemas equivalentes. No grupo controle todos apresentaram pigmentação cutânea devido a clofazimina. Os resultados deste estudo demonstraram que o esquema com rifampicina, ofloxacinae minociclina, teve eficácia e segurança equivalente a poliquimioterapia convencional para multibacilar. Além disso, não causa pigmentação cutânea, pode ser totalmente supervisionado, podendo ser utilizado como esquema alternativo

Two therapeutic schemes in multibacillary leprosy patients were compared. The control group with 14 patients received the conventional treatment (MDT-MB). The test group with 12 patients, received the association rifampin 600 mg, ofloxacin 400 mg and minocycline 100 mg (ROM), administrated under supervision once a month, during two years. Initial evaluations include clinical, bacilloscopic and histological exams. The bacilloscopy and the biopsy were repeated at the end of first and second year of treatment. Clinical evaluations were performed monthly. All patients presented skin lesions characteristic of the lepromatous type. In the control group, the bacterial index (BI) before treatment ranged from 2 to 4.8 and in the test group it ranged from 1.6 to 4.8. Histological picture resembled active lepromatous leprosy, except one patient from the test group. At the end of the first year of treatment all patients showed clinical improvement, decreased BI and regressive histological picture. This tendency was maintained and at a final evaluation at the end of the second year all patients showed improvement on clinical, bacilloscopic and histological evaluations. Statistical analysis showed no significant differences between the groups, therefore, the two schemes were similar. In the control group all patients presented skin pigmentation after clofazimine intake. The results demonstrated that monthly administration of ROM is as efficacious and safe as MDT-MB. Besides, it doesn’t cause skin pigmentation, it can be given under supervision and can be used as alternative scheme.

MDT-MB therapy in paucibacillary leprosy: a clinicopathological assessment.

BACKGROUND: The World Health Organization recommends treatment regimens for paucibacillary (PB) and multibacillary (MB) leprosy, which differ in their duration and components. Hence accurate classification of the disease is required. To overcome difficulties in classification Uniform Multi Drug Therapy (U-MDT) has been recommended. AIM : To evaluate the benefit of adding clofazimine to paucibacillary regimens in leprosy patients by measuring clinical and histological resolution. METHODS: Forty-four paucibacillary patients were included in the study. Twenty-two patients were given MDT-PB regimen and the remaining MDT-MB regimen for six months . Skin biopsies were done before the commencement and at the end of treatment. Clinical and histological resolutions were measured according to the standard criteria a laid down. The results were analyzed using Fishers' test and Crammers' V test. RESULTS: Clinical improvement was observed in 90.9% in the MB group as compared to 27.3% in the PB group. Regression in the nerve swelling was observed in 70% in the MB group and in 37.5% in the PB group while histological resolution was observed in 72.8% and 54.5% respectively. CONCLUSIONS: Addition of clofazimine helps to resolve leprosy lesions both clinically and histologically, thus justifying the concept of Uniform MDT regimen for all patients.

Incidence of neuritis among paucibacillary leprosy patients during treatment and surveillance.

A cohort study was done on 180 patients receiving the standard WHO PB-MDT regimen at the TLM Hospital in Kolkata, during MDT and 2 years of surveillance to determine the incidence of neuritis. Neuritis occurred in only 2 out of the 180 patients, confirming that the current WHO treatment for PB-MDT is attendant with minimal risk of neuritis. No risk factors were found, except pregnancy in a female patient. While addition of clofazimine in the new U-MDT under trial might take care of the occasional neuritis, further clinical research might be useful to identify sub-groups of PB patients at risk of neuritis.

Eritema discrómico perstans (dermatosis cenicienta) / Erythema dyschromicum perstans (ashy dermatosis)

El Eritema Discrómico Perstans (EDP) o Dermatosis Cenicienta es una condición poco común y se caracteriza por máculas grisáceas bien definidas y de contornos policíclicos. En la histopatología los hallazgos son característicos, pero no patognomónicos, y corresponden a una dermatitis liquenoide. La causa del EDP continúa siendo un misterio; se han propuesto causas infecciosas, alteraciones del sistema inmune, e incluso, factores ambientales. Para el diagnóstico, la mayoría de las veces el cuadro clínico es muy típico. Aún no existe un tratamiento efectivo probado para el EDP, sin embargo, la clofazimina parece ser la mejor alternativa.

Tratamento da hanseniase / ?

O controle da hanseniase e considerado uma das prioridades da OMS, por ser uma endemia com potencial incapacitante importante. Os autores fazem uma revisao do tratamento da hanseniase desde a utilizacao do oleo de chaulmugra em 1854, passando pela introducao da sulfona em 1941, ao aparecimento da resistencia secundaria e primaria a sulfona, razao da associacao de outras drogas no tratamento da doenca. O esquema dividia os pacientes em multibacilares e paucibacilares, usando regimes com tres drogas (Rifampicina, Clofazimina e Dapsona) para as formas multibacilares e duas drogas (Rifampicina e Sulfona) para os paucibacilares. Foram realizadas mudancas na duracao do tratamento, e novas drogas como as quinolonas, claritromicina e minociclina mostraram eficacia contra o M. leprae possam ser utilizadas em esquemas alternativos.