O risco de hanseníase em pacientes com imunossupressão induzida por medicamentos para o tratamento de doenças dermatológicas e reumatológicas : um estudo de coorte

Tese (doutorado)—Universidade de Brasília, Faculdade de Ciências Médicas, Programa de Pós-Graduação em Ciências Médicas, 2020.Introdução: A hanseníase permanece predominante em países em desenvolvimento, onde a incidência de doenças imunomediadas é crescente. O objetivo do estudo foi avaliar o risco de adquirir hanseníase em pacientes em uso de imunossupressores para o tratamento de doenças dermatológicas e reumatológicas, incluindo aqueles que receberam profilaxia para tuberculose latente (TBL). Métodos: Realizamos um estudo de coorte prospectivo de 2014 a 2019. O principal fator de risco foi a imunossupressão induzida por medicamentos, e o desfecho principal foi o diagnóstico de hanseníase. Foram realizados reação em cadeia da polimerase (PCR) de amostras de sangue para detectar o Mycobacterium leprae e ensaio de imunoabsorção enzimática (ELISA) para o anticorpo anti- glicolípido antifenólico-I (anti- PGL-1). A razão de riscos (HRs) e curvas de sobrevivência foram avaliados. Resultados: Quatrocentos e cinco pacientes foram incluídos (268 imunossuprimidos e 137 imunocompetentes). Dez casos de hanseníase foram diagnosticados (9 em pacientes imunossuprimidos). Corticosteróides, abatacept ou inibidores do TNF estavam envolvidos em todos os casos de imunossupressão. A PCR previu hanseníase em 7 pacientes menos de 2 anos antes das manifestações clínicas. O uso de secuquinumabe e rituximabe em 2 pacientes foi eficaz no controle das reações hansênicas. Embora nenhum paciente que usou isoniazida tenha desenvolvido hanseníase, a profilaxia para TBL não teve influência no risco de hanseníase. Na análise multivariada, o modelo de riscos proporcionais de Cox mostrou que o contato domiciliar (HR = 29,6, 95% IC = 5,7-154), contato social (HR = 5,70, IC 95% = 1,6- 21) e uma imunossupressão de alto grau (HR = 7,9; IC 95% = 1,5-41) foram fatores de risco significativos para o desenvolvimento da hanseníase. Discussão e Conclusão: Podemos concluir que pacientes em uso de imunossupressores de alto grau, principalmente corticosteroides e anti-TNF, apresentam maior risco de desenvolver hanseníase do que pacientes imunocompetentes. Uma história de contato familiar e social com hanseníase deve ser investigada cuidadosamente. Novas estratégias, como o tratamento profilático para pacientes PCR-positivos e o uso de imunossupressores modernos, devem ser estudadas, além de avaliações clínicas rigorosas e periódicas.Introduction: Leprosy remains prevalent in developing countries, where the incidence of immune-mediated diseases is rising. The aim of the study was to assess the risk of acquiring leprosy in patients using immunosuppressants for the treatment of dermatological and rheumatological diseases, including those who received prophylaxis for latent tuberculosis (LTB). Methods: We conducted a prospective cohort study from 2014 to 2019. The main risk factor was drug-induced immunosuppression, and the main outcome was the diagnosis of leprosy. There were performed polymerase chain reaction (PCR) of blood samples to detect Mycobacterium leprae and enzyme-linked immunosorbent assay (ELISA) for the anti-phenol- I-glycolipid antibody (anti-PGL-1). The hazard ratios (HR) and survival curves were assessed. Results: Four hundred and five patients were included (268 immunosuppressed and 137 immunocompetent). Ten leprosy cases were diagnosed (9 in immunosuppressed patients). Corticosteroids, abatacept or TNF inhibitors were involved in all cases of immunosuppression. PCR predicted leprosy in 7 patients less than 2 years before clinical manifestations. The use of secukinumab and rituximab in 2 patients was effective in controlling leprosy reactions. Although no patient who used isoniazid developed leprosy, prophylaxis for TBL had no influence on the risk of leprosy. In the multivariate analysis, Cox's proportional hazards model showed that home contact (HR = 29.6, 95% CI = 5.7- 154), social contact (HR = 5.70, 95% CI = 1.6 -21) and high-grade immunosuppression (HR = 7.9; 95% CI = 1.5-41) were significant risk factors for the development of leprosy. Discussion and Conclusion: We can conclude that patients using strong immunosuppressants, mainly corticosteroids and anti-TNF, are at a higher risk of developing leprosy than immunocompetent patients. A history of family and social contact with leprosy should be carefully investigated. New strategies, such as prophylactic treatment for PCR-positive patients and the use of modern immunosuppressants, must be studied, in addition to rigorous and periodic clinical evaluations

A comprehensive systematic review of leishmaniasis in patients undergoing drug-induced immunosuppression for the treatment of dermatological, rheumatological and gastroenterological diseases

Immunosuppression is an important risk factor for leishmaniasis. We assessed the clinical profile, geographic distribution and prevalence of leishmaniasis in patients undergoing immunosuppressive therapy for dermatological, rheumatological or gastroenterological autoimmune diseases. We identified relevant studies in PubMed, EMBASE, Scopus, Web of Science and LILACS on July 3rd, 2018. We included articles that reported at least one case of leishmaniasis in patients undergoing immunosuppressive treatment for dermatological, rheumatological or gastroenterological diseases. Our protocol was registered in PROSPERO (CRD42018103050). We assessed the quality of the included studies with the Joanna Briggs Institute Critical Appraisal Tool. After the removal of duplicates, 5,431 articles were collected and screened. We included 138 articles; the prevalence of leishmaniasis in six methodologically similar studies varied from three to 1,282 cases per 100,000 patients using anti-TNFα drugs, but the results were significantly heterogeneous . Leishmaniasis in patients treated with immunosuppressive drugs is a health problem mostly reported in European countries bordering the Mediterranean Sea; sporadic activities, such as travelling, seem not to be associated with a significant risk of leishmaniasis, although effective control measures must always be observed

Accuracy of mucocutaneous leishmaniasis diagnosis using polymerase chain reaction : systematic literature review and meta-analysis

The diagnosis of mucocutaneous leishmaniasis (MCL) is hampered by the absence of a gold standard. An accurate diagnosis is essential because of the high toxicity of the medications for the disease. This study aimed to assess the ability of polymerase chain reaction (PCR) to identify MCL and to compare these results with clinical research recently published by the authors. A systematic literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA Statement was performed using comprehensive search criteria and communication with the authors. A meta-analysis considering the estimates of the univariate and bivariate models was performed. Specificity near 100% was common among the papers. The primary reason for accuracy differences was sensitivity. The meta-analysis, which was only possible for PCR samples of lesion fragments, revealed a sensitivity of 71% [95% confidence interval (CI) = 0.59; 0.81] and a specificity of 93% (95% CI = 0.83; 0.98) in the bivariate model. The search for measures that could increase the sensitivity of PCR should be encouraged. The quality of the collected material and the optimisation of the amplification of genetic material should be prioritised

Active search for leprosy cases in Midwestern Brazil: a serological evaluation of asymptomatic household contacts before and after prophylaxis with bacillus Calmette-Guérin

Leprosy is a disease caused by Mycobacterium leprae that carries a high risk of disability, making early diagnosis mandatory. This study aimed to determine the applicability of anti-PGL-1 IgM antibody detection, using the ML FLOW technique, as an assistant tool for the detection of leprosy infection in asymptomatic household contacts (AHHC) of multibacillary leprosy index cases from Midwest Brazil. Serological changes induced by the prophylaxis of these household contacts with Bacillus Calmette-Guérin (BCG) were also verified. A total of 91 AHHC were assessed, among which, 18.68% (n = 17) presented both positive bacilloscopy and positive anti-PGL-1 IgM serology. Positivity concordance between these two laboratorial exams (Kappa Index = 1; p < 0.001) was indicated, however, one case did not demonstrate concordance between the semiquantitative assessment of anti-PGL-1 IgM and the bacilloscopy index (Kappa Index = 0.96; p < 0.001). Among the 17 AHHC with positive bacilloscopy, eight were reassessed after prophylaxis with BCG and two of them presented negative anti-PGL-1 IgM serology, being these patients who had presented a bacilloscopy index of < 2[+] in the initial assessment. This study shows that anti-PGL-1 IgM detection may be used as a tool to determine the bacillary load in AHHC and to detect immune changes related to prophylaxis by nonspecific vaccination

Busca ativa por casos de hanseníase no centro-oeste do Brasil : avaliação sorológica dos contatos domiciliares assintomáticos antes e após a profilaxia com bacillus Calmette-Guérin

A hanseníase é doença causada pelo Mycobacterium leprae, apresentando elevado potencial incapacitante, o que torna indispensável seu diagnóstico precoce. O estudo visa determinar a aplicabilidade da detecção de anticorpos anti-PGL1-IgM por meio da técnica do ML FLOW como ferramenta adjuvante ao diagnóstico de hanseníase em contatos domiciliares assintomáticos (AHHC) de pacientes multibacilares procedentes da região Centro-Oeste do Brasil, bem como, documentar o comportamento sorológico após a profilaxia com a vacina Bacillus Calmette-Guérin (BCG). Foram avaliados 91 AHHC atendidos no Hospital Universitário de Brasília - Brasil, dos quais 18,68% (n = 17) apresentaram positividade para baciloscopia e anti-PGL1-IgM, totalizando uma concordância completa entre os dois grupos (Índice Kappa = 1; p < 0,001). Em apenas um dos casos não observou-se concordância entre a avaliação semi-quantitativa do anti-PGL1-IgM e índice baciloscópico (Índice Kappa = 0,96; p < 0,001). Oito dos 17 AHHC com baciloscopia positiva foram reavaliados após profilaxia com BCG e apenas dois apresentaram negativação dos títulos anti-PGL1-IgM, sendo tais casos correspondentes aos que haviam apresentado índice baciloscópico menor do que 2[+] na avaliação inicial. O estudo corrobora o potencial do anti-PGL1-IgM como ferramenta de predição da carga bacilar em AHHC da região Centro-Oeste do Brasil, e surpreende alterações imunes relacionadas à profilaxia obtida pela vacinação não específica com BCG.Leprosy is a disease caused by Mycobacterium leprae that carries a high risk of disability, making early diagnosis mandatory. This study aimed to determine the applicability of anti-PGL-1 IgM antibody detection, using the ML FLOW technique, as an assistant tool for the detection of leprosy infection in asymptomatic household contacts (AHHC) of multibacillary leprosy index cases from Midwest Brazil. Serological changes induced by the prophylaxis of these household contacts with Bacillus Calmette-Guérin (BCG) were also verified. A total of 91 AHHC were assessed, among which, 18.68% (n = 17) presented both positive bacilloscopy and positive anti-PGL-1 IgM serology. Positivity concordance between these two laboratorial exams (Kappa Index = 1; p < 0.001) was indicated, however, one case did not demonstrate concordance between the semiquantitative assessment of anti-PGL-1 IgM and the bacilloscopy index (Kappa Index = 0.96; p < 0.001). Among the 17 AHHC with positive bacilloscopy, eight were reassessed after prophylaxis with BCG and two of them presented negative anti-PGL-1 IgM serology, being these patients who had presented a bacilloscopy index of < 2[+] in the initial assessment. This study shows that anti-PGL-1 IgM detection may be used as a tool to determine the bacillary load in AHHC and to detect immune changes related to prophylaxis by nonspecific vaccination