Immunosuppressors and immunomodulators in Neurology - Part I: a guide for management of patients underimmunotherapy / Imunossupressores e imunomoduladores em Neurologia - Parte I: um guia para o manejo de pacientes em imunoterapia

ABSTRACT For patients with autoimmune diseases, the risks and benefits of immunosuppressive or immunomodulatory treatment are a matter of continual concern. Knowledge of the follow-up routine for each drug is crucial, in order to attain better outcomes and avoid new disease activity or occurrence of adverse effects. To achieve control of autoimmune diseases, immunosuppressive and immunomodulatory drugs act on different pathways of the immune response. Knowledge of the mechanisms of action of these drugs and their recommended doses, adverse reactions and risks of infection and malignancy is essential for safe treatment. Each drug has a specific safety profile, and management should be adapted for different circumstances during the treatment. Primary prophylaxis for opportunistic infections and vaccination are indispensable steps during the treatment plan, given that these prevent potential severe infectious complications. General neurologists frequently prescribe immunosuppressive and immunomodulatory drugs, and awareness of the characteristics of each drug is crucial for treatment success. Implementation of a routine before, during and after use of these drugs avoids treatment-related complications and enables superior disease control.

RESUMO Pacientes com doenças autoimunes exigem uma constante preocupação com os riscos e benefícios do tratamento imunossupressor ou imunomodulador. O conhecimento das rotinas no uso de cada uma dessas drogas é fundamental para o bom desfecho clínico, evitando a piora da doença ou efeitos colaterais. As drogas imunossupressoras e imunomoduladoras agem em diferentes pontos da resposta imunológica a fim de controlar a doença para qual são indicadas. O conhecimento do mecanismo de ação, principais posologias, efeitos adversos e os riscos de infecções e neoplasias relacionadas ao uso dessas medicações são fundamentais para um tratamento seguro. Cada uma delas apresenta um perfil específico de complicações e o manejo deve ser individualizado em diferentes cenários ao longo do seguimento do paciente. O uso de medicações para profilaxia primária de infecções e a vacinação são pontos essenciais no planejamento do tratamento, prevenindo potenciais complicações infecciosas ao longo do acompanhamento. O uso de imunossupressores e imunomoduladores é uma frequente realidade no dia-a-dia do neurologista, e o conhecimento das características de cada droga é crucial para o sucesso do tratamento. A realização de uma rotina antes, durante e depois do uso dessas medicações evita complicações relacionadas com o tratamento e alcança um melhor controle da doença.

Prevalência e tempo de desenvolvimento da hipertensão arterial sistêmica em pacientes após transplante de fígado / Prevalence and time of development of systemic arterial hypertension in patients after liver transplantation

ABSTRACT BACKGROUND: The use of immunosuppressive drugs after liver transplantation (LT) is associated with the development of systemic arterial hypertension (SAH), in addition to other comorbidities of metabolic syndrome. OBJECTIVE: Therefore, the purpose of this study was to analyze the time after use immunosuppressive drugs the patient progresses to SAH, as well as to identify its prevalence and the factors that may be correlated to it. METHODS: A retrospective and longitudinal study was conducted, based on the analysis of medical records of 72 normotensive patients, attended in the transplant unit of a university hospital, between 2016 and 2019. RESULTS: It was observed, on average, 9±6.98 months after immunosuppressive use, the patients were diagnosed with hypertension, and the prevalence of transplanted patients who evolved to SAH in this study was 59.64% (41 patients). In addition, there was a correlation between serum dosage of tacrolimus and the development of SAH (P=0.0067), which shows that tacrolimus has a significant role in the development of SAH. Finally, it was noticed that the development of post-transplantation hypertension indicates a higher risk of the patient presenting the other parameters of metabolic syndrome, as well as a higher impairment in its renal function (P=0.0061). CONCLUSION: This study shows that the patients evolved to SAH in an average of 9±6.98 months after immunosuppressive drug use. We have also found high prevalence of systemic arterial hypertension (59.64%) in patients after liver transplantation, who used calcineurin inhibitors, especially when associated with the use of tacrolimus.

RESUMO CONTEXTO: O uso de imunossupressores pós-transplante de fígado (TF) está associado ao desenvolvimento de hipertensão arterial sistêmica (HAS), além de outras alterações da síndrome metabólica. OBJETIVO: Sendo assim, o objetivo deste estudo foi analisar a partir de quando tempo após o uso do imunossupressor o paciente evolui para HAS, assim como, identificar a sua prevalência e outros fatores que podem estar relacionados, como injuria renal. MÉTODOS: Realizou-se um estudo retrospectivo, longitudinal, baseado em análise de 72 prontuários de pacientes, atendidos na unidade de transplante de um hospital universitário, que não apresentavam hipertensão arterial prévia, entre período de 2016 a 2019. RESULTADOS: Observou-se que, em média, 9±6,98 meses após uso do imunossupressor, os pacientes foram diagnosticados com hipertensão arterial sistêmica, sendo que a prevalência de pacientes transplantados que evoluíram para HAS, neste estudo, foi de 59,64% (41 pacientes). Além disso, verificou-se uma correlação entre a dosagem sérica de tacrolimus e o desenvolvimento de HAS (P=0,0067), o que evidencia que o tacrolimus tem uma atuação significativa no desenvolvimento da hipertensão arterial sistêmica. Por fim, percebeu-se que o desenvolvimento de HAS pós-transplante indica um maior risco de paciente apresentar os outros parâmetros da síndrome metabólica, como também maior prejuízo na sua função renal (P=0,0061). CONCLUSÃO: Este estudo mostra que os pacientes evoluíram para HAS em média 9±6,98 meses após o início do uso do imunossupressor. Verificou-se também alta prevalência de hipertensão arterial sistêmica (59,64%) em pacientes pós-transplante de fígado, que usavam inibidores de calcineurina, principalmente, quando associado ao uso de tacrolimus.

Tuberculosis pulmonar asociada a Infliximab: a propósito del primer caso reportado en Cuba / Infliximab-associated pulmonary tuberculosis: regarding the first case reported in Cuba

La terapia con fármacos antagonistas del factor de necrosis tumoral alfa ha sido beneficiosa en el tratamiento de varias enfermedades como las del tejido conectivo e inflamatorias del intestino, pero no está exenta de riesgos. Las principales complicaciones de estas drogas inmunosupresoras son las infecciones, y la tuberculosis pulmonar es una de las principales afecciones, que se pueden observar en los pacientes con este tipo de tratamiento.Se presentó una mujer de 31 años, atendida en el Hospital Clínico Quirúrgico Hermanos Ameijeiras, La Habana, Cuba, con antecedentes de colitis ulcerativa, que hace 3 meses recibe terapia con Infliximab. Acude al hospital por referir 4 días previos al ingreso, fiebre de 390 C dos veces al día, acompañándose de cefalea, pérdida del apetito y dolor en la región perineal. Se le realizó radiografía de tórax, donde se describe radiopacidad heterogénea que va desde el cuerno superior del hilio derecho hasta planos axilares, en la tomografía axial de tórax reportan consolidación en segmento anterior del lóbulo superior derecho con presencia de broncograma aéreo y en el lavado bronquial microbiológico para bacilos ácido-alcohol resistentes se informó codificación 8, positivo a Mycobacterium tuberculosis. El diagnóstico preciso de tuberculosis relacionada con el uso de fármacos antagonistas del factor de necrosis tumoral alfa requiere un alto índice de sospecha y una investigación detallada. Existe un alto grado de complejidad diagnóstica, por la existencia de un amplio espectro clínico y la necesidad de excluir otras enfermedades.

Tumor necrosis factor alpha antagonist drug therapy has been beneficial in the treatment of several diseases such as connective tissue and inflammatory bowel diseases, but it is not without risks. The main complications of these immunosuppressive drugs are infections, and pulmonary tuberculosis is one of the main conditions, which can be observed in patients with this type of treatment. A 31-year-old woman, treated at the Hermanos Ameijeiras Clinical Surgical Hospital, Havana, Cuba, with a history of ulcerative colitis, who has been receiving Infliximab therapy for 3 months, presented. He went to the hospital for referring 4 days prior to admission, a fever of 390 C twice a day, accompanied by headache, loss of appetite and pain in the perineal region. A chest X-ray was performed, which described heterogeneous radiopacity that goes from the upper horn of the right hilum to axillary planes, in the chest axial tomography they report consolidation in the anterior segment of the right upper lobe with the presence of air bronchogram and in the bronchial lavage microbiological for acid-fast bacilli coding 8, positive for mycobacterium tuberculosis was reported. Accurate diagnosis of tuberculosis related to the use of tumor necrosis factor alpha antagonist drugs requires a high index of suspicion and detailed investigation. There is a high degree of diagnostic complexity, due to the existence of a wide clinical spectrum and the need to exclude other diseases.

Safety and effectiveness of mycophenolate mofetil associated with tacrolimus for liver transplantation immunosuppression: a systematic review and meta-analysis of randomized controlled trials

A combination of immunosuppressants may improve outcomes due to the synergistic effect of their different action mechanisms. Currently, there is no consensus regarding the best immunosuppressive protocol after liver transplantation. This review aimed to evaluate the effectiveness and safety of tacrolimus associated with mycophenolate mofetil (MMF) in patients undergoing liver transplantation. We performed a systematic review and meta-analysis of randomized clinical trials. Eight randomized trials were included. The proportion of patients with at least one adverse event related to the immunosuppression scheme with tacrolimus associated with MMF was 39.9%. The tacrolimus with MMF immunosuppression regimen was superior in preventing acute cellular rejection compared with that of tacrolimus alone (risk difference [RD]=-0.11; p =0.001). The tacrolimus plus MMF regimen showed no difference in the risk of adverse events compared to that of tacrolimus alone (RD=0.7; p=0.66) and cyclosporine plus MMF (RD=-0.7; p=0.37). Patients undergoing liver transplantation who received tacrolimus plus MMF had similar adverse events when compared to patients receiving other evaluated immunosuppressive regimens and had a lower risk of acute rejection than those receiving in the monodrug tacrolimus regimen.

Efficacy and safety of mycophenolate mofetil versus cyclophosphamide in the treatment of Henoch-Schönlein purpura nephritis with nephrotic-range proteinuria in children: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVE@#To study the efficacy and safety of mycophenolate mofetil (MMF) versus cyclophosphamide (CTX) in the treatment of children with Henoch-Schönlein purpura nephritis (HSPN) and nephrotic-range proteinuria.@*METHODS@#A prospective clinical trial was conducted in 68 pediatric patients who were admitted to the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics and who were diagnosed with HSPN and nephrotic-range proteinuria from August 2016 to November 2019. The patients were randomly divided into two groups:MMF treatment (@*RESULTS@#At months 3, 6, and 12 of treatment, there was no significant difference in the complete remission rate and the response rate between the MMF treament and CTX treatment groups (@*CONCLUSIONS@#MMF and CTX have similar efficacy and safety in the treatment of HSPN children with nephrotic-range proteinuria.

Estrategias en el manejo y actualización de las enfermedades autoinmunes y reumáticas en la epidemia por SARSCoV-2 y la COVID-19 Sociedad Cubana de Reumatología y su Grupo Nacional / Strategies in its Management and Updating of the Autoimmune-rheumatic Diseases in the SARSCoV-2 Pandemic and COVID-19 Cuban Rheumatology Society and its National Group

Al igual que en las enfermedades autoinmunes y reumáticas, las infecciones por virus pueden ser disparadores de mecanismos inmunopatogénicos. El SARSCoV-2 puede causar la liberación de citocinas y provocar un daño tisular grave, sobre todo pulmonar, con peligro para la vida. Se suma a ello el riesgo del uso de medicamentos inmunosupresores, empleados en los protocolos de tratamiento de las afecciones autoinmunes y también contra la infección viral de COVID-19. Hoy no contamos con conocimientos y evidencias científicas suficientemente sólidas para el enfrentamiento a la COVID-19, y cómo puede impactar entre los pacientes inmunodeprimidos por afecciones reumáticas. El Grupo Nacional de Atención y Enfrentamiento a la COVID-19 de la Sociedad Cubana de Reumatología se propuso elaborar un documento científico actualizado con las bases teórico-prácticas que permita acceder al conocimiento acerca de la infección por SARSCoV-2 y la COVID-19, y su repercusión sobre los pacientes con enfermedades autoinmunes y reumáticas para esbozar una estrategia de trabajo y ofrecer recomendaciones para los reumatólogos y pacientes cubanos. Se realizó un estudio de revisión y actualización acerca de la asociación entre las enfermedades reumáticas y autoinmunes y la COVID-19. Se emplearon las palabras clave enfermedades reumáticas, lupus eritematoso sistémico, artritis reumatoide, virus SARSCoV-2 y COVID-19. Se realizó una amplia búsqueda en MEDLINE y LILACS, y se revisaron más de 150 artículos, boletines de actualización de los sitios Web, páginas de salud de Cuba, resúmenes seleccionados por su calidad metodológica, revisiones y metaanálisis sobre el tema. A partir de la información recogida, se estableció una discusión y análisis considerando las principales experiencias internacionales, criterios de expertos, experiencias previas con otros virus en el Sistema de Salud de Cuba, con la participación de su red de científicos liderados por la Sociedad Cubana de Reumatología y su Grupo Nacional y el apoyo de la comunidad de reumatólogos(AU)

The outbreak of the infection by the new coronavirus SARSCoV-2, COVID-19, in December in Wuhan Province of China, has become a pandemic and health emergency given the deficiency of antiviral therapy for the acute respiratory syndrome that generates danger to life. The debut of the epidemic was in China, then the epicenter developed in Europe, northern Italy that suffered a severe blow. Worldwide, more than 10 million people are infected with the virus that has impacted on health systems until it practically collapsed, resulting in thousands of deaths. Today the epicenter of the pandemic has shifted to the Americas. Alarming figures highlight the United States of North America with some 2,737,600 infected and more than 128,471 deaths, followed by the South American giant Brazil with 1.3 million infections and 57,659 deaths. The Caribbean has a better setting. In Cuba, by the end of June, 2,340 cases of patients infected with deaths from COVID-19 were reported. We conducted a review, analysis and evaluation study of more than 150 articles from international journals, update bulletins of the WEB sites, health pages of the MINSAP of Cuba, and summaries selected for their methodological quality, and reviews, on the subject COVID-19 and autoimmune-rheumatic diseases by MEDLINE: database prepared by the National Library of Medicine of The USA contains bibliographic references and abstracts from more than 4,000 biomedical journals published in the United States and in 70 other countries, We also use Latin American and Caribbean Center for Information on Health Sciences: System, in Latin America and the Caribbean, since 1982. Our objective and results achieved have been to develop the theoretical-practical bases in an updated scientific document that allow access in an essential and summarized way to current knowledge about the infection by SACOV-2, COVID-19, and its repercussion and impact on patients suffering from rheumatic autoimmune diseases, and thus outline a coping and action strategy with recommendations for the Cuban rheumatologists in their health care work, and for patients as a guideline, given their well-founded concerns and fears given their underlying condition and the immunosuppressive drugs prescribed in an unfavorable context of a pandemic. The information is based on international experiences with the most published scientific evidence and those treasured national experiences in the face of similar situations of epidemics, faced by the vast health system and achievements of Cuban science(AU)

Hepatotoxicidade induzida por azatioprina em portadora da síndrome de Vogt-Koyanagi-Harada / Azathioprine-induced hepatotoxicity in a Vogt-Koyanagi-Harada syndrome patient

Este relato teve como objetivo apresentar um caso de hepatotoxicidade colestática induzida por azatioprina em portadora da síndrome de Vogt-Koyanagi-Harada. À admissão, apresentava icterícia +3/+4, acolia fecal e colúria, além de aumento de marcadores hepáticos, sendo compatível com síndrome colestática, cuja etiologia foi confirmada após exclusão de outras causas possíveis e retirada da azatioprina. A paciente evoluiu, após 1 semana de retirada do fármaco, com diurese livre de coloração menos escura e evacuação presente, sem acolia. Além disso, houve melhora nos exames que precederam a alta hospitalar

This report aimed at presenting a case of azathioprine-induced cholestatic hepatotoxicity in a patient with Vogt-Koyanagi-Harada syndrome. On admission, she presented with jaundice +3/+4, acholic feces, and choluria, as well as increased hepatic markers, all consistent with cholestatic syndrome, the etiology of which was confirmed after other possible causes were ruled out and azathioprine was discontinued. After 1 week of the drug discontinuation, the patient progressed with free diuresis of lighter color and defecation, with no acholia. In addition, tests performed before discharge were improved.

Rituximab use in adult glomerulopathies and its rationale / Uso do rituximabe em glomerulopatias em adultos e justificativas

Abstract Glomerulopathies are one of the leading causes of end-stage renal disease. In the last years, clinical research has made significant contributions to the understanding of such conditions. Recently, rituximab (RTX) has appeared as a reasonably safe treatment. The Kidney Disease: Improving Global Outcomes guidelines (KDIGO) recommended RTX only as initial treatment in antineutrophil cytoplasm antibody associated vasculitis (AAV) and in non-responders patients with lupus nephritis (LN), but these guidelines have not been updated since 2012. Nowadays, RTX seems to be at least as effective as other immunosuppressive regimens in idiopathic membranous nephropathy (IMN). In minimal-change disease, (MCD) this drug might allow a long-lasting remission period in steroid-dependent or frequently relapsing patients. Preliminary results support the use of RTX in patients with pure membranous LN and immunoglobulin-mediated membranoproliferative glomerulonephritis (MPGN), but not in patients with class III/IV LN or complement-mediated MPGN. No conclusion can be drawn in idiopathic focal segmental glomerulosclerosis (FSGS) and anti-glomerular basement membrane antibody glomerulonephritis (anti-GBM GN) because studies are small, heterogeneous, and scarce. Lastly, immunosuppression including RTX is not particularly useful in IgA nephropathy. This review presents the general background, outcomes, and safety for RTX treatment in different glomerulopathies. In this regard, we describe randomized controlled trials (RCTs) performed in adults, whenever possible. A literature search was performed using clinicaltrials.gov and PubMed.

Resumo As glomerulopatias figuram entre as principais causas de doença renal terminal. Nos últimos anos, a pesquisa clínica efetuou contribuições significativas para a compreensão desse grupo de patologias. Recentemente, o rituximabe (RTX) surgiu como um tratamento razoavelmente seguro. As diretrizes do Kidney Disease: Improving Global Outcomes (KDIGO) recomendam o RTX apenas como tratamento inicial na vasculite associada ao ANCA (VAA) e em pacientes não respondedores com nefrite lúpica (NL), embora não sejam atualizadas desde 2012. Atualmente, o RTX parece ser pelo menos tão eficaz quanto outros esquemas imunossupressores na nefropatia membranosa idiopática (NMI). Na doença por lesão mínima (DLM), o medicamento pode proporcionar um período de remissão duradouro em pacientes córtico-dependentes ou com recidivas frequentes. Resultados preliminares corroboram o uso de RTX em pacientes com NL membranosa pura e glomerulonefrite membranoproliferativa (GNMP) mediada por imunoglobulina, mas não em pacientes com NL classe III/IV ou GNMP mediada por complemento. Os achados a respeito de glomeruloesclerose segmentar e focal (GESF) idiopática e doença por anticorpo antimembrana basal glomerular (anti-MBG) não são conclusivos em função do pequeno número, porte e heterogeneidade dos estudos publicados até o presente momento. Por fim, a imunossupressão com RTX não é particularmente útil na nefropatia por IgA. A presente revisão apresenta o racional da prescrição de RTX nas diferentes glomerulopatias, desfechos e segurança. Nesse sentido, foram incluídos ensaios clínicos randomizados (ECRs) realizados em adultos, sempre que possível. Pesquisas bibliográficas foram realizadas nas bases de dados do clinictrials.gov e no PubMed.

Los reumatólogos en la pandemia COVID-19 / Rheumatologists in the COVID-19 pandemic

Desde fines del 2019 enfrentamos el brote de una nueva infección por coronavirus llamada COVID-19, que rápidamente se transformó en una pandemia y llegó a nuestro país a principios del 2020. Esto ha traído muchas preguntas y desafíos, específicamente en nuestros pacientes con enfermedades autoinmunes, que tienen tradicionalmente mayor riesgo de contraer infecciones y de complicarse por estas. Por otra parte, en el tratamiento actual del síndrome respiratorio agudo severo causado por el coronavirus SARS-CoV-2 se están usando e investigando varios medicamentos inmunosupresores e inmunomoduladores del arsenal reumatológico para controlar la respuesta inmune exagerada que se produce en el huésped en el COVID-19 grave. En esta revisión analizamos la literatura existente hasta el momento sobre pacientes reumatológicos y COVID-19, medicamentos reumatológicos en investigación y en uso para el manejo de la infección por SARS-CoV-2, y resumimos ciertas recomendaciones de manejo específicas para nuestros pacientes.

Since the end of 2019 we have been facing the outbreak of a new coronavirus infection called COVID-19, which quickly turned into a pandemic arriving in Chile in early 2020. This has brought with it many questions and challenges, specifically for our patients with autoimmune diseases, which have an increased risk of infections due to their disease and the use of immunosuppresant and corticosteroid drugs. On the other hand, in the current treatment of severe acute respiratory syndrome caused by the SARS-CoV-2 coronavirus, several immunosuppressive and immunomodulatory drugs in the rheumatologic arsenal are being used and investigated to control the exaggerated immune response that occurs in the host in serious COVID -19 cases. In this review we investigated the literature to date on rheumatology patients and COVID-19, rheumatology drugs under investigation and in use for the management of SARS-CoV-2 infection, and have summarized certain specific management recommendations for our patients

Incidence and risk factors for major infections in hospitalized children with nephrotic syndrome / Incidência e fatores de risco para infecções graves em crianças hospitalizadas com síndrome nefróticas

ABSTRACT Introduction: Children with nephrotic syndrome are at increased risk of infections because of disease status itself and use of various immunosuppressive agents. In majority, infections trigger relapses requiring hospitalization with increased risk of morbidity and mortality. This study aimed to determine the incidence, spectrum, and risk factors for major infections in hospitalized children with nephrotic syndrome. Methods: All consecutive hospitalized children between 1-12 years of age with nephrotic syndrome were enrolled in the study. Children with acute nephritis, secondary nephrotic syndrome as well as those admitted for diagnostic renal biopsy and intravenous cyclophosphamide or rituximab infusion were excluded. Results: A total of 148 children with 162 admissions were enrolled. Incidence of major infections in hospitalized children with nephrotic syndrome was 43.8%. Peritonitis was the commonest infection (24%), followed by pneumonia (18%), urinary tract infection (15%), and cellulitis (14%), contributing with two thirds of major infections. Streptococcus pneumoniae (n = 9) was the predominant organism isolated in children with peritonitis and pneumonia. On logistic regression analysis, serum albumin < 1.5gm/dL was the only independent risk factor for all infections (OR 2.6; 95% CI, 1.2-6; p = 0.01), especially for peritonitis (OR 29; 95% CI, 3-270; p = 0.003). There were four deaths (2.5%) in our study, all due to sepsis and multiorgan failure. Conclusions: Infection remains an important cause of morbidity and mortality in children with nephrotic syndrome. As Pneumococcus was the most prevalent cause of infection in those children, attention should be paid to the pneumococcal immunization in children with nephrotic syndrome.

RESUMO Introdução: Crianças com síndrome nefrótica apresentam maior risco de infecções devido ao próprio status da doença e ao uso de vários agentes imunossupressores. Em grande parte, as infecções desencadeiam recidivas que exigem hospitalização, com risco aumentado de morbidade e mortalidade. Este estudo teve como objetivo determinar a incidência, o espectro e os fatores de risco para infecções graves em crianças hospitalizadas com síndrome nefrótica. Métodos: Todas as crianças hospitalizadas consecutivamente entre 1 e 12 anos de idade com síndrome nefrótica foram incluídas no estudo. Crianças com nefrite aguda, síndrome nefrótica secundária, bem como aquelas admitidas para biópsia renal diagnóstica e infusão intravenosa de ciclofosfamida ou rituximabe foram excluídas. Resultados: Foram cadastradas 148 crianças com 162 internações. A incidência de infecções graves em crianças hospitalizadas com síndrome nefrótica foi de 43,8%. A peritonite foi a infecção mais comum (24%), seguida por pneumonia (18%), infecção do trato urinário (15%) e celulite (14%), contribuindo com dois terços das principais infecções. Streptococcus pneumoniae (n = 9) foi o organismo predominantemente isolado em crianças com peritonite e pneumonia. Na análise de regressão logística, a albumina sérica < 1,5gm / dL foi o único fator de risco independente para todas as infecções (OR 2,6; 95% CI, 1,2-6; p = 0,01), especialmente para peritonite (OR 29; IC95% 3 -270, p = 0,003). Houve quatro mortes (2,5%) em nosso estudo, todas devido a sepse e falência de múltiplos órgãos. Conclusões: A infecção continua sendo uma importante causa de morbimortalidade em crianças com síndrome nefrótica. Como o Pneumococo foi a causa mais prevalente de infecção nessas crianças, deve-se atentar para a imunização pneumocócica em crianças com síndrome nefrótica.

Oral carcinoma development after 23 years of renal transplantation

Renal transplant patients are treated with immunosuppressive drugs that decrease the effectiveness of the immune system, making them more prone to developing cancer. Skin and lip carcinomas are common malignancies encountered after transplantation, whereas oral carcinomas are rare. We report the case of a 51-year-old female Caucasian patient, with no history of smoking, who presented white lesions on the tongue and an ulcerated lesion on the lower lip beginning 4 months prior. Diagnosis of squamous cell carcinoma for both lesions was made following incisional biopsies. Interestingly, the patient reported a renal transplantation 23 years prior, and was maintained on a combination of cyclosporine, mycophenolate sodium and prednisone. The patient also presented a history of several basal and squamous cell carcinomas on sun-exposed areas of the skin. Both lesions were surgically excised. No sign of recurrence or new lesions in the oral cavity have been observed; however, new skin lesions are frequently diagnosed. This case report highlights that oral cancers may occur in transplant patients in the absence of classical risk factors. Thus, clinicians must be aware of the importance of thorough oral examination in transplant patients in routine follow-up.

Absceso cerebral por Cladophialophora bantiana en un paciente con trasplante renal: reporte de un caso / Brain abscess caused by Cladophialophora bantiana after renal allograft loss: A case report

Resumen Las feohifomicosis cerebrales son infecciones graves causadas por mohos dematiáceos, entre los cuales Cladophialophora bantiana es una de las especies más comúnmente aislada. Esta tiene tropismo por el sistema nervioso central y frecuentemente produce abscesos cerebrales en pacientes inmunocompetentes; además, en los inmunocomprometidos también puede ocasionar infección diseminada. Pese a la disponibilidad de medicamentos antifúngicos de amplio espectro, a menudo se requiere también la intervención quirúrgica; de todas maneras, la mortalidad es elevada. El diagnóstico debe hacerse interviniendo para tomar la muestra y hacer el cultivo y las pruebas de sensibilidad. Se presenta aquí el caso de un paciente con trasplante renal que presentó un absceso cerebral por C. bantiana, el cual se extrajo mediante resección quirúrgica. El paciente recibió tratamiento con voriconazol, con adecuada respuesta, mejoría y sin secuelas neurológicas.

Abstract Cerebral feohifomycosis are severe infections caused by dematiaceous fungi. Cladophialophora bantiana is one of the most commonly isolated species; it has central nervous system tropism and it often manifests as a brain abscess in immunocompetent patients. In immunocompromised patients, it can lead to brain abscesses and disseminated infections. Despite the availability of broad-spectrum antifungal drugs, it is a must to perform surgical management, in addition to drug therapy. However, mortality is high. The diagnostic approach must be invasive to establish a timely diagnosis and direct treatment based on culture and susceptibility tests. We report a case of brain abscess caused by C. bantiana in an immunosuppressed patient who was treated with surgical resection and voriconazole with an adequate response to therapy and without neurological sequels.

Moderate to severe plaque psoriasis - treatment with drugs of the classic scheme

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Guidelines of the Brazilian Society of Rheumatology for the treatment of systemic autoimmune myopathies

Abstract Background: Recommendations of the Myopathy Committee of the Brazilian Society of Rheumatology for the management and therapy of systemic autoimmune myopathies (SAM). Main body: The review of the literature was done in the search for the Medline (PubMed), Embase and Cochrane databases including studies published until June 2018. The Prisma was used for the systematic review and the articles were evaluated according to the levels of Oxford evidence. Ten recommendations were developed addressing the management and therapy of systemic autoimmune myopathies. Conclusions: Robust data to guide the therapeutic process are scarce. Although not proven effective in controlled clinical trials, glucocorticoid represents first-line drugs in the treatment of SAM. Intravenous immunoglobulin is considered in induction for refractory cases of SAM or when immunosuppressive drugs are contra-indicated. Consideration should be given to the early introduction of immunosuppressive drugs. There is no specific period determined for the suspension of glucocorticoid and immunosuppressive drugs when individually evaluating patients with SAM. A key component for treatment in an early rehabilitation program is the inclusion of strengthbuilding and aerobic exercises, in addition to a rigorous evaluation of these activities for remission of disease and the education of the patient and his/her caregivers.

Challenging management of hepatitis B infection in ankylosing spondylitis patients in an endemic area during immunosuppressive therapy

Abstract Hepatitis B infection is a global health issue. When considering patients with rheumatic diseases, this is no different. By using immunosuppressant drugs, such as DMARDs and biologics, viral reactivation is possible, leading to serious consequences on the patient. We report 3 cases of association between ankylosing spondylitis and hepatitis B with the use of immunosuppressant drugs. Case 1 was a patient with previous HBV infection using DMARD. Cases 2 and 3 were patients chronically infected by HBV during immunosuppressant therapy. The management of HBV infection during immunosuppressant therapy is challenging and needs multidisciplinary support.

Angiomixoma agresivo postrasplante renal / Aggresive angiomyxoma after renal transplantation

La condición de inmunosuprimido aumenta el riesgo de cáncer en trasplantados renales, en comparación a la población general. La mejor supervivencia de esta población en los últimos años ha convertido a las neoplasias y a la enfermedad cardiovascular en las principales causas de morbi-mortalidad. Presentamos el caso de un paciente trasplantado renal que desarrolló cuatro años después del trasplante una forma inusual de tumor mesenquimatoso, el angiomixoma agresivo, que requirió resección quirúrgica amplia.

The condition of immunosuppressed increases the risk of cancer in kidney transplant patients, as compared to the general population. The best survival of inmunosupressed patients in recent years has turned both neoplasms and cardiovascular diseases into the main causes of morbidity and mortality. We present the case of a renal transplanted patient who developed an unusual form of mesenchymal tumor such as the aggressive angiomyxoma, four years after the implant and requiring wide surgical resection.

Risk factors for new-onset diabetes mellitus after kidney transplantation (NODAT): a Brazilian single center study

ABSTRACT Objectives: This study aims to verify the new-onset diabetes after kidney transplant (NODAT) incidence in recipients within 1 year after kidney transplantation from a single center in Southern Brazil and to assess the associated conditions. Subjects and methods: A retrospective study of 258 post-renal transplant patients was performed. Demographic (gender, age, ethnic background) and clinical (origin of graft, associated infections, body mass index (BMI) at transplant time and 6 and 12 months after, causes of renal failure, and comorbidities) data were analyzed. All patients were on tacrolimus, mycophenolate mofetil, and prednisone treatment. Patients with and without NODAT were compared. Results: A NODAT incidence of 31.2% was noted 1 year post transplantation. In the univariate analysis, patients with NODAT were older (p = 0.001), mostly had African-American ethnic background (p = 0.02), and had renal failure secondary to high blood pressure (HBP) (p = 0.001). The group of patients with NODAT also had more incidence of post-transplant HBP (p = 0.01), heart failure (p = 0.02), and dyslipidemia (p = 0.001). Logistic regression showed that African-American ethnic background, post-transplant HBP, and dyslipidemia were independently associated with NODAT. Conclusion: This study shows a NODAT incidence that is greater in patients with African-American ethnic background and that is associated with HBP and dyslipidemia.

Miocardiopatía hipertrófica en un recién nacido pretérmino con madre trasplantada renal / Hypertrophic cardiomyopathy in preterm newborn with kidney transplanted mother

La miocardiopatía hipertrófica en el recién nacido es una entidad poco frecuente y de etiología heterogénea. Se han descrito formas transitorias en hijos de madres con diabetes gestacional y en recién nacidos pretérminos expuestos a corticoides tanto prenatal como posnatalmente. Se presenta un caso de un recién nacido pretérmino, hijo de madre trasplantada renal al que se le detectó una miocardiopatía hipertrófica y que había estado expuesto prenatalmente a corticoides y tacrolimus que recibía la madre como tratamiento inmunosupresor. Ambos fármacos cruzan la barrera placentaria y, al llegar al feto, podrían haber favorecido su desarrollo. La miocardiopatía hipertrófica puede ser un efecto secundario poco común del tratamiento con tacrolimus en adultos y niños, y es reversible al retirarlo. En nuestro conocimiento, es el primer caso publicado de miocardiopatía hipertrófica transitoria tras la exposición fetal tanto a corticoides como a tacrolimus en un hijo de madre trasplantada renal.

Hypertrophic cardiomyopathy in the newborn is a rare entity with heterogeneous etiology. Transient forms have been described in children of mothers with gestational diabetes and in preterm infants exposed both to prenatal and postnatal corticosteroids. We report a case of a preterm infant son of a mother who received renal transplant in whom hypertrophic cardiomyopathy was detected. He had been prenatally exposed to corticosteroids and tacrolimus that received the mother as immunosuppressive therapy. Both drugs cross the placental barrier and, on reaching the fetus, could have favored its development. Hypertrophic cardiomyopathy may be an uncommon side effect of treatment with tacrolimus in adults and children and it is reversible upon withdrawal. To our knowledge, it is the first published case of transient hypertrophic cardiomyopathy after fetal exposure to both corticosteroids and tacrolimus in the son of a renal transplanted mother.

Variantes genéticas de la tiopurina metiltransferasa e incidencia de eventos adversos en pacientes con indicación de azatioprina / Genetic polymorphisms of thiopurine methyltransferase and incidence of adverse events in patients with medical indication of azathioprine

La azatioprina es una tiopurina que presenta rango terapéutico estrecho y marcada toxicidad hematológica y hepática. La tiopurina S-metiltransferasa es una enzima que metaboliza ese grupo de drogas. Mutaciones en el gen que codifica dicha enzima aumentan el riesgo de presentar eventos adversos, por lo que su estudio farmacogenético permite contar con información para el diseño de la estrategia terapéutica. Sin embargo, su utilidad en el medio local no está completamente establecida. Fueron incluidos 45 sujetos (13 hombres) con indicación de azatioprina. Se determinó la presencia de las mutaciones *2, *3A, *3B y *3C de TMPT por PCR-RFLP y se analizó la relación entre el genotipo y la incidencia de eventos adversos relacionados al fármaco. Nueve portaban al menos un alelo no funcional, uno de ellos con genotipo *3A/*3A. Se detectó toxicidad en 3 de los 18 que iniciaron tratamiento con azatioprina: 2 pacientes con genotipo normal presentaron eventos adversos leves, y el único evento adverso de gravedad (aplasia medular) ocurrió en el sujeto con genotipo homocigota mutado. El único que presentó genotipo homocigota mutado desarrolló el más grave de los eventos adversos registrados, a pesar de estar en tratamiento con dosis bajas de azatioprina. Por este motivo, la determinación del genotipo de la tiopurina metiltransferasa pareciera ser de utilidad, pero no reemplaza la necesidad de seguimiento clínico y bioquímico en pacientes en tratamiento con tiopurinas.

Azathioprine is a thiopurine which has a narrow therapeutic index and marked hematological and hepatic toxicity. Thiopurine s-methyltransferase is an enzyme involved in the metabolism of thiopurines. Mutations in the gene that encodes the enzyme may augment the risk of adverse events. For that reason, pharmacogenetic determinations prior to the initiation of therapy can provide useful information for the future therapeutic strategy. Nevertheless, its utility in the local environment is not completely established. Forty-five subjects (13 men) who had been prescribed azathioprine were included. The presence of *2, *3A, *3B and *3C mutations were determined by PCR-RFLP, and the relationship between genotype and incidence of adverse events related to the drug was analyzed. Nine carried at least one non-functional allele, one of them with *3A/*3A genotype. Among the eighteen patients who initiated treatment with azathioprine, toxicity was detected in 3 cases: 2 mild events were observed in patients with normal genotype, and the only serious event (bone marrow suppression) occurred in the individual with homozygous mutant genotype. The only homozygous mutant patient developed the most severe of the registered events, in spite of being under treatment with low doses of azathioprine. This is the reason why enzymatic determination could be of utility, even though it does not replace clinical and biochemical follow-up in patients under thiopurine treatment.

Tuberculosis asociada a antagonistas del factor de necrosis tumoral alfa, presentación de un caso y análisis de los casos reportados en Colombia / Tuberculosis associated with tumor necrosis factor-α antagonists, case description and analysis of reported cases in Colombia

Resumen El factor de necrosis tumoral alfa (FNTα) es una citocina fundamental en la reacción inmunitaria frente al cáncer y a infecciones tales como la tuberculosis. Esta molécula también desempeña un papel fundamental en la patogenia de enfermedades complejas y de difícil tratamiento, como la artritis reumatoidea, la espondilitis anquilosante, la enfermedad de Crohn, la psoriasis y la colitis ulcerativa, condiciones que suelen requerir el uso de medicamentos que antagonizan la función del factor de necrosis tumoral alfa, el cual se ha relacionado con un incremento del riesgo de desarrollar tuberculosis, micosis y otras infecciones graves. Se reporta el caso de un hombre de 68 años de edad con diagnóstico de enfermedad de Crohn, a quien se le administró tratamiento con antagonistas del FNTα, debido a lo cual desarrolló tuberculosis diseminada. El diagnóstico se hizo con base en los hallazgos histológicos y mediante pruebas de biología molecular. Se discuten la presentación clínica y el manejo del caso, y se hace un análisis comparativo de los casos de tuberculosis asociados al tratamiento con antagonistas del FNTα reportados en Colombia durante los últimos diez años, con especial énfasisen la detección y el tratamiento de la tuberculosis latente.

Abstract Tumor necrosis factor-α (TNF-α) is an important fundamental cytokine during the immune response against cancer and infections such as tuberculosis. This molecule also plays a key pathogenic role in complex and difficult-to-treat diseases such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, psoriasis and ulcerative colitis. The treatment of these diseases frequently needs TNF-αantagonists, which has been related to an increased risk of developing tuberculosis, mycoses, and other severe infections. We report the case of a 68-year-old man with Crohn's disease, who developed disseminated tuberculosis due to anti-TNF-α immunosuppressive therapy. The diagnosis was based on the histopathological findings and molecular biology assays. We discuss the clinical presentation and workup of this case, and we present a comparative analysis of tuberculosis cases associated with anti-TNF-α reported in Colombia during the last 10 years emphasizing on the diagnosis and treatment of latent tuberculosis.