Compromiso inmunológico en pacientes con síndrome de Down. Serie de casos / Immune compromise in patients with Down syndrome. A case series

El síndrome de Down, o trisomía 21, tiene una mortalidad mayor que la población general, debido principalmente a infecciones respiratorias. El objetivo de este trabajo es describir el compromiso inmunológico en una serie de casos de pacientes con síndrome de Down derivados a Inmunología por infecciones recurrentes o por hallazgo patológico de laboratorio, entre el 1 de junio de 2016 y el 31 de mayo de 2022. Se describe el compromiso de la inmunidad en 24 pacientes. Doce pacientes presentaron falla de respuesta a polisacáridos y recibieron quimioprofilaxis antibiótica y/o gammaglobulina sustitutiva. En 3 pacientes, se observó agammaglobulinemia con linfocitos B presentes y se indicó gammaglobulina sustitutiva. En 9 pacientes, se observó linfopenia T y en 1 paciente, compromiso inmune combinado.

Down syndrome, or trisomy 21, has a higher mortality than the general population, mainly due to respiratory tract infections. The objective of this study was to describe immune compromise in a series of cases of patients with Down syndrome referred to the Pediatric Immunology Section due to recurrent infections or pathological laboratory findings between 6/1/2016 and 5/31/2022. Here we describe immune compromise in 24 patients. Twelve patients failed to develop a polysaccharide response and received antibiotic chemoprophylaxis, or gamma globulin replacement therapy. Three patientsdeveloped agammaglobulinemia with presence of B cells and gamma globulin replacement therapy was indicated. Nine patients had T-cell lymphopenia and 1 patient, combined immune compromise.

Immune compromise in patients with Down syndrome. A case series. / Compromiso inmunológico en pacientes con síndrome de Down. Serie de casos.

Down syndrome, or trisomy 21, has a higher mortality than the general population, mainly due to respiratory tract infections. The objective of this study was to describe immune compromise in a series of cases of patients with Down syndrome referred to the Pediatric Immunology Section due to recurrent infections or pathological laboratory findings between 6/1/2016 and 5/31/2022. Here we describe immune compromise in 24 patients. Twelve patients failed to develop a polysaccharide response and received antibiotic chemoprophylaxis, or gamma globulin replacement therapy. Three patients developed agammaglobulinemia with presence of B cells and gamma globulin replacement therapy was indicated. Nine patients had T-cell lymphopenia and 1 patient, combined immune compromise.

El síndrome de Down, o trisomía 21, tiene una mortalidad mayor que la población general, debido principalmente a infecciones respiratorias. El objetivo de este trabajo es describir el compromiso inmunológico en una serie de casos de pacientes con síndrome de Down derivados a Inmunología por infecciones recurrentes o por hallazgo patológico de laboratorio, entre el 1 de junio de 2016 y el 31 de mayo de 2022. Se describe el compromiso de la inmunidad en 24 pacientes. Doce pacientes presentaron falla de respuesta a polisacáridos y recibieron quimioprofilaxis antibiótica y/o gammaglobulina sustitutiva. En 3 pacientes, se observó agammaglobulinemia con linfocitos B presentes y se indicó gammaglobulina sustitutiva. En 9 pacientes, se observó linfopenia T y en 1 paciente, compromiso inmune combinado.

Myasthenia gravis in the complex scenario of LRBA-related immune dysregulation / Miastenia gravis no cenário clínico complexo das imunodesregulações relacionadas ao gene LRBA

Autoimmune diseases have been progressively recognized as a potential complication of primary immunodeficiency, especially for some genetic subtypes of common variable immunodeficiency. Although often associated with other autoimmune disorders, autoimmune myasthenia gravis is occasionally identified as a neuromuscular complication of primary immunodeficiency. We report the case of a Brazilian woman with common variable immunodeficiency-8 due to an LRBA variant, in which myasthenia gravis was identified in association with anti-acetylcholine receptor antibody. Marked clinical improvement occurred after intravenous immunoglobulin therapy.

Doenças autoimunes foram progressivamente reconhecidas como complicações potenciais das imunodeficiências primárias, especialmente para alguns subtipos genéticos das imunodeficiências comuns variáveis. Embora se associe comumente a outras doenças autoimunes, a Miastenia gravis autoimune adquirida foi raramente associada como complicação neuromuscular de imunodeficiências primárias. É descrito neste artigo o caso de paciente brasileira do sexo feminino com diagnóstico de Imunodeficiência Comum Variável tipo 8 por variante no gene LRBA, na qual foi identificada Miastenia gravis em associação a anticorpos antirreceptor de acetilcolina. Ela evoluiu com marcante melhora clínica após a introdução de terapêutica com imunoglobulina endovenosa.

Recomendaciones para el cuidado, prevención de infecciones y quimioprofilaxis en los errores innatos de la inmunidad / Recommendations for care, prevention of infections and chemoprophylaxis in inborn errors of immunity

Los errores innatos de la inmunidad (EII), antes llamados inmunodeficiencias primarias (IDP), son un grupo heterogéneo de trastornos genéticos con defectos en uno o más componentes del sistema inmune. Los pacientes afectados por EII presentan aumentada susceptibilidad a microorganismos únicos o múltiples que se manifestará con infecciones recurrentes de diferente tipo y gravedad dependiendo del tipo de la localización del defecto. La prevención de infecciones es uno de los pilares fundamentales en el abordaje integral de los pacientes con EII. En este trabajo se resumen las conclusiones consensuadas en el Grupo de Trabajo de Inmunología Pediátrica de la Sociedad Argentina de Pediatría, sobre la base de la revisión de la evidencia disponible, respecto a los principios esenciales para el cuidado, la prevención de infecciones y la quimioprofilaxis en los errores innatos de la inmunidad para la orientación del pediatra y especialista dedicados al seguimiento de estas enfermedades.

Inborn errors of immunity, previously named primary immunodeficiency are a heterogeneous group of genetic defects of different components of the immune system. Patients present high susceptibility to an only or several microorganisms, developing recurrent infections; the severity is related to the specific genetic type of immunity defect. The main strategy on the management of these illness is the prevention of infections. These consensus guidelines made by the Pediatric Immunology Work Group of Sociedad Argentina de Pediatría, givese main approaches of infection prevention in order to provide a useful tool for all practitioners who are involved in the management of these patients, based on scientific evidence and broad consensus of a specialized panel expert.

[Recommendations for care, prevention of infections and chemoprophylaxis in inborn errors of immunity]. / Recomendaciones para el cuidado, prevención de infecciones y quimioprofilaxis en los errores innatos de la inmunidad.

Inborn errors of immunity, previously named primary immunodeficiency are a heterogeneous group of genetic defects of different components of the immune system. Patients present high susceptibility to an only or several microorganisms, developing recurrent infections; the severity is related to the specific genetic type of immunity defect. The main strategy on the management of these illness is the prevention of infections. These consensus guidelines made by the Pediatric Immunology Work Group of Sociedad Argentina de Pediatría, givese main approaches of infection prevention in order to provide a useful tool for all practitioners who are involved in the management of these patients, based on scientific evidence and broad consensus of a specialized panel expert..

Los errores innatos de la inmunidad (EII), antes llamados inmunodeficiencias primarias (IDP), son un grupo heterogéneo de trastornos genéticos con defectos en uno o más componentes del sistema inmune. Los pacientes afectados por EII presentan aumentada susceptibilidad a microorganismos únicos o múltiples que se manifestará con infecciones recurrentes de diferente tipo y gravedad dependiendo del tipo de la localización del defecto. La prevención de infecciones es uno de los pilares fundamentales en el abordaje integral de los pacientes con EII. En este trabajo se resumen las conclusiones consensuadas en el Grupo de Trabajo de Inmunología Pediátrica de la Sociedad Argentina de Pediatría, sobre la base de la revisión de la evidencia disponible, respecto a los principios esenciales para el cuidado, la prevención de infecciones y la quimioprofilaxis en los errores innatos de la inmunidad para la orientación del pediatra y especialista dedicados al seguimiento de estas enfermedades.

Biomarcadores para el diagnóstico del síndrome de reconstitución inmune / Biomarkers for the diagnosis of immune reconstitution syndrome

Introducción: el síndrome inflamatorio de reconstitución inmune es una complicación clínica dada en algunas personas infectadas con el virus de la inmunodeficiencia humana (VIH) luego de empezar la terapia antirretroviral; se destaca por la producción de citoquinas proinflamatorias, que se han estudiado como posibles biomarcadores que puedan orientar para el diagnóstico y pronóstico de esta condición clínica. Objetivo: llevar a cabo una revisión actualizada de los avances en los biomarcadores para el diagnóstico de SIRI, resaltando la importancia de las moléculas inflamatorias y los exosomas, tanto en su patogénesis como un posible Gold estándar para la confirmación de este estado inflamatorio. Metodología: se realizó una revisión bibliográfica en bases de datos, como Science Direct, PubMed, Scopus y Medline, partiendo de los siguientes términos MeSH: síndrome inflamatorio de reconstitución, enfermedades del sistema inmune, biomarcadores, fármacos antiVIH, plasma. Conclusión: cada vez existen más avances en la identificación de moléculas que pueden servir como biomarcadores de SIRI, buscando un oportuno diagnóstico, monitoreo de la progresión clínica, mejor respuesta al tratamiento y más hallazgos sobre la fisiopatología, pero persiste la necesidad de encontrar un Gold estándar que proporcione criterios para su sospecha y confirmación.

Introduction: The inflammatory syndrome of immune reconstitution (IRIS) is a clinical complication given in some people infected with the human immunodeficiency virus (HIV), after they begin antiretroviral therapy (ART), which stands out for the production of abundant proinflammatory cytokines, which have been studied as possible biomarkers that can guide the diagnosis and prognosis of this clinical condition. Objective: Review the advances in biomarkers for the diagnosis of IRIS,and the importance of inflammatory molecules and exosomes, so their pathogenesis and as a possible Gold standard for confirmation of this inflammatory. Methodology: A bibliographic review was carried out in databases, such as Science Direct, Pubmed, Scopus and Medline based on the following MeSH terms: Inflammatory reconstitution syndrome, Immune system diseases, Biomarkers, Anti-HIV drugs, Plasma. Conclusion: There are more and more advances in the identification of various molecules that can serve as biomarkers of IRIS, seeking timely diagnosis, monitoring of clinical progression, better response to treatment and more findings on the pathophysiology of IRIS, but the urgent need to find a gold standard that provides criteria for its suspicion and confirmation persists.

Uso de micofenolato mofetilo fuera de registro en enfermedades inmunomediadas / Off-label use of mycophenolate mofetil in immune-mediated diseases

BACKGROUND: Mycophenolate mofetil (MMF) is a largely used immunosuppressive agent in the prevention of transplant rejection and lupus nephritis. Its use has been extended to other immune-mediated diseases (ID). AIM: To assess the off-label use of MMF, its performance as a glucocorticoid sparing agent, the therapeutic response, and its adverse effects. MATERIAL AND METHODS: A retrospective study was performed. One hundred-seven patients aged 58 ± 16 years (83% females) who received MMF for ID in off label uses between 2016 and 2018 were included. The study variables were cause of MMF indication, sex, age, use as a first- or second-line treatment and maintenance dosing. The cumulative doses of glucocorticoids six months before and after MMF indication were compared. RESULTS: MMF was used as a second-line therapy in 66 patients (62%). The mean maintenance dose of MMF was 1,500 ± 540 mg/day. Prednisone cumulative doses were 3,908 ± 2,173 and 1,672 ± 1,083 milligrams six months before and six months after starting MMF, respectively (p < 0.01). Adverse effects were identified in 21 (20%) cases, none of them serious. CONCLUSIONS: Mycophenolate has a favorable response profile as a second line immunosuppressive agent. It is effective as a glucocorticoid sparing drug. The safety profile is also favorable as adverse effects were scanty and mild.

Modelo para historia clínica en inmunodeficientes primarios, Pinar del Río / Model for clinical history in primary immunodeficient patients, Pinar del Rio

RESUMEN Introducción: los errores innatos de la inmunidad o inmunodeficiencias primarias se caracterizan por susceptibilidad incrementada a infecciones por defectos del desarrollo o función del sistema inmune. Para el diagnóstico debe incluirse la evaluación clínica, la analítica inmunológica, la evaluación genética, el seguimiento rutinario, la rediscusión diagnóstica y del tratamiento clínico. No existe una guía clara respecto a este asunto en condiciones de recursos limitados. Objetivo: diseñar un modelo para la confección de historia clínica en el paciente con sospecha de error innato de la inmunidad. Métodos: se realizó un trabajo de revisión de síntomas a contemplar en la historia clínica de pacientes con errores innatos de la inmunidad. Se formaron grupos de trabajo entre miembros del grupo provincial de Inmunología de Pinar del Río, con la posterior discusión de los aspectos que se incluyen en la historia. Resultados: se diseñaron cinco tablas que recogen: consentimiento informado; antecedentes patológicos personales relacionados con 148 manifestaciones clínicas en correspondencia con los fenotipos alérgico, infeccioso, inflamatorio, autoinmune, no inmunológico, neoplásico y otros. Se exponen antecedentes patológicos familiares y árbol genealógico; el examen físico y el resumen de los fenotipos clínicos, discusión diagnóstica y clasificación del paciente. Conclusiones: el interrogatorio, el examen físico, los antecedentes patológicos personales y familiares, así como la confección adecuada de la historia clínica son elementos imprescindibles para la aproximación al diagnóstico de los errores innatos de la inmunidad. Se debe contar con un registro de pacientes que posibilite el diagnóstico precoz y el tratamiento oportuno de la inmunodeficiencia primaria.

ABSTRACT Introduction: inborn errors of immunity or primary immunodeficiencies are characterized by increased susceptibility to infections due to defects in the development or functioning of the immune system. Diagnosis should include clinical evaluation, immunological analysis, genetic evaluation, routine follow-up, diagnostic re-discussion and clinical management. There is no clear guidance on this issue under resource-limited conditions. Objective: to design a model for clinical history in patients with suspected inborn error of immunity. Methods: a review of symptoms to be considered in the clinical history of patients with inborn errors of immunity was carried out. Working groups were formed among members of the provincial group of Immunology in Pinar del Rio province, with the subsequent discussion of the aspects to be included in the history. Results: five tables were designed to collect: informed consent; personal pathological antecedents related to 148 clinical manifestations in correspondence with allergic, infectious, inflammatory, autoimmune, non-immune, neoplastic and other phenotypes. Family pathologic history and family tree; physical examination and summary of clinical phenotypes, diagnostic discussion and classification of the patient are presented. Conclusions: the interviews, physical examination, personal and family pathologic history, as well as the adequate design of the clinical history, are considered essential elements for the approach to the diagnosis of inborn errors of immunity. A patient registry should be available to enable early diagnosis and timely treatment of primary immunodeficiency.

Relación entre las enfermedades sistémicas y las enfermedades bucales en el adulto mayor / Relationship between Systemic diseases and Oral diseases in the elderly

RESUMEN Introducción: El envejecimiento es un proceso biológico, dinámico, irre versible, inevitable y progresivo que cursan todos los seres humanos. En la actualidad constituye un problema sociodemográfico serio, donde sus altas cifras cada vez más crecientes de adultos mayores, constituyen un desafío para el sistema de salud. Objetivo: Actualizar los conocimientos sobre la relación que existe entre las enfermedades sistémicas y las enfermedades bucales en el adulto mayor. Métodos: Se realizó una revisión de la literatura entre abril y julio de 2021. Se revisaron artículos disponibles en las bases de datos SciELO, BVS, PudMed, Scopus, LILACS, en el motor de búsqueda Google Scholar y revistas de la Web of Sciences, resultando un total de 30 referencias bibliográficas utilizadas, donde el 50 % y 83,3 % se circunscribió a literatura de los últimos tres y cinco años respectivamente. Como estrategia de búsqueda de información se utilizaron frases claves como: adulto mayor; cavidad bucal; enfermedades sistémicas; enfermedades degenerativas; enfermedades bucales. Se tuvo presente su relevancia y novedad en correspondencia sobre el tema. Resultados: El envejecimiento es marcado por la ocurrencia de numerosos cambios que hacen más propensos a los adultos mayores a presentar enfermedades sistémicas y bucales, donde son numerosos los trabajos publicados que demuestran que una de ellas puede influir siendo causa o consecuencia en el desarrollo de la otra. Conclusiones: Es importante conocer la relación bidireccional entre las enfermedades sistémicas y las enfermedades bucales en el adulto mayor, donde se precisa de un mayor cuidado y una atención sistemática en estos pacientes.

ABSTRACT Introduction: Aging is an inevitable and progressive process that currently constitutes a serious sociodemographic problem, where its high numbers constitute a challenge for the health system. Objective: To update knowledge about the relationship between systemic diseases and oral diseases in the elderly. Methods: A literature review was conducted between April and July 2021. Articles available in the SciELO, BVS, PudMed, Scopus, LILACS databases, in the Google Scholar search engine and Web of Sciences journals were reviewed, resulting in a total of 30 bibliographic references used, where 50 % and 83.3 % were limited to literature from the last three and five years respectively. Its relevance and novelty were taken into account in correspondence on the subject. Results: Aging is marked by the occurrence of systemic and oral diseases, where there are numerous published works that show that one of them can influence, being a cause or a consequence, in the development of the other. Conclusions: It is important to know the bidirectional relationship between systemic diseases and oral diseases in the elderly, requiring greater care and systematic attention in these patients.

Apresentação atípica de síndrome de hiper-IgM ligada ao X simulando doença inflamatória intestinal / Atypical presentation of X-linked hyper-IgM syndrome simulating inflammatory bowel disease

Relatamos o caso de um paciente do sexo masculino, que iniciou quadro de úlceras em trato gastrointestinal, associado a febre recorrente e diarreia com muco e sangue aos 10 meses de vida, suspeitado inicialmente de doença inflamatória intestinal, no entanto, não apresentou melhora do quadro com terapia imunossupressora, sendo realizada investigação para erro inato da imunidade. Nos exames laboratoriais, apresentou níveis baixos de IgG e IgA e níveis elevados de IgM e neutropenia persistente. Diante disso, foi realizado teste genético que confirmou diagnóstico de síndrome de hiper-IgM ligada ao X. Os erros inatos da imunidade podem se manifestar com doenças do trato gastrointestinal, de forma relativamente frequente, devendo entrar como diagnóstico diferencial de diarreia crônica. Inclusa nesse grupo de doenças, as síndromes de hiper-IgM constituem um grupo heterogêneo de doenças, possuindo em comum níveis significativamente baixos ou ausentes de IgG e IgA e níveis normais ou elevados de IgM, o que predispõe a infecções e febre recorrente; além de outras alterações laboratoriais, como neutropenia, que pode estar associada a úlceras no trato gastrointestinal e proctite, simulando apresentação clínica de doença inflamatória intestinal. Para o paciente relatado, foi iniciada terapia com imunoglobulinas de forma periódica, além de antibioticoprofilaxia para infecções, evoluindo com resposta clínica satisfatória. O artigo possui objetivo principal de alertar para o diagnóstico diferencial de erros inatos da imunidade diante do quadro apresentado, visando o diagnóstico precoce e a instituição da terapia adequada.

We report the case of a male patient, who started with ulcers in the gastrointestinal tract, associated with recurrent fever and diarrhea with mucus and blood at 10 months of life, initially suspected of inflammatory bowel disease, however, he did not improve the condition with immunosuppressive therapy, being investigated for inborn error of immunity. In laboratory tests, he had low levels of IgG and IgA and high levels of IgM and persistent neutropenia. Therefore, a genetic test was performed and confirmed the diagnosis of X-linked hyper IgM syndrome. Inborn errors of immunity can manifest relatively frequently with diseases of the gastrointestinal tract, and should be included as a differential diagnosis of chronic diarrhea. Included in this group of diseases, hyper-IgM syndromes constitute a heterogeneous group of diseases, having in common significantly low or absent levels of IgG and IgA and normal or high levels of IgM, which predispose to infections and recurrent fever; in addition to other laboratory alterations, such as neutropenia, which may be associated with ulcers in the gastrointestinal tract and proctitis, simulating the clinical presentation of inflammatory bowel disease. For the reported patient, therapy with immunoglobulins was started periodically, in addition to antibiotic prophylaxis for infections, evolving with a satisfactory clinical response. The main objective of the article is to alert to the differential diagnosis of inborn errors of immunity in view of the presented condition, aiming at early diagnosis and the institution of adequate therapy.

Supervivenciade pacientes pediátricos con inmunodeficiencias primarias en un hospital público del occidente de México / Survival of pediatric patients with primary immunodeficiencies in a public hospital in western Mexico

Se presenta una serie de casos de inmunodeficiencias primarias y se describen las variables asociadas a supervivencia en pacientes ≤ 16 años. Los diagnósticos fueron acordes a los criterios de la Unión Internacional de las Sociedades de Inmunología. Se realizó un análisis de supervivencia mediante curvas de Kaplan-Meier.Entre los años 2004 y 2019, se diagnosticaron 40 pacientes con inmunodeficiencias primarias. Las más frecuentes fueron inmunodeficiencias que afectaban la inmunidad celular y humoral, el 32,5 %, y deficiencias predominantemente de anticuerpos, el 32,5 %. La mediana de edad al inicio de los síntomas y al momento del diagnóstico fue de 3,01 y 10,4 meses, respectivamente. Fallecieron el 35 % y el riesgo fue mayor en pacientes con inmunodeficiencias que afectaban la inmunidad celular y humoral y en quienes presentaron manifestaciones clínicas y tuvieron el diagnóstico en los primeros seis meses de vida.

A case series of primary immunodeficiencies is presented and outcome measures associated with survival among patients ≤ 16 years old are described. Diagnoses were made based on the criteria by the International Union of Immunological Societies. Survival was analyzed using Kaplan-Meier curves.Between 2004 and 2019, 40 patients were diagnosed with primary immunodeficiencies. The most common were immunodeficiencies affecting humoral and cell-mediated immunity (32.5 %) and predominantly antibody deficiencies (32.5 %). The median age at the onset of symptoms and at the time of diagnosis was 3.01 and 10.4 months, respectively. Thirty-five percent of patients died, and the risk was higher among those with immunodeficiencies affecting humoral and cell-mediated immunity and those who developed clinical manifestations and were diagnosed in the first 6 months of life

Survival of pediatric patients with primary immunodeficiencies in a public hospital in western Mexico. / Supervivencia de pacientes pediátricos con inmunodeficiencias primarias en un hospital público del occidente de México.

A case series of primary immunodeficiencies is presented and outcome measures associated with survival among patients ≤ 16 years old are described. Diagnoses were made based on the criteria by the International Union of Immunological Societies. Survival was analyzed using Kaplan-Meier curves. Between 2004 and 2019, 40 patients were diagnosed with primary immunodeficiencies. The most common were immunodeficiencies affecting humoral and cell-mediated immunity (32.5 %) and predominantly antibody deficiencies (32.5 %). The median age at the onset of symptoms and at the time of diagnosis was 3.01 and 10.4 months, respectively. Thirty-five percent of patients died, and the risk was higher among those with immunodeficiencies affecting humoral and cell-mediated immunity and those who developed clinical manifestations and were diagnosed in the first 6 months of life.

Se presenta una serie de casos de inmunodeficiencias primarias y se describen las variables asociadas a supervivencia en pacientes ≤ 16 años. Los diagnósticos fueron acordes a los criterios de la Unión Internacional de las Sociedades de Inmunología. Se realizó un análisis de supervivencia mediante curvas de Kaplan-Meier. Entre los años 2004 y 2019, se diagnosticaron 40 pacientes con inmunodeficiencias primarias. Las más frecuentes fueron inmunodeficiencias que afectaban la inmunidad celular y humoral, el 32,5 %, y deficiencias predominantemente de anticuerpos, el 32,5 %. La mediana de edad al inicio de los síntomas y al momento del diagnóstico fue de 3,01 y 10,4 meses, respectivamente. Fallecieron el 35 % y el riesgo fue mayor en pacientes con inmunodeficiencias que afectaban la inmunidad celular y humoral y en quienes presentaron manifestaciones clínicas y tuvieron el diagnóstico en los primeros seis meses de vida.

Manejo em longo prazo de glicogenose tipo 1b: experiência de um centro terciário brasileiro / Long term management of glycogen storage disease type 1b: a brazilian tertiary center experience

ABSTRACT BACKGROUND Glycogen storage disease (GSD) type 1b is a multisystemic disease in which immune and infectious complications are present, in addition to the well-known metabolic manifestations of GSD. Treatment with granulocyte-colony stimulating factor (G-CSF) is often indicated in the management of neutropenia and inflammatory bowel disease. OBJECTIVE To report on the demographics, genotype, clinical presentation, management, and complications of pediatric patients with glycogen storage disease type 1b (GSD 1b), with special attention to immune-related complications. METHODS Retrospective case series of seven patients with GSD 1b diagnosed and followed at a tertiary university hospital in Brazil, from July/2000 until July/2016. RESULTS Mean age at referral was fourteen months. Diagnosis of GSD 1b was based on clinical and laboratory findings and supported by genetic studies in five cases. All patients presented suffered from neutropenia, managed with G-CSF - specifically Filgrastim. Hospitalizations for infections were frequent. Two patients developed inflammatory bowel disease. Six patients remained alive, one died at age 14 years and 9 months. The mean age at the end of the follow-up was 11.5 years. Compliance to treatment was suboptimal: poor compliance to medications, starch and dietetic management of GSD were documented, and outpatient appointments were frequently missed. CONCLUSION Managing GSD 1b is challenging not only for the chronic and multisystemic nature of this disease, but also for the additional demands related dietary restrictions, use of multiple medications and the need for frequent follow-up visits; furthermore in Brazil, the difficulties are increased in a scenario where we frequently care for patients with unfavorable socioeconomic status and with irregular supply of medications in the public health system.

RESUMO CONTEXTO Glicogenose (GSD) tipo 1b é uma doença multissistêmica em que complicações imunológicas e infecciosas estão presentes, além das manifestações metabólicas bem conhecidas da GSD. O tratamento com fator estimulador de colônias de granulócitos (G-CSF) é frequentemente indicado no tratamento da neutropenia e doença inflamatória intestinal. OBJETIVO Relatar sobre a dados demográficos, genótipo, apresentação clínica, manejo e complicações de pacientes pediátricos com GSD tipo 1b (GSD 1b), com atenção especial às complicações relacionadas ao sistema imunológico. MÉTODOS Série de casos retrospectiva de sete pacientes com GSD 1b diagnosticados e acompanhados em um hospital universitário terciário no Brasil, de julho/2000 a julho/2016. RESULTADOS A idade média no encaminhamento foi de 14 meses. O diagnóstico de GSD 1b foi baseado em achados clínicos e laboratoriais e apoiado por estudos genéticos em cinco casos. Todos os pacientes apresentaram neutropenia, tratada com G-CSF - especificamente Filgrastim. As hospitalizações por infecções foram frequentes. Dois pacientes desenvolveram doença inflamatória intestinal. Seis pacientes permanecem vivos, um morreu aos 14 anos e 9 meses de idade. A média de idade ao final do acompanhamento foi de 11,5 anos. A adesão ao tratamento foi sub-ótima: má adesão aos medicamentos, amido e manejo dietético de GSD foram documentados, e consultas ambulatoriais foram frequentemente perdidas. CONCLUSÃO O manejo da GSD 1b é um desafio, não apenas pela natureza crônica e multissistêmica desta doença, mas também pelas demandas adicionais relacionadas a restrições dietéticas, uso de múltiplos medicamentos e a necessidade de consultas de acompanhamento frequentes; no Brasil, isso ainda é dificultado em um cenário em que frequentemente atendemos pacientes com situação socioeconômica desfavorável e com oferta irregular de medicamentos no sistema público de saúde.

Validación de cuestionario sobre interacción de factores genéticos y ambientales en la aparición del asma bronquial / Validation of a questionnaire on the interaction of genetic and environmental factors in the development of bronchial asthma

RESUMEN Introducción: el asma bronquial es la clásica enfermedad dentro de las afecciones alérgicas, y tiene gran impacto en la salud mundial. Es una enfermedad compleja tanto genética como fenotípicamente, y las interacciones genética-ambientales la complejizan aún más. Objetivo: validar un cuestionario para el estudio de los factores genéticos y su interacción con factores ambientales en la aparición de los trastornos inmunitarios por asma bronquial. Métodos: el estudio se generó en el departamento de Inmunología del Hospital Pediátrico Provincial Docente Pepe Portilla de la provincia Pinar del Río. Se seleccionó el grupo coordinador de la técnica a realizar. Se utilizó la Metodología Delphi, en sus cuatro fases: definición del tema, selección de expertos, ejecución de rondas de consultas y evaluación de los resultados. Para determinar las similitudes y concordancias de las respuestas, se calculó el coeficiente de concordancia de Kendall y Friedman. Resultados: se seleccionaron 21 expertos con altos niveles de competencia de acuerdo al cálculo de los coeficientes de conocimiento y argumentación. En la tercera versión del cuestionario existió similitud en las respuestas de los expertos a favor de la categoría superior de Muy imprescindible, así como concordancia en el nivel de respuesta. Conclusiones: el cuestionario diseñado alcanza niveles óptimos de validez de contenido y factibilidad para determinar la contribución de los factores genéticos y su interacción con factores ambientales en la aparición de los trastornos inmunitarios por asma bronquial.

ABSTRACT Introduction: bronchial asthma is the classic disease among allergic conditions, and has great impact on health worldwide. It is a complex disease both genetically and phenotypically, and genetic-environmental interactions make it even more complex. Objective: to validate a questionnaire for the study of the involvement of genetic factors and their interaction with environmental factors in the onset of immune disorders due to bronchial asthma. Methods: the study was developed in the Department of Immunology at Pepe Portilla Provincial Pediatric Teaching Hospital in Pinar del Río province. The coordinating group of the technique to be carried out was selected and comprised three professionals responsible for the proposed research. The Delphi Methodology was used, completing its four phases: definition of the topic, selection of experts, implementation of consultation rounds and assessment of results. To determine the agreement or similarities of the responses of the evaluators respectively, the Kendall and Friedman concordance coefficient was calculated. Results: twenty-one (21) experts with high levels of competence were selected according to the calculation of the coefficients of knowledge and argumentation. In the third version of the questionnaire, there was similarity in the responses of the experts in favor of the higher category of Very Essential, as well as agreement in the level of response of the experts. Conclusions: the designed questionnaire reaches optimal levels of content validity and feasibility to determine the contribution of genetic factors and their interaction with environmental factors on the onset of immune disorders due to bronchial asthma.

CD40 Ligand Deficiency.

CD40 ligand deficiency (CD40L), currently classified as an inborn error of immunity affecting cellular and humoral immunity, prevalently emerges in boys within the first two years of life. It manifests itself as a decrease in serum IgG, IgA and IgE, with normal or high IgM, defects in T cell proliferation, and decrease in soluble CD40L. These accompany sinopulmonary and/or gastrointestinal infections, and there may be infections caused by pyogenic bacteria, opportunistic infections, autoimmune diseases, and neoplasms. Mild and moderate cases of this deficiency may respond well to prophylactic antibiotic therapy or to human immunoglobulin replacement therapy, in addition to the early treatment of infections. Severe cases can be treated with hematopoietic stem cell transplantation, which allows the healing of such patients, rather than sequelae and a poor progression. Thus, its differential diagnosis with other inborn errors of immunity is essential, especially CD40 deficiency and variable common immunodeficiency; the reason why we have proposed the present literature review.

Imunodeficiência comum variável associada à doença de Crohn-like: relato de caso e revisão da literatura / Common variable immunodeficiency associated with Crohn-like disease: case report and literature review

OBJETIVOS: relatar o caso de um paciente diagnosticado com imunodeficiência comum variável e doença de Crohn-like, descrevendo o quadro clínico, o processo de investigação diagnóstica, as abordagens terapêuticas e a evolução clínica do paciente. Realizar revisão bibliográfica de relatos de caso que abordem pacientes com a associação imunodeficiência comum variável e doença de Crohn-like. Enfatizar a importância do diagnóstico e tratamento precoces. DESCRIÇÃO DO CASO: Um paciente masculino foi diagnosticado com imunodeficiência comum variável aos nove anos de idade e doença inflamatória intestinal inespecífica aos 10 anos, após realização de colonoscopia e biópsia colônica indicando moderado infiltrado linfoplasmocitário, eosinofílico e alguns neutrófilos em lâmina própria, com ausência de granulomas. Aos 14 anos, foi confirmado o diagnóstico de doença de Crohn-like por especialista após correlação entre história clínica e exames complementares. Atualmente com 18 anos, o paciente está em tratamento com imunoglobulina humana endovenosa, infliximabe e azatioprina, com estabilização do quadro clínico. CONCLUSÕES: A revisão da literatura identificou 11 relatos de caso sobre a associação imunodeficiência comum variável e doença de Crohnlike, inexistindo trabalhos brasileiros, o que ressalta a raridade de tal associação. Neste relato, o paciente recebeu tratamentos amplos e empíricos devido à dificuldade em se chegar a um diagnóstico específico, o qual somente foi realizado aos 14 anos, quando se iniciou tratamento mais direcionado e individualizado. Apesar de atualmente estável, o paciente apresentou diversas complicações durante a investigação diagnóstica, o que ressalta a importância de diagnóstico precoce e tratamento mais preciso e dirigido às necessidades de saúde desses pacientes.

AIMS: To report the case of a patient diagnosed with common variable immunodeficiency and Crohn-like disease, describing the clinical picture, the diagnostic investigation process, the therapeutic approaches and the clinical outcome of the patient. To carry out a literature review of case reports addressing patients with the common variable immunodeficiency and Crohn-like disease association. Emphasize the importance of early diagnosis and treatment. CASE DESCRIPTION: A male patient was diagnosed with common variable immunodeficiency at nine years of age and with non-specific inflammatory bowel disease at 10 years, after colonoscopy and colonic biopsy indicated moderate lymphoplasmacytic, eosinophilic infiltrate and some neutrophils in lamina propria, with absence of granulomas. At age 14, the diagnosis of Crohn-like disease was confirmed by specialist after correlation between clinical history and complementary exams. Currently with 18 years of age, the patient is under treatment with intravenous human immunoglobulin, infliximab and azathioprine, with stabilization of the clinical picture. CONCLUSIONS: The literature review identified 11 case reports on the association between common variable immunodeficiency and Crohn-like disease, with no Brazilian studies, which highlights the rarity of such association. In this report, the patient received extensive and empirical treatments due to the difficulty in reaching a specific diagnosis, which was only performed at age 14, when more targeted and individualized treatment was started. Although currently stable, the patient presented several complications during the diagnostic investigation, which emphasizes the importance of early diagnosis and more precise treatment, targeted to meet the health needs of these patients.

Diagnostic Delay of Primary Immunodeficiencies at a Tertiary Care Hospital in Peru- Brief Report.

OBJECTIVE: The aim of the study was to assess the diagnostic delay in pediatric patients with primary immunodeficiencies (PID) at a tertiary care hospital in Peru. METHODS: A descriptive study was carried out in which patients from a third-level referral center in Peru were included. Those without a specific diagnosis of PID were excluded. Data was collected by reviewing the medical records and interviewing patients' family members. RESULTS: A total of 45 patients with a mean of 7.4 years (SD = 4.3) were studied. The most frequent diagnosis was predominant antibody defects (35.5%), and the diagnostic delay had a median of 12.17 months (IQR 5.1-30.3). CONCLUSIONS: The most frequently diagnosed group of PID was predominant antibody deficiency. The overall median diagnostic delays for PID and predominant antibody deficiency were 12 and 14 months, respectively. Even though early detection of PIDs is crucial for effective treatment, current available laboratory tests required for PID diagnosis are both complex and expensive. Early detection and management of these pathologies cannot be achieved without training non-specialist health professionals in the diagnosis of PID, as well as integrating multidisciplinary and multi-center cooperation at both national and international levels.

II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies / II Consenso Brasileiro sobre o uso de imunoglobulina humana em pacientes com imunodeficiências primárias

ABSTRACT In the last few years, new primary immunodeficiencies and genetic defects have been described. Recently, immunoglobulin products with improved compositions and for subcutaneous use have become available in Brazil. In order to guide physicians on the use of human immunoglobulin to treat primary immunodeficiencies, based on a narrative literature review and their professional experience, the members of the Primary Immunodeficiency Group of the Brazilian Society of Allergy and Immunology prepared an updated document of the 1st Brazilian Consensus, published in 2010. The document presents new knowledge about the indications and efficacy of immunoglobulin therapy in primary immunodeficiencies, relevant production-related aspects, mode of use (routes of administration, pharmacokinetics, doses and intervals), adverse events (major, prevention, treatment and reporting), patient monitoring, presentations available and how to have access to this therapeutic resource in Brazil.

RESUMO Nos últimos anos, novas imunodeficiências primárias e defeitos genéticos têm sido descritos. Recentemente, produtos de imunoglobulina, com aprimoramento em sua composição e para uso por via subcutânea, tornaram-se disponíveis em nosso meio. Com o objetivo de orientar o médico no uso da imunoglobulina humana para o tratamento das imunodeficiências primárias, os membros do Grupo de Assessoria em Imunodeficiências da Associação Brasileira de Alergia e Imunologia produziram um documento que teve por base uma revisão narrativa da literatura e sua experiência profissional, atualizando o I Consenso Brasileiro publicado em 2010. Apresentam-se novos conhecimentos sobre indicações e eficácia do tratamento com imunoglobulina nas imunodeficiências primárias, aspectos relevantes sobre a produção, forma de utilização (vias de administração, farmacocinética, doses e intervalos), efeitos adversos (principais efeitos, prevenção, tratamento e notificação), monitorização do paciente, apresentações disponíveis e forma de obtenção deste recurso terapêutico em nosso meio.

Type and location of bronchiectasis in a cohort of adults with common variable immunodeficiency / Tipo y localización de bronquiectasias en una cohorte de adultos con inmunodeficiencia común variable

Background: Bronchiectasis are permanent dilatations of the bronchi. Its prevalence in patients with variable common immunodeficiency (CVID) is high, however there is little information regarding the type and location of the same; therefore the objective of this study is to know the type and location of bronchiectasis in a cohort of adult patients with CVID. Methods: It has been made a transversal, observational and descriptive study that included 32 adult patients with diagnosis of CVID according to the criteria of the European Society of Immunodeficiencies (ESID). All patients underwent high resolution pulmonary computed tomography (HRCT), which were interpreted by an expert radiologist. The frequency, type and location of bronchiectasis were reported using descriptive statistics. Results: Thirty-two adult patients, ten men (31.25%) and 22 women (68.7%), were included. 40.6% had bronchiectasis. 23% had a lobe involvement, 15.3% two lobes, 46.1% 3 lobes and 15.3% complete involvement of the parenchyma. The types of bronchiectasis were distributed as follows: tubular 38.4%, varicose 23% and cystic and tubular combinations 15.3%, cystic and varicose 15.3% and cystic, tubular and varicose 7.6%. Conclusions: Our results show that 40% of adult patients with CVID have BQs, usually affecting three pulmonary lobes, located mainly in the right and middle lower lobe; The tubular type, is the most common. Their timely diagnosis and treatment can improve survival and reduce costs for patients and health care.

Introducción: Las bronquiectasias (BQs) son dilataciones permanentes de los bronquios. Su prevalencia en pacientes con inmunodeficiencia común variable (IDCV) es alta, sin embargo existe escasa información respecto al tipo y localización de las mismas. El objetivo de este estudio es conocer el tipo y localización de las bronquiectasias en una cohorte de pacientes adultos portadores de IDCV. Métodos: Estudio transversal, observacional y descriptivo que incluyó a 32 pacientes adultos con diagnóstico de IDCV de acuerdo con los criterios de la Sociedad Europea de Inmunodeficiencias. A todos se les realizó tomografía de alta resolución pulmonar, las cuales fueron interpretadas por un médico radiólogo experto. Se reportó la frecuencia, tipo y localización de las bronquiectasias mediante estadística descriptiva.Resultados: se incluyeron 32 pacientes adultos, diez hombres y 22 mujeres. El 40.6% presentaron bronquiectasias. El 23% tenía afección en un lóbulo, el 15.3% dos lóbulos, 46.1% 3 lóbulos y el 15.3% afectación completa del parénquima; distribuidos de la siguiente manera: tubulares 38.4%, varicosas 23% y las combinaciones quísticas y tubulares 15.3%, quísticas y varicosas 15.3% y quísticas, tubulares y varicosas 7.6%. Conclusión: Nuestros resultados muestran que el 40% de los pacientes adultos con IDCV tienen BQs, suelen afectar tres lóbulos pulmonares, el tipo más común fue el tubular. Su diagnóstico y tratamiento oportuno puede mejorar la supervivencia y reducir los costos para el paciente y las instituciones de salud.