El reto del internista ante las enfermedades autoinmune reumáticas / The Challenge Faced by Internists in Rheumatological Autoimmune Diseases

El progreso científico de un continente o de un país en específico puede medirse a través de los estudios bibliométricos que tienen como objeto el tratamiento y el análisis cuantitativo de las publicaciones científicas. Este se basa en el número de publicaciones, autores, citas bibliográficas y áreas de investigaciones comunes.1 En Latinoamérica estos datos sobre las enfermedades autoinmunes (EA) resultan poco conocidos. Entre los años de 2007 a 2017 se encontraron 7184 publicaciones sobre este tema, y es el lupus eritematoso sistémico (LES) el tópico más publicado seguido de las enfermedades inflamatoria intestinal y artritis reumatoide (AR). Cuba precedida por Perú ocupó el octavo lugar. Estas cifras resultan bajas en relación con líderes como Brasil, México y Argentina, aunque se considera meritorio que Cuba esté entre los 10 primeros países entre 24 naciones del continente.2 No obstante, al evaluar cuanto se ha logrado, nos enfrentamos al reto de profundizar aún más en el conocimiento sobre la epidemiología, los complejos mecanismos patogénicos y las disímiles formas clínicas de expresión de estas entidades, para continuar el avance en las dianas terapéuticas. Los estudios epidemiológicos comunitarios para el control de la prevalencia de las enfermedades reumáticas y la discapacidad asociada están bajo la iniciativa de la Organización Mundial de la Salud y la Liga Internacional de Reumatología (COPCORD/WHO/ILAR), que se realiza en Cuba, publicados en (Journal Clinical of Rheumatology) en el 2009; esto ha permitido establecer la prevalencia de la AR en el 1,2 por ciento y el lupus en 60/100,000 habitantes.3 Los datos citados por la comunidad internacional han sentado las bases para subsiguientes estudios de investigación, para así propiciar a los directivos de la salud tomas de decisiones en cuanto a las necesidades de los recursos materiales y humanos. La AR es una enfermedad inflamatoria crónica, caracterizada por la presencia de autoanticuerpos causales de una cascada de citoquinas proinflamatorias determinantes en el daño articular irreversible. El tratamiento se ha basado en el uso de drogas convencionales, como el metotrexato, leflunomida, azulfidina y sus combinaciones, las cuales ofrecen algunos beneficios pero sus efectos están limitados por la toxicidad.4 El uso de drogas biológicas para la AR, como los anticuerpos anti-TNF-α, el tocilizumab que va dirigido contra el receptor de IL-6, abatacept que previene la coestimulación, el rituximab Ac, anticélulas B CD20 y el tofacitinib como un nuevo inhibidor de las Janus quinasa (JAK, por sus siglas en inglés) de reciente aprobación por las agencias regulatorias de Estados Unidos (FDA) y la agencia europea (EMA) han mejorado sustancialmente la eficacia terapéutica antes alcanzada.5 Las experiencias de los reumatólogos cubanos fueron recogidas en el documento Nacional de Consenso realizado en nuestro país sobre tratamiento de la AR, a partir de la consideración del documento de postura latinoamericano discutido en la localidad chilena de Reñaca con la presencia de eminentes reumatólogos cubanos.6 La atención en la práctica diaria de los pacientes con LES en la fase de la actividad severa y con daño acumulado, presupone un desafío para los especialistas. Se trata de una enfermedad poligénica asociada a la producción de autoanticuerpos, con pérdida de la autotolerancia, el desarrollo de una respuesta inmune alterada y la expresión de diversas manifestaciones clínicas que difícultan establecer un diagnóstico temprano, aunque, cuenta con criterios de clasificación y diagnóstico por La Liga Europea y el Colegio Americano de Reumatología (ACR).7) Además, puede remedar afecciones como la tuberculosis y la infección por el virus de la inmunodeficiencia humana (VIH/SIDA). Esta nueva terapia de antirretrovirales ha sido muy efectiva, por lo tanto ha aumentado la supervivencia de los pacientes con el (VIH), pero a partir de la emergencia sobre los nuevos desórdenes autoinmunes reumáticos se convierte para los especialistas en un nuevo reto clínico.8,9 Cuba está entre los 21 países fundadores del Grupo Latinoamericano para el estudio del LES (GLADEL), con la participación y coautoría de múltiples estudios y publicaciones internacionales de impacto.10,11,12 Consideramos una fortaleza que los especialistas cubanos como Marlene Guibert y Gil Reyes hayan logrado la inclusión de una serie proporcional de pacientes en las cohortes internacionales de pacientes con AR, con lupus y que han asumido el reto de la coautoría de las primeras Guías Latinoamericanas de Tratamiento acerca del lupus eritematoso sistémico.13 En el caso de la ES es una rara enfermedad del tejido conectivo en la cual intervienen mediadores profibróticos como el factor vascular endotelial de crecimiento (VEGF), el factor 4 de activación de plaquetas (PF4), y el sistema inmune innato con inflamación, vasculopatía y fibrosis, incluso intersticial pulmonar en 35-52 por ciento de los casos y la mortalidad con el 20-40 por ciento14,15 En general resultan escasos los estudios publicados en el país. En la Revista Cubana de Reumatología aparecen 2 estudios epidemiológicos de nuestra autoría: uno publicado en el año 2007 y el otro en el año 2014, ambos artículos mostraron una evaluación clínico-epidemiológica de una serie de 34 pacientes en dos centros de referencia nacional, que describen las manifestaciones gastrointestinales severas en pacientes con ES realizadas en el hospital CIMEQ. Como limitaciones señalamos que el estudio realizado fue descriptivo y desarrollado en una pequeña serie.16Pérez y otros,17 en el hospital Hermanos Ameijeiras, mostraron los resultados satisfactorios del tratamiento en 2 grupos de pacientes con ES, enfermedad pulmonar......(AU)

Autoimmune bullous diseases in pregnancy: clinical and epidemiological characteristics and therapeutic approach

Abstract Autoimmune bullous dermatoses are a heterogeneous group of diseases with autoantibodies against structural skin proteins. Although the occurrence of autoimmune bullous dermatoses during pregnancy is low, this topic deserves attention, since the immunological and hormonal alterations that occur during this period can produce alterations during the expected course of these dermatoses. The authors review the several aspects of autoimmune bullous dermatoses that affect pregnant women, including the therapeutic approach during pregnancy and breastfeeding. Gestational pemphigoid, a pregnancy-specific bullous disease, was not studied in this review.

Biomarcadores salivares no diagnóstico e no monitoramento de patologias orais e sistêmicas / Biomarcadores salivares en el diagnóstico y monitoreo de enfermedades bucales y sistémicas / Salivary biomarkers for the diagnosis and monitoring of oral and systemic diseases

RESUMO Introdução: A saliva humana é constituída de um vasto arsenal de produtos secretórios com imenso potencial informativo e útil para detecção de determinadas patologias. A facilidade de obtenção e a especificidade dos biomarcadores, faz desta uma importante ferramenta clínica como método diagnóstico. Objetivo: Verificar, através de uma revisão de literatura, a utilização da saliva como método diagnóstico para doenças orais e sistêmicas. Métodos: Foram selecionados artigos publicados em inglês, no banco de dados online PubMed com descritores "saliva", "biomarkers" e "diagnosis", entre o período de 2013 a setembro 2018. Foram incluídos artigos no idioma inglês, dos últimos 5 anos. Foram obtidos 245 artigos. O estudo se conteve em 17 destes. Análise e integração da informação: Foi notória a aplicabilidade da saliva como método diagnóstico para uma variedade de doenças, entre as quais se podem citar: doenças bacterianas como a cárie dentária, pela detecção do Streptococcus mutans e Lactobacillus spp.; doenças autoimunes como a Síndrome de Sjögren, indicada não apenas pela redução do fluxo salivar, como também pelo aumento na concentração de sódio, cloro, Imunoglobulina A (IgA), Imunoglobulina G (IgG), e Prostaglandina E2 (PGE2); doenças virais como no diagnóstico auxiliar do HIV 1 e 2 pela expressão de IgG e também no diagnóstico precoce de enfermidades malignas como o carcinoma de células escamosas e o câncer de mama, pela detecção de anticorpos frente à proteína p53 e pela presença de marcadores tumorais como o c-erbB-2. Conclusão: O diagnóstico molecular na cavidade oral por meio da saliva mostra ser um método simples, não invasivo e muito promissor para o diagnóstico e monitoramento de inúmeras patologias(AU)

RESUMEN Introducción: La saliva humana está constituida de un considerable arsenal de productos secretorios con inmenso potencial informativo y útil para la detección de determinadas enfermedades. La facilidad de obtención y la especificidad de los biomarcadores, hace de esta una importante herramienta clínica como método diagnóstico. Objetivo: Verificar, por medio de una revisión bibliográfica, la utilización de la saliva como método diagnóstico para enfermedades bucales y sistémicas. Métodos: Se seleccionaron artículos publicados en inglés, en la base de datos online PubMed con descriptores "saliva", "biomarkers" y "diagnosis", entre el período de 2013 a septiembre de 2018. Se incluyeron artículos en idioma inglés, de los últimos 5 años. Se obtuvieron 245 artículos. El estudio se circunscribió a 17. Análisis e integración de la información: Se observó la aplicabilidad de la saliva como método diagnóstico para una variedad de enfermedades, entre las que cabe citar: enfermedades bacterianas como la caries, por la detección del Streptococcus mutans y Lactobacillus spp.; las enfermedades autoinmunes como el síndrome de Sjögren, indicado no solo por la reducción del flujo salivar, sino también por el aumento en la concentración de sodio, cloro, Inmunoglobulina A (IgA), Inmunoglobulina G (IgG), y Prostaglandina E2 (PGE2); las enfermedades virales como el diagnóstico auxiliar del VIH 1 y 2 por la expresión de IgG y también el diagnóstico precoz de enfermedades malignas como el carcinoma de células escamosas y el cáncer de mama, por la detección de anticuerpos contra la proteína p53 y por la presencia de marcadores tumorales como el c-erbB-2. Conclusiones: El diagnóstico molecular en la cavidad bucal por medio de la saliva muestra ser un método simple, no invasivo y muy prometedor para el diagnóstico y monitoreo de innumerables enfermedades(AU)

ABSTRACT Introduction: Human saliva consists of a vast arsenal of secretory products with huge information potential useful for the detection of certain diseases. The easy availability and the specificity of biomarkers make them an important clinical tool as a diagnostic method. Objective: By means of a bibliographic review, verify the use of saliva as a diagnostic method for oral and systemic diseases. Methods: A bibliographic search was conducted in the online database PubMed for papers published in English from 2013 to September 2018, using the search terms "saliva", "biomarkers" and "diagnosis". Papers written in English in the last five years were selected. Of the 245 papers obtained, the study considered 17. Data analysis and integration: It was found that saliva may be used as a diagnostic method for a variety of diseases. These include bacterial diseases such as dental caries, by detection of Streptococcus mutans and Lactobacillus spp.; autoimmune diseases such as Sjögren's syndrome, indicated not only by the decrease in salivary flow, but also by the increase in the concentration of sodium, chlorine, immunoglobulin A (IgA), immunoglobulin G (IgG), and prostaglandin E2 (PGE2); viral diseases as in the auxiliary diagnosis of HIV 1 and 2 by IgG expression and also in the early diagnosis of malignant diseases such as squamous cell carcinoma and breast cancer by detection of antibodies against p53 protein and the presence of tumor markers such as c-erbB-2. Conclusions: Molecular diagnostic examination of the oral cavity using saliva has shown to be a simple, non-invasive and very promising method for the diagnosis and monitoring of numberless diseases(AU)

Miastenia gravis: Registro de 190 casos en un centro único / Myasthenia gravis. Register of 190 cases in a single center

La miastenia gravis (MG) es una enfermedad autoinmune mediada por anticuerpos dirigidos contra proteínas post sinápticas de la unión neuromuscular. El objetivo de este estudio fue describir los aspectos clínicos, epidemiológicos y serológicos de pacientes con MG en un Hospital Público de la Ciudad de Buenos Aires. Se realizó un análisis retrospectivo sobre 190 enfermos con diagnóstico de MG. La edad media de inicio de la enfermedad fue de 38 años; 57 (30%) fueron MG de inicio tardío (inicio de síntomas > 50 años). La relación mujer/hombre fue 1.7/1. La enfermedad se inició más tempranamente en las mujeres que en los hombres, media 32 vs. 48 años (p < 0.0001). La MG familiar autoinmune representó el 3.2 % (6 casos). La forma más común de presentación fue con manifestaciones oculares puras (52%). El 12.1% (23/190) fue considerada MG ocular en el seguimiento. La MG asociada a timoma se presentó en 22 casos (11.6%). El 27.1% presentó otra enfermedad autoinmune asociada, siendo las tiroideas las más frecuentes. El 81.4% tuvo anticuerpos anti-receptores de acetilcolina (ACRA) positivos y 22.7% de los ACRA negativos fueron positivos para anticuerpos anti-tirosina quinasa musculo especifica (anti-MusK). La evolución clínica fue favorable, hallándose más de la mitad de los casos en remisión o manifestaciones mínimas en la última visita. La mayoría requirió inmunosupresión para control de la sintomatología, el 78% recibió corticoides y el 48% un inmunosupresor no esteroideo.

Myasthenia gravis (MG) is an antibody-mediated autoimmune disease of the neuromuscular junction. The aim of this study was to evaluate clinical, epidemiological and serological features of patients with MG in a Public Hospital of Buenos Aires City. A retrospective analysis of 190 patients diagnosed with MG was performed. The mean age of MG onset was 38 years, 30% had late-onset MG (onset age > 50 years). The female/male ratio was 1.7 / 1. Disease started earlier in women than in men, mean 32 vs. 48 years (p < 0.0001). Familial autoimmune MG represented 3.2% of the cases. Most of the patients initiated their disease with a pure ocular form (52%). 12.1% (23/190) were considered ocular MG at follow-up. Thymoma-associated MG represented 11.6% of cases. 27.1% had other associated autoimmune disease, thyroid disorders were the most frequent. 81.4% were anti-acetylcholine receptor antibody (AChR-ab) positive MG; 22.7% of AChR-ab negatives were positive for anti-muscle specific kinase (MusK) antibodies. Clinical outcome was relatively good; more than half of cases were in remission or minimal manifestations at the last visit. The majority of patients required immunosuppression to control the symptoms, 78% received corticosteroids and 48%, a non-steroidal immunosuppressant.

Clinical characteristics and associations of palmoplantar pustulosis: an observational study

Abstract Background: Palmoplantar pustulosis is a chronic and relapsing disease of the palms and soles, which is characterized by scattered clusters of pinhead-sized, sterile pustules. Objective: The aim of the present study was to determine demographic features, co-morbidities, and relation of palmoplantar pustulosis with psoriasis. Methods: A total of 48 patients (M/F: 15/33) were enrolled in the present study. A detailed history regarding age of onset, palmoplantar pustulosis duration, number of recurrences, personal and family history of psoriasis, accompanying arthritis, sternoclavicular tenderness, dental fillings, smoking status, and autoimmune disease was obtained; thorough dermatological examination was carried out. Patch testing results and laboratory investigations for thyroid autoimmunity were recorded. Results: Thirty-five of 48 patients (72.9%) were current smokers. Twenty of the 48 patients (41.7%) had dental fillings. There was not any significant correlation between palmoplantar pustulosis duration and dental filling duration (p = 0.170). Psoriasis was not detected in any patients either in history or in dermatological examination. Nail involvement and joint complaints were observed in seven of 48 patients (14%) and in nine of 48 patients (18%), respectively. Autoimmune thyroiditis was observed in four of 48 patients (12%). Patients with patch testing positivity (12.5% of patients, M/F: 1/5) had no considerable association for history of external contact with these materials. Study limitations: Retrospective analysis. Conclusion: Palmoplantar pustulosis appears to be a distinct entity from psoriasis. Routine thyroid functions test could be analyzed, but patch testing is not required in patients with palmoplantar pustulosis. Also, patients with palmoplantar pustulosis must be evaluated for musculoskeletal symptoms and signs.

Evaluation of adult celiac disease from a tertiary reference center: a retrospective analysis

SUMMARY OBJECTIVE It has been observed that celiac disease (CD) is not restricted to a single type characterized by diarrhea but also has atypical, asymptomatic (silent), and latent forms. The prevalence of this autoimmune disease, which affects approximately 1% of the world, is estimated to be around 3%, including atypical and asymptomatic cases. In our study, we aimed to evaluate adult celiac patients. METHODS Between December 2008-2015, patients diagnosed with CD over the age of 18 years old were included in the study. Patients' symptoms at admission, frequency and type of anemia, transaminase levels, and celiac antibody positivity, and autoimmune diseases diagnosed at follow up were evaluated retrospectively. RESULTS Of 195 patients, 151 (77.4%) were female. The mean age of the patients was 35.73 ± 12.19 years (range, 18-71 years). A hundred patients (51.3%) had gastrointestinal symptoms. At the time of admission, 118 patients (60.5%) had anemia, and 52 (26.7%) had hypertransaminasemia. During the mean follow-up period of 58 months (36-120 months), 84 (43.1%) of the patients presented at least one autoimmune disease, and this rate was 96.6% in individuals diagnosed above the age of 50 years. CONCLUSION In adult CD, resistant anemia, dyspepsia, and hypertransaminasemia are very common findings at the time of diagnosis, and the association with other autoimmune diseases, especially Hashimoto's thyroiditis, is high.

RESUMO OBJETIVOS Observou-se que a doença celíaca (DC) não se restringe a um único tipo caracterizado por diarreia, mas também tem formas atípicas, assintomáticas (silenciosas) e latentes. Estima-se que a prevalência desta doença autoimune, que afeta aproximadamente 1% da população do mundo, seja em torno de 3%, incluindo casos atípicos e assintomáticos. Em nosso estudo, objetivou-se avaliar pacientes celíacos adultos. MÉTODOS Entre dezembro de 2008 e 2015, pacientes diagnosticados como DC com idade acima de 18 anos foram incluídos no estudo. Os sintomas dos pacientes na admissão, frequência e tipo de anemia, níveis de transaminases e positividade de anticorpos celíacos e doenças autoimunes diagnosticadas no seguimento foram avaliados retrospectivamente. RESULTADOS Dos 195 pacientes, 151 (77,4%) eram do sexo feminino. A média de idade dos pacientes foi de 35,73±12,19 anos (variação de 18 a 71 anos). Cem pacientes (51,3%) foram encaminhados com sintomas gastrointestinais. No momento da internação, 118 pacientes (60,5%) apresentavam anemia e 52 (26,7%) apresentavam hipertransaminemia. Durante o período médio de acompanhamento de 58 meses (36-120 meses), 84 (43,1%) pacientes estavam acompanhados por pelo menos uma doença autoimune, e essa taxa foi de 96,6% em indivíduos diagnosticados acima dos 50 anos de idade. CONCLUSÃO No adulto DC, anemia resistente, dispepsia e hipertransaminasemia são achados muito comuns no momento do diagnóstico e a associação com outras doenças autoimunes, especialmente tireoidite de Hashimoto, é alta.

Inmunodeficiencias primarias y citopenias / Primary immunodeficiencies and cytopenias

Introducción: La visión actual de las enfermedades por inmunodeficiencia primaria (IDP) incluye un número creciente de síndromes que están asociados con la desregulación inmune y la autoinmunidad como características predominantes. Las citopenias autoinmunes pueden ser el primer signo de desregulación que precede a la presentación clásica de inmunodeficiencia primaria, con infecciones recurrentes u oportunistas. El conocimiento de un espectro de enfermedades potencialmente involucradas (hematológicas, reumatológicas e inmunológicas) es crucial para la identificación de una cierta proporción de genotipos y fenotipos de otros diagnósticos descritos. También permitirá excluir desórdenes como lupus eritematoso sistémico, inmunodeficiencia variable común, síndrome linfoproliferativo autoinmune; así como realizar diagnósticos diferenciales noveles como la deficiencia de GATA2, deficiencia de CD27, deficiencia de sensibilidad a lipopolisacáridos, síndrome fosfoinositol-3-quinasa delta activada, inmunodeficiencia ligada a X con déficit de magnesio y otros. Objetivo: Proporcionar una sinopsis conceptual de la aparición de citopenias en las IDP con el propósito de actualizar el conocimiento actual sobre dicho tema y de aumentar la percepción, tanto de hematólogos como inmunólogos, en relación a la presentación de citopenias como manifestación de estas enfermedades. Métodos: Se revisaron artículos originales y de corte experimental publicados en la década 2009 - 2019, en algunas bases de datos de la Biblioteca Virtual de Salud (BVS) de Cuba. Conclusiones: Al igual que las formas benignas autolimitadas de citopenia autoimmune post o parainfecciosas, o la neutropenia autoimmune adquirida de la infancia, que generalmente ocurren independientemente de una IDP subyacente reconocida, muchas de las citopenias que acompañan a esta enfermedad (pero no todas) están mediadas por autoanticuerpos. Es esencial entonces, que los médicos valoren, ante la evidencia clara de citopenia, que esta puede ser autoinmune(AU)

Introduction: The current view of primary immunodeficiency diseases (IDP) includes an increasing number of syndromes that are associated with immune dysregulation and autoimmunity as predominant characteristics. Autoimmune cytopenias may be the first sign of dysregulation that precedes the classic presentation of primary immunodeficiency, with recurrent or opportunistic infections. The knowledge of a spectrum of potentially involved diseases (hematological, rheumatological and immunological) is crucial for the identification of a certain proportion of genotypes and phenotypes of other diagnoses described. It will also allow excluding disorders such as systemic lupus erythematosus, common variable immunodeficiency, autoimmune lymphoproliferative syndrome; as well as making novel differential diagnoses such as GATA2 deficiency, CD27 deficiency, lipopolysaccharide sensitivity deficiency, activated delta phosphoinositol-3-kinase syndrome, X-linked immunodeficiency with magnesium deficiency and others. Objective: This review provides a conceptual synopsis of the appearance of cytopenias in the IDPs with the purpose of updating current knowledge on this topic and increasing the perception, of both hematologists and immunologists, in relation to the presentation of cytopenias as manifestation of these diseases. Methodos: Original and experimental articles published in the 2009-2019 decade were reviewed in some databases of the Virtual Health Library (VHL) of Cuba. Conclusions: As the self-limited benign forms of post or parainfectious autoimmune cytopenia, or childhood acquired autoimmune neutropenia, which generally occur independently of a recognized underlying IDP, many of the cytopenias that accompany this disease (but not all) mediated by autoantibodies. It is essential, then, that doctors assess, given the clear evidence of cytopenia, that it may be autoimmune(AU)

Síndrome de Turner: nuestra experiencia en la creación del Registro Institucional y de la Unidad Interdisciplinaria en el Hospital Italiano de Buenos Aires: un primer paso para el mejor seguimiento / Turner syndrome: our experience in the creation of the Registry Institutional and Interdisciplinary Unit at the Italian Hospital of Buenos Aires: a first step to the best follow-up

El síndrome de Turner (ST) resulta de la ausencia completa o parcial del segundo cromosoma sexual en fenotipos femeninos. Tiene una incidencia de 1:2000- 2500 nacidas vivas. Recién en la última década se ha puesto atención a la salud de las adultas con ST. La mortalidad es 3 veces superior respecto de la población general debido al riesgo de disección aórtica por anomalías cardiovasculares estructurales y aterosclerosis vinculada a hipertensión arterial, diabetes, dislipidemia y obesidad. También presentan elevada prevalencia de enfermedades autoinmunitarias. Objetivo: evaluar la calidad del seguimiento clínico de pacientes adultas con ST, comparando los controles de salud preconformación y posconformación del Registro y de la Unidad Interdisciplinaria. En el año 2017 fuimos convocados para integrar el Programa de Enfermedades Raras del Hospital Italiano de Buenos Aires. A partir de la creación del Registro Institucional y del equipo multidisciplinario obtuvimos mejoría significativa en los controles por las especialidades de cardiología, endocrinología y otorrinolaringología, en los controles bioquímicos del metabolismo lipídico, hidrocarbonado, hepatograma, TSH y anticuerpos para celiaquía e imágenes cardiovasculares y densitometría ósea. En conclusión, el seguimiento sistematizado e institucional, mediante el Registro y la creación de la Unidad Interdisciplinaria de Síndrome de Turner, permitió encontrar las falencias del sistema de atención y optimizar el seguimiento de esta población. (AU)

Turner syndrome (TS) results from the complete or partial absence of the second sex chromosome in female phenotypes. It has an incidence of 1: 2000-2500 girls born alive. Only in the last decade has been paid attention to the health of adults women with TS. Mortality is 3 times higher than in the general population due to the risk of aortic dissection cause to structural cardiovascular anomalies and atherosclerosis related to hypertension, diabetes, dyslipidemia and obesity. They also have a high prevalence of autoimmune diseases. Until nowadays in Argentina do not exist a national registry of this disease that complies with the international follow-up recommendations for these patients. We proposed to develop the institutional register at 2014 and a multidisciplinary team was created to care and follow up girls and women with TS during 2015. It was indexed to Italian Hospital of Buenos Aires' Rare Diseases Program since 2017. After the creation of the institutional registry and the multidisciplinary team we obtained a significant improvement in cardiology, endocrinology and otorhinolaryngology schedule visits, in lipids and hydrocarbon metabolism, liver, thyroid and celiac diseases biochemical controls and in the performance of cardiovascular MNR and bone densitometry. In conclusion, the systematized and institutional follow-up, through the registry and the creation of the Interdisciplinary Unit of Turner Syndrome, allowed us to find the flaws of the care system and to optimize the follow up of this population. (AU)

Marcadores serológicos de hepatopatías virales y autoinmunes en pacientes celíacos atendidos en el Instituto de Gastroenterología / Serologic markers of viral and autoimmune liver diseases in celiac patients treated at the Institute of Gastroenterology

Introducción: El espectro del compromiso hepático en la enfermedad celíaca es muy amplio e incluye hepatopatías virales y autoinmunes. Objetivo: Caracterizar el comportamiento de los marcadores serológicos de hepatopatías virales y autoinmunes en pacientes celíacos adultos atendidos en el Instituto de Gastroenterología. Materiales y Métodos: Se realizó un estudio observacional descriptivo transversal en el período comprendido entre marzo de 2016 y marzo 2017 en 43 pacientes adultos celíacos atendidos en el Instituto de Gastroenterología de La Habana. A todos, previo consentimiento informado se les realizaron estudios bioquímicos y serológicos para identificar infección por virus de hepatitis B, C y respuesta inmune humoral frente a autoanticuerpos hepáticos y sistémicos. Para el análisis estadístico se emplearon distribuciones de frecuencia y para la comparación entre los grupos se utilizó la probabilidad exacta de Fisher. Se consideró significativo una p < 0,05. Resultados: El 58,1 por ciento de los pacientes presentó hipofosfatasemia y 14 por ciento hipertransaminasemia, sin coincidencias entre los casos registrados. El 100 por ciento de los celíacos fue negativo para el virus de hepatitis C. La positividad de autoanticuerpos hepáticos se registró entre 2,3 por ciento y 14 por ciento de los pacientes evaluados. Existió asociación significativa entre hipertransaminasemia y la presencia de anticuerpos séricos contra la transglutaminasa tisular. Conclusiones: La expresión de marcadores de autoinmunidad hepática en los pacientes celíacos evaluados es frecuente, no así la presencia de marcadores de hepatopatías virales(AU)

Introduction: The spectrum of hepatic involvement in celiac disease is very broad and includes viral and autoimmune hepatopathies. Objective: To characterize the behavior of serologic markers of viral and autoimmune hepatopathies in adult celiac patients treated at the Institute of Gastroenterology. Materials and Methods: A cross-sectional observational study was conducted in 43 adult celiac patients treated at the Institute of Gastroenterology of Havana from March 2016 to March 2017. Prior informed consent, biochemical and serologic studies were carried out in all cases, in order to identify hepatitis B and C virus infections and humoral immune response to liver and systemic autoantibodies. Frequency distributions were used for statistical analysis, and Fisher's exact test was used for the comparison between groups. Results: 58.1 percent of the patients presented hypophosphatasemia and hypertransaminasemia in 14 percent, with no coincidence between the cases recorded. The 100 percent of the celiac patients were negative for hepatitis C virus. The positivity of liver autoantibodies was recorded between 2,3 percent and 14 percent of the patients evaluated. There was a significant association between hypertransaminasemia and the presence of serum antibodies against tissue transglutaminase. Conclusions: The expression markers of liver autoimmunity in celiac patients was frequent, but not the presence of markers of viral hepatopathy(AU)

Pancitopenia em pacientes com anemia perniciosa. Estudo descritivo de 33 casos. / Pancytopenia in patients with pernicious anemia. Descriptive study of 33 cases.

Objetivo: Discriminar as variáveis de sexo e idade nos pacientes com anemia perniciosa; estudar seu perfil hematimétrico; verificar a prevalência de outras doenças autoimunes e anemia perniciosa; analisar a incidência da pancitopenia e sua relação com alterações laboratoriais comum na doença; e avaliar a frequência dos autoanticorpos anticélulas parietais e antifator intrínseco. Métodos: Estudo transversal descritivo, de base clínica e laboratorial, de 33 prontuários de pacientes com anemia perniciosa, diagnosticados em um ambulatório de hospital terciário de atenção à saúde, no período de junho de 2009 a junho de 2014. Para analisar a relação da presença e da ausência de pancitopenia com os níveis da enzima lactato desidrogenase e vitamina B12, foi utilizado o teste qui quadrado. O programa utilizado foi o software Epi Info, versão 7. Resultados: Na amostra, 63,6% eram mulheres, e a idade média geral foi de 47,3 anos. Doenças autoimunes estavam associadas em 30,3% dos pacientes. A pancitopenia esteve presente em 39,4% dos pacientes. Houve significância estatística na relação da pancitopenia com os níveis de enzima lactato desidrogenase (p<0,05). A prevalência do antifator intrínseco foi de 69,7% e dos autoanticorpos anticélulas parietais foi de 72,7%. Conclusão: A pancitopenia mostrou-se um achado significante na população com anemia perniciosa, assim como níveis elevado de LDH, acrescentando a anemia perniciosa como um diagnóstico diferencial de tais alterações laboratoriais.(AU)

Objective: To discriminate the gender and age variables in patients with pernicious anemia; to study erythrocyte profile; to check the prevalence of other autoimmune diseases and pernicious anemia; to analyze the incidence of pancytopenia and its relationship with common laboratory abnormalities in the disease; to evaluate the frequency of anti-gastric parietal cell antibodies, and anti-intrinsic factor antibodies. Methods: Descriptive, cross-sectional study of clinical and laboratorybased medical records of 33 patients with pernicious anemia diagnosed in an outpatient's department of a tertiary healthcare center, in the period between June 2009 and June 2014. To analyze the relationship between the presence and absence of pancytopenia with levels of lactate dehydrogenase enzyme and levels of Vitamin B12 we used the chi-squared test. The software used was Epininfo version 7. Results: The sample showed 63.6% women and 36.4% men with a mean age of 47.3 years. Autoimmune diseases were associated in 30.3% of the patients. Pancytopenia was present in 39.4% of patients. There was statistically significant relationship of pancytopenia with lactate dehydrogenase enzyme levels (p <0.05). The frequency of anti-intrinsic factor antibodies was 69.7%, and the antigastric parietal cell antibodies was 72.7%. Conclusion: Pancytopenia proved to be a significant finding among the population with pernicious anemia and high levels of LDH, which includes pernicious anemia as a differential diagnosis of such laboratory alterations.(AU)

Colangitis biliar primaria. Parte 1. Actualización: generalidades, epidemiología, factores involucrados, fisiopatología y manifestaciones clínicas / Primary biliary cholangitis. Part 1. State of the art, epidemiology, physiopathology and clinical manifestations

La colangitis biliar primaria (CBP), es una colangiopatía crónica caracterizada por la destrucción selectiva de las células epiteliales biliares de conductos hepáticos de pequeño y mediano calibre, que afecta principalmente a mujeres. Los principales síntomas son la fatiga y el prurito, sin embargo, gran porcentaje de los pacientes pueden ser asintomáticos. El diagnóstico se basa en anticuerpos antimitocondriales (AMA) con títulos >1:40, fosfatasa alcalina >1,5 veces del límite superior normal por más de 24 semanas e histología hepática compatible con la patología. Se asocia con múltiples enfermedades principalmente de carácter autoinmune extra hepáticas, enfermedades tiroideas, óseas, entre otras. El tratamiento de primera línea es el ácido ursodesoxicólico (AUDC) que a pesar que no cura la enfermedad, mejora las pruebas del perfil hepático, así como el retraso en la progresión a cirrosis. Actualmente se encuentran en estudio nuevos tratamientos y terapias adyuvantes. El propósito de esta revisión es ofrecer una actualización de este tema que se presenta en los servicios de medicina interna y gastroenterología; para su realización se conformó un equipo interdisciplinario que desarrolló una búsqueda en la base Medline a través de PubMed con las palabras claves correspondientes y se procedió a una lectura crítica y analítica de títulos, resúmenes y textos completos para el filtro, extracción y síntesis de la información encontrada

Primary biliary cholangitis (PBC) is a chronic autoimmune cholangiopathy characterized by a selective destruction of biliary epithelial cells of small and medium caliber hepatic ducts, which mainly affects women. The main symptoms are fatigue and pruritus, however, a large proportion of patients may be asymptomatic. The diagnosis is based on AMA titers >1:40, alkaline phosphatase >1.5 times the upper limit for more than 24 weeks and compatible liver histology. It is associated with multiple autoimmune diseases mainly extrahepatic, thyroid diseases, bone diseases, among others. The first line treatment is ursodeoxycholic acid (UDCA), that improves liver function tests and delay the progression to cirrhosis. Currently, there are new treatments and adjuvant therapies on study. The purpose of this review is to offer an update in this topic, which is very important in gastroenterology and internal medicine. We formed an interdisciplinary team to search in the database Medline thorough PubMed with the key words describe below, we made a critical lecture of the titles and abstracts of each article to write this paper

Association between demyelinating disease and autoimmune rheumatic disease in a pediatric population / Associação entre doença desmielinizante e doença reumática autoimune em uma população pediátrica

ABSTRACT Introduction: Multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating diseases of the central nervous system. Autoimmunity in patients with demyelinating disease and in their families has been broadly investigated and discussed. Recent studies show a higher incidence of rheumatic autoimmune diseases among adult patients with MS or NMO and their families, but there are no studies in the pediatric population. Objective: To evaluate an association of MS and NMO with autoimmune rheumatic diseases in pediatric patients. Method: 22 patients younger than 21 years old with MS or NMO diagnosed before the age of 18 years were evaluated regarding epidemiological data, clinical presentation, association with autoimmune diseases, family history of autoimmune diseases, laboratory findings, imaging studies and presence of auto-antibodies. Results: Among the patients studied, there was a prevalence of females (68.1%). The mean age of symptoms onset was 8 years and 9 months and the mean current age was 16 years and 4 months. Two patients (9%) had a history of associated autoimmune rheumatic disease: one case of juvenile dermatomyositis in a patient with NMO and another of systemic lupus erythematosus in a patient with MS. Three patients (13%) had a family history of autoimmunity in first-degree relatives. Antinuclear antibody was found positive in 80% of patients with NMO and 52% of patients with MS. About 15% of antinuclear antibody-positive patients were diagnosed with rheumatologic autoimmune diseases. Conclusion: Among patients with demyelinating diseases diagnosed in childhood included in this study there was a high frequency of antinuclear antibody positivity but a lower association with rheumatologic autoimmune diseases than that observed in studies conducted in adults.

RESUMO Introdução: Esclerose múltipla (EM) e neuromielite óptica (NMO) são doenças desmielinizantes do sistema nervoso central. A autoimunidade entre pacientes com doenças desmielinizantes e seus parentes tem sido amplamente investigada e discutida. Estudos recentes demonstram maior incidência de doenças reumáticas autoimunes entre pacientes adultos com EM e NMO e seus parentes, mas não há estudos na população pediátrica. Objetivo: Avaliar a associação de EM e NMO com doenças reumáticas autoimunes em pacientes pediátricos. Método: Foram incluídos 22 pacientes menores de 21 anos com diagnóstico de EM ou NMO antes dos 18 anos e avaliados dados epidemiológicos, clínicos, associação com doenças autoimunes, história familiar de doenças autoimunes, exames laboratoriais, exames de imagem e presença de autoanticorpos. Resultados: Entre os pacientes estudados, houve prevalência do sexo feminino (68,1%). A média de idade de início dos sintomas foi de oito anos e nove meses e a média de idade dos pacientes na avaliação foi 16 anos e quatro meses. Dois pacientes (9%) apresentaram doença reumática autoimune associada, um caso de dermatomiosite juvenil em paciente com NMO e outro de lúpus eritematoso sistêmico juvenil em paciente com EM. Três pacientes (13%) apresentaram história familiar de autoimunidade em parentes de primeiro grau. Anticorpo antinuclear (ANA) positivo foi encontrado em 80% dos pacientes com NMO e em 52% dos pacientes com EM. Cerca de 15% dos pacientes com ANA positivo apresentaram diagnóstico definitivo de doença autoimune reumática associada. Conclusão: Entre os pacientes com doenças desmielinizantes diagnosticadas durante a infância incluídos nesta pesquisa houve uma alta frequência de ANA positivo, mas uma menor taxa de associação com doenças reumáticas autoimunes do que a encontrada em trabalhos conduzidos em adultos.

Manifestaciones mucocutáneas del paciente pediátrico con enfermedades autoinmunes del Hospital Roberto del Río / Mucocutaneous manifestations of the pediatric patient with autoimmune diseases of the Roberto del Río Hospital

Las enfermedades autoinmunes son desórdenes heterogéneos que pueden comprometer distintos órganos. Su frecuencia es baja, se estima que 3 de cada 1.000 niños cursan con alguna condición reumatológica. Las patologías reumatológicas más comunes en la edad pediátrica son la artritis idiopática juvenil (AIJ) seguida por el lupus eritematoso sistémico (LES), dermatomiositis juvenil (DMJ), vasculitis primarias y la esclerodermia. Materiales y Métodos: Se efectuó un estudio descriptivo retrospectivo de pacientes pediátricos atendidos en el servicio de inmunología del Hospital Roberto del Rio entre los años 1990 y 2011. Se pesquisaron un total de 102 pacientes, con diagnósticos de AIJ, LES y DMJ. Se diseñó una ficha de protocolo, con los datos: edad, sexo, antecedentes familiares, manifestaciones cutáneas al diagnóstico y a lo largo de la evolución. Para el análisis estadístico de variables, se utilizó el programa STATA 8.0. Resultados: El 45,45% de los pacientes con AIJ presentó lesiones cutáneas, sin embargo, sólo un 20% de ellas, relacionadas a esta enfermedad. El 91,7% de los pacientes con LES presentó manifestaciones cutáneas, siendo la vasculitis cutánea y el eritema malar, las más frecuentes. En los pacientes con DMJ, el eritema heliotropo y pápulas de Gottron fueron las manifestaciones cutáneas más comunes. Conclusión: Los hallazgos cutáneos cobran un rol muy importante en el diagnostico enfermedades autoinmunes. Estos datos demuestran la importancia de un examen dermatólogico exhaustivo para su diagnóstico precoz y evitar sus complicaciones.

Background: Autoimmune diseases are disorders that can compromise different organs. Its frequency is low, it is estimated that 3 out of every 1,000 children are affected with any rheumatologic condition. The most common rheumatic diseases in children are juvenile idiopathic arthritis (JIA) followed by systemic lupus erythematosus (SLE), juvenile dermatomyositis (DMJ), primary vasculitis and esclerodermia.2 Materials and Methods: A retrospective study was conducted in pediatric patients seen in the Department of Immunology from the Roberto del Rio Hospital between 1990 and 2011. Records of 105 patients with the diagnosis of juvenile idiopathic arthritis (JIA), systemic lupus erythematosus (SLE) and juvenile dermatomyositis (JDM) have been included. We designed a protocol file with the given data: Age, sex, family history, skin manifestations at the diagnosis and throughout the evolution. The program STATA 8.0 was used for statistical analysis of variable. Results: 45.45% of JIA patients had some type of skin lesions, however, only 20% of them related to this disease. 91.7% of SLE patients presented cutaneous manifestations, the most common being cutaneous vasculitis and malar erythema. In patients with JDM, heliotrope erythema and papules Gottron were the most common skin manifestations. Discussion: Cutaneous manifestations have a very important role in autoimmune diseases. While the diagnosis and management of these diseases require a multidisciplinary team, these data demonstrate the importance of an exhaustive physical examination for early diagnosis and thereby reduce complications. Conclusions: This study highlights the importance of the dermatologist in an early diagnosis of rheumatic diseases.

Organ Correlation in IgG4-Related Diseases

IgG4-related disease (IgG4-RD) is a potentially multiorgan disorder. In this study, clinical and serological features from 132 IgG4-RD patients were compared about organ correlations. Underlying pathologies comprised autoimmune pancreatitis (AIP) in 85 cases, IgG4-related sclerosing cholangitis (IgG4-SC) in 12, IgG4-related sialadenitis (IgG4-SIA) in 56, IgG4-related dacryoadenitis (IgG4-DAC) in 38, IgG4-related lymphadenopathy (IgG4-LYM) in 20, IgG4-related retroperitoneal fibrosis (IgG4-RF) in 19, IgG4-related kidney disease (IgG4-KD) in 6, IgG4-related pseudotumor (IgG4-PT) in 3. Sixty-five patients (49%) had multiple IgG4-RD (two affected organs in 36 patients, three in 19, four in 8, five in 1, and six in 1). Serum IgG4 levels were significantly higher with multiple lesions than with a single lesion (P<0.001). The proportion of association with other IgG4-RD was 42% in AIP, the lowest of all IgG4-RDs. Serum IgG4 level was lower in AIP than in other IgG4-RDs. Frequently associated IgG4-RDs were SIA (25%) and DAC (12%) for AIP; AIP (75%) for IgG4-SC; DAC (57%), AIP (38%) and LYM (27%) for IgG4-SIA; AIP (26%) and LYM (26%) for IgG4-DAC; SIA (75%), DAC (50%) and AIP (45%) for IgG4-LYM; SIA (58%), AIP (42%) and LYM (32%) for IgG4-RF; AIP (100%) and SIA (67%) for IgG4-KID; and DAC (67%) and SIA (67%) for IgG4-PT. Most associated IgG4-RD lesions were diagnosed simultaneously, but IgG4-SIA and IgG4-DAC were sometimes identified before other lesions. About half of IgG4-RD patients had multiple IgG4-RD lesions, and some associations were seen between specific organs.

Prevalence of Vitiligo and Associated Comorbidities in Korea

PURPOSE: Vitiligo prevalence and its associated comorbidities rate have been reported variably among different populations. We aimed to determine the prevalence of vitiligo in Korea along with the baseline rate of comorbidities and compared the risks to the general population using hospital visit information of the total population in Korea. MATERIALS AND METHODS: We assessed demographic characteristics of vitiligo patients in Korean population from 2009 to 2011 in a nationwide data from Health Insurance Review Assessment Service. Patients who had at least one visit to Korea's primary, secondary, or tertiary referral hospitals with International Classification of Diseases, 10th Revision, Clinical Modification diagnosis code for vitiligo were identified. As a supplementary study, comorbidities associated with vitiligo were selected for further review to calculate relative risks compared to the general population. RESULTS: The annual prevalence of vitiligo determined by hospital-visiting rate in Korea was 0.12% to 0.13% over a three year period. In sync with other previous epidemiological studies, there was bimodal distribution among the age groups and no difference between genders. Also, vitiligo in Korean population was associated with various autoimmune/non-autoimmune diseases such as thyroiditis, atopic dermatitis, and psoriasis. CONCLUSION: This study was by far the most comprehensive review on prevalence of vitiligo using a data of total population in Korea. The prevalence is within a range of those reported in previous literatures, and increased risk of comorbidities such as thyroid diseases and psoriasis in vitiligo might aid clinicians in the initial work up of vitiligo patients and concurrent follow ups.

Reações infusionais imediatas a agentes imunobiológicos endovenosos no tratamento de doenças autoimunes: experiência de 2.126 procedimentos em um centro de infusão não oncológico / Immediate infusional reactions to intravenous immunobiological agents for the treatment of autoimmune diseases: experience of 2126 procedures in a non-oncologic infusion centre

Introdução: Com o crescimento do uso de drogas imunobiológicas (IBD) ampliamos o conhecimento sobre sua eficácia e segurança. Objetivo: Analisar as reações infusionais imediatas (RII) às IBD endovenosas - infliximabe (IFX), rituximabe (RTX), abatacepte (ABT) e tocilizumabe (TCZ) - no tratamento de doenças autoimunes. Método: Avaliamos 2.126 infusões feitas no CID (Centro de Infusão) em 268 pacientes. A droga usada, a indicação clínica, o tempo de infusão e o uso de pré-medicação foram determinados pelo médico prescritor. Foram consideradas RII todas as intercorrências apresentadas durante a infusão e/ou período observacional de 30 minutos. A conduta adotada nas RII seguiu os protocolos do CID. Resultados: Em relação ao tipo de IBD, as infusões foram distribuídas em: IFX (1.584; 74,5%), TCZ (226; 10,63%), RTX (185; 8,7%) e ABT (131; 6,16%). As RII foram descritas em 87 procedimentos (4,09%): 77 no grupo IFX e 10 no grupo RTX. Não foram descritas RII nos grupos de ABT e TCZ. A maioria foi considerada leve (n = 5; 41,17%) ou moderada (n = 50; 58,81%) e não houve reações graves. Das infusões interrompidas, 79 (92,9%) foram reiniciadas e concluídas com êxito. Apenas seis (0,28%) não foram concluídas por causa das RII. Conclusão: Apesar da diferença entre o número de procedimentos por droga, trata-se de uma análise de "vida real", na qual a incidência de RII foi semelhante à descrita na literatura. A baixa incidência de RII corrobora os dados de segurança tanto de forma quantitativa como qualitativa e ressalta a importância do acompanhamento médico especializado durante a infusão. .

Introduction: With the increasing use of immunobiological drugs (IBD), the knowledge about their effectiveness and safety has increased. Objective: To analyze the immediate infusional reactions (IIR) to intravenous IBD: infliximab (IFX), rituximab (RTX), abatacept (ABT) and tocilizumab (TCZ) on the treatment of autoimmune diseases. Method: 2126 infusions performed in the Infusion Centre - CID in 268 patients were analyzed. The used drug, its clinical indication, infusion time, and use of premedication were determined by the prescribing physician. All intercurrences presented during infusion and/or during a thirty minutes observation period were considered as IIR. The approach adopted in IIR followed the protocols of the Infusion Centre - CID. Results: Regarding the type of IBD, the infused drugs given were: IFX (1584, 74.5%), TCZ (226, 10.63%), RTX (185, 8.7%) and ABT (131, 6,16%). IIR were described in 87 procedures (9.4%): 77 - IFX group and 10 - RTX group. IIR were not described in ABT and TCZ groups. Most were considered as mild (n = 5; 41.17%) or moderate (n = 50, 58.81%) reactions; there were no serious reactions. Regarding to discontinue infusions, 79 (92.9%) were resumed and completed successfully. Only six (0.28% of infusions) were not completed because of IIR. Conclusion: Despite the differences between the number of procedures per drug, ours is a "real life" analysis, where the incidence of IIR was similar to that described in the literature. The low incidence of IIR corroborates the safety data, both quantitatively and qualitatively, and underscores the importance of specialized medical support during infusion. .

Incidência de neoplasias nas doenças reumatológicas autoimunes mais prevalentes: uma revisão sistemática / Incidence of neoplasms in the most prevalent autoimmune rheumatic diseases: a systematic review

O presente artigo é uma revisão sistemática da literatura que aborda a coexistência de neoplasias e doenças reumatológicas autoimunes, suas principais associações, tipos de cânceres e os possíveis fatores de riscos associados, com ênfase nos estudos de base populacional existentes, além de verificar a relação dessa ocorrência com o uso dos fármacos utilizados no tratamento de doenças autoimunes. Foi realizada uma busca de artigos científicos indexados na Cochrane/BVS, Pubmed/Medline e Scielo/Lilacs no período de 2002 a 2012. Também foi consultada a IBICT (biblioteca digital brasileira de teses e mestrados), com os descritores em português e inglês para as palavras: "Esclerose sistêmica", "Artrite reumatoide", "Lúpus Eritematoso Sistêmico" e "Síndrome de Sjögren", correlacionando cada um com o descritor AND "neoplasias". Os resultados mostraram que, na base de dados IBICT, preencheram os critérios de inclusão uma tese e uma dissertação para o descritor LES, nenhuma para AR e uma tese para SS. Na base de dados Lilacs/Scielo foram encontrados dois artigos sobre "Artrite Reumatoide" AND "neoplasias". No Pubmed/Medline, a busca inicial resultou em 118 artigos; destes, preencheram os critérios e foram secionados 41 artigos. Esta revisão observou relação entre neoplasias e as doenças reumatológicas autoimunes, tanto como fator de risco quanto de proteção, embora os mecanismos fisiopatológicos não estejam totalmente elucidados.

This article is a systematic review of the literature about the coexistence of cancer and autoimmune rheumatic diseases, their main associations, cancers and possible risk factors associated, with emphasis on existing population-based studies, besides checking the relation of this occur with the use of the drugs used in the treatment of autoimmune diseases. A search was conducted of scientific articles indexed in the Cochrane / BVS, Pubmed / Medline and Scielo / Lilacs in the period from 2002 to 2012. Also consulted was the IB-ICT (Brazilian digital library of theses and Masters), with descriptors in Portuguese and English for "Systemic sclerosis", "Rheumatoid Arthritis", " Systemic Lupus Erythematosus" and "Sjögren's syndrome", correlating each one with the descriptor AND "neoplasms". The results showed that in the database IBICT a thesis and a dissertation for the descriptor SLE met the inclusion criteria, none met RA one thesis to SS. Lilacs in the database/Scielo found two articles on "Rheumatoid Arthritis" AND "neoplasms". In Pubmed/Medline the inicial search resulted in 118 articles, and 41 were selected. The review noted the relationship between cancer and autoimmune rheumatic diseases, as well as a risk factor for protection, although the pathophysiological mechanisms are not known.

Frecuencia y características clínicas de la orbitopatía asociada al tiroides en pacientes hipertiroideos de reciente diagnóstico / Frequency and clinical characteristics of thyroid-associated orbitopathy in recently diagnosed hyperthyroid patients

Introducción: la orbitopatía asociada al tiroides es una complicación frecuente del hipertiroidismo. Objetivo: describir la frecuencia y características de la orbitopatía asociada a la enfermedad autoinmune del tiroides, en pacientes con diagnóstico reciente de hipertiroidismo. Métodos: estudio descriptivo transversal. A cada caso se le determinó al diagnóstico hormonas tiroideas, y anticuerpos antiperoxidasa. Se examinaron al diagnóstico para evaluar la presencia de orbitopatía, y se identificaron los síntomas y signos oculares presentes en los que la presentaron. Se compararon los resultados a través de estadística descriptiva, utilizando chi². La significación estadística fue para una p< 0,05. Resultados: el 70 por ciento de los pacientes presentó orbitopatía tiroidea al diagnóstico. Predominó el sexo femenino y la raza blanca en el grupo de estudio. La forma leve inactiva prevaleció en los pacientes con orbitopatía, y ninguno presentó la forma severa de esta. El signo más frecuente fue la retracción palpebral, con 90,32 por ciento. No hubo asociación estadística con la edad, el hábito de fumar, el color de piel, las hormonas tiroideas ni los anticuerpos. Conclusiones: la orbitopatía es frecuente al diagnóstico del hipertiroidismo, la retracción palpebral es su signo más común, y no se asoció con los factores clínicos y bioquímicos estudiados(AU)

Introduction: thyroid-associated orbitopathy is a frequent complication of hyperthyroidism. Objective: to describe the frequency and the characteristics of orbitopathy related to autoimmune disease of thyroids in patients who were recently diagnosed as hyperthyroidism cases. Methods: cross-sectional descriptive study. Every case was detected thyroid hormones and antiperoxidase antibodies at time of diagnosis. They were examined to evaluate the possible presence of orbitopathy whose ocular symptoms and signs were identified in those who had it. The comparison of results was made through summary statistics by using chi-square test. The statistical significance was p< 0.05. Results: seventy percent of patients had thyroid orbitopathy at the time of diagnosis. Females and Caucasians prevailed in the study group. The slight inactive form prevailed whereas the severe form was absent. The most common sign was palpebral retraction accounting for 90.32 percent. There was no statistical association with age, smoking, race, thyroid hormone or antibody presence. Conclusions: orbitopathy is common at time of diagnosis of hyperthyroidism, palpebral retraction is the commonest sign and it was not associated to the studied clinical and biochemical factors(AU)

Association between pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections disease and tumor necrosis factor-α gene−308 g/a, −850 c/t polymorphisms in 4-12-year-old children in Adana/Turkey.

OBJECTIVES: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is a newly defined disease in neuropsychiatry and occurs with an autoimmune mechanism after Group A Beta Hemolytic Streptococcus (GABHS) infection. Tumor necrosis factor (TNF), encoded by TNF-α gene has an important role in the apoptotic mechanisms of autoimmune diseases. Recently, TNF-α polymorphisms and autoimmune/psychiatric disorders have been reported to be related. In this regard, we focused on to investigate a possible relation between the TNF-α gene promoter region−308 G/A and − 850 C/T polymorphisms and PANDAS. MATERIALS AND METHODS: In this study, ages of PANDAS patient and control groups were ranging from 4 years to 12-year-old. Patient group includes childhood onset PANDAS patients (n = 42) and control group includes healthy children (n = 58). Diagnoses have been carried out according to Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) criteria with Affective Disorders and Schizophrenia-Present and Lifetime (KSAD-S-PL) and Children Yale-Brown Obsessive Compulsive Scale Moreover, PANDAS criteria established by the American National Psychiatry Institute have been employed for diagnoses. For identifying polymorphisms; Polymerase Chain Reaction, Restriction Fragment Length Polymorphism and Polyacrylamid Gel Electrophoresis were used. RESULTS AND DISCUSSION: For −308 polymorphism, 37 of 42 PANDAS patients’ results and for −850 C/T polymorphism, 38 of 42 PANDAS patients’ results were obtained. According to our statistical analysis there is a positive relationship between PANDAS patients for −308 G/A polymorphism but not for −850 C/T polymorphism. There is no positive relationship between −308 G/A polymorphism and antistrep-tolysin O (ASO) titers and no relationship between −850 C/T polymorphism and ASO titers. We found, however, positive relationship between genders of patients (boys) and the disease. According to our results, we propose that the AA polymorphism of −308 G/A polymorphism can be used as a molecular indicator for PANDAS.