Encefalitis de Hashimoto. Presentación de un caso / Hashimoto Encephalitis. Case Report

INTRODUCCIÓN La Encefalitis de Hashimoto (EH) es una encefalopatía de naturaleza autoinmune, con buena respuesta al tratamiento con corticoides, títulos séricos elevados de anticuerpos antitiroideos y de curso subagudo con recaídas-remisiones. Es una enfermedad poco frecuente, con una presentación clínica variable y fisiopatología aún desconocida. PRESENTACIÓN DEL CASO: Paciente femenina de 76 años con antecedentes de hipotiroidismo primario. Ingresó con un síndrome confusional agudo. Al examen físico vigil, Glasgow 13/15, subfebril (37.8°C) desorientada temporoespacialmente, ecolalia, pupilas isocóricas y reactivas, sin focalidad neurológica. Signos meníngeos negativos. Laboratorio: Hipocalcemia leve (7.8mg/dl), hipopotasemia (K 3,2 mmol/l), PCR 221.9 mg/L. Test rápido para VIH negativo. TC de encéfalo sin alteraciones. Punción lumbar líquido cristal de roca, proteínas 1 g/l, glucosa 0.67 g/l, láctico 1.3, leucocitos 77 células/microL (100% mononucleares). Se interpretó inicialmente como Encefalitis de etiología viral y se le indicó aciclovir. Presentó sensorio alternante, excitación psicomotriz y convulsión tónica clónica generalizada. Debido a deterioro súbito del sensorio, se realizó intubación orotraqueal y se trasladó a Unidad de Terapia Intensiva (UTI). Permaneció bajo asistencia mecánica ventilatoria y con vasopresores. Laboratorio: VDRL, p24 y anticuerpos HIV negativos, TSH 27,82, T4 0,41. PCR de LCR: Virus herpes simple 1 y 2, citomegalovirus y JC negativos. Hemocultivos negativos. Ante sospecha clínica de Encefalitis de Hashimoto, se solicitaron anticuerpos antitiroideo peroxidasa (aTPO), antitiroglobulina (aTG) y Anticuerpos Anti-Receptor de TSH (TRABS), que resultaron positivos. Recibió tratamiento con levotiroxina endovenosa e hidrocortisona. Normaliza valores. Por fallo en el weaning, se realizó traqueostomía. Luego de 21 días de internación en Terapia Intensiva pasó a clínica con posterior alta hospitalaria. Discusión: La EH se puede considerar como diagnóstico, solo después de descartar otras causas. En el caso expuesto se llegó al diagnóstico luego de descartar otras causas posibles, con anticuerpos antitiroideos positivos en altas concentraciones y respuesta al tratamiento con corticoides. Conclusión: Se destaca la necesidad de ampliar el conocimiento de esta patología con el fin de disminuir el subdiagnóstico y promover un inicio precoz del tratamiento, mejorando así su progresión y calidad de vida de los pacientes.

INTRODUCTION: Hashimoto's Encephalitis (HE) is an autoimmune encephalopathy, with a good response to treatment with corticosteroids, high serum titers of antithyroid antibodies and a subacute course with relapses-remissions. It is a rare disease, with a variable clinical presentation and still unknown pathophysiology. CASE REPORT: A 76-year-old female patient with a history of primary hypothyroidism. She was admitted with acute confusional syndrome. On physical examination, she was awake, she was Glasgow 13/15, she was subfebrile (37.8°C), disoriented temporally, echolalia, isochoric and reactive pupils, without neurological focality. Negative meningeal signs. Laboratory: Mild hypocalcemia (7.8 mg/dl), hypokalemia (K 3.2 mmol/l), CRP 221.9 mg/L. Rapid test for HIV negative. Brain CT without alterations. Lumbar puncture rock crystal liquid, proteins 1 g/l, glucose 0.67 g/l, lactic acid 1.3, leukocytes 77 cells/microL (100% mononuclear). It was initially interpreted as Encephalitis of viral etiology and acyclovir was prescribed. He presented alternating sensory, psychomotor excitement, and generalized tonic-clonic seizure. Due to sudden deterioration of the sensorium, orotracheal intubation was performed and he was transferred to the Intensive Care Unit. He remained under mechanical ventilatory assistance and with vasopressors. Laboratory: VDRL, p24 and HIV antibodies negative, TSH 27.82, T4 0.41. CSF PCR: Herpes simplex virus 1 and 2, cytomegalovirus and JC negative. Negative blood cultures. Due to clinical suspicion of Hashimoto's Encephalitis, anti-thyroid peroxidase (aTPO), anti-thyroglobulin (aTG) antibodies and Anti-TSH Receptor Antibodies (TRABS) were requested, which were positive. She was treated with intravenous levothyroxine and hydrocortisone. Normalized values. Due to weaning failure, a tracheostomy was performed. After 21 days of hospitalization in the Intensive Care Unit, she was admitted to the clinic and subsequently discharged from the hospital. Discussion: HD can be considered as a diagnosis, only after ruling out other causes. In the case presented, the diagnosis was made after ruling out other possible causes, with positive antithyroid antibodies in high concentrations and response to treatment with corticosteroids. Conclusion: The need to expand knowledge of this pathology is highlighted in order to reduce underdiagnosis and promote early initiation of treatment, thus improving its progression and quality of life of patients.

Espondiloencondrodisplasia con desregulación inmune relacionada a ACP5. Reporte de cuatro casos / Spondyloenchondrodysplasia with immune dysregulation related to ACP5. A report of 4 cases

La espondiloencondrodisplasia con desregulación inmune relacionada a ACP5 (SPENCDI #607944, por la sigla de spondyloenchondrodysplasia with immune dysregulation y el número que le corresponde en OMIM, Online Mendelian Inheritance in Man) es una displasia inmuno-ósea poco frecuente con manifestaciones heterogéneas y gravedad variable. Presenta lesiones espondilometafisarias, disfunción inmune y compromiso neurológico. Se reportan aspectos clínicos, radiológicos y genéticos de cuatro niñas con SPENCDI en un hospital pediátrico. Todas presentaron manifestaciones esqueléticas y tres de ellas enfermedad inmunológica grave. Se encontró en tres pacientes la variante probablemente patogénica c.791T>A; p.Met264Lys en homocigosis, y en una paciente las variantes c.791T>A; p.Met264Lys y c.632T>C; p.lle211Thr (variante de significado incierto con predicción patogénica según algoritmos bioinformáticos) en heterocigosis compuesta en ACP5. La presencia de la variante repetida c.791T>A sugiere la posibilidad de un ancestro en común en nuestra población. El reconocimiento y diagnóstico de esta entidad es importante para lograr un oportuno abordaje, que deberá ser multidisciplinario, orientado hacia la prevención de posibles complicaciones.

Spondyloenchondrodysplasia with immune dysregulation related to ACP5 (SPENCDI, OMIM number 607944) is an uncommon immune-skeletal dysplasia with heterogeneous manifestations and variable severity. It is characterized by spondylar and metaphyseal lesions, immune dysfunction, and neurological involvement. Here we report the clinical, radiological and genetic aspects of 4 girls with SPENCDI treated at a children's hospital. They all had skeletal manifestations and 3 developed severe immune disease. In 3 patients, the likely pathogenic variant c.791T>A; p.Met264Lys (homozygous mutation) was observed, while 1 patient had variants c.791T>A; p.Met264Lys and c.632T>C; p.lle211Thr (variant of uncertain significance with pathogenic prediction based on bioinformatics algorithms) caused by a compound heterozygous mutation in ACP5. The repeated presence of variant c.791T>A suggests the possibility of a common ancestor in our population. The recognition and diagnosis of this disorder is important to achieve a timely approach, which should be multidisciplinary and aimed at preventing possible complications.

Encefalitis autoinmune posherpética. Caso clínico pediátrico / Autoimmune post-herpes simplex encephalitis. A pediatric clinical case report

La encefalitis por virus herpes simple (VHS) es una causa frecuente de encefalitis grave y potencialmente fatal. La encefalitis autoinmune posherpética (EAPH) afecta a un porcentaje de los pacientes que han presentado encefalitis herpética (EH) y se caracteriza por la aparición de nuevos síntomas neurológico/psiquiátricos, y/o por el empeoramiento de los déficits adquiridos durante la infección viral dentro de un lapso temporal predecible. Se produce por un mecanismo no relacionado con el VHS, sino por fenómenos autoinmunes, y es susceptible de tratamiento con inmunomoduladores. Se presenta el caso de un varón de 5 años de edad con EAPH que requirió tratamiento inmunomodulador, de primera y segunda línea, con buena evolución y remisión de los síntomas.

Herpes simplex virus (HSV) encephalitis is a common cause of severe and potentially fatal encephalitis. Autoimmune post-herpes simplex encephalitis (AIPHSE) affects a percentage of patients who developed herpes simplex encephalitis (HSE) and is characterized by the onset of new neurological/psychiatric symptoms and/or worsening of deficits acquired during the herpes infection within a predictable time frame. It is caused by a mechanism not related to HSV, but by autoimmune conditions, and is susceptible to treatment with immunomodulators. Here we describe the case of a 5-year-old boy with AIPHSE who required first- and second-line immunomodulatory treatment, with an adequate course and remission of symptoms.

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)

Papel inmunomodulador de la vitamina D y los ácidos grasos poliinsaturados omega-3 en trastornos autoinmunes: Revisión de la Literatura / Immunomodulatory role of vitamin D and omega-3 polyunsaturated fatty acids in autoinmune disorders: Literature Review

Los trastornos autoinmunes representan una familia de al menos 80 condiciones diferentes que surgen de una respuesta aberrante del sistema inmunológico resultando finalmente en la destrucción de tejidos y órganos específicos del cuerpo. Es importante destacar que durante las últimas tres décadas los estudios epidemiológicos han proporcionado evidencia de un aumento constante en la incidencia y prevalencia de trastornos autoinmunes. En los últimos años, varios estudios han demostrado que la vitamina D y los ácidos grasos poliinsaturados (AGPs) omega-3 ejercen propiedades inmunomoduladoras y antiinflamatorias sinérgicas que pueden aprovecharse positivamente para la prevención y el tratamiento de trastornos autoinmunes. En este sentido, el reciente ensayo clínico denominado VITAL (ensayo de vitamina D y omega 3); un estudio a gran escala, aleatorizado, doble ciego, controlado con placebo encontró que la suplementación conjunta de vitamina D y AGPs omega-3 (VIDOM) puede reducir la incidencia de enfermedades autoinmunes. En esta revisión de la literatura, resumimos los mecanismos moleculares detrás de las propiedades inmunomoduladoras y antiinflamatorias de la vitamina D y los AGPs omega-3, así como la posible interacción bidireccional entre el metabolismo de la vitamina D y el metabolismo de los AGPs omega-3 que justifica la co- suplementación VIDOM en trastornos autoinmunes(AU)

Autoimmune disorders represent a family of at least 80 different conditions that arise from an aberrant immune system response, which ultimately results in the destruction of specific body tissues and organs. It is important to highlight that during the last three decades epidemiological studies have provided evidence of a steady increase in the incidence and prevalence of autoimmune disorders. In recent years, several studies have shown that vitamin D and omega-3 polyunsaturated fatty acids (PUFAs) exert synergistic immunomodulatory and anti-inflammatory properties that can be positively harnessed for the prevention and treatment of autoimmune disorders. In this sense, the recent clinical trial called VITAL (Vitamin D and Omega 3 trial) - a large, randomized, double-blind, placebo- controlled study - found that co-supplementation of vitamin D and omega-3 PUFAs (VIDOM) can reduce the incidence of autoimmune diseases. In this literature review, we summarize the molecular mechanisms behind the immunomodulatory and anti-inflammatory properties of vitamin D and omega-3 PUFAs, as well as the possible bidirectional interaction between vitamin D metabolism and omega-3 PUFA metabolism that justifies VIDOM co- supplementation in autoimmune disorders(AU)

Presencia de autoanticuerpos anti islotes pancreáticos en diabetes tipo 1 durante la edad pediátrica / Presence of anti-pancreatic islet autoantibodies in type 1 diabetes in children

En la Diabetes tipo 1 (DM1) la pérdida de células ß pancreáticas es consecuencia de un proceso de autoinmunidad que cursa con la presencia de autoanticuerpos anti-islotes pancreáticos (AAPs). Estos AAPs son marcadores útiles para la clasificación de la enfermedad. En un centro pediátrico de tercer nivel se analizó la frecuencia de presentación de GADA, IA-2A, ZnT8A e IAA en un grupo con reciente debut entre enero 2018 y agosto 2021 (n= 90). Además, se investigó la frecuencia de presentación y relación de los AAPs con la edad, sexo y tiempo de evolución en pacientes en seguimiento (n= 240). En el grupo de debut se obtuvo positividad de GADA, IA-2A, ZnT8A y IAA en 77,8; 60; 62 y 47,8% de los pacientes respectivamente, un 4% no presentó AAPs. El 95,6% de los pacientes presentaron al menos un AAPs positivo. La frecuencia de IAA en el grupo en debut fue mayor en menores de 5 años. En el grupo en seguimiento el 75,2% resultaron GADA positivo (85,7% en mujeres y 62,8% en varones) p<0,05. IA-2A y ZnT8A fueron positivos en 45 y 51.7% respectivamente. El 91% presentaron al menos un AAP positivo. En este grupo se evidenció una menor positividad en función del tiempo de evolución. Se pudo determinar la frecuencia de presentación de los AAPs en un grupo en debut y la relación con la edad, sexo y tiempo de evolución en pacientes en seguimiento. La determinación de APPs facilita la correcta clasificación y elección de la terapia adecuada (AU)

In type 1 diabetes (DM1) the loss of pancreatic ß-cells is a consequence of an autoimmune process that results in the presence of pancreatic anti-islet autoantibodies (PAAs). PAAs are useful markers for the classification of the disease. The frequency of presentation of GADA, IA-2A, ZnT8A, and IAA in a group with recent debut seen between January 2018 and August 2021 (n= 90) was analyzed in a tertiary pediatric center. In addition, we investigated the frequency of presentation and association of PAAs with age, sex, and time of evolution in patients in follow-up (n= 240). In the debut group, GADA, IA2A, ZnT8A, and IAA positivity was found in 77.8, 60, 62, and 47.8% of patients, respectively; no PAAs were observed in 4% of the patients. Overall, 95.6% presented at least one positive PAA. The frequency of IAA in the debut group was higher in children younger than 5 years. In the follow-up group, 75.2% were GADA positive (85.7% of females and 62.8% of males) p<0.05. IA-2A and ZnT8A were positive in 45 and 51.7% respectively. Ninety-one percent presented with at least one positive PAA. In this group, a lower positivity was evidenced as a function of the time of evolution. The frequency of presentation of PAAs in a debut group and the relationship with age, sex, and time of evolution in patients in follow-up was demonstrated. The assessment of PAAs facilitates the correct classification and choice of adequate therapy (AU)

Uso adecuado de las pruebas de laboratorio para la evaluación de la función tiroidea en pediatría / Appropriate use of laboratory tests for evaluation of thyroid function in pediatrics

Las pruebas de función tiroidea (PFT) son esenciales para el diagnóstico preciso y el seguimiento eficaz de la disfunción tiroidea. Existe un incremento progresivo y estable de los pedidos de PFT, incluso se han incorporado las mismas a los exámenes de salud anuales en niños sanos. Representan más del 60% de las pruebas realizadas en el laboratorio de endocrinología, tanto en adultos como en los laboratorios especializados en pediatría. Para hacer un uso eficiente de las PFT, antes de solicitarlas debemos preguntarnos… ¿Para quién? ¿Cuándo solicitarlas? ¿Qué pruebas solicitar? ¿Cómo solicitarlas? y ¿Cómo interpretar correctamente los resultados? Un resultado anormal en las PFT no siempre implica patología tiroidea asociada. Las PFT tienen importante variabilidad intra e interindividual lo que hace más compleja su correcta interpretación. La pesquisa de enfermedad tiroidea neonatal es un importante aporte a la prevención de la deficiencia mental en la infancia, su aplicación obligatoria posibilita un diagnóstico temprano, para asegurar su éxito debe considerarse en el marco de un programa integral de detección con estrategias de confirmación, tratamiento temprano y seguimiento a corto, mediano y largo plazo. No debe hacerse un uso indiscriminado de la prueba de estímulo con TRH en el diagnóstico de la patología tiroidea. En pediatría la estrategia de tamiz de enfermedad tiroidea es conveniente realizarla mediante la medición de por lo menos TSH y T4 libre e incluir la determinación de ATPO en grupos de riesgo, a diferencia de la determinación aislada de TSH como es recomendado en adultos. (AU)

Thyroid function tests (TFTs) are essential for accurate diagnosis and effective monitoring of thyroid dysfunction. There is a progressive and steady increase in requests for TFTs, and they have even been incorporated into annual health examinations in healthy children. They represent more than 60% of the tests performed in the endocrinology laboratory, both in adults and in specialized pediatric laboratories. To efficiently use TFTs, before requesting them we should ask ourselves... For whom? When to request them? Which tests to request? How to request them? and How to correctly interpret the results? An abnormal TFT result does not always imply thyroid disease. TFTs have significant intra- and inter-individual variability, which makes their correct interpretation more complex. Screening for newborn thyroid disease is an important contribution to the prevention of intellectual disability in childhood and its mandatory use enables early diagnosis; however, to ensure the test to be successful, it should be considered within the framework of a comprehensive screening program with strategies for confirmation, early treatment, and short-, medium-, and long-term follow-up. The TRH stimulation test in the diagnosis of thyroid disease should not be used indiscriminately. In children, the screening strategy for thyroid disease should be performed by measuring at least TSH and free T4 and include the measurement of TPO-ab in risk groups, as opposed to the isolated measurement of TSH as recommended in adults. (AU)

Uso de PCR digital para definir terapéuticas específicas y seguimiento en enfermedades autoinflamatorias / Use of digital PCR to define specific therapeutics and follow-up in autoinflammatory diseases

Las enfermedades autoinflamatorias (AIDs) son un grupo heterogéneo de desórdenes monogénicos o poligénicos, con características de disregulación inmune innata y/o adaptativa, cuyo mecanismo central es la autoinflamación pero también pueden presentarse con autoinmunidad e inmunodeficiencia. En estos últimos años el desarrollo de las tecnologías de secuenciación masiva han provocado una explosión en el descubrimiento de nuevos genes responsables de AIDs monogénicas. Esto remarca la importancia de implementar este tipo de estudios para llegar a un diagnóstico definitivo sobre todo en este grupo de patologías genéticamente muy diversas donde los fenotipos clínicos se solapan. Sin embargo, dada la presencia de variantes de significación incierta (VUS), los resultados pueden no ser concluyentes planteándose la necesidad de desarrollar pruebas funcionales para determinar la patogenicidad de dichas variantes genéticas. En nuestro grupo de trabajo estamos aplicando la PCR digital en gotas (ddPCR), una técnica cuantitativa de 3era generación altamente sensible, especifica y reproducible que no necesita de curvas de calibración, para desarrollar pruebas funcionales que permitan no sólo reclasificar variantes VUS para lograr diagnósticos definitivos sino también estudiar los mecanismos responsables de las principales AIDs que permitan una estratificación de las terapéuticas especificas a aplicar y de esta manera poder contribuir al diagnóstico, tratamiento y seguimiento de nuestros pacientes en forma personalizada. (AU)

Autoinflammatory diseases (AIDs) are a heterogeneous group of monogenic or polygenic disorders, with characteristics of inborn and/or adaptive immune dysregulation, whose central mechanism is autoinflammation but may also present with autoimmunity and immunodeficiency. In recent years the development of massive sequencing technologies has led to an exponential increase in the discovery of new genes responsible for monogenic AIDs. This emphasizes the importance of the implementation of this type of studies to make a definitive diagnosis, especially in this group of genetically very diverse diseases with overlapping clinical phenotypes. However, given the presence of variants of uncertain significance (VUS), the results may not be conclusive, raising the need to develop functional tests to determine the pathogenicity of these genetic variants. In our working group we are applying droplet digital PCR (ddPCR), a highly sensitive, specific and reproducible third generation quantitative technique that does not require calibration curves, to develop functional tests that allow not only to reclassify VUS variants to achieve definitive diagnoses but also to study the mechanisms responsible for the main AIDs that allow for the stratification of specific treatments to be used and thereby contribute to the individualized diagnosis, treatment, and follow-up of our patients (AU)

Reabilitação com prótese bucomaxilofacial: revisão de literatura / Rehabilitation with maxillofacial prosthetics

A odontologia reabilitadora tem como um dos seus ramos a especialidade de Prótese Bucomaxilofacial (PBMF), que visa restaurar ou substituir estruturas perdidas na região facial e no sistema estomatognático artificialmente, podendo ser ou não removidos pelo paciente. O presente trabalho objetiva revisar a leitura a respeito da reabilitação com PBMF e a sua aplicabilidade na clínica odontológica. Os indivíduos com alguma perda de estrutura na região de cabeça e pescoço, devido a traumas físicos e/ou químicos, defeitos congênitos, doenças autoimunes, neoplasias, infecções e parasitas, são pacientes para os quais há a indicação da reposição da parte ausente. As reconstruções podem ser perdas intraorais (área da maxila, mandíbula), extraorais (oculopalpebral, ocular, nasal, facial extensa e auricular) ou conjugadas. Esse é um trabalho multidisciplinar, com especialistas de áreas abrangentes e todos os especialistas trabalham de forma conjunta. Pode-se concluir que, embora seja uma das especialidades mais nobres da odontologia, ainda é muito desconhecida por parte dos estudantes e profissionais das áreas da saúde e são próteses absolutamente fundamentais para a reabilitação e qualidade de vida dos indivíduos que tem a necessidade do uso da prótese PBMF(AU)

Rehabilitating dentistry has as one of its branches the specialty of Oral and Maxillofacial Prosthesis (PBMF), which aims to restore or replace structures lost in the facial region and in the stomatognathic system artificially, which may or may not be removed by the patient. The present study aims to review the reading about rehabilitation with PBMF and its applicability in dental clinic. Individuals with some loss of structure in the head and neck region, due to physical and/or chemical trauma, birth defects, autoimmune diseases, neoplasms, infections and parasites, are patients in whom there is an indication for replacement of the absent part. Reconstructions can be intraoral (maximal area, mandible), extraoral (oculopalpebral, ocular, nasal, extensive facial and auricular) or conjugated losses. It is a multidisciplinary work, with specialists from the comprehensive areas and that all specialists work together. It can be concluded that although it is one of the noblest specialties of dentistry, it is still very unknown to students and health professionals, and they are absolutely fundamental prostheses for the rehabilitation and quality of life of individuals who need the use the PBMFprosthesis(AU)

Diabetes tipo 1 y Miastenia Gravis / Type-1 Diabetes and Myasthenia Gravis

Introducción: El desarrollo de la tolerancia inmunológica frente a los autoantígenos se denomina autotolerancia. La Diabetes Mellitus tipo 1A (1ADM) es un trastorno metabólico secundario a la destrucción autoinmune de las células beta pancreáticas e insulitis. La miastenia grave (MG) es una enfermedad autoinmune causada por el bloqueo postsináptico de la placa mioneural por AAcs contra los receptores de acetilcolina (ACRA) o contra moléculas de la membrana postsináptica. La asociación entre DM1A y MG se puede observar en el síndrome poliglandular tipo III, caracterizado por enfermedad autoinmune de la glándula tiroides asociada con otras entidades autoinmunes. Método: Reporte de Casos, cuatro pacientes entre 7-19 años, con asociación de MG y DM1A atendidos en el Hospital Garrahan. Conclusión: La Tiroiditis de Hashimoto y la Enfermedad Celíaca son las enfermedades autoinmunes relacionadas más frecuentemente con DM1A en nuestra población. La bibliografía describe la asociación de MG y Tiroiditis de Hashimoto y su coexistencia con DM1A se describe en el Síndrome Poliglandular III. En este trabajo presentamos 4 casos de DM1A asociado con MG fuera de dicho síndrome (AU)

Introduction: The development of immune tolerance to autoantibodies (AAbs) is referred to as self-tolerance. Type 1A Diabetes Mellitus (1ADM) is a metabolic disorder secondary to autoimmune destruction of pancreatic beta cells and insulitis. Myasthenia gravis (MG) is an autoimmune disease caused by postsynaptic blockade of the myoneural plate by AAbs against acetylcholine receptors (Acra) or against postsynaptic membrane molecules. The association between 1ADM and MG may be observed in polyglandular syndrome type III, characterized by autoimmune disease of the thyroid associated with other autoimmune conditions. Methods: Case report; four patients between 7-19 years old, with an association of MG and 1ADM seen at the Garrahan Hospital. Conclusion: Hashimoto's thyroiditis and celiac disease are autoimmune diseases most frequently related to 1ADM in our population. In the literature, the association of MG and Hashimoto's thyroiditis has been described and its coexistence with 1ADM is reported in polyglandular syndrome III. In this study we present 4 cases of 1ADM associated with MG unrelated to this syndrome. (AU)

Impact de la pandémie de COVID-19 sur le suivi des maladies systémiques: enquête transversale multicentrique à Dakar / How the outbreak of COVID-19 did affected the follow-up of patients known for an autoimmune or autoinflammatory systemic diseases in Dakar

Introduction : La pandémie de covid-19 a eu un impact sur les systèmes de santé, entravant la prise en charge optimale des maladies chroniques. L'objectif de notre étude était d'évaluer son impact sur le suivi des pathologies systémiques. Patients - Méthodes : Nous avons mené une enquête transversale multicentrique dans les services de Médecine Interne, de Rhumatologie et de Néphrologie à Dakar. Les patients étaient inclus en accord avec les critères de consensus internationaux. L'enquête a porté sur les dossiers concernant 13 questions et a été complétée par un entretien téléphonique avec 38 questions potentielles. Les réponses étaient collectées grâce à une application Web puis exportées et analysées avec le logiciel SPSS 26.0. Résultats : Du 1er Août au 31 Octobre 2021, 131 patients ont été inclus avec un âge moyen de 41,5 ans (+/-12,4) et un sex-ratio de 0,08. Les pathologies inflammatoires étaient dominées par la polyarthrite rhumatoïde (47,3%) et le lupus systémique (22,9%). Les patients ont rapporté avoir raté un ou plusieurs rendez-vous de suivi dans 45% des cas. Les motifs étaient dominés par une difficulté d'obtenir un rendez-vous de suivi (18,6%) et la peur de fréquenter les hôpitaux (16,9%). Une rupture médicamenteuse a été notée dans 33,6% des cas et concernait notamment l'hydroxychloroquine (40,9%) ou le méthotrexate (47,7%) avec comme raison principale les ruptures de stock en pharmacie et les difficultés économiques. Une poussée de la maladie systémique a été rapportée dans 31% des cas corrélée à la rupture médicamenteuse. Onze (11) patients ont présenté une infection confirmée à SARS CoV-2. Conclusion : La pandémie de covid-19 a eu un impact non négligeable sur le suivi des patients atteints de maladies inflammatoires systémiques. Elle a mis en exergue l'intérêt de la réorganisation de la prise en charge de ces patients en période de crise sanitaire, l'éducation thérapeutique des patients et le recours à la télémédecine pour assurer la continuité des soins.

Introduction: The covid-19 pandemic has had an impact on health systems, compromising the optimal management of chronic diseases such as systemic autoimmune and autoinflammatory diseases. The aim of our study was to assess its impact on the follow-up of systemic diseases in Dakar. Patients - Methods: We conducted a multicentre cross-sectional survey in the departments of Internal Medicine, Rheumatology and Nephrology in Dakar. Patients were included in accordance with international consensus criteria. The survey was based on records of 13 questions and was completed by a telephone interview with 38 potential questions. Responses were collected using a web-based application and then exported and analyzed using SPSS 26.0 software. Results: From 1 August to 31 October, 131 patients were included with a mean age of 41.5 years (+/-12.4) and a sex-ratio of 0.08. Inflammatory diseases were dominated by rheumatoid arthritis (47.3%) and systemic lupus erythematosus (22.9%). Patients reported missing one or more follow-up appointments in 45% of the cases. The reasons were dominated by difficulty in obtaining a follow-up appointment (18.6%) and fear of attending hospitals (16.9%). A drug shortage was also reported in 33.6% of the cases and concerned in particular hydroxychloroquine (40.9%) or methotrexate (47.7%), with the main reason being stock shortages in pharmacies and economic difficulties. A flare-up of the systemic disease was reported in 31% of the cases correlated with the drug rupture. Only 11 patients had a confirmed SARS CoV-2 infection. Conclusion: The covid-19 pandemic has had a significant impact on the follow-up of patients with systemic inflammatory diseases. It highlighted the interest of reorganizing the follow-up of these patients during a health crisis, the patient education and the use of telemedicine to ensure continuity of care

Anti-HMGCR immune-mediated necrotizing myopathy: A case report / 北京大学学报(医学版)

The patient was a 55-year-old man who was admitted to hospital with "progressive myalgia and weakness for 4 months, and exacerbated for 1 month". Four months ago, he presented with persistent shoulder girdle myalgia and elevated creatine kinase (CK) at routine physical examination, which fluctuated from 1 271 to 2 963 U/L after discontinuation of statin treatment. Progressive myalgia and weakness worsened seriously to breath-holding and profuse sweating 1 month ago. The patient was post-operative for renal cancer, had previous diabetes mellitus and coronary artery disease medical history, had a stent implanted by percutaneous coronary intervention and was on long-term medication with aspirin, atorvastatin and metoprolol. Neurological examination showed pressure pain in the scapularis and pelvic girdle muscles, and V- grade muscle strength in the proximal extremities. Strongly positive of anti-HMGCR antibody was detected. Muscle magnetic resonance imaging (MRI) T2-weighted image and short time inversion recovery sequences (STIR) showed high signals in the right vastus lateralis and semimembranosus muscles. There was a small amount of myofibrillar degeneration and necrosis, CD4 positive inflammatory cells around the vessels and among myofibrils, MHC-Ⅰ infiltration, and multifocal lamellar deposition of C5b9 in non-necrotic myofibrils of the right quadriceps muscle pathological manifestation. According to the clinical manifestation, imageological change, increased CK, blood specific anti-HMGCR antibody and biopsy pathological immune-mediated evidence, the diagnosis of anti-HMGCR immune-mediated necrotizing myopathy was unequivocal. Methylprednisolone was administrated as 48 mg daily orally, and was reduced to medication discontinuation gradually. The patient's complaint of myalgia and breathlessness completely disappeared after 2 weeks, the weakness relief with no residual clinical symptoms 2 months later. Follow-up to date, there was no myalgia or weakness with slightly increasing CK rechecked. The case was a classical anti-HMGCR-IMNM without swallowing difficulties, joint symptoms, rash, lung symptoms, gastrointestinal symptoms, heart failure and Raynaud's phenomenon. The other clinical characters of the disease included CK as mean levels >10 times of upper limit of normal, active myogenic damage in electromyography, predominant edema and steatosis of gluteus and external rotator groups in T2WI and/or STIR at advanced disease phase except axial muscles. The symptoms may occasionally improve with discontinuation of statins, but glucocorticoids are usually required, and other treatments include a variety of immunosuppressive therapies such as methotrexate, rituximab and intravenous gammaglobulin.

Application and Effectiveness of Chinese Medicine in Regulating Immune Checkpoint Pathways / 中国结合医学杂志

Immunotherapy targeting immune checkpoint molecules has emerged as a key approach in cancer treatment, representing the forefront of antitumor research. However, studies on immune checkpoint molecules have mainly focused on targeted therapies. Chinese medicine (CM) research as a complementary medicine has revealed that immune checkpoint molecules also undergo disease-specific changes in the context of autoimmune diseases. This review article presents a comprehensive analysis of CM studies on immune checkpoint molecules in the last 5 years, with a focus on their role in different diseases and treatment modalities. CM research predominantly utilizes oral administration of herbal plant extracts or acupuncture techniques, which stimulate the immune system by activating specific acupoints through temperature and needling. In this study, we analyzed the modulation and mechanisms of immune checkpoint molecules associated with different coinhibitory and costimulatory molecules, and reviewed the immune functions of related molecules and CM studies in treating autoimmune diseases and tumors. By summarizing the characteristics and research value of CM in regulating immune checkpoint molecules, this review aims to provide a useful reference for future studies in this field.

Clinical characteristics of fetal cardiac disease in patients with anti-SSA antibody positive / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical manifestations and laboratory indicators of anti-Sjögren's-syndrome-related antigen A (SSA) antibody associated fetal cardiac disease.@*METHODS@#Pregnant women hospitalized at Peking University People's Hospital from January 2013 to July 2023 were included. Eleven patients with anti-SSA antibody positive were eventually diagnosed with fetal cardiac di-sease. And patients with anti-SSA antibody positive without fetal cardiac disease were selected as controls. Clinical manifestations, laboratory indications and drug usage were compared between the two groups.@*RESULTS@#Among these 11 patients, congenital heart block was confirmed in seven, which was the most common manifestations of fetal cardiac malformation. The proportion of the patients diagnosed with autoimmune disease before pregnancy in fetal cardiac malformation group was significantly lower than that in the control group (P=0.032), while most of the patients in the fetal cardiac malformation group received immune-related examinations for the first time because of this time's fetal cardiac diagnosis. While most of the patients in the control group received routine examinations because of autoimmune diseases diagnosed before pregnancy. During pregnancy, the white blood cell level [(9.29±2.58)×109/L vs. (7.10±1.90×109/L, t=3.052, P=0.004], erythrocyte sedimentation rate [(49.50 (48.00, 51.00) mm/h vs. 23.00 (15.00, 30.25) mm/h, Z=-2.251, P=0.024], IgA level [3.46 (2.30, 5.06) g/L vs. 2.13 (1.77, 2.77) g/L, Z=-2.181, P=0.029], and antinuclear antibody (ANA) titers [1∶320 (1∶160, 1∶320) vs. 1∶80 (1∶40, 1∶160), Z=-3.022, P=0.003] were significantly higher in fetal cardiac malformation group than in the control group. The proportion of positive anti-SSB antibody during pregnancy did not show a statistically significant difference between the two groups (37.5% vs. 7.7%, P=0.053). There was no significant difference in hydroxychloroquine dosage and initiation time between the two groups. The dosage of prednisone in the second and third trimesters was significantly higher in the cardiac malformation group than that in the control group, but there was no significant difference in the first trimester.@*CONCLUSION@#Fetal cardiac disease is rare in pregnant women with anti-SSA antibody. White blood cell, erythrocyte sedimentation rate, IgA, the titer of ANA positivity were higher in the fetal heart disease group during pregnancy. Since congenital heart block is difficult to reverse, its prevention and monitoring are more important than remedial treatment.

Protection of inactivated vaccine against SARS-CoV-2 infections in patients with comorbidities: a prospective cohort study / 医学前沿

Protection against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection of inactivated vaccines is not well characterized in people with comorbidities, who are at high risk of severe infection. We compared the risk of SARS-CoV-2 infection after complete vaccination with Sinopharm/BBIBP in people with comorbidities (e.g., autoimmune diseases, cardiovascular disease, chronic lung disease, and diabetes) with healthy individuals using a Cox-proportional hazard model. In July-September 2021, a total of 10 548 people (comorbidities, 2143; healthy, 8405) receiving the complete primary series of vaccination with Sinopharm/BBIBP in Bangkok, Thailand were prospectively followed for SARS-CoV-2 infection through text messaging and telephone interviewing for 6 months. A total of 295 infections from 284 participants were found. HRs (95% CI) of individuals with any comorbidities did not increase (unadjusted, 1.02 (0.77-1.36), P = 0.89; adjusted, 1.04 (0.78-1.38), P = 0.81). HRs significantly increased in the subgroup of autoimmune diseases (unadjusted, 2.64 (1.09-6.38), P = 0.032; adjusted, 4.45 (1.83-10.83), P = 0.001) but not in cardiovascular disease, chronic lung disease, or diabetes. The protection against SARS-CoV-2 infection of the Sinopharm vaccine was similar in participants with any comorbidities vs. healthy individuals. However, the protection appeared lower in the subgroup of autoimmune diseases, which may reflect suboptimal immune responses among these people.

Expert consensus on quality control for detecting autoantibodies / 中华内科杂志

Autoantibodies are important biomarkers of autoimmune diseases and crucial for disease diagnosis, differential diagnosis, and the evaluation of disease activity and prognosis. Specifying the requirement of quality control for detecting autoantibodies is essential for accurately reporting relevant results. In 2023, National Clinical Research Center for Dermatologic and Immunologic Diseases (Peking Union Medical College Hospital), Experimental Diagnosis Research Committee, Rheumatology and Immunology Physicians Committee of Chinese Medical Doctor Association, Autoantibodies Detection Committee, Chinese Rheumatism Data Center invited relevant clinical and laboratory experts to develop the current consensus based on the national standards, the industry guidelines, the national situation, and the experience of quality control regarding autoantibody detection. This consensus aims to standardize the quality control of autoantibody detection in relevant laboratories in China.

Research progress in treatment of Sjögren's syndrome by traditional Chinese medicine / 中国中药杂志

Sj9gren's syndrome(SS) is an autoimmune disease with glandular dysfunction caused by the massive infiltration of the exocrine glands by lymphocytes. The pathogenesis of this disease is related to the chronic inflammatory response of the exocrine glands due to excessive activation of B cells and T cells. In addition to dry mouth and eyes, SS can also cause damage to other organs and systems in the human body, seriously affecting the quality of life of patients. Traditional Chinese medicine(TCM) has definite clinical efficacy in the treatment of SS as it can alleviate symptoms and regulate immune disorders without causing adverse reactions, demonstrating high safety. This paper reviews the current status of preclinical and clinical trials about the TCM treatment of SS in the past decade. TCM mainly mitigates SS symptoms such as dry mouth, dry eyes, dry skin, and joint pain and improves the prognosis and quality of life of patients by regulating the abnormally activated B cells and T cells, inhibiting the autoimmune response, restoring the balance between pro-inflammatory and anti-inflammatory cytokines, and reducing the pathological damage caused by immune complexes to exocrine glands and joints in SS patients.

IL-27: a novel cytokine mediating immune related diseases / 生理学报

Interleukin 27 (IL-27) is a pleiotropic cytokine that is involved in the regulation of the body's innate and adaptive immunity. Previous studies have shown that IL-27 mediates a variety of inflammatory responses in vivo. With the development of animal models and technical tools, several studies have shown that it is also closely associated with autoimmune diseases and other immune related diseases, and is considered as an important candidate for the treatment of viral disease, autoimmune diseases, tumors and obesity. Therefore, this paper reviews recent progress on the role of IL-27 in acquired immunodeficiency syndrome (AIDS), rheumatoid arthritis, tumors and obesity, with the aim of providing new ideas for the treatment of immune related diseases.

The critical importance of epigenetics in autoimmune-related skin diseases / 医学前沿

Autoimmune-related skin diseases are a group of disorders with diverse etiology and pathophysiology involved in autoimmunity. Genetics and environmental factors may contribute to the development of these autoimmune disorders. Although the etiology and pathogenesis of these disorders are poorly understood, environmental variables that induce aberrant epigenetic regulations may provide some insights. Epigenetics is the study of heritable mechanisms that regulate gene expression without changing DNA sequences. The most important epigenetic mechanisms are DNA methylation, histone modification, and noncoding RNAs. In this review, we discuss the most recent findings regarding the function of epigenetic mechanisms in autoimmune-related skin disorders, including systemic lupus erythematosus, bullous skin diseases, psoriasis, and systemic sclerosis. These findings will expand our understanding and highlight the possible clinical applications of precision epigenetics approaches.