Seroprevalencia de enfermedad celiaca en pacientes con infertilidad. Un estudio de casos y controles / Celiac disease seroprevalence in patients with infertility. A case-control study

Resumen Antecedentes: Aunque los pacientes con enfermedad celiaca (EC) tienen en su mayoría manifestaciones digestivas, algunos pueden presentarlas de índole extraintestinal (atípicas), como anemia crónica, ataxia y trastornos de la fertilidad. Objetivo: Determinar la prevalencia de anticuerpos relacionados con EC en mujeres mexicanas con trastornos de la fertilidad. Material y métodos: Estudio de casos y controles de mujeres que acudieron a valoración por trastornos de la fertilidad en un centro especializado. Se cuantificó h-tTG IgA, gliadina IgA II y gliadina IgG II; los títulos > 30 UI fueron considerados como positivos. Resultados: Se incluyeron 171 casos y 171 controles; 137 pacientes (80.1 %) tuvieron infertilidad y 34 (19.9 %), esterilidad. Ocho pacientes (4.6 %, IC 95 % = 2.3-8.9) tuvieron al menos un marcador positivo para EC comparadas con una mujer del grupo control (0.5 %, IC 95 % = 0.01-3, p = 0.04, razón de momios = 8.3). Seis de las ocho pacientes presentaron infertilidad inexplicable. Conclusiones: Hasta 4.6 % de las mujeres con infertilidad presentó al menos un marcador positivo para EC. Al igual que en otras partes del mundo, podría recomendarse el escrutinio para EC en mujeres con infertilidad, en especial en quienes padecen infertilidad inexplicable.

Abstract Background: Although most patients with celiac disease (CD) have digestive manifestations, in some of them they may be of extraintestinal (atypical) nature, such as chronic anemia, ataxia, and fertility disorders. Objective: To determine the prevalence of CD-related antibodies in Mexican women with fertility disorders. Material and methods: Case-control study of women who attended evaluation for fertility disorders in a specialized center. h-tTG-IgA, gliadin IgA II and gliadin IgG II were quantified; titers > 30 IU were considered positive. Results: One-hundred and seventy-one cases and 171 controls were included; 137 patients (80.1%) had infertility, and 34 (19.9%), sterility. Eight patients (4.6%, 95% CI = 2.3-8.9) had at least one positive marker for CD in comparison with one woman in the control group (0.5%, 95% CI = 0.01-3, p = 0.04, odds ratio = 8.3). Six of the eight patients had unexplained infertility. Conclusions: Up to 4.6% of women with infertility had at least one positive marker for CD. As in other parts of the world, screening for CD could be recommended in women with infertility, especially in those with unexplained infertility.

Impasses do diagnóstico precoce da doença celíaca e suas repercussões clínicas e sociais / Impasses in the early diagnosis of celiac disease and its clinical and social repercussions / Impasos del diagnóstico temprano de la enfermedad celámica y su impacto clínico y social

A turva Doença Celíaca (DC) demonstra sua opacidade através dos aspectos clínicos de difícil detecção precoce. Essa delonga em identificar o enfermo e orientá-lo acerca dos hábitos de vida indispensáveis à saúde do portador de DC, acarreta desdobramentos prognósticos negativos, visto que o consumo crônico dos agentes irritantes gera lesões inflamatórias insistentes que, paulatinamente agridem o tecido gastrintestinal em diferentes níveis. Para além das lesões epiteliomucosas, as dores enfrentadas por esses pacientes permeiam a exclusão e a fobia social, as patologias psiquiátricas e as síndromes de humor deprimido. Além da demora diagnóstica que compromete de curto a extenso prazo os doentes, nota-se evidente falha nos dados epidemiológicos, que parecem se relacionar com o subdiagnóstico. Assim, reunimos estudos de epidemiologia de diferentes regiões e, em progressão de tempo, que demonstram aumento nos índices diagnósticos, além de teorias fisiopatológicas que parecem contribuir para o aumento de diagnósticos precoces. Para isso, extensas revisões literárias em livros referência dentre a prática médica e pesquisas complementares, tanto em artigos de aprofundamento e atualização literária, quanto diretrizes nacionais de manejo, constroem o presente estudo. Enfim, demonstra-se as importantes lacunas de conhecimento acerca dessa patologia cada vez mais prevalente.

The blurred celiac disease demonstrates its opacity through clinical aspects that are difficult to detect early. This delay in identifying the patient and guiding him about the life habits essential to the health of the CD patient, leads to negative prognostic consequences, since the chronic consumption of irritating agents generates persistent inflammatory lesions that, gradually attack the gastrointestinal tissue at different levels . In addition to epitheliomucosal lesions, the pain faced by these patients permeates exclusion and social phobia, psychiatric pathologies and depressed mood syndromes. In addition to the diagnostic delay that compromises patients in the short to long term, there is an evident failure in the epidemiological data, which seems to be related to underdiagnosis. Thus, we gathered epidemiology studies from different regions and, over time, that demonstrate an increase in diagnostic rates, in addition to pathophysiological theories that seem to contribute to the increase in early diagnoses. For this, extensive literary reviews in reference books within medical practice and complementary research, both in deepening articles and literary updating, as well as national management guidelines, build the present study. Finally, it demonstrates the important gaps in knowledge about this increasingly prevalent pathology.

La Enfermedad Celular Nublada (DC) demuestra su opacidad a través de los aspectos clínicos de difícil detección en una etapa temprana. Este retraso en la identificación del enfermo y en el asesoramiento sobre los hábitos de vida indispensables para la salud del portador de DC, trae consigo un desarrollo pronóstico negativo, ya que el consumo crónico de agentes irritantes genera lesiones inflamatorias insistente que, gradualmente, dañan el tejido gastrointestinal a diferentes niveles. Además de las lesiones epiteliomucosiales, el dolor que enfrentan estos pacientes permea la exclusión social y la fobia, los trastornos psiquiátricos y los síndromes deprimidos. Además del retraso en el diagnóstico que pone en peligro a los pacientes en el corto y largo plazo, es evidente que los datos epidemiológicos, que parecen estar relacionados con el subdiagnóstico, han fracasado. Por lo tanto, reunimos estudios epidemiológicos de diferentes regiones y, en una progresión del tiempo, que demuestran un incremento en los índices diagnósticos, además de teorías fisiopatológicas que parecen contribuir a un aumento en los diagnósticos precoces. Para ello, se construyen en este estudio amplias revisiones literarias en libros de referencia entre la práctica médica y las investigaciones complementarias, tanto en artículos de profundización y actualización literaria como en directrices nacionales para su manejo. En resumen, se están demostrando las importantes lagunas de conocimiento sobre esta patología cada vez más prevalente.

Enteropatías congénitas y la implicación diagnóstica en la displasia intestinal o enteropatía en penacho

RESUMEN Introducción: la displasia epitelial intestinal o enteropatía en penacho, es una rara y grave enfermedad debido a mutaciones genéticas, categorizada como enteropatía congénita por defecto del transporte de los enterocitos y su polaridad. Objetivo: Examinar los conocimientos más recientes para la orientación diagnóstica de las enteropatías congénitas en el contexto clínico de las diarreas crónicas intratables del período posnatal y primeros meses de vida. Métodos: Análisis de publicaciones en español e inglés en PubMed, Scimago, ScIELO hasta abril 2021 relacionadas con esta temática. Se usaron los términos diarreas intratables, enteropatías congénitas, displasia epitelial intestinal, enteropatía en penacho y enfermedades para diagnóstico diferencial. Análisis e integración de la información: Se describieron criterios sobre diarreas intratables, enteropatías congénitas; su clasificación. Se revisaron rasgos de la displasia epitelial intestinal y sus manifestaciones de formas clínicas, histopatológicas y mutaciones genéticas, epidemiología, diagnóstico de certeza y diferencial por afecciones debido a defectos congénitos relacionados con el tránsito epitelial y polaridad; tratamiento, pronóstico y actualización sobre trascendencia de las enfermedades raras. Conclusiones: Se revisan los conocimientos más recientes relacionados con enfermedades raras por enteropatías congénitas y en particular sobre la displasia epitelial intestinal o enteropatía en penacho. Se describen sus manifestaciones clínicas, histopatológicas y genéticas. La epidemiología, el tratamiento y sus retos. Se enfatizó en criterios sobre la trascendencia diagnóstica de enfermedades raras relacionadas con enteropatías congénitas.

ABSTRACT Introduction: Intestinal epithelial dysplasia or plume enteropathy is a rare and serious disease due to genetic mutations, categorized as congenital enteropathy due to the defect of enterocyte transport and their polarity. Objective: Examine the most recent knowledge on the diagnostic orientation of congenital enteropathies in the clinical context of intractable chronic diarrhea of the postnatal period and first months of life. Methods: Analysis of publications in Spanish and English in PubMed, Scimago, ScIELO until April 2021 related to this topic. The terms intractable diarrhea, congenital enteropathies, intestinal epithelial dysplasia, plume enteropathy and diseases were used for differential diagnosis. Analysis and integration of information: Criteria on intractable diarrhea, and congenital enteropathies were described; and their classification. Features of intestinal epithelial dysplasia and its manifestations of clinical, histopathological forms and genetic mutations, epidemiology, diagnosis of certainty and differential for conditions due to congenital defects related to epithelial transit and polarity were reviewed; treatment, prognosis and update on the importance of rare diseases. Conclusions: The most recent knowledge related to rare diseases due to congenital enteropathies and in particular about intestinal epithelial dysplasia or plume enteropathy is reviewed. Its clinical, histopathological and genetic manifestations are described, epidemiology, treatment and its challenges. Emphasis was placed on criteria on the diagnostic significance of rare diseases related to congenital enteropathies.

Severe congenital diarrhea secondary to tufting enteropathy. case report

ABSTRACT Introduction: Tufting enteropathy is a rare cause of congenital diarrhea in neonates. It is characterized by the abnormal distribution of epithelial adhesion molecules, which causes enterocytes to shed into the lumen, forming the characteristic tufts. Case summary: A 15-day-old female neonate was taken by her parents to the emergency department of a tertiary care hospital due to diarrheal stools she had been experiencing since birth. The patient presented with dehydration, abnormal weight loss, metabolic acidosis, and acute kidney failure. She received treatment with alizapride, loperamide, zinc sulfate, and probiotics, but after 75 days of treatment she was still symptomatic. An upper tract endoscopy and colonoscopy were performed, finding flattening of the villi and lymphoid cells in the lamina propria. However, the symptoms persisted, and she died at the age of ten months. A post-mortem exome sequencing reported tufting enteropathy. Conclusions. When congenital diarrhea is present, tufting enteropathy should be considered. An early molecular study would allow to evaluate the possibility of performing an intestinal transplant or modifying the treatment to meet the patient's palliative care needs.

RESUMEN Introducción. La enteropatía en penacho es una causa rara de diarrea congénita en neonatos; esta se caracteriza por una alteración de la adhesión epitelial que ocasiona desprendimiento de enterocitos hacia el lumen y, en consecuencia, forma los característicos penachos. Se describe el caso de una paciente con esta patología. Presentación del caso. Neonata de 15 días de vida, quien fue llevada por sus padres al servicio de urgencias de un hospital de tercer nivel debido a que desde su nacimiento tuvo deposiciones diarreicas y a causa de esto presentó deshidratación, pérdida de peso, acidosis metabólica e insuficiencia renal aguda. La paciente recibió manejo con alizaprida, loperamida, sulfato de zinc y probióticos, pero a los 75 días de tratamiento continuaba sintomática. Se le practicó una endoscopia de vías digestivas y una colonoscopia que mostraron aplanamiento de las vellosidades e infiltrado de células linfoides en la lámina propia. Los síntomas continuaron y la menor falleció a los 10 meses de nacida. El resultado del exoma post mortem reportó enteropatía en penacho. Conclusiones. Ante la presencia de diarrea congénita, se debe sospechar de una enteropatía en penacho y considerar el estudio molecular temprano, pues este permite evaluar la posibilidad de realizar un trasplante intestinal o modificar el tratamiento según las necesidades de cuidado paliativo del paciente.

Enterocolopatía sprue-like asociada a la toma de olmesartán / Olmesartan-induced sprue-like enteropathy

Resumen La diarrea crónica es una patología frecuente con un amplio diagnóstico diferencial. Presentamos el caso de un paciente con diarrea crónica secundaria a enterocolopatía por la toma prolongada de olmesartán. Se trata de una patología infradiagnosticada por desconocimiento de la entidad, pero que debe considerarse en base a la frecuencia de uso del grupo farmacológico. En nuestro caso, la buena evolución clínica tras la retirada del fármaco nos muestra la necesidad de considerarlo como causa directa del cuadro clínico. Un adecuado enfoque terapéutico en estos pacientes nos permitirá evitar pruebas complementarias, costos innecesarios y se traducirá en una mejora diagnóstica y del pronóstico de estos pacientes. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2203).

Abstract Chronic diarrhea is a common pathology with a broad differential diagnosis. We present the case of a patient with chronic diarrhea secondary to enteropathy due to prolonged consumption of olmesartan. This is an underdiagnosed pathology due to lack of knowledge regarding this entity, but it should be considered, given the frequency with which this pharmacological group is used. In our case, the favorable clinical progression after withdrawing the medication indicates the need to consider it as the direct cause of the clinical picture. An appropriate therapeutic approach to these patients will allow us to avoid complementary tests and unnecessary costs, and will translate into a better diagnosis and prognosis in these patients. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2203).

Portal hypertensive enteropathy: A disease that should not be ignored among the complications of portal hypertension / 临床肝胆病杂志

Although portal hypertensive enteropathy (PHE) is similar to portal hypertensive gastroenteropathy, it has various endoscopic manifestations with a lack of specificity, and there are still no unified diagnostic criteria. It is easily ignored by clinicians due to great individual differences and the absence of symptoms for quite a long period of time. Based on the patients' conditions and local expert experience, the treatment methods include symptomatic supportive treatment, pharmacotherapy, endoscopic therapy, radioactive intervention therapy, and surgical interventions. Although there have been reports on the endoscopic manifestations and treatment of PHE in recent years, the diagnosis, treatment, and prognosis of this disease should be taken seriously by clinicians.

Primer reporte en Cuba de enteropatía congénita en penachos / First report of congenital tufting enteropathy in Cuba

Introducción: La enteropatía en penacho, conocida como displasia epitelial intestinal, es una afección congénita muy poco frecuente que se presenta con diarrea refractaria en lactantes. Objetivo: Describir el primer reporte en Cuba de enteropatía congénita en penachos. Presentación del caso: Se presentó el primer caso de la enfermedad en Cuba a partir de los hallazgos histopatológicos y se describieron los aspectos clínicos, diagnósticos y terapéuticos abordados. Conclusiones: La enteropatía en penachos supone un reto diagnóstico al no exhibir un cortejo clínico patognomónico. La concomitancia de diarrea crónica con los trastornos malformativos debe hacer saltar las alarmas y orientar el pensamiento clínico y la metodología diagnóstica hacia posibles trastornos genéticos(AU)

Introduction: Tufting enteropathy, also known as intestinal epithelial dysplasia, is a very infrequent congenital disorder presenting as refractory diarrhea in infants. Objective: Describe the first report of congenital tufting enteropathy in Cuba. Case presentation: A presentation is provided of the first case of the disease in Cuba based on histopathological findings and accompanied by a description of the clinical, diagnostic and therapeutic aspects addressed. Conclusions: Tufted enteropathy poses a diagnostic challenge as it does not exhibit a pathognomonic clinical courtship. The concomitance of chronic diarrhea with malformation disorders should set off alarms and guide clinical thinking and diagnostic methodology towards possible genetic disorders(AU)

Reto Diagnóstico: Hipoacusia, Enteropatía Autoinmune y Linfadenopatia de Kikuchi ­ un Debut Inusual de LES / Diagnostic challenge: hearing loss, autoimmune enteropathy and Kikuchi lymphadenopathy - An unusual debut of SLE

El lupus eritematoso sistémico (LES) puede presentarse de muchas maneras y puede ser difícil de diagnosticar. En ocasiones puede ser difícil distinguir la enfermedad subyacente, ya que se sabe que el LES mismo causa síntomas gastrointestinales e incluso malabsorción. Este caso refleja los desafíos de diagnóstico que enfrentamos durante la larga y complicada hospitalización de una adolescente con compromiso sistémico, síndrome febril, malabsorción, marcadores inflamatorios elevados, hipoacusia, nefritis, linfadenitis necrotizante histiocítica

Systemic lupus erythematosus (SLE) can present in many ways and can be difficult to diagnose. It can sometimes be difficult to distinguish the underlying disease, as SLE itself is known to cause gastrointestinal symptoms and even malabsorption. This case reflects the diagnostic challenges we faced during the long and complicated hospitalization of an adolescent with systemic compromise, febrile syndrome, malabsorption, elevated inflammatory markers, hearing loss, nephritis, histiocytic necrotizing lymphadenitis

Establishment of a production process for a novel vaccine candidate against Lawsonia intracellularis

BACKGROUND: Lawsonia intracellularis remains a problem for the swine industry worldwide. Previously, we designed and obtained a vaccine candidate against this pathogen based on the chimeric proteins: OMP1c, OMP2c, and INVASc. These proteins formed inclusion bodies when expressed in E. coli, which induced humoral and cellular immune responses in vaccinated pigs. Also, protection was demonstrated after the challenge. In this study, we established a production process to increase the yields of the three antigens as a vaccine candidate. RESULTS: Batch and fed-batch fermentations were evaluated in different culture conditions using a 2 L bioreactor. A fed-batch culture with a modified Terrific broth medium containing glucose instead of glycerol, and induced with 0.75 mM IPTG at 8 h of culture (11 g/L of biomass) raised the volumetric yield to 627.1 mg/L. Under these culture conditions, plasmid-bearing cells increased by 10% at the induction time. High efficiency in cell disruption was obtained at passage six using a high-pressure homogenizer and a bead mill. The total antigen recovery was 64% (400 mg/L), with a purity degree of 70%. The antigens retained their immunogenicity in pigs, inducing high antibody titers. CONCLUSIONS: Considering that the antigen production process allowed an increment of more than 70-fold, this methodology constitutes a crucial step in the production of this vaccine candidate against L. intracellularis.

Use of oral fluids to detect anti Lawsonia intracellularis antibodies in experimentally infected pigs / Utilização de fluidos orais para detecção de anticorpos anti Lawsonia intracellularis em suínos experimentalmente infectados

Several pathogens and antibodies derived from serum or produced in tissues associated with the oral cavity are present in the oral fluid (OF). Considering the applicability of this alternative sample, recent studies in veterinary medicine have tested OF as a replacement for serum in diagnostic assays. The aim of this study was to standardize the immunoperoxidase monolayer assay (IPMA) to detect anti-Lawsonia intracellularis immunoglobulin A (IgA) and immunoglobulin G (IgG) in OF samples from experimentally infected pigs. Sixty-two pigs were divided into two groups: control (T1, n=30) and inoculated with L. intracellularis (T2, n=32). Blood, OF and fecal samples were collected at 0, 7, 14, 21, 28 and 42 days post-inoculation (dpi). Some adaptations of the standard technique for serum were made to IPMA for the detection of IgA and IgG in OF. The IPMA showed high specificity and sensitivity for serum samples and high specificity and moderate sensitivity for the detection of IgA and IgG in OF. There was high agreement between the results of serum IgG and OF IgA and IgG. Based on our results, oral fluid samples may be used for the evaluation and determination of anti-L. intracellularis antibodies in pigs, but not for individual diagnosis of swine proliferative enteropathy.(AU)

Vários patógenos e anticorpos derivados do soro ou produzidos em tecidos associados a cavidade oral estão presentes no fluido oral (FO). Considerando a aplicabilidade dessa amostra alternativa, estudos recentes em medicina veterinária têm testado o FO como substituto do soro para testes diagnósticos. O objetivo desse estudo foi padronizar a imunoperoxidase em monocamada de célula (IPMC) para a detecção de imunoglobulina A e imunoglobulina G anti-Lawsonia intracellularis em amostras de FO de suínos experimentalmente infectados. Um total de 62 suínos foram divididos em dois grupos: controle (T1, n=30) e inoculados com L. intracellularis (T2, n=32). Sangue, FO e amostras de fezes foram coletados aos 0, 7,14, 21, 28 e 42 dias após a inoculação (dpi). Algumas adaptações da técnica foram realizadas na técnica padrão da IPMC para a detecção de IgA e IgG. A IPMC demostrou alta especificidade e sensibilidade para amostras de soro e alta especificidade de moderada sensibilidade para a detecção de IgA e IgG em FO. Houve alta concordância entre resultados de detecção de IgG em soro com a IgA e IgG em amostras de FO. Baseado em nossos resultados, amostras de fluido oral podem ser usadas em avaliações e detecção de anticorpos anti-L. intracellularis em suínos, porém não de forma individual.(AU)

Hemorragia digestiva y enfermedad celíaca complicada en paciente anticoagulado / Gastrointestinal bleeding and complicated celiac disease in anticoagulated patient

Resumen La enfermedad celíaca tiene una considerable frecuencia en nuestro medio. La mayoría de los pacientes presenta mejoría clínica, serológica y endoscópica al poco tiempo de iniciada la dieta libre de gluten. Un muy bajo porcentaje puede presentar o desarrollar una "enfermedad celíaca complicada", entidad que comprende el esprue refractario, la yeyunitis ulcerativa y el linfoma intestinal, que conllevan pronósticos desfavorables, con requerimiento de tratamientos más radicales. Presentamos aquí el caso de un paciente de 77 años evaluado en nuestro centro, que ingresó para estudio de hemorragia digestiva aguda y se realizó finalmente diagnóstico de enfermedad celiaca complicada, requiriendo inicio de tratamiento con corticoides sistémicos y seguimiento estrecho ambulatorio.

Abstract Celiac disease is considerably frequent in our media. Gluten-free diet shows clinical, serological and endoscopic improvement in most patients shortly after its start. A few patients may present or develop a "complicated celiac disease", an entity that includes refractory sprue, ulcerative jejunitis and intestinal lymphoma, which carry unfavorable prognoses, requiring more radical treatments. We present here the case of a 77-year-old male patient evaluated in our center, who was admitted for study of acute gastrointestinal bleeding. Complicated celiac disease was diagnosed, systemic corticosteroids were started and a close follow-up was carried out.

Enfermedad Celíaca en el adulto. Un reto en el nuevo milenio / Celiac disease in adulto. A challenge in the new millennium / Doença celíaca em adultos. Um desafio no novo milênio

RESUMEN La enfermedad celíaca una afección autoinmune producida por intolerancia alimentaria permanente al gluten y prolaminas con carácter genético. Uno de los problemas de esta enfermedad en el adulto es el infra diagnóstico, ya que por cada caso diagnosticado hay un promedio de cinco casos sin diagnosticar, debido a la sintomatología atípica, mínima, o incluso ausente. Por ello se realiza una revisión del tema con el objetivo de describir la enfermedad celíaca en el adulto y proporcionar elementos para su diagnóstico en pacientes con síntomas sugestivos. Para la obtención de la información se efectuó una búsqueda en bases de datos bibliográficas de literatura científica de la BVS de Cuba como PubMed/Medline y Lilacs. También se consultaron algunas fuentes de información disponibles a texto completo como Clinical Key, Cochrane Library, Ebsco y SciELO Cuba. Se realizó además una búsqueda en internet de portales de instituciones de reconocido prestigio en el ámbito sanitario como la World Gastroenterology Organisation, Instituto Nacional de Gastroenterología de Cuba, documentos oficiales de la Organización Mundial de la Salud, entre otras y se llegó a la conclusión quela Enfermedad Celíaca requiere un alto índice de sospecha clínica, el diagnóstico debe basarse en la presencia de alguno o varios síntomas relacionados con la afectación intestinal o de cualquiera de los órganos o sistemas asociados, en Cubano existen datos epidemiológicos de la enfermedad en adultos, por lo que es necesario la implementación de un protocolo para el diagnóstico de estos pacientes, pues el retraso o ausencia en el diagnóstico tiene consecuencias para la salud del individuo.

ABSTRACT Celiac disease is an autoimmune condition caused by permanent food intolerance to gluten and genetic prolamins. One of the problems of this disease in the adult is the infra diagnosis, since for each case diagnosed there is an average of five cases without diagnosis, due to the atypical, minimal, or even absent symptomatology. Therefore, a review of the subject is carried out with the objective of describing celiac disease in adults and providing elements for diagnosis in patients with suggestive symptoms. To obtain the information, a search was made in bibliographic databases of scientific literature of the VHL of Cuba as PubMed / Medline and Lilacs. Some sources of information available in full text such as Clinical Key, Cochrane Library, Ebsco and SciELO Cuba were also consulted. An internet search was also carried out on portals of institutions of recognized prestige in the healthcare field such as the World Gastroenterolog and Organization, National Institute of Gastroenterology of Cuba, official documents of the World Health Organization, among others and the conclusion was reached that Celiac Disease requires a high index of clinical suspicion, The diagnosis must be based on the presence of any or several symptoms related to intestinal involvement or any of the associated organs or systems, in Cuba there are epidemiological data of the disease in adults, so it is necessary to implement a protocol for the diagnosis of these patients, because the delay or absence in the diagnosis has consequences for the health of the individual.

RESUMO A doença celíaca é uma condição auto-imune causada pela intolerância alimentar permanente ao glúten e prolaminas com caráter genético. Um dos problemas desta doença em adultos é o subdiagnóstico, pois para cada caso diagnosticado há uma média de cinco casos não diagnosticados, devido a sintomas atípicos, mínimos ou até ausentes. Por esse motivo, é realizada uma revisão do assunto com o objetivo de descrever a doença celíaca em adultos e fornecer elementos para seu diagnóstico em pacientes com sintomas sugestivos. Para obter as informações, foi realizada uma busca em bancos de dados bibliográficos da literatura científica da BVS de Cuba, como PubMed / Medline e Lilacs. Algumas fontes de informações em texto completo também foram consultadas, como Clinical Key, Cochrane Library, Ebsco e SciELO Cuba. Também foi realizada uma busca na Internet por portais de instituições de reconhecido prestígio no campo da saúde, como a Organização e Gastroenterologia Mundial, o Instituto Nacional de Gastroenterologia de Cuba, documentos oficiais da Organização Mundial da Saúde, entre outros, e foi concluído A doença celíaca requer um alto índice de suspeita clínica, o diagnóstico deve ser baseado na presença de um ou mais sintomas relacionados ao envolvimento intestinal ou a qualquer um dos órgãos ou sistemas associados; em Cuba, existem dados epidemiológicos da doença em adultos, motivo pelo qual é necessária a implementação de um protocolo para o diagnóstico desses pacientes, uma vez que o atraso ou ausência no diagnóstico tem consequências para a saúde do indivíduo.

Nueva mutación identificada en el gen FOXP3 en lactante menor con diarrea crónica como manifestación de enteropatía autoinmune - síndrome IPEX / New mutation in FOXP3 gene identified in an infant with chronic diarrhea as manifestation of autoinmune enteropathy - IPEX syndrome

INTRODUCCIÓN: El síndrome IPEX (inmunodesregulación, poliendocrinopatía y enteropatía autoinmune ligada a X) causado por mutaciones en el gen FOXP3, se caracteriza por diarrea prolongada, alteraciones endocrinológicas y dermatitis. El tratamiento consiste en la administración de medicamentos inmunosupresores, siendo el trasplante de médula ósea la única cura potencial. OBJETIVO: Describir una nueva mutación del gen FOXP3, así como los hallazgos y evolución de un paciente con síndrome IPEX. CASO CLÍNICO: Lactante menor masculino que debutó al mes de vida con diarrea cró nica, falla intestinal e infecciones recurrentes. Exámenes de laboratorio y biopsia intestinal sugerentes de enteropatía autoinmune. Durante el seguimiento, el paciente presentó refractariedad al manejo inmunosupresor con esteroides, ciclosporina y tacrolimus, falleciendo a los 7 meses de edad por complicaciones vasculares. Antecedente familiar por línea materna de múltiples muertes en hombres menores de 1 año. Ante la sospecha de síndrome IPEX se realizó exoma en trío que reportó una mutación probablemente patogénica en el gen FOXP3. CONCLUSIÓN: Se documentó una nueva mutación del gen FOXP3 en paciente con síndrome IPEX. A pesar de la baja prevalencia de esta enfermedad, es importante el reconocimiento de síntomas no específicos pero sugerentes del diagnóstico.

INTRODUCTION: The IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syn drome is caused by the mutations of the FOXP3 gene, characterized by persistent diarrhea, endo crine disorders, and dermatitis. The treatment is the administration of immunosuppressive drugs, where hematopoietic stem cell transplantation is the only potential cure. OBJECTIVE: To describe a new FOXP3 gene mutation, as well as the findings and evolution of a patient with IPEX syndrome. CLINICAL CASE: Male infant presenting at one month of age with chronic diarrhea, intestinal failure, and recurrent infections. Lab tests and intestinal biopsy suggested autoimmune enteropathy. During follow-up, the patient presented resistance to immunosuppressive treatment with corticosteroids, cyclosporine, and tacrolimus, dying at 7 months of age due to vascular complications. He had a ma ternal family history of multiple deaths of men under 1 year of age. IPEX syndrome was suspected therefore a trio whole-exome sequencing was performed that showed a probably pathogenic FOXP3 gene mutation. CONCLUSION: A new FOXP3 gene mutation is reported in a patient with IPEX syndro me. Despite the low prevalence of this disease, it is important to recognize non-specific but suggestive symptoms for its diagnosis.

Seroprevalencia a Mycobacterium avium subsp. paratuberculosis en bovinos criollos colombianos Romosinuano y costeño con cuernos / Seroprevalence to Mycobacterium aviumsubsp. paratuberculosis in the colombian creole cattle Romosinuano and costeño con cuernos

RESUMEN Objetivo. Determinar la seroprevalencia y los factores epidemiológicos asociados a Mycobacterium avium subsp Paratuberculosis (MAP) en dos razas de bovinos criollos del centro de investigación AGROSAVIA-Turipaná. Materiales y métodos. Se realizó un estudio epidemiológico de corte transversal. Fueron muestreados 848 bovinos criollos, 403 Romosinuanos y 445 costeño con cuernos (CCC); para el diagnóstico serológico de anticuerpos se utilizó la prueba Elisa Indirecta mediante el kit comercial Parachek® de Prionics. Las variables sexo, edad, raza y tipo de hato fueron los factores epidemiológicos evaluados y correlacionados con la presencia de anticuerpos contra MAP; la asociación estadística fue determinada mediante Odds Ratio y con un modelo multivariado de regresión logística, utilizando un nivel de significancia con p<0.05. Resultados. La seroprevalencia general de los bovinos criollos a MAP fue de 2.35% (IC 95%, 1.34-3.38); sin embargo, en los Romosinuano fue de 0.74% y en los CCC fue de 3.82%, siendo las diferencias estadísticamente significativas (valor p=0.003). También, empleando un análisis univariado, fueron más afectados las hembras y los animales mayores a un año. El análisis multivariado identificó como factores epidemiológicos las variables raza y sexo. Conclusiones. En las razas criollas del centro de investigación AGROSAVIA-Turipaná, la seroprevalencia a MAP fue baja; sin embargo, en la raza CCC el riesgo de contraer la enfermedad es seis veces mayor con relación a la raza Romosinuano. Más aún, se pudo evidenciar que las hembras tienen mayor riesgo de adquirir la enfermedad.

ABSTRACT Objective. Determine the seroprevalence and epidemiological factors associated with Mycobacterium avium subsp. paratuberculosis (MAP) in two Creole cattle breeds of the Turipaná research center -AGROSAVIA. Materials and methods. A cross-sectional epidemiological study was conducted,a total of 848 Creole bovine animals were sampled, 403 Romosinuano and 445 costeño con cuernos (CCC); for the serological diagnosis of antibodies, the Elisa Indirect test was used with the commercial kit Parachek®2 by Prionics. The variables sex, age, breed and herd type were the epidemiological factors evaluated and correlated with the presence of antibodies against MAP; the statistical association was established using the Odds Ratio and a multivariate logistic regression model, employing a significance level with p<0.05. Results. The general seroprevalence of the Creole cattle to MAP was 2.35% (95% CI, 1.34-3.38); however, in the Romosinuano it was 0.74% and in the CCC it was 3.82%, being this difference statistically significant (p=0.003). Furthermore, employing a univariate way analysis, females and animals older than one year of age were more affected. The multivariate analysis identified the breed and sex variables as epidemiological factors. Conclusions. In the Creole breeds of the AGROSAVIA-Turipaná research center, MAP seroprevalence was low; however, in the Costeño Con Cuernos breed, the risk of contracting the disease is six times higher than in the Romosinuano breed. Moreover, it was shown that females have a higher risk of acquiring the disease.

Monomorphic epitheliotropic intestinal T-cell lymphoma: a clinicopathological analysis of twelve cases / 中华病理学杂志

Objective@#To investigate the clinicopathological features, diagnosis and differential diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL).@*Methods@#A total of 12 specimens were collected, which were surgically resected and verified as MEITL by postoperative pathology, immumohistochemical staining and gene rearrangement at the First Affiliated Hospital of Nanjing Medical University from 2012 to 2018, and all of these had complete clinical and pathological data. The MEITL cases were reviewed to compare the clinicopathological characteristics, including morphologic and immunophenotypic features and followed up by telephone and clinic visit.@*Results@#All the cases were diagnosed with MEITL. There were 8 males and 4 females. Male to female ratio was 2∶1, at a median age of 54 years. The sites of involvement included jejunum (4 cases), ileum (5 cases), duodenum (1 case), ileocecal junction (1 case) and rectum (1 case). The neoplastic cells were monotonous of small to intermediate cells in size with round to slightly irregular nuclei in 11 cases. The immunophenotyping showed that CD3 (12/12), CD8 (11/12), CD43 (11/12), CD56 (11/12), TIA-1 (12/12) were positive; CD5 (12/12), Gran B (9/12), and perforin (7/12) were negative. Two cases aberrantly expressed the B-cell marker CD20. A high proliferation index was demonstrated by Ki-67 immunostaining. In situ hybridization for EBER was all negative(12/12). The whole exome sequencing(WES) mutational landscape of MEITL was remarkably homogeneous, showing significantly enriched clusters among histone modifier genes, JAK-STAT and MAPK-signal pathways. Histonelysine N-methytransferase SETD2 gene was mutated in 2/4 tumors. All the patients analyzed harbored at least one mutation in the JAK-STAT signal pathway, including STAT5B (2/4), JAK3 (3/4) and STAT5A (2/4). Furthermore, frequent alterations (TP53) were observed in the MAPK pathway in 3/4 of MEITL cases. The CNV analysis derived from WES data identified multiple regions of frequent gains and losses. In particular, gains in 1q, 7q and 9q, and recurrent losses involving 7p and 8p were observed.@*Conclusions@#MEITL is a rare and aggressive type of extranodal T-cell lymphoma. The differential diagnosis of MEITL includes EATL, extranodal NT/T-cell lymphoma and other types of PTCL. Diagnosis should be correlated to clinical symptoms while the final diagnosis is mainly based on the pathological features, immunophenotypes and genetic testing.

Fontan Conversion for Patients with Protein-Losing Enteropathy after a Björk Procedure with Patent Right Atrium to Innominate Vein Bypass / 日本心臓血管外科学会雑誌

A 37-year-old male patient who had previously undergone left original Blalock-Taussig shunt, original Glenn shunt, left pulmonary artery patch plasty, and a Björk procedure was referred to our hospital due to protein-losing enteropathy. Because he suffered from severe low-cardiac output syndrome immediately after the Björk procedure, mechanical circulatory support and construction of the bypass between the right atrial appendage and the innominate vein using an artificial graft were required. We performed a Fontan-revision operation : total cavopulmonary connection with extra-cardiac conduit, right atrial ablation, pacemaker lead implantation, construction of fenestration between the conduit and the atrium, and reconstruction of the left pulmonary artery in front of the ascending aorta successfully. His postoperative course was uneventful and protein-losing enteropathy had not recurred 3 years after the operation.

An unusual cause of edema in a child with congenital heart disease post Fontan procedure

Protein Losing Enteropathy Post Fontan procedure. Protein Losing Enteropathy (PLE) is an uncommon cause of edema in children with congenital heart disease. Protein-Losing Enteropathy may be defined as excessive loss of proteins across the intestinal mucosa and is due to either a primary gastrointestinal abnormality or secondary to cardiac disease. Protein-losing enteropathy (PLE) is a rare complication of the Fontan palliation for functional single-ventricle. Although PLE occurs in about 3.5% of patients post-Fontan, it confers marked morbidity and high mortality within 5 years of diagnosis. The pathogenesis of Fontan-related PLE is not completely understood, and it is unclear why it develops in some patients post-Fontan and not others. We describe a child with Double Inlet Right Ventricle who had undergone Fontan procedure, and presented to us with generalised oedema. The child had hypoproteinaemia, the common causes for which were ruled out and was diagnosed as Protein Losing Enteropathy (PLE) related to his surgical intervention. Though, not frequently encountered it should be kept in mind as one of the causes of anasarca.

Short stature as a significant marker in celiac disease

Background: Celiac disease (CD) is a genetically determined gluten-sensitive enteropathy resulting in nutrient malabsorption, can have extra gastrointestinal tract (GIT) presentations, short stature may be the only presenting clinical feature, even in the absence of gastrointestinal symptoms. The aim and objective of this study was toMethods: This cross-sectional study was performed on 1000 children between ages 5 to 10 year of different schools, in Jaipur, district of Rajasthan. An anthropometric measurement (height, weight) was done for all children. Serum samples were analyze for IgA antibodies to human tissue transglutaminase (tTG) with lower detection limit of 1.0 U/ml and 15 U/ml. Positive samples for tTG antibodies were reanalyzed human endomysial autoantigens (EmA).Results: Out 1000 children screened, six were seropositive, of those four were females and two were males. The serological proportion of CD in this population was 1:166. These Six seropositive group tends to have lower height, weight than the seronegative group, but the difference was only significant for height (P=<0.01).Conclusions: Although gastrointestinal manifestations are important presentation of celiac disease, nevertheless short stature alone or in combination with other symptoms of celiac disease has been present.

Clinical, immunological and genetic characteristic of patients with clinical phenotype associated to LRBA-deficiency in Colombia / Características clínicas, inmunológicas y genéticas de pacientes con el fenotipo asociado a deficiencia LRBA en Colombia

Abstract Background: LPS-responsive beige -like anchor protein (LRBA) deficiency is a primary immunodeficiency disease caused by loss of LRBA protein expression, due to biallelic mutations in LRBA gene. LRBA deficiency patients exhibit a clinically heterogeneous syndrome. The main clinical complication of LRBA deficiency is immune dysregulation. Furthermore, hypogammaglobulinemia is found in more than half of patients with LRBA-deficiency. To date, no patients with this condition have been reported in Colombia Objective: To evaluate the expression of the LRBA protein in patients from Colombia with clinical phenotype associated to LRBA-deficiency. Methods: In the present study the LRBA-expression in patients from Colombia with clinical phenotype associated to LRBA-deficiency was evaluated. After then, the clinical, the immunological characteristics and the possible genetic variants in LRBA or other genes associated with the immune system in patients that exhibit decrease protein expression was evaluated. Results: In total, 112 patients with different clinical manifestations associated to the clinical LRBA phenotype were evaluated. The LRBA expression varies greatly between different healthy donors and patients. Despite the great variability in the LRBA expression, six patients with a decrease in LRBA protein expression were observed. However, no pathogenic or possible pathogenic biallelic variants in LRBA, or in genes related with the immune system were found. Conclusion: LRBA expression varies greatly between different healthy donors and patients. Reduction LRBA-expression in 6 patients without homozygous mutations in LRBA or in associated genes with the immune system was observed. These results suggest the other genetic, epigenetic or environmental mechanisms, that might be regulated the LRBA-expression.

Resumen Antecedentes: la deficiencia de LRBA (del inglés, LPS-responsive beige -like anchor protein) es una inmunodeficiencia primaria causada por la pérdida de la expresión de la proteína LRBA, debido a mutaciones bialélicas en el gen LRBA. Los pacientes con deficiencia de LRBA exhiben un síndrome clínicamente heterogéneo. La principal complicación clínica de la deficiencia de LRBA es la desregulación inmune. Además, la hipogammaglobulinemia se encuentra en más de la mitad de los pacientes con deficiencia de LRBA. Hasta la fecha, no se han reportado pacientes con esta afección en Colombia Objetivo: Evaluar la expresión de la proteína LRBA en pacientes de Colombia con fenotipo clínico asociado a deficiencia de LRBA Métodos: En el presente estudio se evaluó la expresión de LRBA en pacientes de Colombia con fenotipo clínico asociado a deficiencia de LRBA. Después de eso, se evaluaron las características clínicas, inmunológicas y las posibles variantes genéticas en LRBA o en otros genes asociadados con el sistema inmune en pacientes que exhiben una disminución de la expresión de la proteína. Resultados: En total, se evaluaron 112 pacientes con diferentes manifestaciones clínicas asociadas al fenotipo clínico LRBA. La expresión de LRBA varía mucho entre diferentes donantes sanos y pacientes. A pesar de la gran variabilidad en la expresión de LRBA, se observaron seis pacientes con una disminución en la expresión de la proteína LRBA. Sin embargo, no se encontraron variantes bialélicas patógenas o posibles patógenas en LRBA, o en genes relacionados con el sistema inmune. Conclusión: La expresión de LRBA varía mucho entre diferentes donantes sanos y pacientes. Se observó reducción de la expresión de LRBA en 6 pacientes sin mutaciones homocigotas en LRBA o en genes asociados. Estos resultados sugieren los otros mecanismos genéticos, por ejemplo epigenéticos o ambientales, que podrían estar regulados por la expresión de LRBA

Serum levels of intestinal alkaline phosphatase in type 2 diabetic patients with enteropathy

Background: Type 2 diabetes mellitus patients frequently have various distressing gastrointestinal signs and symptoms and intestinal alkaline phosphatase (IAP) may be linked to it. Even after extensive search, there was dearth of literature related to IAP levels in serum of diabetic enteropathy subjects. So, using a case-control design, levels of IAP in the serum of T2DM subjects were determined.Methods: Serum IAP was measured by ELISA in 73 type 2 diabetic patients with enteropathy (group 1) and 71 type 2 diabetic patients without enteropathy (group 2). Statistical analysis of the data was performed by using Statistical Package for Social Sciences (SPSS version 16) and inferences were drawn.Results: Serum IAP was highly significantly reduced in group 1 (3.9 U/L) compared to group 2 (4.2 U/L).Conclusions: Enteropathy in T2DM may be related to reduction in IAP levels in serum. Estimation of serum IAP may be considered in type 2 diabetic patients with enteropathy, for the elaboration of treatment strategy and monitoring.