Genotype and phenotype characterization of primary hypertrophic osteoarthropathy type 2 and chronic enteropathy associated with SLCO2A1: Report of two cases and literature review.

Autosomal recessive type 2 primary hypertrophic osteoarthropathy (PHOAR2) and chronic enteropathy associated with SLCO2A1 (CEAS) are two entities caused by pathogenic variants (PVs) in the SLCO2A1 gene that can coexist or occur independently from one another. We report two cases of PHOAR2 in Mexico with concomitant CEAS and conducted a review of the literature of the reported cases of PHOAR2 and/or CEAS to analyze the relationship between their genotype and phenotype presentation. The patients from our Institution with classical PHOAR2 phenotype and CEAS, harbored SLCO2A1 c.547G > A and c.1768del variants. We reviewed 232 cases, of which 86.6% were of Asian origin, and identified 109 different variants in SLCO2A1. Intron 7, exon 13, and exon 4 were predominantly affected. The two most common PVs were c.940 + 1G > A and c.1807C > T. We found a statistically significant association between SLCO2A1 variants located in intron 7, exons 12, and 13 and the development of CEAS. Missense variants were more frequent in isolated PHOAR2, while a greater proportion of protein-truncating variants (PTVs) were found in CEAS. Further investigation is imperative to elucidate the underlying pathophysiological mechanisms associated with CEAS, thereby facilitating the identification of effective therapeutic interventions.

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.

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

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.

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.

Linfoma T intestinal monomórfico CD56+. Primer caso informado en Colombia y revisión de la literatura / Monomorphic Intestinal T-Cell Lymphoma. First reported case in Colombia and review of the literature

Se informa el caso de una mujer de 80 años con hallazgo incidental de masa abdominal en mesogastrio. Se le realiza resección de intestino delgado por sospecha de absceso con síndrome adherencial. El estudio patológico de la pieza quirúrgica demostró compromiso por linfoma no Hodgkin T monomórfico CD56+. Los linfomas T del tubo digestivo son inusuales; corresponden al 5% de las neoplasias linfoides de esta localización. El linfoma intestinal T monomórfico CD56+ corresponde a 10-20% de los linfomas T intestinales. Se presenta en regiones donde la enfermedad celiaca es infrecuente y no se asocia a enteropatía. Su curso es agresivo y habitualmente se manifiesta como una emergencia quirúrgica por obstrucción o perforación intestinal.

80 year old woman with incidental finding of abdominal mass in midgut, in which small bowel resection is performed for suspected abscess associated to surgical adhesions. Pathological examination of the surgical specimen showed a monomorphic CD56+ T cell lymphoma. T-cell lymphomas of the digestive tract are rare, accounting for 5% of all lymphoid neoplasms in this location. Monomorphic CD56+ intestinal T cell lymphoma corresponds to 10 - 20% of T cell intestinal lymphomas. This tumor occurs in regions where celiac disease is rare and it is not associated with enteropathy. Its course is aggressive and usually manifests as a surgical emergency by intestinal obstruction or perforation.

Enteropathy-associated T-cell lymphoma (type II): a Brazilian case report.

Enteropathy-associated T-cell Lymphoma (EATL) is a rare form of aggressive T-cell lymphoma. It is more prevalent in men over 60 years and the prognosis is very poor. EATL is classified into two groups based on morphology, immunohistochemistry, and genetic profile. EATL type I is highly associated with celiac disease and is more common in Western countries. EATL type II predominates over type I in Asia, where celiac disease is uncommon. We report a case of a 78-year-old previously healthy white male who presented with a 2-month history of diarrhea, weight loss and edema. The abdomen was distended and painful, and a tumor mass was palpable in the hypogastrium. Laboratory tests showed hypoalbuminemia. Serological tests for HIV, viral hepatitis and HTLV-1 were negative. The chest radiography showed pneumoperitoneum, and an exploratory laparotomy revealed perforation of the small bowel. An advanced stage (Ann Arbor IV B/Lugano IIE2B) EATL type II was diagnosed. Four cycles of chemotherapy were interspersed with several complications (anthracycline-induced cardiotoxicity, chemotherapy-induced neutropenic fever and severe sepsis). Performance status progressively worsened and he died 6 months after the diagnosis. This is an illustrative report of a rare and aggressive primary intestinal lymphoma. To the best of our knowledge, this is the first report of EATL type II in Brazil.

Enfermedad Celiaca y Obstrucción Intestinal por Linfoma de Células T / Celiac disease and intestinal obstruction by T cell lymphoma

Paciente varón de 55 años, raza blanca (ascendencia española), natural y procedente de Ayacucho, que ingresó por una enfermedad de seis meses de evolución, caracterizada por dolor abdominal tipo cólico y baja ponderal de 10 Kg. Había estado hospitalizado seis meses antes y dado de alta con el diagnóstico de síndrome de intestino irritable. Entre sus antecedentes refería intolerancia a la lactosa y artritis reumatoidea. Los exámenes mostraron: Hb:12 g/dl, leucocitos: 5260 cel/mm, abastonados: 11%, albúmina: 2,7 mg/ml y VSG: 33mm/h. El resto de exámenes -incluyendo los marcadores tumorales- fueron normales. El tránsito gastrointestinal mostraba las asas delgadas con fragmentación del bario y dilatación focal moderada de un asa yeyunal distal. La tomografía de tórax, abdomen y pelvis sin alteraciones; Rx tórax normal. La colonoscopia fue normal; el íleon tenía pocos pliegues y pequeñas nodulaciones, las biopsias indicaron "ileitis inespecífica". La endoscopia mostró gastritis y una cicatriz de úlcera duodenal; la mucosa duodenal mostraba áreas con aspecto de mosaico rosado-blanquecino. La biopsia duodenal evidenció acortamiento de vellosidades, infiltrado inflamatorio crónico e incremento de linfocitos intraepiteliales, hallazgos compatibles con los criterios de celiaquía Marsh-tipo 3. Los anticuerpos IgA antiendomisio y antitransglutaminasa tisular estaban incrementados. Durante su hospitalización aumentó el dolor y aparecieron signos de obstrucción. En la laparotomía se encontraron una tumoración yeyunal estenosante y una perforación adyacente. El espécimen mostró un linfoma intestinal de células T. Se ha demostrado que existen más celiacos subclínicos que celiacos con esprue clásico; el conocimiento de esta situación nos debe llevar a tenerla presente por sus complicaciones o asociaciones, una de las cuales es el linfoma primario intestinal.

A male patient, 55 years old, born in Ayacucho, with Spanish ancestors, was hospitalized through emergency referring abdominal pain, and 10 kilograms weight loss. Six months before he was diagnosed as having irritable bowel syndrome. His previous diseases were rheumatoid arthritis and intolerance to lactose. Laboratory results were: Hb 12 gr./dL, white cells 5200 per mm3, albumin 2.7 gr./dL, erythrocyte sedimentation rate 32 mm/hr., and tumor markers were negative. Radiographic study of the small bowel showed barium fragmentation, and a focal dilation in distal jejunum. Chest X-ray and CT scan of thorax, abdomen and pelvis were normal. Colonoscopy was normal for colonic mucosa, but in ileum it showed an irregular mucosa, little nodules and fewer folds than usual. Biopsy from ileum demonstrated unspecific inflammation. Upper endoscopy showed gastritis, a duodenum scar ulcer and an irregular mosaic pattern pink and white. Duodenum biopsy demonstrated short villi, chronic inflammation and an increase in the number of intraepithelial lymphocytes, all these was consistent with celiac disease Marsh 3. Antibodies anti-endomisium and anti-transglutaminase were positive. After some days he developed signs of bowel obstruction and was operated. A tumor was found in jejunum with a bowel perforation. Pathological study showed a small bowel T-cell lymphoma. Fortunately this patient did well, and was sent home to continue treatment on ambulatory basis. Celiac disease is more common than what is thought, and it has been demonstrated that there are more persons with subclinical celiac disease, than those with the typical clinical pattern. It is necessary to be aware of this disease to improve diagnosis in order to avoid late complications as small bowel lymphoma.