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.

Enfermedad por inclusión microvellositaria como causa de diarrea congénita severa: caso clínico / Microvillous inclusion disease as a cause of severe congenital diarrhea: case report

Las diarreas congénitas son patologías graves de baja frecuencia y alta mortalidad. Se manifiestan durante los primeros días o meses de vida con severa diarrea, generando insuficiencia intestinal y dependencia de nutrición parenteral. Se debe sospechar ante un recién nacido o lactante con pérdidas masivas hidroelectrolíticas, y se diagnostican utilizando parámetros clínicos, endoscópicos, histológicos y eventualmente genéticos. El tratamiento es de soporte, con reposición hidroelectrolítica intensa y nutricional. OBJETIVO: Presentar un caso de diarrea congénita, identificada como Enfermedad por Inclusión Microvellositaria, de presentación neonatal. CASO CLÍNICO: Paciente varón edad actual 3 años, hijo de padres consanguíneos, quien debutó a los 10 días de vida con diarrea secretora severa, requiriendo ingreso a unidad de paciente crítico y nutrición parenteral permanente. Inicialmente además con síndrome de Fanconi, que luego se recupera. Se confirmó la sospecha de Enfermedad de Inclusión Microvellositaria utilizando microscopia óptica, electrónica e inmunohistoquímica. Se obtuvo una favorable evolución utilizando nutrición parenteral total (NPT) a domicilio. CONCLUSIONES: Se presenta el primer caso conocido en Chile de un paciente con diarrea congénita por inclusión microvellositaria manejado y su evolución.

Congenital diarrheas correspond to a severe and low frequency digestive disease, with a high mortality. They start a few days or months after birth, leading to intestinal insufficiency and dependence on parenteral nutrition. It must be highly suspected in newborns or infants with diarrhea and severe electrolyte disorders. The diagnosis is based on clinical, endoscopic, histologic and eventually genetic findings. Treatment is supportive with intensive correction of electrolyte imbalances as well as parenteral nutrition. OBJECTIVE: To present a case report of congenital diarrhea identified as microvillous inclusion disease presenting in the neonatal period. CASE REPORT: Male patient currently 3 years of age, son of consanguineous parents. At 10 days of age presents a severe secretory diarrhea, requiring treatment in a critical care unit and parenteral nutrition. Initially he also presented with Fanconi syndrome, which improved afterwards. The suspicion of congenital microvillous inclusion was confirmed later by optic and electronic microscopy, and inmunohistochemistry. A succesful evolution was later achieved maintaining home parenteral nutrition after discharge. CONCLUSION: We present the first known case in Chile of congenital diarrhea due to microvillous inclusión disease and his evolution.

Enteropatia com formação de tufos epiteliais e mutação do gene EpCAM: relato de caso / Tufting enteropathy with EpCAM mutation: case report

Tufting enteropathy (TE), also known as intestinal epithelial dysplasia (IED), is a rare congenital enteropathy related to an earlyonset of severe intractable diarrhea due to specific abnormalities of the intestinal epithelium and mutations of the EpCAM gene. TE is characterized by clinical and histological heterogeneity, such as with low or without mononuclear cell infiltration of the lamina propria, and abnormalities of basement membrane. TE can be associated with malformations, other epithelial diseases, or to abnormal enterocytes development and/or differentiation. The authors report a case of a Brazilian child with TE associated with c.556-14A>G mutation in the EpCAM gene (NM_002354.2)...

Enteropatia com formação de tufos epiteliais (ETE), também conhecida como displasia epitelial intestinal (DEI), é uma rara enteropatia congênita relacionada com um início precoce de diarreia intratável grave devido a anormalidades específicas do epitélio intestinal e mutações do gene EpCAM. ETE caracteriza-se por uma heterogeneidade clínica e histológica, como ausência ou leve infiltrado de células mononucleares na lâmina própria e anormalidades de membrana basal. Pode ser associada a malformações, outras doenças epiteliais ou anormalidades no desenvolvimento/na diferenciação dos enterócitos. Os autores relatam um caso de ETE, em uma criança brasileira, associada à mutação c.556-14A> g do gene EPCAM (NM_002354.2)...

Microvillous Inclusion Disease: An analysis of 4 cases

Microvillous inclusion disease (MID) or congenital microvillous atrophy is a rare cause of intractable, persistent secretory diarrhea shortly after birth or at birth. The prognosis of MID is very poor and most of the reported patients have died within 6.5 years. Diagnosis is based on the ultrastructural demonstration of intracytoplasmic inclusion of microvilli. There have been several cases reported in the literature. To evaluate the clinicopathologic features of MID, we have reviewed 4 cases of MID which was confirmed by the ultrastructural study of the duodenal biopsy. All patients suffered from life-threatening diarrhea since birth. Many other radiologic or laboratory findings were of no value in the evaluation of causative agents. One of the patients died of the disease and remaining patients have been alive on intravenous fluids or total parenteral nutrition. Histological findings of all cases were similar and characterized by varying degrees of mucosal atrophy and chronic inflammatory cell infiltration in the duodenal mucosa. PAS stain revealed a discontinuous brush border over the atrophic villous surface with or without small vacuoles in the cytoplasm of the surface epithelium. Ultrastructural changes were found mainly in the surface epithelium of the duodenal mucosa and characterized by the presence of membrane bound inclusions lined by intact or degenerating microvilli, as well as degeneration of surface epithelial cells with loss of microvilli, or with sparse, short microvilli.

A Case of Intractable Diarrhea Associated with Early Onset Secondary Amyloidosis in Rheumatoid Arthritis / 대한류마티스학회지

Amyloidosis is a disease that characterized by accumulation of an amorphous, proteinaceous materials in the various tissues and organs, but its origin is unknown. Recent clinical study showed that incidence of amyloidosis in rheumatoid arthritis was near 10% to 21%. Secondary amyloidosis is caused by accumulation of serum amyloid. A which is doing the acute phase behavior faster than C reactive protein. Symptoms of amyloidosis are various according to the involved organ. Gastrointestinal symptoms are obstruction, ulcer, malabsorption, and bleeding. Diarrhea is very intractable with the conventional antidiarrheal agent, the mechanism of that is infiltration of amyloid material in the intestinal myenteric plexus, sympathetic nerve and ganglion. We report a case of 65 years old woman with rheumatoid arthritis presented with abdominal pain, intractable diarrhea which was not controlled by antidiarrheal agents. Duration of arthritis is only 2 years. Immunohistochemical stain showed AA type which meant secondary form. We treated with Octreotide analogue and total parenteral nutrition for chronic diarrhea.

Clinical Studies of Intractable Diarrhea During Infancy

PURPOSE: Intractable diarrhea during infancy is one of the major causes of infant mortality. But, its etiology, clinical courses, or methods of treatment are not well known. Therefore, we conducted a clinical approach to intractable diarrhea during infancy. METHODS: We have retrospectively evaluated clinical characteristics, laboratory findings, methods of treatment, days required for recovery, in 23 infants who were admitted with intractable diarrhea, from January 1993 to December 1996. RESULTS: The onset age was 18.4 +/- 17.8 days and the duration of diarrhea was 28.8 +/- 16.5 days. All patients were fed artificial milk before the onset of diarrhea. The possible causes of diarrhea were infection (60.8%), change of milk, milk concentration (17.4%), or an unknown origin (21.8%). Laboratory findings on admission showed hemoglobin 9.5 +/- 2.2g/dL, serum albumin 2.9 +/- 0.7g/dL. E. coli was cultured in urine in 1 case. Stool rotavirus antibody was positive in 1 case. Nineteen patients (82.6%) required total parenteral nutrition for 18.3 +/- 13.6 days and antibiotics were administered to 20 patients (86.9%). Twenty-two patients (95.7%) were fed special element formula milk. All but one who died of necrotizing enterocolitis, recovered. Special element fomula milk was used for 92.6 +/- 20.5 days after discharge, and there were no cases of recurrence. CONCLUSION: We considered appropriate oral element fomulas, total parenteral nutrition and the proper treatment of infection as important factors in future outcome of intractable diarrhea during infancy. We thought the short-term administration of special formula milk can be substituted for normal milk or a weaning diet. However, encouraging breast feeding may perhaps be a more effective way of preventing this problem.

Clinical Studies of Intractable Diarrhea During Infancy

PURPOSE: Intractable diarrhea during infancy is one of the major causes of infant mortality. But, its etiology, clinical courses, or methods of treatment are not well known. Therefore, we conducted a clinical approach to intractable diarrhea during infancy. METHODS: We have retrospectively evaluated clinical characteristics, laboratory findings, methods of treatment, days required for recovery, in 23 infants who were admitted with intractable diarrhea, from January 1993 to December 1996. RESULTS: The onset age was 18.4 +/- 17.8 days and the duration of diarrhea was 28.8 +/- 16.5 days. All patients were fed artificial milk before the onset of diarrhea. The possible causes of diarrhea were infection (60.8%), change of milk, milk concentration (17.4%), or an unknown origin (21.8%). Laboratory findings on admission showed hemoglobin 9.5 +/- 2.2g/dL, serum albumin 2.9 +/- 0.7g/dL. E. coli was cultured in urine in 1 case. Stool rotavirus antibody was positive in 1 case. Nineteen patients (82.6%) required total parenteral nutrition for 18.3 +/- 13.6 days and antibiotics were administered to 20 patients (86.9%). Twenty-two patients (95.7%) were fed special element formula milk. All but one who died of necrotizing enterocolitis, recovered. Special element fomula milk was used for 92.6 +/- 20.5 days after discharge, and there were no cases of recurrence. CONCLUSION: We considered appropriate oral element fomulas, total parenteral nutrition and the proper treatment of infection as important factors in future outcome of intractable diarrhea during infancy. We thought the short-term administration of special formula milk can be substituted for normal milk or a weaning diet. However, encouraging breast feeding may perhaps be a more effective way of preventing this problem.

A Case of "Intractable Ulcerating Enterocolitis" of Infant

Intractable ulcerating enterocolitis of infancy is uncommon, inhereditary disease characterized by ulcerating stomatitis, severe perianal disease, affecting the whole gastrointestinal tract, mainly colon with flask shaped large ulcer. It was first described by Sanderson et al in 5 cases of infant with intractable diarrhea having above clinical manifestation. It should be differentiated with Crohn's disease and Behcet's disease. We experienced a case of intractable ulcerating enterocolitis in an infant. A 17 month old patient was admitted because of intractable diarrhea since 2 months of age. Radilogical and endoscopic examination revealed chronic ulcerative inflammation with pseudopolyps involving ileum and entire colon. Ileocolectomy was performed because of its unresponsiveness to medical theraphy. The histology of resected specimen showed large flask shaped ulcer with underlying edge in the colon, terminal ileum. No evidence of granuloma suggesting Crohn's disease or vasculitis suggesting Behcet's colitis were noted. We report this case as an example of Intractable ulcerating enterocolitis (Sanderson et al).