Diagnóstico y manejo de la colitis microscópica / Diagnosis and management of microscopic colitis

Microscopic colitis (MC) is a clinical condition characterized by chronic watery diarrhea, normal colonic mucosa and characteristic histological findings. It is composed of two main entities: collagenous colitis (CC) and lymphocytic colitis (LC). Its incidence has been increasing, currently accounting for between 8 to 16% of studies for chronic diarrhea. It is more frequent in elderly women and is strongly associated with other autoimmune disorders. Its pathogenesis is not very well understood, but it supposes the immune activation secondary to the exposure of the colonic mucosa to different luminal antigens, mainly drugs. Management includes suspension of the potential causative agent and the use of anti-diarrheal medications. Oral budesonide has proven to be effective in induction and maintenance of remission, but with a high rate of recurrence upon discontinuation. Immune-modulators drugs such as azatioprine and metrotrexate have been tested in patients dependent to corticoids with variable results. Antibodies against tumor necrosis factors (TNF) are under studies, with promising results.

La colitis microscópica (CM) es una condición clínica caracterizada por diarrea crónica acuosa con mucosa colónica normal y hallazgos histológicos característicos. Está compuesta por dos entidades principales: la colitis colágena (CC) y la colitis linfocítica (CL). Su incidencia ha ido en aumento, siendo en la actualidad la responsable del 8 a 16% de los casos por diarrea crónica. Es más frecuente en mujeres de edad avanzada con una fuerte asociación a otras enfermedades autoinmunes. Su etiopatogenia no es del todo conocida, pero se cree juega un rol la activación inmune secundaria a la exposición de la mucosa colónica a diferentes antígenos luminales, principalmente fármacos. Dentro del manejo se incluye la suspensión del potencial agente causal y el uso de fármacos antidiarreicos. La budesonida oral ha demostrado alta efectividad en la inducción y mantención de la remisión, pero con una alta tasa de recurrencia al suspenderla. Fármacos inmunomoduladores como azatioprina y metrotrexato se han probado en pacientes corticodependendientes con resultados variables. El uso de anticuerpos monoclonales anti factor de necrosis tumoral (TNF) se encuentra en estudio, con resultados prometedores.

Microscopic colitis: A literature review / Colite microscópica: uma revisão da literatura

SUMMARY Microscopic colitis (MC) refers to chronic inflammation of the colon which is characterized by histologic changes at the level of a radiologically and endoscopically normal mucosa. It is a common cause of chronic non-bloody diarrhea that occurs primarily in older individuals; however, there are few studies in the literature with strong scientific evidence compared to other inflammatory bowel diseases (IBD), which limits the knowledge of physicians and pathologists. This article aims to review the information on MC, describing diagnostic methods and drugs available for treatment. We conducted a search of the Pubmed database and CAPES Portal using the keywords “microscopic colitis”, “collagenous colitis”, “lymphocytic colitis”, and “review” for selection of articles published between 1996 and 2015 related to the topic. Based on the studies discussed in this review, we conclude that MC is a relatively new gastrointestinal disorder, most studies are incipient particularly with respect to pathophysiology and immunology, and budesonide is the best documented short-term treatment. However, further studies are needed to elucidate the best strategy for treatment in the long term.

RESUMO Colite microscópica (CM) corresponde à inflamação crônica do cólon que se manifesta por modificações histológicas em nível de uma mucosa radiológica e endoscopicamente normal. É uma causa comum de diarreia crônica não sanguinolenta que ocorre principalmente em indivíduos idosos; porém, há poucos trabalhos na literatura com forte evidência científica quando comparada à de outras doenças inflamatórias intestinais (DII), o que limita seu conhecimento por médicos e patologistas. Este artigo tem como objetivo revisar as informações referentes à CM descrevendo os meios diagnósticos e os medicamentos disponíveis para o tratamento. Foi realizada uma pesquisa na base de dados Pubmed e no Portal da CAPES entre 1996 e 2015 utilizando as palavras-chave “colite microscópica”, “colite colagenosa”, “colite linfocítica” e “revisão” para seleção de artigos relacionados ao tema. Diante dos trabalhos analisados, conclui-se que a CM é uma desordem gastrointestinal relativamente nova, a maioria dos estudos são incipientes, principalmente quanto à imunologia e fisiopatologia, e a budesonida é o tratamento em curto prazo mais bem documentado. Todavia são necessários novos estudos para elucidar qual é a melhor estratégia em longo prazo.

Etiología de la diarrea crónica en el adulto mayor del Hospital Edgardo Rebagliati - Lima-Perú: estudio retrospectivo 2005-2011 / Etiology of chronic diarrhea in the elderly in Hospital Edgardo Rebagliati, Lima-Peru

INTRODUCCION: El impacto de la diarrea crónica en el adulto mayor es desproporcionado por diversos factores provocando mayor morbilidad y mortalidad. OBJETIVO: Describir las principales características acerca de la diarrea crónica en los pacientes ancianos del hospital Nacional Edgardo Rebagliati (Lima-Perú) durante el periodo enero del 2005 a diciembre del 2011, METODO: Estudio descriptivo y retrospectivo en la cual se revisaron las historias clínicas de los pacientes adultos mayores con el diagnostico de diarrea crónica, vertiéndose los datos en una ficha de recolección. RESULTADOS: Se revisaron las historias clínicas de 202 pacientes. La edad media fue de 73,5±6,7 años, siendo la mayoría mujeres (57.43%). Las principales comorbilidades fueron las cardiovasculares (60,4%) y endocrinas (27,2%). El tiempo de enfermedad medio fue de 21.6 ± 13.6 semanas. Los exámenes más solicitados fueron hemograma, bioquímica (glucosa, urea y creatinina), albumina, coprofuncional, parasitologico y colonoscopia. El tipo de diarrea más frecuente fue organica (84,16%). Dentro de las principales causas se encontró a la colitis microscópica (35,15%), parasitosis (15,84%), síndrome de intestino irritable (14,85%) y sobrecrecimiento bacteriano (8,42%). CONCLUSIONES: Las causas más frecuentes de diarrea crónica en el anciano son colitis microscópica, parasitosis, síndrome de intestino irritable y sobrecrecimiento bacteriano.

INTRODUCTION: The impact of chronic diarrhea in the elderly is disproportionate by several factors causing increased morbidity and mortality. OBJECTIVE: To describe the main features about the chronic diarrhea in elderly patients from Edgardo Rebagliati Hospital (Lima-Peru) during the period January 2005 to December 2011, METHOD: A descriptive and retrospective study in which we reviewed the medical records of elderly patients with the diagnosis of chronic diarrhea, pouring in a data collection sheet. RESULTS: We reviewed the medical records of 202 patients. The mean age was 73.5 ± 6.7 years, with most women (57.43%). Major comorbidities were cardiovascular (60.4%) and endocrine (27.2%). The half time of illness was 21.6 ± 13.6 weeks. The most requested tests were CBC, biochemistry, albumin, coprofuncional, parasitological and colonoscopy. The most common type of diarrhea was the organic (84.16%). Among the main causes were found microscopic colitis (35.15%), parasites (15.84%), irritable bowel syndrome (14.85%) and bacterial overgrowth (8.42%). CONCLUSIONS: The most common causes of chronic diarrhea in the elderly are microscopic colitis, parasites, irritable bowel syndrome and bacterial overgrowth.

Contribuição da histopatologia na diarreia com colonoscopia normal: análise crítica e revisão da literatura / Contribution of the histopathology in diarrhea with normal colonoscopy: critical analysis and literature review

Introdução- dentre as várias indicações para a realização de colonoscopias, duas das mais frequentes são a hematoquezia (20,5%) e diarreia de etiologia inexplicável (8,8%). Cerca de 40% das colonoscopias, em estudos retrospectivos, são normais e a realização de biópsias para histopatologia complementar não tem sido uma rotina nos diversos serviços de endoscopia. Objetivos- avaliar a contribuição da histopatologia para o esclarecimento diagnóstico em pacientes diarreicos e com colonoscopias normais. Método- foi realizado um levantamento bibliográfico no PubMed, Scielo, Medline e Biblioteca Cochrane com as palavras chave diarreia e colonoscopia normal, e levantados retrospectivamente os resultados da histopatologia de pacientes com diarreia e com colonoscopias normais. Resultados- num período de 2 anos, foram realizadas 1.342 vídeocolonoscopias. Destes, 119 (8,86%) foram por diarreia, diarreia + dor abdominal ou descargas intestinais, sendo 74 (5,51%) submetidos a biópsias endoscópicas, 34 (2,53%) com alguma anormalidade macroscópica, e 40 (2,98%) com colonoscopias normais. Destes 40, foram analisados os laudos histopatológicos de 30, e 10 foram excluídos por impossibilidade de recuperação da histopatologia. Dos 30, 29 são leucodérmicos (96,7%) e 1 melanodérmico (3,3%), com idade entre 16 anos e 64 anos, sendo 13 masculinos (43,3%) e 17 femininos (56,7%). O íleo terminal foi examinado em 11 pacientes (36,7%) e não foi possível a ileoscopia em 19 (63,3%). As biópsias foram no retossigmoide em 26 pacientes (86,7%), no retossigmoide, cólon esquerdo e cólon direito no mesmo exame em 1 (3,3%) e somente no íleo terminal em 3 (10%). Das 30 histopatologias revistas foram definidas como sem alterações dignas de nota em 27 (90%), alterações inespecíficas em 1 (3,3%) e colite inespecífica em 2 (6,7%). Em 5 pacientes havia registro da presença de edema (16,7%), em 4, ausência de edema (13,3%), e em 21 não havia menção sobre edema (70%). Houve 22 relatos de que as criptas estavam preservadas (73,3%) e em 8 não havia menção sobre as mesmas (26,7%). Presença de infiltrado linfocitário ou linfoplasmocitário em 10 (33,3%), ausência deste infiltrado em 3 (10%) e sem menção sobre o mesmo em 17 (56,7%). Presença de eosinófilos em 3 (10%), ausência em 8 (26,7%) e sem relato sobre eosinófilos em 19 (63,3%). Menção sobre conteúdo caliciforme adequado em 2 (6,7%), e nenhum registro sobre este conteúdo em 28 (93,3%). Nos íleos examinados houve infiltrado linfocitário em 2 (6,7%), infi ltrado linfocitário com atrofia em 1 (3,3%), infiltrado linfocitário e eosinofílico com atrofia em 2 (6,7%), infiltrado neutrofílico em 1 (3,3%), sem alterações dignas de nota em 3 (10%), e não biopsiados 2 (6,7%). Dados negativos- ausência de granuloma, fibrose, micro-organismos e malignidade em 3 (10%); malignidade em 4 (13,3%); inflamação micro-organismos e malignidade em 2 (6,7%); abscesso, granuloma, e micro-organismos em 3 (10%); malignidade e especificidade em 3 (10%); e abscesso, granuloma e parasitas em 1 (3,3%). Não houve relato de dados negativos em 14 casos (46,7%). Conclusões- para o diagnóstico de colite microscópica, a literatura sugere biópsias do íleo e de vários níveis do cólon. Na análise de 30 casos, não houve uma afirmativa definitiva de colite linfocítica, eosinofílica ou colágena nos laudos histopatológicos, e não houve um padrão uniforme para a descrição dos achados microscópicos e para a definição diagnóstica. Sugere-se uma discussão com uniformização decritérios histopatológicos para diagnóstico à semelhança do que foi feito com o sistema Sidnei para a classificação das gastrites.

Introduction- among many indications for colonoscopy two very frequent are hematoquezia (20,5%) and diarrhea of obscure etiology (8,8%). Forty percent of colonoscopies in retrospective studies are normal and biopsies have not being a routine. Objective- to evaluate the contribution of histopathology in the diagnostic of patients with diarrhea and normal colonoscopies. Method- it was performed a bibliographic study in PubMed, Scielo, Medline and Cochrane Library using the key words diarrhea and normal colonoscopy, furthermore were studied retrospectively the results of histopathology of patients with diarrhea and normal colonoscopies. Results- in two years, 1.342 colonoscopies were performed. From all 119 (8,86%) the indication was diarrhea, diarrhea plus abdominal pain or diarrhea flushes, 74 (5,51%) undergone to endoscopy biopsies, 34 (2,53%) having any macroscopic abnormalit, and 40 (2,98%) with normal colonoscopies. In thirty out of this 40 cases was possible to analyse the histopatological report, and 10 were discharged because of impossibility of recovering the report. Twenty nine (96,7%) leucodermic and 1 (3,3) melanodermic, ranging from 16 to 64 years old, 13 (43,3%) male and 17 (56,7%) female. The terminal ileum was examined in 11 patients (36,7%) and in 19 (63,3%) it was not possible. The biopsies were taken in the recto and sigmoid in 26 (86,7%) patients, in recto sigmoid left colon and right colon in the same examination in 1 (3,3%), and only in terminal ileum in 3 (10%). From the 30 histopathology reports information were collected about no important alteration in 27 (90%), unspecific alterations in 1 (3,3%) and unspecific colitis in 2 (6,7%). In 5 (16,7%) there were report of edema, in 4 (13,3%) absence of edema and in 21 (70%) no report about edema. In 22 (73,3%) there were report of preserved crypts and in 8 (26,7%) no report about crypts. Presence of lymphocyte or lymphoplasmocitary infiltrate in 10 (33,3%) absence of these infiltrate in 3 (10%) and no report about infiltrates in 17 (56,7%). Presence of eosinophils in 3 (10%), absence in 8 (26,7%) and no report of eosinophils in 19 (63,3%). Report of adequate caliciform lining in 2 (6,7%) and no report of this in 28 (93,3%). In the terminal ileum examined there were lymphocyte infiltrate in 2 (6,7%), lymphocyte infiltrate with atrophy in 1 (3,3%), lymphocity and eosinophil infiltrate with atrophy in 2 (6,7%), neutrophil infiltrate in 1 (3,3%), no important finding in 3 (10%), and 2 (6,7%) not submitted to biopsies. There were negative data: absence of granuloma fibrosis microorganisms and malignity in 3 (10%), malignity in 4 (13,3%), inflammation microorganisms and malignity in 2 (6,7%), abscess granuloma granuloma microorganisms in 3 (10%), malignity and specificity in 3 (10%), abscess granuloma and parasites in 1 (3,3%). There were no report of negative data in 14 cases (46,7%). Conclusions- for the diagnose conclusion in microscopic colitis the literature sugest biopsies of the ileum and in many parts of the colon. Analyzing our 30 cases there were not a definitive conclusion of lymphocyte, eosinophil or collagencolitis in the histopathology reports, and there were not a uniform pattern to describe the findings to conclude the diagnosis. We suggest a discussion in order to uniform de histopathology criteria to reach the diagnose, as the Sydnei system used to classify the gastritis.

Colitis microscópica: Patogénesis / Microscopic colitis: Pathogenesis

Introducción: Colitis microscópica (CM) es el proceso inflamatorio crónico observado en biopsias del colon de pacientes con diarrea crónica acuosa. Se denomina microscópica porque el diagnóstico es histológico ya que las características microscópicas de la endoscopía del colon son normales. Incluye 2 patrones: Colitis microscópica Linfocítica y la Colítis microscópica Colagenosa. La causa es desconocida y los mecanismos patógenos propuestos señalan un fenómeno inmunológico; de acuerdo a este concepto los autores del presente estudio suponemos que la infiltración linfocítica en la lámina propia podrían corresponder a linfocitos citotóxicos CD8 como ejecutores del daño tisular colónico. Objetivos: Probar la hipótesis de la patogénesis inmunológica de la CM. Material y Método: 38 pacientes con diagnóstico de CM reclutados durante los 4 últimos años en el laboratorio de patología Clínica Ricardo Palma. Se seleccionaron 22 biopsias de colon con lesiones histológicas más severas, correspondientes a 17 pacientes, 5 de ellos tuvieron 2 biopsias en 2 sesiones colonoscópicas, las biopsias fueron fijadas en formol neutro. Y procesadas por el método de inclusión en parafina, tenidas con hematoxilina y eosina y tricrómica de Masson para tejido colágeno. La inmunohistoquímica se hizo en secciones histológicas de 4 y 5 micras de espesor precesadas por el método de la Inmunopereoxidasa. Resultados: 19 biopsias correspondieron a CM Linfocítica y 3 a CM Colagenosa. El CM Linfocítica mostró linfocitosis intraepitelial, daño epitelial distrófico en las áreas de infiltración linfocítica, inflamación de la lámina propia con linfocitos y célula plasmática, membrana basal normal. La CM Colagenosa mostró membrana basal engrosada por la presencia de una banda colágena, linfocitos Intra epiteal leve a moderado vacuolización y frecuente desprendimiento del epitelio cobertor. Los estudios de Inmunohistoquímica fueron positivos en las 22 biopsias estudiadas.

Introduction: Microscopic colitis (MC) is a chronic inflammatory process observed in colon biopsies of patients with chronic aqueous diarrhea. It is called microscopic because diagnosis is determined by histological studies since the microscopic characteristics of the colon endoscopy are normal. Two patterns exist: Lymphocytic Microscopic Colitis and Collagenous Microscopic Colitis. Etiology is unknown, and the proposed pathogenic mechanisms indicate an immunological phenomenon. Based on this, the authors of this study hypothesize that lymphocytic infiltration of the lamina propria could be related to cytotoxic lymphocytes CD8 as causative agents of colon tissue damage. OBJECTIVES: Prove hypothesis of immunological pathogenesis of MC. Apparatus and Methods: Thirty eight (38) patients with diagnosed MC were recruited for the last four years in the Pathology Laboratory at Ricardo Palma University. Twenty two (22) colon biopsies with the most severe histological lesions were selected. Thesebiopsies were obtained from 17 patients: 5 patients had 2 biopsies in 2 colonoscopy sessions. Biopsies were fixed in neutral formaldehyde, processed through the paraffin inclusion method, and stained with hematoxiline-eosine and Masson trichromic to distinguish collagenous tissue. Immunohistochemistry was conducted in 4- or 5-micron-thick histological sectionsprocessed through the immunoperoxidase method. RESULTS: Nineteen (19) biopsies corresponded to Lymphocytic MC and 3 to Collagenous MC. Lymphocytic MC showed intraepithelial lymphocytosis, dystrophic epithelial damage in the areas of lymphocytic infiltration, lamina propria inflammation with lymphocytesand plasma cells, and normal basement membrane. Collagenous MC showed thickened basement membrane due to the presence of a collagenous band, mild to moderate intraepithelial lymphocytosis, vacuolization, and frequent detachment of protective epithelium. Twenty two (22) biopsies were positive in the immunohistochemical...

[ epidemiologic study of microscopic colitis in a university related clinic]

Microscopic colitis has been generally recognized as lymphocytic colitis and collagenous colitis: two inflammatory diseases of large intestine without a definite origin. The colon appears normal by colonoscopy. So, biopsy of the colonic mucosa is mandatory for diagnosis. As a descriptive design we assessed epidemiological, clinical and laboratory findings of patients diagnosed as microscopic colitis from 2001 to 2003, retrospectively. This study had been conducted in one of the University related clinics in Tehran. Results: In this setting, 12 patients were diagnosed as microscopic colitis [3 collagenous colitis, and 9 lymphocytic colitis]. Most of these patients were female [11 patients]. The average of the patients' age at the time of the diagnosis was: 47.6 +/- 18.1 years. The delay of diagnosis was distributed from 2 months to 27 years [average: 8 years]. The most prominent complaint was diarrhea [100%]. Most of the cases were presented as a chronic intermittent manner [6 patients- 50%]. Hyperthyroidism, atrophic gastritis, and type 1 diabetes mellitus, each of them were detected in 3 separate patients. After treatment initiation, recurrence of the disease was not seen during 2 years of follow-up. Most of the time, microscopic colitis is mis-diagnosed as irritable bowel syndrome. Clinical suspicion plays the main role in diagnosis of microscopic colitis cases among patients with watery diarrhea and normal colonoscopy