WARNING TO DELAY IN DIAGNOSING MICROSCOPIC COLITIS IN OLDER ADULTS. A SERIES OF CASES.

BACKGROUND: Microscopic colitis (MC) is a chronic inflammatory bowel disease causing non-bloody diarrhea, and several cases are undiagnosed as a hidden cause of chronic diarrhea. OBJECTIVE: We aimed to report the symptoms, delay diagnosis and the treatment of MC in a case series. METHODS: All patients were treated at a Gastroenterology reference office from May 2022 to June 2023. Personal history including preexisting disorders, use of medications and smoking habits were collected. The delay between the onset of symptoms and the correct diagnosis was informed. All patients consented to use budesonide MMX (Corament®) off label. RESULTS: During the study period, six Caucasoid patients were diagnosed with MC, five females and one male, between the ages of 65 and 74. All patients had comorbities and were taking multiple prescription drugs. Laboratory findings showed negative serology for celiac disease for all patients, normal levels of albumin and vitamin B12. The delay between the symptoms and the MC diagnosis varied from 2 months to 6 years. All patients had a previous diagnosis of irritable bowel syndrome. All patients were in complete clinical remission during the treatment and referred no side effects of the drug. CONCLUSION: Older females using high-risk medications are suggestive of MC. Preventing delay in the diagnosis of MC is crucial to improvement in patients´ quality of life. Budesonide MMX appears to be effective, safe and well-tolerated. BACKGROUND: • Microscopic Colitis is a chronic inflammatory bowel disease causing non-bloody diarrhea. BACKGROUND: • Several cases are undiagnosed and can be a hidden cause of chronic diarrhea. BACKGROUND: • Treatment with budesonide MMX (Corament®, off label) was effective and safe.

Alerta de atraso no diagnóstico de colite microscópica em idosos. Uma série de casos / Warning to delay in diagnosing microscopic colitis in older adults. a series of cases

ABSTRACT Background: Microscopic colitis (MC) is a chronic inflammatory bowel disease causing non-bloody diarrhea, and several cases are undiagnosed as a hidden cause of chronic diarrhea. Objective: We aimed to report the symptoms, delay diagnosis and the treatment of MC in a case series. Methods: All patients were treated at a Gastroenterology reference office from May 2022 to June 2023. Personal history including preexisting disorders, use of medications and smoking habits were collected. The delay between the onset of symptoms and the correct diagnosis was informed. All patients consented to use budesonide MMX (Corament®) off label. Results: During the study period, six Caucasoid patients were diagnosed with MC, five females and one male, between the ages of 65 and 74. All patients had comorbities and were taking multiple prescription drugs. Laboratory findings showed negative serology for celiac disease for all patients, normal levels of albumin and vitamin B12. The delay between the symptoms and the MC diagnosis varied from 2 months to 6 years. All patients had a previous diagnosis of irritable bowel syndrome. All patients were in complete clinical remission during the treatment and referred no side effects of the drug. Conclusion: Older females using high-risk medications are suggestive of MC. Preventing delay in the diagnosis of MC is crucial to improvement in patients´ quality of life. Budesonide MMX appears to be effective, safe and well-tolerated.

RESUMO Contexto: A colite microscópica (CM) é uma doença inflamatória intestinal crônica que causa diarreia não sanguinolenta, e vários casos não são diagnosticados como uma causa oculta de diarreia crônica. Objetivo: Esse estudo visou relatar os sintomas, qual o atraso diagnóstico e o tratamento da CM em uma série de casos. Métodos: Todos os pacientes foram atendidos em um consultório de referência em Gastroenterologia no período de maio de 2022 a junho de 2023. Foram coletados antecedentes pessoais, incluindo distúrbios preexistentes, uso de medicamentos e tabagismo. Foi buscado o período entre o início dos sintomas e o diagnóstico correto. Todos os pacientes consentiram em usar budesonida MMX (Corament®) off label. Resultados: Durante o período do estudo, seis pacientes caucasóides foram diagnosticados com CM, cinco mulheres e um homem, com idades entre 65 e 74 anos. Todos os pacientes apresentavam comorbidades e faziam uso de vários medicamentos prescritos. Os achados laboratoriais mostraram sorologia negativa para doença celíaca em todos os pacientes, níveis normais de albumina e vitamina B12. O atraso entre os sintomas e o diagnóstico de CM variou de 2 meses a 6 anos. Todos os pacientes tinham diagnóstico prévio de síndrome do intestino irritável. Todos os pacientes apresentaram remissão clínica completa durante o tratamento e não referiram efeitos colaterais da droga. Conclusão: As mulheres mais velhas que usam medicamentos de alto risco são sugestivas de CM. Evitar o atraso no diagnóstico de CM é fundamental para melhorar a qualidade de vida dos pacientes. A budesonida MMX foi eficaz, segura e bem tolerada.

MICROSCOPIC COLITIS: CONSIDERATIONS FOR GASTROENTEROLOGISTS, ENDOSCOPISTS, AND PATHOLOGISTS.

•Diagnosis of microscopic colitis necessitates effective communication among gastroenterologists, endoscopists, and pathologists. •The gastroenterologist should refer every patient with chronic watery diarrhea to perform a colonoscopy in spite of the benign course of the disease and the absence of alarm symptoms. •The endoscopist should take 2 or 3 biopsy samples of the colonic mucosa from the right and left colon, put in separate recipients, despite that the mucosa looked macroscopically normal. •The pathologist should be encouraged to use objective histological criteria to make the diagnosis. Microscopic colitis is a chronic inflammatory bowel disease characterized by non-bloody diarrhea that can range from mild to severe. It is difficult to attribute up to 10-20% of chronic diarrhea to microscopic colitis. The three determinants factors of the diagnosis are characteristic clinical symptoms, normal endoscopic picture of the colon, and pathognomonic histological picture. This manuscript aimed to update considerations and recommendations for professionals involved (gastroenterologist, endoscopists and pathologist) in the diagnosis of MC. In addition, a short recommendation about treatment.

Colite microscópica: considerações para gastroenterologistas, endoscopistas e patologistas / Microscopic colitis: considerations for gastroenterologists, endoscopists, and pathologists

ABSTRACT Microscopic colitis is a chronic inflammatory bowel disease characterized by non-bloody diarrhea that can range from mild to severe. It is difficult to attribute up to 10-20% of chronic diarrhea to microscopic colitis. The three determinants factors of the diagnosis are characteristic clinical symptoms, normal endoscopic picture of the colon, and pathognomonic histological picture. This manuscript aimed to update considerations and recommendations for professionals involved (gastroenterologist, endoscopists and pathologist) in the diagnosis of MC. In addition, a short recommendation about treatment.

RESUMO A colite microscópica é uma doença intestinal inflamatória crônica caracterizada por diarreia não sanguinolenta que pode variar de leve a grave. Atribui-se que cerca de 10-20% das diarreias crônicas são devidas à colite microscópica. Os três fatores determinantes para o diagnóstico são sintomas clínicos característicos, quadro endoscópico normal do cólon e quadro histológico patognomônico. Este manuscrito tem como objetivo atualizar e trazer recomendações para os profissionais envolvidos (gastroenterologista, endoscopista e patologista) no diagnóstico de colite microscópica. Adicionalmente, uma breve recomendação sobre o tratamento.

Upper gastrointestinal complaints in celiac patients at diagnosis. Association with endoscopic and histopathological findings.

This study investigated the prevalence of upper gastrointestinal symptoms in Brazilian patients at the time of diagnosis with celiac disease (CD), associating them with endoscopic and histopathological findings. A retrospective study was performed including adult patients diagnosed with CD from January 2013 to December 2019.

THE MANAGEMENT OF DERMATITIS HERPETIFORMIS BY THE GASTROENTEROLOGIST. A SERIES OF CASES.

BACKGROUND: Dermatitis herpetiformis (DH) is considered a skin celiac disease (CD). The individuals can be seen by primary care professionals or by dermatologists that could refer the patient to a gastroenterologist. OBJECTIVE: The study aimed to investigate the clinical profile of patients diagnosed with DH and referred to a gastroenterologist and evaluate the treatment response. METHODS: We retrospectively studied patients with DH referred to the same gastroenterologist at a private office in Curitiba, Brazil, between January 2010 to December 2019. We included adult patients with a confirmed DH diagnosis. Symptoms, clinical signs, laboratory and histological data, as well as treatment response, were collected. RESULTS: Thirty-three patients were studied (60.6% women, mean age at diagnosis 40.8±12.61 years). The median delay for DH diagnosis was four years. Skin involvement was mild in 33.3%, moderate in 18.2%, and severe in 48.5%. The more frequent gastrointestinal complaints were abdominal distension (78.8%), flatulence (75.7%), and gastroesophageal reflux (51.5%). Depression and anxiety were observed in 81.8% and anemia in 51.1%. A higher prevalence of bone disorders was associated with higher age at DH diagnosis (P=0.035). Duodenal biopsy showed changes in all patients. Improvement after treatment only with a gluten-free diet (GFD) plus dapsone was verified in 81.2%. CONCLUSION: Patients with DH referred to a gastroenterologist showed a high frequency of gluten intolerance and systemic complaints. Duodenal histological alterations were found in all the cases. The treatment based on GFD plus dapsone was effective in most patients.

O manejo de dermatitis herpetiformis pelo gastroenterologista. Uma série de casos / The management of dermatitis herpetiformis by the gastroenterologist. a series of cases

ABSTRACT BACKGROUND: Dermatitis herpetiformis (DH) is considered a skin celiac disease (CD). The individuals can be seen by primary care professionals or by dermatologists that could refer the patient to a gastroenterologist. OBJECTIVE: The study aimed to investigate the clinical profile of patients diagnosed with DH and referred to a gastroenterologist and evaluate the treatment response. METHODS: We retrospectively studied patients with DH referred to the same gastroenterologist at a private office in Curitiba, Brazil, between January 2010 to December 2019. We included adult patients with a confirmed DH diagnosis. Symptoms, clinical signs, laboratory and histological data, as well as treatment response, were collected. RESULTS: Thirty-three patients were studied (60.6% women, mean age at diagnosis 40.8±12.61 years). The median delay for DH diagnosis was four years. Skin involvement was mild in 33.3%, moderate in 18.2%, and severe in 48.5%. The more frequent gastrointestinal complaints were abdominal distension (78.8%), flatulence (75.7%), and gastroesophageal reflux (51.5%). Depression and anxiety were observed in 81.8% and anemia in 51.1%. A higher prevalence of bone disorders was associated with higher age at DH diagnosis (P=0.035). Duodenal biopsy showed changes in all patients. Improvement after treatment only with a gluten-free diet (GFD) plus dapsone was verified in 81.2%. CONCLUSION: Patients with DH referred to a gastroenterologist showed a high frequency of gluten intolerance and systemic complaints. Duodenal histological alterations were found in all the cases. The treatment based on GFD plus dapsone was effective in most patients.

RESUMO CONTEXTO: A dermatite herpetiforme (DH) é considerada como a doença celíaca (DC) da pele. Os pacientes podem ser atendidos por profissionais do atendimento primário ou por dermatologistas que podem encaminhar o paciente a um gastroenterologista. OBJETIVO: Os objetivos do estudo foram investigar o perfil clínico dos pacientes com diagnóstico de DH encaminhados a um gastroenterologista e avaliar a resposta ao tratamento. MÉTODOS: Foram investigados retrospectivamente pacientes com DH encaminhados ao mesmo gastroenterologista em consultório particular em Curitiba, Brasil, entre janeiro de 2010 a dezembro de 2019. Foram incluídos pacientes adultos com diagnóstico confirmado de DH. Dados sobre sintomas e sinais clínicos, dados laboratoriais, histológicos e resposta ao tratamento foram coletados. RESULTADOS: Foram estudados 33 pacientes (60,6% mulheres, média de idade 40,8±12,61 anos). O atraso médio para o diagnóstico de DH foi de 4 anos. O envolvimento cutâneo foi considerado leve em 33,3%, moderado em 18,2% e grave em 48,5%. As queixas gastrointestinais mais frequentes foram distensão abdominal (78,8%), flatulência (75,7%) e refluxo gastroesofágico (51,5%). Depressão e ansiedade foram observadas em 81,8% e anemia em 51,1%. Maior prevalência de alterações ósseas foi associada à maior idade ao diagnóstico de DH (P=0,035). A biópsia duodenal mostrou alterações em todos os pacientes. A melhora após o tratamento apenas com dieta sem glúten e/ou dapsona foi verificada em 81,2%. CONCLUSÃO: Pacientes com DH encaminhados ao gastroenterologista apresentaram alta frequência de queixas gastrointestinais e sistêmicas. Alterações histológicas duodenais foram encontradas em todos os casos. O tratamento à base de dieta sem glúten e/ou dapsona foi eficaz na maioria dos pacientes.

Aspectos reprodutivos de mulheres celíacas no Brasil / Reproductive aspects in brazilian celiac women

ABSTRACT BACKGROUND: Celiac disease (CD) is a chronic enteropathy in response to ingestion of gluten. CD was associated with gynecological disorders. OBJECTIVE: In this retrospective study, we aimed to investigate the age of menarche, age of menopause, number of pregnancies and abortions in Brazilian celiac patients. METHODS: We studied 214 women diagnosed with CD and as control group 286 women were investigated. RESULTS: Regarding the mean age of menarche, a significant difference was found (12.6±1.40 in CD and 12.8±1.22 years in healthy group; P=0.04). Regarding abortions, in CD women 38/214 (17.8%) and 28/286 (9.8%) in the control group reported abortion (P=0.0092, OR:1.98; CI95%=1.1- 3.3). There was no significant difference in the mean age of menopause nor number of pregnancies per woman. CONCLUSION: In this study, we found that celiac women had a higher mean age of menarche and higher risk of spontaneous abortions.

RESUMO CONTEXTO: A doença celíaca é uma enteropatia crônica em resposta à ingestão de glúten e já foi associada a distúrbios ginecológicos. OBJETIVO: Neste estudo retrospectivo, visamos investigar a idade da menarca, idade da menopausa, número de gestações e abortos em pacientes celíacas brasileiras. MÉTODOS: Foram estudadas 214 mulheres com diagnóstico de doença celíaca e no grupo controle, 286 mulheres foram investigadas. RESULTADOS: Em relação à média de idade da menarca foi encontrada diferença significativa (12,6±1,40 na doença celíaca e 12,8±1,22 anos no grupo controle; P=0,04). Em relação aos abortos, nas mulheres com doença celíaca 38/214 (17,8%) relataram ter tido pelo menos um abortamento espontâneo, enquanto que 28/286 (9,8%) no grupo controle relataram aborto (P=0,0092, OR: 1,98; IC95% = 1,1-3,3). Não houve diferença significativa na idade média da menopausa nem no número de gestações por mulher. CONCLUSÃO: Neste estudo, constatamos que as mulheres celíacas apresentaram maior idade média de menarca e maior risco de abortos espontâneos.

Doenças imunomediadas em pacientes com doença celíaca e em seus familiares: um estudo comparativo entre idade e sexo / Immune mediated diseases in patients with celiac disease and their relatives: a comparative study of age and sex

ABSTRACT BACKGROUND: Up to 15% of other immune-mediated diseases (IMDs) can occur in patients with CD throughout their lives and are associated with multiple factors, including sex and sex hormone levels. Moreover, sex is associated with differences in clinical presentation, onset, progression, and outcomes of disorders. OBJECTIVE: To investigate the prevalence of IMDs at diagnosis in patients with celiac disease (CD) and their first-degree relatives and to compare the findings between female and male patients of different age. METHODS: A retrospective study including Brazilian patients with CD who visited the same doctor during January 2012 to January 2017 was performed. Demographic and medical history data were collected through self-administered questionnaires and medical charts of the patients. In total, 213 patients were examined at diagnosis: 52 males (mean age, 40.0 years) and 161 females (mean age, 41.4 years). The patients were divided into two groups according to sex and age. RESULTS: IMDs were observed in 60.2% of the female (97/161) and 42.3% of the male patients (22/52; P=0.22). However, the frequency of IMDs was significantly higher in females aged 51-60 years than in males with same age (P=0.0002). Dermatitis herpetiformis (DH) was significantly more prevalent in males (P=0.02), whereas atopy was more prevalent in females (P=0.02). IMDs observed in first-degree relatives were similar to those observed in patients (70.9%; P<0.001), with a higher number observed in female relatives. CONCLUSION: The frequency of IMDs in CD patients was similar in all age groups and both sexes, except women diagnosed with CD after 51 years of age presented with an increased frequency of IMDs compared with males. Dermatitis herpetiformis was more prevalent in males, whereas atopy was more prevalent in females. No difference was observed in the type of IMDs between the first-degree relatives of both sexes.

RESUMO CONTEXTO: Até 15% das outras doenças imunomediadas (DIMs) podem ocorrer em pacientes com doença celíaca ao longo de suas vidas e estão associados a múltiplos fatores, incluindo sexo e níveis de hormônios sexuais. Além disso, o sexo está associado a diferenças na apresentação, início, progressão e desfecho das doenças. OBJETIVO: Investigar a prevalência de DIMs ao diagnóstico de doença celíaca e em seus familiares de primeiro grau e comparar os resultados entre sexo feminino e masculino em diferentes idades. MÉTODOS: Estudo retrospectivo incluindo pacientes brasileiros com diagnóstico de doença celíaca que realizaram acompanhamento com o mesmo médico no período de janeiro 2012 a janeiro de 2017. Dados demográficos e histórico médico foram coletados através de um questionário auto administrado e prontuários médicos dos pacientes envolvidos. No total, 213 pacientes eram portadores de doença celíaca, dos quais 52 do sexo masculino (idade média 40,0 anos) e 161 do sexo feminino (idade média 41,4 anos). Os pacientes foram divididos em dois grupos de acordo com o sexo e idade. RESULTADOS: DIMs foram observadas em 60,2% das pacientes femininas (97/161) e 42,4% dos pacientes masculinos (22/52; P=0,22). Entretanto, a frequência de DIMs foi significantemente maior em pacientes do sexo feminino com idade entre 51-60 anos que em pacientes masculinos da mesma idade (P=0,0002). Dermatite herpetiforme apresentou maior prevalência no sexo masculino (P=0,02), enquanto atopia obteve maior prevalência nas pacientes do sexo feminino (P=0,02). DIMs observadas em familiares de primeiro grau foram similares as encontradas nos pacientes (70,9%; P<0,001), com um maior número observado em familiares femininos. CONCLUSÃO: A frequência de DIMs em pacientes com doença celíaca foi similar nos grupos etários e ambos sexos, exceto as mulheres com diagnóstico de doença celíaca após a idade de 51 anos, as quais apresentaram um aumento na frequência de DIMs em comparação com os pacientes do sexo masculino. Dermatite herpetiforme apresentou maior prevalência em pacientes do sexo masculino, enquanto que atopia foi mais prevalente no sexo feminino. Em relação ao sexo, não foi observada diferença no tipo de DIMs observada entre os familiares de primeiro grau.

Alert for bone alterations and low serum concentrations of vitamin D in patients with intestinal inflammatory disease.

BACKGROUND: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic inflammation of the intestine that can reduce the absorption of nutrients such as vitamin D and calcium. OBJECTIVE: To investigate bone alterations and serum levels of vitamin D in patients with IBD. METHOD: This was a cross-sectional study based on a review of medical records of patients from a private office in Curitiba, PR, Brazil. Serum levels of vitamin D and bone densitometry were measured at diagnosis of IBD. A total of 105 patients were included; 38 (58.4%) with CD; 27 (41.6%) with UC and 40 with irritable bowel syndrome (IBS) as comparison group. RESULTS: When compared to patients with UC, CD patients showed a higher prevalence of bone alterations, being 15.8% with osteoporosis and 36.8% with osteopenia. In UC, bone alterations occurred in 29.6% of cases, 3.7% with osteoporosis and 25.9% with osteopenia. As for vitamin D levels, among CD patients, 10.5% had vitamin deficiency, 65.8% insufficiency and 23.7% were sufficient. In UC, 7.4% of cases had deficiency, 74.1% insufficiency and 18.5% had sufficient serum levels of vitamin D. In the group with IBS, deficiency was observed in 17.5% of cases, insufficiency in 55% and sufficiency in 27.5% of them. There was no significant difference between groups. CONCLUSION: IBD patients have a high prevalence of bone changes, especially those with CD. Serum levels of vitamin D are below the recommended in all the evaluated groups.

Alert for bone alterations and low serum concentrations of vitamin D in patients with intestinal inflammatory disease / Alerta para alterações ósseas e baixas concentrações séricas de vitamina D em pacientes com doença inflamatória intestinal

Summary Background: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic inflammation of the intestine that can reduce the absorption of nutrients such as vitamin D and calcium. Objective: To investigate bone alterations and serum levels of vitamin D in patients with IBD. Method: This was a cross-sectional study based on a review of medical records of patients from a private office in Curitiba, PR, Brazil. Serum levels of vitamin D and bone densitometry were measured at diagnosis of IBD. A total of 105 patients were included; 38 (58.4%) with CD; 27 (41.6%) with UC and 40 with irritable bowel syndrome (IBS) as comparison group. Results: When compared to patients with UC, CD patients showed a higher prevalence of bone alterations, being 15.8% with osteoporosis and 36.8% with osteopenia. In UC, bone alterations occurred in 29.6% of cases, 3.7% with osteoporosis and 25.9% with osteopenia. As for vitamin D levels, among CD patients, 10.5% had vitamin deficiency, 65.8% insufficiency and 23.7% were sufficient. In UC, 7.4% of cases had deficiency, 74.1% insufficiency and 18.5% had sufficient serum levels of vitamin D. In the group with IBS, deficiency was observed in 17.5% of cases, insufficiency in 55% and sufficiency in 27.5% of them. There was no significant difference between groups. Conclusion: IBD patients have a high prevalence of bone changes, especially those with CD. Serum levels of vitamin D are below the recommended in all the evaluated groups.

Resumo Introdução: A doença inflamatória intestinal (DII), como a doença de Crohn (DC) e a retocolite ulcerativa (RU), caracterizam-se pela inflamação crônica no intestino, que pode reduzir a absorção de vitamina D e cálcio. Objetivo: Investigar as alterações ósseas presentes em pacientes com DII e as dosagens séricas de vitamina D. Método: Estudo transversal analítico baseado na revisão de prontuários de pacientes com DII de um consultório privado de Curitiba, PR. Em todos os pacientes, foram dosadas as concentrações séricas de vitamina D e foi feita a densitometria óssea. Cento e cinco pacientes foram incluídos no estudo, dos quais 38 (58,4%) foram diagnosticados com DC, 27 (41.6%) com RU e 40 com síndrome do intestino irritável (SII) como grupo de comparação. Resultados: Quando comparados com pacientes com RU, os pacientes com DC apresentaram maior prevalência de alterações ósseas, sendo 15,8% com osteoporose e 36,8% com osteopenia. Na RU, as alterações ósseas ocorreram em 29,6% dos casos, 3,7% com osteoporose e 25,9% com osteopenia. Em relação às dosagens de vitamina D, dentre os pacientes com DC, 10,5% apresentavam deficiência, 65,8%, insuficiência e 23,7%, suficiência. Na RU, 7,4% dos casos tinham deficiência, 74,1%, insuficiência e 18,5%, suficiência. No grupo com SII, observaram-se deficiência em 17,5%, insuficiência em 55% e suficiência em 27,5%. Não foi observada diferença significativa entre os grupos. Conclusão: Pacientes com DII apresentaram alta prevalência de alterações ósseas, principalmente aqueles com DC. As concentrações séricas de vitamina D estão abaixo do recomendado em todos os grupos avaliados.

Tratamento da doença celíaca: estado da arte / Celiac disease treatment; state of the art

A falta de opções terapêuticas para a Doença Celíaca (DC) tornou-se um problema de grande relevância no setor farmacêutico em decorrência do aperfeiçoamento das técnicas sorológicas de diagnóstico e, consequentemente, do aumento do número de indivíduos com diagnóstico confirmado para esta doença. Até o momento, a única terapia eficaz na DC é a dieta isenta de glúten, um tratamento aparentemente simples, mas que tem enormes reflexos nos hábitos nutricionais e sociais do paciente. O conhecimento do complexo mecanismo patogênico da DC permitiu o gradual desenvolvimento de pesquisas em busca de novas opções terapêuticas, entre as quais podemos destacar a ingestão oral de enzimas capazes de hidrolisar o glúten, inibidores da enzima transglutaminase tecidual, inibidores da permeabilidade intestinal, e indutores da tolerância oral ao glúten. Este estudo, além de descrever algumas características da Doença Celíaca e sua relação com a estrutura do glúten, compila informações de diversos autores sobre o desenvolvimento de novos tratamentos para a doença, com objetivo de identificar as opções terapêuticas que apresentam os maiores avanços e, portanto, tem potencial para estarem à disposição dos pacientes celíacos em um futuro próximo.

The lack of therapeutic options for celiac disease (CD) has become a relevant issue in the pharmaceutical sector, as a result of the improvement on technical diagnostic serological and the following increase in the number of individuals with confirmed diagnosis for this disease. To date, the only effective therapy to CD is the gluten-free diet, a seemingly simple treatment, but that has enormous repercussions in the social and nutritional habits of the patient. New findings on the complex pathogenic mechanism of CD allowed gradually the development of researches to look for new therapeutic options, among which we can highlight the oral intake of enzymes capable to hydrolyze the gluten, inhibitors of tissue transglutaminase enzyme, inhibitors of intestinal permeability, and tolerance induction of gluten. This study, besides to describing some features of celiac disease and its relationship with the structure of gluten, compiles information from several authors regarding the development of new treatment of this disease, with the goal of identifying therapeutic options that present the biggest advances and, therefore, has the potential to be at the disposal of celiac patients in a near future.

LOW BONE MINERAL DENSITY IN BRAZILIAN PATIENTS AT DIAGNOSIS OF CELIAC DISEASE / Alterações ósseas em celíacos brasileiros ao diagnóstico

BackgroundLow bone mineral density is considered an extra-intestinal manifestation of celiac disease with reduced bone mass, increased bone fragility, and risk of fractures. Celiac disease is considered a condition at high risk for secondary osteoporosis and the evaluation of bone density is very important in the clinical management of these patients.ObjectiveThe present study aimed to investigate bone alterations in celiac patients from Curitiba, South Region of Brazil at diagnosis, correlating the findings with age and gender.MethodsPatients who were included in the study were attended to in a private office of the same physician from January 2009 to December 2013. The diagnosis of celiac disease was done through clinical, serological and histological findings. All data were collected from the medical charts of the patients. After the diagnosis of celiac disease, evaluation for low bone mineral density was requested by dual-energy X-ray absorptiometry (DEXA). DEXA bone densitometer was used to estimate low bone mineral density at the lumbar spine and femur.ResultsA total of 101 patients, 82 (81.2%) female and 19 (18.8%) male subjects, with mean age of 39.0±3.03 years were included. At celiac disease diagnosis, 36 (35.6%) were younger than 30 years, 41 (40.6%) were between 31 and 50 years, and 24 (23.8%) were older than 50 years. Among the evaluated patients, 69 (68.3%) presented low bone mineral density, being 47% with osteopenia and 32% with osteoporosis. Patients who were older than 51 years and diagnosed with celiac disease presented low bone mineral density in 83.3% (20/24) of the cases. As expected, age influenced significantly the low bone mineral density findings. Among women, low bone mineral density was present with high frequency (60%) from 30 to 50 years. In patients diagnosed older than 60 years (n=8), all the women (n=5) and two of the three men had osteoporosis.ConclusionThis study demonstrated that 69% of Brazilian patients with celiac disease at diagnosis had low bone mineral density, being more frequent in women older than 50 years.

ContextoBaixa densidade mineral óssea é considerada uma manifestação extra-intestinal da doença celíaca com redução da massa óssea, aumento da fragilidade óssea e risco de fraturas. A doença celíaca é considerada uma condição de alto risco para a osteoporose secundária e a avaliação da densidade óssea é muito importante no manejo clínico dos pacientes.ObjetivoO presente estudo teve como objetivo investigar as alterações ósseas presentes em pacientes com doença celíaca de Curitiba-PR, no momento do diagnóstico, correlacionando os achados com a idade e gênero.MétodosOs pacientes incluídos no estudo foram atendidos por um só médico no período de janeiro/2009 a dezembro/2013. O diagnóstico da doença celíaca foi feito através das manifestações clínicas, sorologia específica e achados histológicos da mucosa duodenal. Todos os dados foram coletados a partir dos prontuários dos pacientes. Após o diagnóstico da doença celíaca, foi solicitada a avaliação de densidade mineral óssea por meio de densitometria (dual-energy X-ray absorptiometry DEXA). DEXA foi utilizada para estimar a densidade mineral óssea na coluna lombar e fêmur.ResultadosUm total de 101 pacientes, 82 (81,2%) mulheres e 19 (18,8%) homens, com idade média de 39,0±3,03 anos foram incluídos. No momento do diagnóstico de doença celíaca, 36 (35,6%) tinham menos de 30 anos, 41 (40,6%) tinham entre 31 e 50 anos, e 24 (23,8%) tinham mais de 50 anos. Entre os pacientes avaliados, 69 (68,3%) apresentaram baixa densidade mineral óssea, 47% deles com osteopenia e 32% com a osteoporose. Os pacientes maiores de 51 anos de idade apresentaram baixa densidade mineral óssea em 83,3% (20/24) dos casos. Como esperado, a idade influenciou significativamente os resultados da baixa densidade mineral óssea. Entre as mulheres, baixa densidade mineral óssea foi observada com alta frequência (60%) também na faixa etária entre 30 a 50 anos. Pacientes diagnosticados mais de 60 anos (n=8), todas as mulheres (n=5) e dois dos três homens tinham osteoporose.ConclusãoO presente estudo demonstrou que 69% dos pacientes brasileiros com doença celíaca no momento do diagnóstico apresentaram baixa densidade mineral óssea, sendo mais frequente em mulheres com mais de 50 anos.

FECAL CALPROTECTIN: levels for the ethiological diagnosis in Brazilian patients with gastrointestinal symptoms / Calprotectina fecal: níveis para o diagnóstico etiológico em pacientes brasileiros com sintomas gastrointestinais

Background Determination of fecal calprotectin can provide an important guidance for the physician, also in primary care, in the differential diagnosis of gastrointestinal disorders, meanly between inflammatory bowel diseases and irritable bowel syndrome. Objectives The aims of the present study were to prospectively investigate, in Brazilian adults with gastrointestinal complaints, the value of fecal calprotectin as a biomarker for the differential diagnosis between functional and organic disorders and to correlate the concentrations with the activity of inflammatory bowel diseases. Methods The study included consecutive patients who had gastrointestinal complaints in which the measurement levels of fecal calprotectin were recommended. Fecal calprotectin was measured using a Bühlmann (Basel, Switzerland) ELISA kit Results A total of 279 patients were included in the study, with median age of 39 years (range, 18 to 78 years). After clinical and laboratorial evaluation and considering the final diagnosis, patients were allocated into the following groups: a) Irritable Bowel Syndrome: 154 patients (102 female and 52 male subjects). b) Inflammatory Bowel Diseases group: 112 patients; 73 with Crohn’s disease; 38 female and 35 male patients; 52.1% (38/73) presented active disease, and 47.9% (35/73) had disease in remission and 39 patients with ulcerative colitis;19 female and 20 male patients; 48.7% (19/39) classified with active disease and 49.3% (20/39) with disease in remission. A significant difference (P<0.001) was observed between the median value of fecal calprotectin in Irritable Bowel Syndrome group that was 50.5 µg/g (IQR=16 - 294 µg/g); 405 µg/g (IQR=29 - 1980 µg/g) in Crohn’s disease patients and 457 µg/g (IQR=25 - 1430 µg/g) in ulcerative colitis patients. No difference was observed between the values found in the patients with Crohn’s disease and ulcerative colitis. Levels of fecal calprotectin were significantly ...

Contexto A calprotectina fecal é um biomarcador que pode fornecer informações importantes para o médico, inclusive no atendimento primário, no diagnóstico diferencial de distúrbios gastrointestinais, principalmente as doenças inflamatórias intestinais e a síndrome do intestino irritável. Objetivos Investigar prospectivamente, em adultos brasileiros com queixas gastrointestinais, o valor da calprotectina fecal como biomarcador para o diagnóstico diferencial de distúrbios funcionais e orgânicos e correlacionar as concentrações com a atividade de doenças inflamatórias intestinais. Método O estudo incluiu pacientes consecutivos que apresentavam queixas gastrointestinais e que a dosagem da calprotectina fecal foi recomendada. A dosagem da calprotectina fecal foi obtida utilizando-se o kit ELISA Buhlmann, (Basel, Suiça). Resultados Um total de 279 foram incluídos no estudo, com idade média de 39 anos (variando entre 18 a 78 anos). Após avaliação clínica e laboratorial, e considerando o diagnóstico final, os pacientes foram alocados nos seguintes grupos: a) Grupo Síndrome do Intestino Irritável: 154 pacientes (102 do sexo feminino e 52 indivíduos do sexo masculino). b) grupo Doenças Inflamatórias Intestinais: 112 pacientes; 73 com doença de Crohn; 38 do sexo feminino e 35 pacientes do sexo masculino; 52,1% (38/73) apresentavam doença ativa, e 47,9% (35/73) tiveram a doença em remissão e 39 pacientes com retocolite ulcerativa; 19 do sexo feminino e 20 pacientes do sexo masculino; 48,7% (19/39) classificadas com a doença ativa e 49,3% (20/39) com a doença em remissão. Foi observada uma diferença significativa (P<0,001) entre o valor médio de calprotectina fecal no grupo Síndrome do Intestino Irritável que foi de 50,5 µg/g (16 a 294 µg/g); 405 µg/g (29 a 1980 µg/g), em pacientes com doença de Crohn e 457 µg/g (25 a1430 µg/g), em pacientes com retocolite ulcerativa. Não foram observadas diferenças entre os valores encontrados nos pacientes com ...

Risk factors for postoperative endoscopic recurrence in Crohn's disease: a Brazilian observational study / Fatores de risco para recorrência endoscópica pós-operatória na doença de Crohn: um estudo observacional brasileiro

Introduction: Postoperative endoscopic recurrence (PER) is the initial event after intestinal resection in Crohn's disease (CD), and after a few years most patients present with progressive symptoms and complications related to the disease. The identification of risk factors for PER can help in the optimization of postoperative therapy and contribute to its prevention. Methods: Retrospective, longitudinal, multicenter, observational study involving patients with CD who underwent ileocolic resections. The patients were allocated into two groups according to the presence of PER and the variables of interest were analyzed to identify the associated factors for recurrence. Results: Eighty-five patients were included in the study. The mean period of the first postoperative colonoscopy was 12.8 (3-120) months and PER was observed in 28 patients (32.9%). There was no statistical difference in relation to gender, mean age, duration of CD, family history, previous intestinal resections, smoking, Montreal classification, blood transfusion, residual CD, surgical technique, postoperative complications, presence of granulomas at histology, specimen extension and use of postoperative biological therapy. The preoperative use of corticosteroids was the only variable that showed a significant difference between the groups in univariate analysis, being more common in patients with PER (42.8% vs. 21%; p = 0.044). Conclusions: PER was observed in 32.9% of the patients. The preoperative use of corticosteroids was the only risk factor associated with PER in this observational analysis. (AU)

Introdução: Recorrência endoscópica pós-operatória (REP) é evento inicial após ressecções intestinais na doença de Crohn (DC) e grande parte dos pacientes progride com sintomas e complicações relacionados à doença em alguns anos. A identificação dos fatores de risco para REP pode auxiliar na otimização da terapia pós-operatória e contribuir para sua prevenção. Método: Estudo retrospectivo, longitudinal, multicêntrico e observacional, realizado com pacientes portadores de DC, submetidos à ressecção ileocólica. Os pacientes foram alocados em dois grupos de acordo com a presença de REP e as variáveis de interesse foram analisadas a fim de se identificar os fatores associados à recorrência. Resultados: Oitenta e cinco pacientes foram incluídos no estudo. O tempo médio da primeira colonoscopia pós-operatória foi de 12,8 (3-120) meses e REP foi observada em 28 pacientes (32,9%). Não houve diferença estatística entre os grupos em relação a gênero, média de idade, duração da DC, história familiar, ressecção intestinal prévia, tabagismo, classificação de Montreal, transfusão sanguínea, DC residual, técnica cirúrgica, complicações pós-operatórias, presença de granuloma, extensão do espécime e utilização de biológicos após a cirurgia. O uso pré-operatório de corticosteroides foi a única variável que apresentou significativa diferença na análise univariada, sendo mais frequente nos pacientes que apresentaram REP (42.8% vs. 21%, p = 0.044). Conclusões: REP foi observada em 32.9% dos pacientes. A utilização pré-operatória de corticosteroides foi o único fator associado à REP nesta análise observacional. (AU)

Adalimumab for maintenance therapy for one year in Crohn's disease: results of a Latin American single-center observational study.

CONTEXT: Adalimumab is a fully-human antibody that inhibits TNF alpha, with a significant efficacy for long-term maintenance of remission. Studies with this agent in Latin American Crohn's disease patients are scarce. OBJECTIVES: The objective of this study was to outline clinical remission rates after 12 months of adalimumab therapy for Crohn's disease patients. METHODS: Retrospective, single-center, observational study of a Brazilian case series of Crohn's disease patients under adalimumab therapy. Variables analyzed: demographic data, Montreal classification, concomitant medication, remission rates after 1, 4, 6 and 12 months. Remission was defined as Harvey-Bradshaw Index ≤ 4, and non-responder-imputation and last-observation-carried-forward analysis were used. The influence of infliximab on remission rates was analyzed by Fischer and Chi-square tests (P<0.05). RESULTS: Fifty patients, with median age of 35 years at therapy initiation, were included. Remission rates after 12 months of therapy were 54% under non-responder-imputation and 88% under last-observation-carried-forward analysis. After 12 months, remission on patients with previous infliximab occurred in 69.23% as compared to 94.59% in infliximab-naïve patients (P = 0.033). CONCLUSIONS: Adalimumab was effective in maintaining clinical remission after 12 months of therapy, with an adequate safety profile, and was also more effective in infliximab naïve patients.

ADALIMUMAB FOR MAINTENANCE THERAPY FOR ONE YEAR IN CROHN?S DISEASE: results of a Latin American single-center observational study / Adalimumabe na terapia de manutenção por um ano na doença de Crohn: resultados de um estudo observacional unicêntrico Latinoamericano

Context Adalimumab is a fully-human antibody that inhibits TNF alpha, with a significant efficacy for long-term maintenance of remission. Studies with this agent in Latin American Crohn’s disease patients are scarce. Objectives The objective of this study was to outline clinical remission rates after 12 months of adalimumab therapy for Crohn’s disease patients. Methods Retrospective, single-center, observational study of a Brazilian case series of Crohn’s disease patients under adalimumab therapy. Variables analyzed: demographic data, Montreal classification, concomitant medication, remission rates after 1, 4, 6 and 12 months. Remission was defined as Harvey-Bradshaw Index ≤4, and non-responder-imputation and last-observation-carried-forward analysis were used. The influence of infliximab on remission rates was analyzed by Fischer and Chi-square tests (P<0.05). Results Fifty patients, with median age of 35 years at therapy initiation, were included. Remission rates after 12 months of therapy were 54% under non-responder-imputation and 88% under last-observation-carried-forward analysis. After 12 months, remission on patients with previous infliximab occurred in 69.23% as compared to 94.59% in infliximab-naïve patients (P = 0.033). Conclusions Adalimumab was effective in maintaining clinical remission after 12 months of therapy, with an adequate safety profile, and was also more effective in infliximab naïve patients. .

Contexto O adalimumabe é um anticorpo monoclonal totalmente humano que inibe o TNF alfa, com eficácia documentada na manutenção da remissão clínica na doença de Crohn. Estudos com pacientes latinoamericanos são escassos nesse cenário. Objetivos O objetivo deste estudo foi analisar as taxas de remissão clínica após 12 meses de terapia com adalimumabe em portadores de doença de Crohn. Métodos Estudo retrospectivo unicêntrico observacional de uma série de casos de pacientes brasileiros portadores de doença de Crohn tratados com adalimumabe. Variáveis analisadas: dados demográficos, classificação de Montreal, medicações concomitants, taxas de remissão após 1, 4, 6 e 12 meses. Remissão foi definida como índice de Harvey-Bradshaw ≤4 e foram utilizadas as análises de imputação de não-resposta e última observação considerada. A influência do infliximab prévio foi analisada pelo teste de Fischer e qui-quadrado (P<0.05). Resultados Cinquenta pacientes, com media de idade de 35 anos no início da terapia foram incluídos. As taxas de remissão após um ano foram de 54% (análise imputação de não-resposta) e 88% (análise de última observação considerada. A remissão clínica ocorreu em 69.23% dos pacientes com infliximab prévio e 94.59% nos virgens de infliximab (P = 0.033). Conclusão O adalimumabe foi efetivo na manutenção da remissão clínica após 1 ano, com adequado perfil de segurança com eficácia maior nos pacientes virgens de infliximab. .

Complications after intestinal resection in Crohn's disease: laparoscopic versus conventional approach / Complicações após ressecções intestinais na doença de Crohn: há diferenças entre as vias convencional e videolaparoscópica?

BACKGROUND: significant advances in medical therapy for Crohn's disease (CD) occurred in the last 12 years, mainly due to the introduction of anti-TNF therapy. Laparoscopic colorectal surgery represented the most important advance on surgical treatment in the management of CD, as it also had developed in the treatment of other conditions. There is a tendency for lower complication rates after laparoscopic bowel resections as compared to open surgery. The aim of this study was to analyze and compare the complication rates after bowel resections for CD between the two approaches in a Brazilian case series. METHODS: this was a retrospective longitudinal study, including CD patients submitted to bowel resections from a single Brazilian Inflammatory Bowel Diseases (IBD) referral center, treated between January 2008 and June 2012 with laparoscopic approach (LA) or conventional approach (CA). VARIABLES ANALYZED: age at surgery, gender, Montreal classification, smoking, concomitant medication, type of surgery, surgical approach, presence and type of complication up to 30 days after the procedures. Readmission and reoperation rates, as well as mortality, were also analyzed. Patients were allocated in two groups regarding the type of procedure (LA or CA), and complication rates and characteristics were compared. Statistical analysis was performed with Mann-Whitney test (quantitative variables) and chi-square test (qualitative variables), with p < 0.05 considered significant. RESULTS: a total of 46 patients (25 men) were included (16 submitted to LA), with mean age of 38.1 (± 12.7) years. The groups were considered homogeneous according to age, gender, CD location, perianal disease and concomitant medications. There were more patients with fistulizing CD on the CA group (p = 0.029). The most common procedure performed was ileocolic resection on both groups (56.7% of the CA and 75% of the LA patients - p = 0.566). Overall, total complications (surgical and medical, including minor and major issues) occurred in 60% (18/30) of the CA group and 12.5% (2/16) of the LA group (p = 0.002). Wound infection was the most frequent complication (10/30 on CA and 1/16 on the LA groups). There were 3 deaths in the CA group. Specific analysis of each complication did not demonstrate any difference between the groups regarding abdominal sepsis, urinary tract infections, pneumonia, readmission, reoperations and deaths (p = 0.074). CONCLUSIONS: there was a higher complication rate in patients operated with CA as compared to LA. This was probably due to patient selection for the laparoscopic approach, with severe cases, mostly due to fistulizing abdominal CD, being operated mainly by open surgery. LA tends to be the recommended approach in most cases of non-complicated CD. (AU)

INTRODUÇÃO: avanços significativos no tratamento medicamentoso da doença de Crohn (DC) ocorreram nos últimos 12 anos, principalmente após a introdução da terapia anti-TNF. A cirurgia laparoscópica colorretal representa um dos maiores progressos no tratamento cirúrgico minimamente invasivo da DC, bem como no manejo de outras afecções. Existe uma tendência a menores taxas de complicações com as ressecções intestinais laparoscópicas quando comparadas a cirurgia convencional. O objetivo deste estudo foi analisar e comparar as taxas de complicações após ressecções intestinais na DC entre as duas vias de acesso em uma série de casos brasileira. MÉTODO: estudo retrospectivo longitudinal, incluindo pacientes com DC submetidos a ressecções intestinais em um centro de referência brasileiro em doença inflamatória intestinal (DII), tratados entre janeiro de 2008 e junho de 2012, com cirurgia laparoscópica (CL) ou cirurgia convencional (CC). As variáveis analisadas foram: idade no momento da cirurgia, gênero, classificação de Montreal, tabagismo, medicações concomitantes, tipo de cirurgia, via de acesso, presença e tipo de complicação em até 30 dias do procedimento. Readmissão, reoperações e mortalidade também foram avaliadas. Os pacientes foram alocados em dois grupos de acordo com a via de acesso (CL ou CC), sendo as taxas de complicações comparadas entre si. Análise estatística foi realizada pelos testes de Mann-Whitney (variáveis quantitativas) e chi-quadrado (qualitativas), com p<0.05 considerado significativo. RESULTADOS: No total, 46 pacientes (25 homens) foram incluídos (16 operados por CL), com média de idade de 38,1 (± 12,7) anos. Os grupos foram considerados homogêneos em relação à idade, gênero, localização da doença, DC perianal e medicações concomitantes. Houve predomínio da forma fistulizante no grupo de cirurgias abertas (p = 0.029). O procedimento mais realizado foi a ileocolectomia direita em ambos os grupos (56,7% na CC e 75% na CL - p = 0.566). No total, complicações pós-operatórias (cirúrgicas e clínicas) ocorreram em 60% (18/30) dos casos após CC e 12,5% (2/16) após a CL (p = 0.002). Infecção da ferida operatória foi a complicação mais frequente (10/30 na CC e 1/16 na CL). Ocorreram 3 óbitos no grupo da CC. Em análise individualizada das complicações, não houve diferença entre os grupos em relação a sepse abdominal, infecções urinárias, pneumonia, reinternações, reoperações e óbitos (p=0.074). CONCLUSÕES: houve maior taxa de complicações nos pacientes operados por CC comparado a CL. A seleção de casos para cirurgia laparoscópica provavelmente contribuiu para este resultado, havendo uma tendência a utilização da cirurgia convencional nos casos mais graves, geralmente com DC abdominal fistulizante. A CL parece ser a via de acesso recomendada na maioria dos casos de DC não-complicada. (AU)