Abstract As the treatment of infectious and parasitic diseases improved, the prevalence of these conditions declined. However, with the expansion of the use of immunobiologicals, opportunistic infections have emerged, especially under atypical presentations. The present study reports the case of a patient treated with infliximab for Crohn's disease, who presented diarrhea, weight loss, abdominal pain, fever, and subcutaneous erythematous nodules that evolved with spontaneous fluctuation and ulceration. With the finding of alcohol-resistant bacilli and Mycobacterium tuberculosis DNA in a cutaneous fragment, through polymerase chain reaction, the diagnosis of gummatous tuberculosis was confirmed, probably secondary to hematogenous dissemination from an intestinal focus.

ABSTRACT Introduction: Acute graft-versus-host disease (GVHD) is one of the major causes of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT) and has become the subject of several studies to understand and treat it. Objective: This study does a descriptive analysis of the apoptotic index (AI) evaluation and intestinal permeability (IP) alterations in association with the clinical, endoscopic and histopathological data on patients undergoing AHSCT, with emphasis on acute intestinal graft-versus-host disease (GVHD) diagnosis. Methods: Thirty-one patients were divided into two groups—one of patients with a clinical GVHD diagnosis and one of those without GVHD diagnosis. Results: Thirteen deaths (41.9%) occurred during the study period, thereby reaffirming the severity of the alterations found in the patients. Fifteen patients subjected to 21 esophagogastroduodenoscopy procedures prior to D + 90 post-transplant had visible endoscopic alterations and 19 biopsies revealed histological alterations to the stomach and duodenum. Higher apoptotic indices, not reaching statistical significance, were observed in patients who died of graft versus host disease (GVHD), in the more acute forms of GVHD and where clinical GVHD was present. The intestinal permeability evaluation was performed on nine patients able to undergo it in the three proposed study periods, which showed alterations, some of which were pronounced even during pre-transplant and, therefore, the pre-conditioning phase. Conclusion: Clinical judgment remains a fundamental tool in the diagnosis of GVHD. This study points to the known limitations of traditional diagnostic aids (endoscopy and histology) and points to new methods not usually employed in clinical practice.

CONTEXTO E OBJETIVO: Mycobaterium avium subsp. paratuberculosis (MAP) tem atraído o interesse de pesquisadores devido às semelhanças entre a paratuberculose e a doença de Crohn (CD). Este estudo objetivou avaliar a frequência de MAP por meio de cultura, histologia e reação da polimerase em cadeia (PCR), em biópsias intestinais de pacientes brasileiros com CD. PCR quantitativa em tempo real (qRT-PCR) foi realizada nas amostras positivas. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico com grupo controle realizado em duas universidades federais. MÉTODOS: Amostras frescas foram coletadas de 25 pacientes; cinco com CD, oito com colite ulcerativa (UC) e 12 controles sem doença inflamatória intestinal (nIBD). Também foram coletadas 149 amostras fixadas em parafina (FFPE): 44 CD, 49 UC e 56 nIBD. RESULTADOS: Nenhuma das amostras frescas foi positiva para MAP. Cinco amostras FFPE (uma CD, duas UC e duas nIBD) e três amostras frescas (uma de cada grupo) foram positivas por IS900-PCR. qRT-PCR foi realizada nessas oito amostras. Nas amostras FFPE, havia 192,12 cópias/μl no grupo CD, 72,28 cópias/μl no UC e 81,43 cópias/μl no nIBD. Nas amostras frescas, havia 432,99 cópias/μl, 167,92 cópias/μl e 249,73 cópias/μl nos grupos CD, UC e nIBD, respectivamente. A maior carga bacteriana foi encontrada no grupo CD. CONCLUSÃO: Este estudo não fornece evidências do papel de MAP na etiologia da CD, embora DNA de MAP tenha sido detectado em pacientes dos três grupos. Este é o primeiro relato da presença de MAP em biópsias intestinais humanas no Brasil.

CONTEXT AND OBJECTIVE: Mycobacterium avium subsp. paratuberculosis (MAP) has attracted the interest of researchers because of similarities between paratuberculosis and Crohn's disease (CD). The aim of this study was to evaluate the frequency of MAP through cultures, histology and polymerase chain reaction (PCR) on intestinal biopsies from Brazilian CD patients. Quantitative real time PCR (qRT-PCR) was performed on positive samples. DESIGN AND SETTING: Analytical cross-sectional study with control group at two federal universities. METHODS: Fresh samples were collected from 25 patients; five with CD, eight with ulcerative colitis (UC) and 12 controls with non-inflammatory bowel disease (nIBD). Formalin-fixed paraffin-embedded (FFPE) samples from 143 patients were also collected: 44 CD, 49 UC and 56 nIBD. RESULTS: None of the fresh samples was positive for MAP. Five FFPE samples (one CD, two UC and two nIBD) and three fresh samples (one in each group) were positive through IS900-PCR. qRT-PCR was performed on these eight samples. Among the FFPE samples, there were 192.12 copies/μl in the CD group, 72.28 copies/μl in UC and 81.43 copies/μl in nIBD. Among the fresh samples, there were 432.99 copies/μl, 167.92 copies/μl and 249.73 copies/μl in the CD, UC and nIBD groups, respectively. The highest bacterial load was in the CD group. CONCLUSION: This study does not provide evidence for a role of MAP in the etiology of CD, although MAP DNA was detected in all three patient groups. This is the first report of MAP presence in human intestinal biopsies in Brazil.

OBJETIVO: avaliar a recorrência da doença de Cröhn e seus possíveis fatores preditores em pacientes submetidos ao tratamento cirúrgico. MÉTODOS: estudo retrospectivo de pacientes com doença de Crohn (DC) submetidos a tratamento cirúrgico entre janeiro de 1992 e janeiro de 2012, em acompanhamento regular no Ambulatório de Intestino Clínico do Hospital das Clínicas da UFMG. RESULTADOS: foram avaliados 125 pacientes, sendo 50,4% do sexo feminino, com média de idade de 46,12 anos, a maioria (63,2%) com diagnóstico entre 17 e 40 anos de idade. O íleo terminal foi envolvido em 58,4%, sendo que o comportamento estenosante foi observado em 44,8% e o penetrante em 45,6% dos pacientes. Doença perianal foi observada em 26,4% dos casos. A média de tempo de acompanhamento foi 152,40 meses. Recorrência cirúrgica foi observada em 29,6%, com um tempo médio de 68 meses até a segunda operação. CONCLUSÃO: a localização ileocólica, o comportamento penetrante e o acometimento perianal (L3B3p) estão associados ao maior risco de recorrência cirúrgica.

OBJECTIVE: to evaluate Crohn's disease recurrence and its possible predictors in patients undergoing surgical treatment. METHODS: We conducted a retrospective study with Crohn's disease (CD) patients undergoing surgical treatment between January 1992 and January 2012, and regularly monitored at the Bowel Clinic of the Hospital das Clínicas of the UFMG. RESULTS: we evaluated 125 patients, 50.4% female, with a mean age of 46.12 years, the majority (63.2%) diagnosed between 17 and 40 years of age. The ileum was involved in 58.4%, whereas stenotic behavior was observed in 44.8%, and penetrating, in 45.6%. We observed perianal disease in 26.4% of cases. The follow-up average was 152.40 months. Surgical relapse occurred in 29.6%, with a median time of 68 months from the first operation. CONCLUSION: The ileocolic location, penetrating behavior and perianal involvement (L3B3p) were associated with increased risk of surgical recurrence.

Objective: The aim of this study was to evaluate the influence of Saccharomyces boulardii on the intestinal permeability, laboratory parameters and MELD and Child-Pugh severity scores in cirrhotic patients eligible for liver transplantation. Methods: Eighteen patients followed in a Transplant Outpatient Clinic were evaluated immediately before the beginning of treatment, after a 30-day period of treatment period with probiotics and at the end of the second study month (after a thirty-day period without probiotics). Fifteen healthy controls also underwent the intestinal permeability test (lactulose/mannitol). Results: Before the probiotic, the median lactulose/mannitol ratio was greater in the cirrhotic patients (0.0209, range 0.0012-0.1984) compared to the healthy controls (0.0030, range 0.0020-0.0013) (p < 0.05). Eight of fifteen patients, half of whom had ascites, showed increased intestinal permeability above the higher value observed in the controls. No significant association was found between the severity scores for liver disease, age, presence of ascites and intestinal permeability immediately before the beginning of study. After treatment with S. boulardii, there was no improvement in intestinal permeability or significant differences in the laboratory parameters for the three evaluations. Conclusions: Patients eligible for liver transplants presented with increased intestinal permeability compared to healthy controls. A thirty-day treatment with S. boulardii did not improve this intestinal permeability or the severity scores, nor did it impact the laboratory parameters.

Objetivo: Evaluar la influencia del Saccharomyces boulardii en la permeabilidad intestinal, parámetros bioquímicos, de MELD y de Child-Pugh en pacientes cirróticos candidatos al trasplante de hígado. Métodos: Dieciocho pacientes seguidos en ambulatorio de Transplantes fueron evaluados inmediatamente antes del inicio del tratamiento con probióticos, después de período de 30 días con probióticos y al final del segundo mes de estudio (período de treinta días sin probióticos). Quince controles sanos también se sometieron a la prueba de permeabilidad intestinal (lactulosa/manitol). Resultados: Antes del probiótico, la relación de lactulosa / manitol media fue mayor en los pacientes cirróticos (0,0209; 0,0012-0,1984) en comparación con los controles sanos (0,0030; 0,0020-0,0013) (p < 0,05). Ocho de los quince pacientes, la mitad de los cuales tenía ascitis, presentaron con aumento de la permeabilidad intestinal por encima del valor más alto observado en los controles. No se observó asociación significativa entre los critérios de Meld, Child-Pugh y la edad, la presencia de ascitis y la permeabilidad intestinal inmediatamente antes del inicio del estudio. El tratamiento con S. boulardii, no resultó en mejoría de la permeabilidad intestinal, de los critérios de Meld y Child-Pugh así como de los los parámetros bioquímicos a lo largo de las tres evaluaciones. Conclusiones: Pacientes en lista de espera para transplantes hepático presentan mayor permeabilidad intestinal en comparación con los controles sanos. El tratamiento de treinta días con S. boulardii no resultó en mejoría de la permeabilidad intestinal, del MELD y Child-Pugh, asi como de los parámetros bioquímicos.

Objective:The objective of this study was to evaluate the intestinal barrier function in leukemia patients before the start of the chemotherapy with an intestinal permeability test using lactulose and mannitol as markers.Methods:The study enrolled 20 patients diagnosed with leukemia (acute and chronic). Ten healthy volunteers were also submitted to the test as a control group.Results:The median lactulose/mannitol ratio was 0.019 for the Leukemia Patient Group, whereas in healthy controls the median was 0.009 (p-value = 0.244). The median lactulose/mannitol ratio in acute leukemia patients was 0.034 giving a p-value of 0.069 when compared to healthy controls. This same comparison was made between acute myeloid leukemia patients and healthy controls with a p-value of 0.149. There was no significant difference in the intestinal permeability between acute and chronic leukemia patients (p-value = 0.098).Conclusion:The intestinal barrier function measured using the intestinal permeability test was similar in leukemic patients overall and healthy controls, but a tendency toward a different pattern was found in the intestinal barrier function of acute leukemia patients.

Contexto A apresentação clínica da doença celíaca é extremamente variável e o diagnóstico se baseia em testes sorológicos, histologia intestinal e respostas clínica e sorológica à dieta sem glúten. Objetivos Correlacionar os aspectos endoscópicos e histológicos de pacientes adultos com suspeita de doença celíaca e avaliar a concordância histológica interobservadores. Métodos Os aspectos endoscópicos de 80 pacientes adultos foram avaliados e correlacionados com os achados histológicos de acordo com a classificação de Marsh-Oberhuber. A concordância histológica foi baseada nos valores kappa. Resultados A sintomatologia clínica foi muito variável com destaque para a diarréia crônica, presente em 48 (60%) pacientes. Os aspectos endoscópicos relacionados à atrofia vilositária duodenal foram observados em 32 (40%) pacientes. Foram confirmados 46 casos de doença celíaca, prevalência de 57.5%. A sensibilidade, a especificidade, o valor preditivo positivo e o valor preditivo negativo dos aspectos endoscópicos para o diagnóstico da doença celíaca foram, respectivamente, 60,9%, 88,2%, 87,5% e 62,5%. A concordância histológica interobservadores foi moderada (kappa = 0,46). Conclusões Os aspectos endoscópicos de atrofia vilositária contribuíram para a suspeita e a indicação das biópsias duodenais com objetivo diagnóstico. A histologia pode ser contraditória e novas biópsias ou a opinião de outro profissional podem propiciar maior concordância diagnóstica.

Context Clinical presentation of celiac disease is extremely variable and the diagnosis relies on serologic tests, mucosal intestinal biopsy and clinic and serologic response to a gluten-free diet. Objectives To correlate the endoscopic and histological aspects of adult patients with suspicion of celiac disease and to evaluate the interobserver histological agreement. Methods Endoscopic aspects of 80 adult patients were evaluated and correlated with the histological features according the Marsh-Oberhuber classification system. The interobserver histological agreement was based on kappa values. Results The symptoms of the patients varied largely, with prominence for chronic diarrhea, present in 48 (60%) patients. The endoscopic aspects related with the duodenal villous atrophy had been observed in 32 (40%) patients. There were confirmed 46 cases of celiac disease, with prevalence of 57.5%. The sensitivity, specificity, positive predictive value and negative predictive value of the endoscopic markers for celiac disease diagnosis were of 60.9%, 88.2%, 87.5% and 62.5%. There was moderate interobserver histological agreement (kappa = 0.46). Conclusions The endoscopic markers of villous atrophy, although not diagnostic, had assisted in the suspicion and indication of the duodenal biopsies for diagnosis proposal. Histology is sometimes contradictory and new biopsies or opinion of another professional can provide greater diagnostic agreement.

Objective To investigate superior mesenteric artery flow measurement by Doppler ultrasonography as a means of characterizing inflammatory activity in Crohn's disease. Materials and Methods Forty patients were examined and divided into two groups – disease activity and remission – according to their Crohn's disease activity index score. Mean superior mesenteric artery flow volume was calculated for each group and correlated with Crohn's disease activity index score. Results The mean superior mesenteric artery flow volume was significantly greater in the patients with active disease (626 ml/min ± 236 × 376 ml/min ± 190; p = 0.001). As a cut off corresponding to 500 ml/min was utilized, the superior mesenteric artery flow volume demonstrated sensitivity of 83% and specificity of 82% for the diagnosis of Crohn's disease activity. Conclusion The present results suggest that patients with active Crohn's disease have increased superior mesenteric artery flow volume as compared with patients in remission. Superior mesenteric artery flow measurement had a good performance in the assessment of disease activity in this study sample.

Os sintomas articulares constituem a manifestação extra-intestinal mais comum em pacientes com doença de Crohn e com retocolite ulcerativa. Reconhecida como artrite colítica, e mais recentemente, artrite enteropática, está classificada como uma das doenças do grupo das espondiloartropatias. Reconhecidamente, há dois padrões de acometimento articular: 1) periférico, habitualmente, associado aos períodos de atividade da doença intestinal e sem associação com o antígeno HLA B27, e 2) axial, caracterizado por espondilite e sacroiliíte, com curso clínico e radiográfico independente da doença intestinal e associado ao HLA B27.

Joint involvement is the most commom extraintestinal manifestation in patients with Crohn's disease and ulcerative colitis. The colitic arthritis, lately called enteropathic arthritis, is classified as one of the diseases of the spondyloarthropathies group. There are two patterns of joint involvement: 1) peripheral arthritis, usually coincides with exacerbations of the inflammatory bowel disease and is not associated with the HLA B27 antigen; and 2) axial involvement, characterized by spondylitis and sacroiliitis, which the clinical course is independent of the intestinal disease, and has an association with HLA B27.

A Doença de Whipple (DW) é doença sistêmica rara, de etiologia infecciosa, que acomete o intestino delgado, mas pode afetar virtualmente qualquer órgão. Apresentamos cinco casos com idade que variou entre 20 e 59 anos, sendo quatro do sexo masculino e um feminino. Todos tinham em comum o comprometimento intestinal, associado ou não às manifestações clínicas ligadas a esse orgão. Em uma paciente, foi observada vegetação na válvula tricúspide, sugerindo endocardite pelo Tropheryma whippelii, com desaparecimento das alterações ecocardiográficas após o tratamento. Em um dos pacientes do sexo masculino, o quadro clínico inicial foi de espondilite sorológica negativa e, em momento algum de sua evolução observou-se diarréia. Acometimento ocular associado à mabsorção intestinal e emagrecimento significativo foi evidenciado em um caso. Nos outros dois, a diarréia foi a manifestação clínica principal. Em todos, o diagnóstico foi feito através do estudo histológico por microscopia ótica e eletrônica da mucosa jejunal e, quando indicado, de tecidos extra-intestinais. Após o tratamento com antibioticoterapia, houve remissão completa dos sintomas, em todos os casos. O controle realizado através da microscopia eletrônica de mucosa jejunal, após doze meses de tratamento com sulfametoxazol-trimetropim, mostrou em quatro, o desaparecimento do T. whippelii. O outro paciente abandonou o seguimento.

Whipple's disease (WD) is a rare systemic disease of infectious etiology which involves the small intestine but can virtually affect any organ. We present here five cases (four males and one female) ranging in age from 20 to 59 years. All patients had intestinal involvement associated or not with clinical manifestations linked to this organ. Vegetation in the tricuspid valve was observed in one patient, suggesting endocarditis caused by Tropheryma whippelii, with disappearance of the echocardiographic alterations after treatment. In one of the male patients the initial clinical manifestation was serologically negative spondylitis, with no diarrhea occurring at any time during follow-up. Ocular involvement associated with intestinal malabsorption and significant weight loss were observed in one case. In the other two cases, diarrhea was the major clinical manifestation. All patients were diagnosed by histological examination of the jejunal mucosa and, when indicated, of extraintestinal tissues by light and electron microscopy. After antibiotic treatment, full remission of symptoms occurred in all cases. A control examination of the intestinal mucosa performed after twelve months of treatment with sulfamethoxazole-trimethoprim revealed the disappearance of T. whippelii in four patients. The remaining patient was lost to follow-up.