M. Rosinach

Spectrum of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease: clinical relevance of lymphocytic enteritis.

Background: Limited data on a short series of patients suggest that lymphocytic enteritis (classically considered as latent coeliac disease) may produce symptoms of malabsorption, although the true prevalence of this situation is unknown. Serological markers of coeliac disease are of little diagnostic value in identifying these patients. Aims: To evaluate the usefulness of human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy for the detection of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease and to assess the clinical relevance of lymphocytic enteritis diagnosed with this screening strategy. Patients and methods: 221 first-degree relatives of 82 DQ2+ patients with coeliac disease were consecutively included. Duodenal biopsy (for histological examination and tissue transglutaminase antibody assay in culture supernatant) was carried out on all DQ2+ relatives. Clinical features, biochemical parameters and bone mineral density were recorded. Results: 130 relatives (58.8%) were DQ2+, showing the following histological stages: 64 (49.2%) Marsh 0; 32 (24.6%) Marsh I; 1 (0.8%) Marsh II; 13 (10.0%) Marsh III; 15.4% refused the biopsy. 49 relatives showed gluten sensitive enteropathy, 46 with histological abnormalities and 3 with Marsh 0 but positive tissue transglutaminase antibody in culture supernatant. Only 17 of 221 relatives had positive serological markers. Differences in the diagnostic yield between the proposed strategy and serology were significant (22.2% v 7.2%, p<0.001). Relatives with Marsh I and Marsh II–III were more often symptomatic (56.3% and 53.8%, respectively) than relatives with normal mucosa (21.1%; p = 0.002). Marsh I relatives had more severe abdominal pain (p = 0.006), severe distension (p = 0.047) and anaemia (p = 0.038) than those with Marsh 0. The prevalence of abnormal bone mineral density was similar in relatives with Marsh I (37%) and Marsh III (44.4%). Conclusions: The high number of symptomatic patients with lymphocytic enteritis (Marsh I) supports the need for a strategy based on human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy in relatives of patients with coeliac disease and modifies the current concept that villous atrophy is required to prescribe a gluten-free diet.

Evolution of the incidence of collagenous colitis and lymphocytic colitis in Terrassa, Spain: A population-based study†

Background: Previous studies suggest an increase in the incidence rate of microscopic colitis in recent decades. The aim was to evaluate changes in the population‐based incidence rate of microscopic colitis and its subtypes over time in Terrassa, Spain. Methods: This was a prospective study during the period 2004–2008, with a comparison of data from the period 1993–1997. The catchment area was a mixed rural‐urban type, with nearly 290,000 inhabitants. All patients with nonbloody chronic diarrhea referred for a diagnostic colonoscopy were included. Multiple biopsy specimen samples were obtained when the macroscopic appearance of the colonic mucosa was normal to rule out microscopic colitis. Crude and adjusted incidence rates based on either the year of diagnosis or the date of onset of symptoms were calculated. Results: Forty patients with collagenous colitis (CC) and 32 with lymphocytic colitis (LC) were identified. The mean annual incidence of CC and LC based on the year of onset of symptoms was 2.6/105 inhabitants (95% confidence interval [CI], 1.9–3.3), and 2.2/105 inhabitants (95% CI, 1.5–3.0), respectively. Incidence rates for CC based on the year of onset of symptoms were significantly higher in the period 2004–2008 than in 1993–1997 (2.6 versus 1.1/105; P = 0.012). The increase in CC incidence was more marked in women (P = 0.047) than in men (P = 0.19). Conclusions: The annual incidence of CC in Terrassa increased over time, mainly in women. Nevertheless, the rates were much lower than those observed in northern Europe, suggesting that there is a north–south difference in the incidence of microscopic colitis. (Inflamm Bowel Dis 2011;)

Paucicellular Lymphocytic Colitis : Is It a Minor Form of Lymphocytic Colitis? A Clinical Pathological and Immunological Study

OBJECTIVES:It has been suggested that paucicellular lymphocytic colitis (PLC) should be considered to be part of the morphological spectrum of microscopic colitis. The aim of the study was to evaluate whether PLC may be considered to be a true microscopic colitis, and in this case, whether it is a minor form of lymphocytic colitis (LC) or a different entity.METHODS:All incident cases of PLC, LC, and collagenous colitis (CC) during the period 2004–2006 were included. The incidence rate and the clinical, histopathological, and immunological features of PLC were assessed and compared with those of both LC and CC. Immunoreactivities to CD25, c-Kit, and FOXP3 in lamina propria were assessed.RESULTS:In all, 19 patients with CC, 19 with LC, and 26 with PLC were identified. CD25+FOXP3+ expression was seen only in classical forms of microscopic colitis: 12 of 19 LC, 14 of 20 CC, and none of 20 PLC cases (P<0.0001). Diarrhea ceased in 21 of the 26 patients, with a decrease in the daily stool number from 5.08±0.44 to 1.7±0.2 (P<0.005). The five patients with no response to therapy fulfilled the Rome II criteria of irritable bowel syndrome (IBS).CONCLUSIONS:The incidence rate of PLC, identified using objective histological criteria, was higher than those of CC and LC. The lack of expression of CD25+FOXP3+ cells in PLC, in contrast to those seen in both LC and CC, would suggest the existence of different pathophysiological mechanisms and does not support that PLC is a minor form of LC.

The prevalence of coeliac disease is significantly higher in children compared with adults.

Background  Some limited studies of coeliac disease have shown higher frequency of coeliac disease in infancy and adolescence than in adulthood. This finding has remained unnoticed and not adequately demonstrated.

Diagnostic value of duodenal antitissue transglutaminase antibodies in gluten-sensitive enteropathy

Background  In gluten‐sensitive enteropathy, antitissue transglutaminase antibodies are synthesized in the duodenum.

Fecal gluten peptides reveal limitations of serological tests and food questionnaires for monitoring gluten-free diet in celiac disease patients

Objectives:Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. However, none of these methods offer an accurate measure of dietary compliance. Our aim was to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of GFD adherence in CD patients and compare it with traditional methods of GFD monitoring.Methods:We performed a prospective, nonrandomized, multicenter study including 188 CD patients on GFD and 84 healthy controls. Subjects were given a dietary questionnaire and fecal GIP quantified by enzyme-linked immunosorbent assay (ELISA). Serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies were measured simultaneously.Results:Of the 188 celiac patients, 56 (29.8%) had detectable GIP levels in stools. There was significant association between age and GIP in stools that revealed increasing dietary transgressions with advancing age (39.2% in subjects ≥13 years old) and with gender in certain age groups (60% in men ≥13 years old). No association was found between fecal GIP and dietary questionnaire or anti-tTG antibodies. However, association was detected between GIP and anti-DGP antibodies, although 46 of the 53 GIP stool-positive patients were negative for anti-DGP.Conclusions:Detection of gluten peptides in stools reveals limitations of traditional methods for monitoring GFD in celiac patients. The GIP ELISA enables direct and quantitative assessment of gluten exposure early after ingestion and could aid in the diagnosis and clinical management of nonresponsive CD and refractory CD. Trial registration number NCT02711397.

Apoptosis resistance of mucosal lymphocytes and IL-10 deficiency in patients with steroid-refractory Crohn's disease.

Background: Apoptosis resistance of T‐cells is considered an abnormality of immune pathways in Crohns disease (CD). It has been previously shown that corticosteroids induce apoptosis of cells involved in inflammation. Thus, our aim was to assess the apoptosis of mononuclear cells and pro/antiinflammatory cytokines in the intestinal mucosa of patients with active CD, related to steroid response, and identify cellular and molecular factors that may predict this response to therapy. Methods: Patients with CD (n = 26), ulcerative colitis (UC) (n = 32), and controls (n = 10) were prospectively studied with mucosal biopsies before and 7‐10 days after corticosteroid treatment. Immunophenotype and apoptosis of T and B lymphocytes, plasma cells, and macrophages were assessed by flow cytometry, immunohistochemistry, and immunofluorescence. The cytokine expression pattern was evaluated by quantitative polymerase chain reaction (PCR). Results: Apoptosis resistance of T and B lymphocytes was observed only in steroid‐refractory and ‐dependent CD patients as compared to responsive patients (P = 0.032; P = 0.004, respectively), being evident after steroid treatment. Interleukin (IL)‐10 was markedly increased at baseline in steroid‐responsive patients compared to the nonresponders (P = 0.006; sensitivity: 88.8%; specificity: 66.6% to predict steroid response). Conclusions: Apoptosis resistance of mucosal T and B cells in steroid‐refractory and ‐dependent CD patients appears during the evolution of the acute phase, limiting its clinical application as a predictor marker. In contrast, increased expression of IL‐10 at an early stage of active steroid‐sensitive CD patients supports its usefulness at predicting a good steroid response. Steroid‐dependent and ‐refractory CD patients share similar molecular and cellular pathophysiological mechanisms. (Inflamm Bowel Dis 2010;)

Are positive serum-IgA-tissue-transglutaminase antibodies enough to diagnose coeliac disease without a small bowel biopsy? Post-test probability of coeliac disease

BACKGROUND It has been suggested that high titres of tTG are associated with elevated positive predictive values (PPV) for celiac disease. However, the PPV of a strongly positive tTG will depend on the celiac disease prevalence in the different risk groups of the disease AIMS To assess the PPV of a strongly positive tTG for celiac disease. In addition, to calculate the post-test probability for celiac disease of a strongly positive tTG in a setting of routine clinical practice. METHODS 145 consecutive celiac disease patients with positive tTG, and with a small bowel biopsy were included. The PPV for different cut-off points of tTG levels for the diagnosis of celiac disease was assessed. In addition, the cut-offs associated with higher PPV were used to calculate the positive likelihood ratio. A simulation in a setting of routine clinical practice was performed to calculate the post-test probability of celiac disease. RESULTS No cut-off level was associated with a PPV of 100%. A cut-off of 80 U/mL (11.4×upper normal limit) was associated with the higher PPV value of 98.6%. In the most frequent clinical situations, which in general have a pre-test probability <10%, the post-test probability after having a strongly positive tTG was 90% or less. CONCLUSIONS A strongly positive tTG should not be enough to diagnose celiac disease in the most frequent clinical situations, small bowel biopsy remaining as the gold standard in these cases.

Randomised clinical trial: colestyramine vs. hydroxypropyl cellulose in patients with functional chronic watery diarrhoea.

Idiopathic bile acid malabsorption (BAM) has been suggested as a cause of chronic watery diarrhoea, with a response to colestyramine in 70% of patients. However, the efficacy of this drug has never been investigated in placebo‐controlled trials.

Comparison of lymphocyte isolation methods for endoscopic biopsy specimens from the colonic mucosa

An ideal method of immune cell isolation should provide maximum cell yield without disturbing functional properties. Intestinal endoscopic biopsies, in contrast to surgical samples, allow the study of all disease stages but have the drawback of a minimum amount of tissue available, making protocol optimization mandatory. We compared for the first time two methods of separation of colonic epithelium and five methods of lamina propria cell isolation for colonic biopsy specimens (mechanical, enzymatic and organ culture protocols). Lymphocyte number, viability and phenotype (CD45+, CD103+, CD3+, CD4+, CD8+, CD19+, CD16-56+) were analyzed by flow cytometry. Neither of the two epithelial detachment protocols achieved proper epithelial separation, though the high intensity ion chelation method was more accurate. Maximum cell yield of lamina propria lymphocytes without phenotypic modification was obtained with overnight smooth enzymatic digestion. High dose collagenase incubation caused a marked decrease in CD4+ lymphocytes of the lamina propria as compared to low enzymatic method (p=0.004). Mechanical and biopsy culture are not advisable methods because of the low cell yield, and phenotypic alterations and high contamination rate, respectively.