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

BACKGROUND: 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. AIM: To evaluate the efficacy of colestyramine as compared with hydroxypropyl cellulose in the treatment of functional chronic watery diarrhoea. METHODS: Patients with chronic watery diarrhoea were randomly assigned to groups given colestyramine sachets 4 g twice daily (n = 13) or identical hydroxypropyl cellulose sachets (n = 13) for 8 weeks. The primary end-point was clinical remission defined as a mean of 3 or fewer stools per day during the week before the visit, with less than 1 watery stool per day. A secondary end-point was the reduction in daily watery stool number. SeHCAT test was performed in all patients, but an abnormal test was not a prerequisite to be included. RESULTS: All included patients had a SeHCAT 7-day retention ≤20%. There were no statistical differences in the percentage of patients in clinical remission at week 8 between colestyramine and hydroxypropyl cellulose with either intention-to-treat (53.8% vs. 38.4%; P = 0.43) or per-protocol (63.6% vs. 38.4%; P = 0.22) analyses. However, the mean per cent decrease in watery stool number was significantly higher with colestyramine than with hydroxypropyl cellulose (-92.4 ± 3.5% vs. -75.8 ± 7.1%; P = 0.048). The rate of adverse events related to study drugs did not differ between groups. CONCLUSIONS: Colestyramine (4 g twice daily) is effective and safe for short-term treatment of patients with chronic watery diarrhoea presumably secondary to BAM. Clinical Trials Register number EudraCT 2009-011149-14.

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. AIM: To assess whether there are age and gender differences in coeliac disease prevalence. METHODS: A total of 4230 subjects were included consecutively (1 to ≥80 years old) reproducing the reference population by age and gender. Sample size was calculated assuming a population-based coeliac disease prevalence of 1:250. After an interim analysis, the paediatric sample was expanded (2010 children) due to high prevalence in this group. Anti-transglutaminase and antiendomysial antibodies were determined and duodenal biopsy was performed if positive. Log-linear models were fitted to coeliac disease prevalence by age allowing calculation of percentage change of prevalence. Differences between groups were compared using Chi-squared test. RESULTS: Twenty-one subjects had coeliac disease (male/female 1:2.5). Coeliac disease prevalence in the total population was 1:204. Coeliac disease prevalence was higher in children (1:71) than in adults (1:357) (P = 0.00005). A significant decrease of prevalence in older generations was observed [change of prevalence by age of -5% (95% CI: -7.58 to -2.42%)]. In the paediatric expanded group (1-14 years), a decrease of coeliac disease prevalence was also observed [prevalence change: -17% (95% CI: -25.02 to -6.10)]. CONCLUSIONS: The prevalence of coeliac disease in childhood was five times higher than in adults. Whether this difference is due to environmental factors influencing infancy, or latency of coeliac disease in adulthood, remains to be demonstrated in prospective longitudinal studies.

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

BACKGROUND: In gluten-sensitive enteropathy, antitissue transglutaminase antibodies are synthesized in the duodenum. AIM: To compare the diagnostic yield of these autoantibodies in cultured duodenal biopsies, duodenal aspirate and serum. METHODS: Patients (n = 315, 135 female, 180 male; age: 37.3 +/- 1.1 years) referred for duodenal biopsies, were recruited and HLA-DQ2/DQ8 haplotyped. Histological measurements were made from duodenal biopsies and cultured duodenal biopsies were used for antitissue transglutaminase antibodies analysis by enzyme-linked immunosorbent assay. Duodenal aspirate was collected in a subgroup of 81 patients. Patients were classified, according to their histology, response to a gluten-free diet and DQ2/DQ8 status, as definite, likely or nongluten-sensitive enteropathy. RESULTS: Histology was normal in 59% of patients; 28% had lymphocytic enteritis, 1% had crypt hyperplasia and 13% showed atrophy. In Marsh III patients, there was complete agreement between duodenal and serological antitissue transglutaminase antibodies measurements. Marsh I patients showed a slight antitissue transglutaminase antibodies sensitivity improvement in cultured duodenal biopsy compared to serum in definite (22% vs. 19%) and likely gluten-sensitive enteropathy (20% vs. 14%) patients. Combined serum and cultured duodenal biopsy antitissue transglutaminase antibodies assessment increased serological sensitivity from 19% to 30% in Marsh I patients. CONCLUSION: Duodenal antitissue transglutaminase antibodies detection improves serological determination sensitivity in Marsh I patients, providing diagnostic value and therapeutic impact.

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.

[Screening for celiac disease in high risk groups]. / Cribado de la enfermedad celíaca en grupos de riesgo.

Several epidemiological studies show that celiac disease with extraintestinal manifestations is 15 times more frequent than celiac disease with intestinal symptoms. Fifteen years ago the iceberg model was proposed to explain the epidemiology of this disease. On the one hand, there are a quantifiable number of patients who are correctly diagnosed since they have symptoms suggestive of this disease and who form the visible part of the iceberg. However, several studies using screening serology demonstrate that for each patient diagnosed, there is a mean of 5-10 patients without a diagnosis. These patients form the submerged part of the iceberg (monosymptomatic or silent celiac disease). The most widely accepted strategy to investigate the submerged part of the "celiac iceberg" is screening of known risk groups through a systematic search for celiac disease in these groups.

Cribado de la enfermedad celíaca en grupos de riesgo / Screening for celiac disease in high risk groups

Diversos estudios epidemiológicos muestran que la enfermedad celíaca con manifestaciones extraintestinales es 15 veces más frecuente que la que se presenta con síntomas intestinales. Hace ya años que se propuso el «modelo del iceberg» para explicar la epidemiología de la enfermedad celíaca. Por un lado, hay un número cuantificable de pacientes que son correctamente diagnosticados porque presentan síntomas sugestivos y forman la parte visible del iceberg. Sin embargo, diversos estudios, que emplean técnicas de cribado mediante serología, demuestran que por cada paciente diagnosticado, hay una media de 5-10 casos que no lo estaban. Estos casos forman la parte sumergida del iceberg (enfermedad celíaca monosintomática o silenciosa). La estrategia más aceptada para investigar la porción sumergida del «iceberg celíaco» es el cribado de grupos de riesgo reconocidos, mediante un proceso de búsqueda sistemática de enfermedad celíaca

Several epidemiological studies show that celiac disease with extraintestinal manifestations is 15 times more frequent than celiac disease with intestinal symptoms. Fifteen years ago the iceberg model was proposed to explain the epidemiology of this disease. On the one hand, there are a quantifiable number of patients who are correctly diagnosed since they have symptoms suggestive of this disease and who form the visible part of the iceberg. However, several studies using screening serology demonstrate that for each patient diagnosed, there is a mean of 5-10 patients without a diagnosis. These patients form the submerged part of the iceberg (monosymptomatic or silent celiac disease). The most widely accepted strategy to investigate the submerged part of the "celiac iceberg" is screening of known risk groups through a systematic search for celiac disease in these groups

[Presinusoidal portal hypertension due to portal thrombosis in a patient with Alagille's syndrome]. / Hipertensión portal presinusoidal por trombosis portal en una paciente con síndrome de Alagille.

We present the case of a 16-year old woman with Alagille's syndrome, who had upper gastrointestinal bleeding due to rupture of esophageal varices secondary to presinusoidal portal hypertension without liver fibrosis. Portal thrombosis is a manifestation previously unreported in association to this syndrome.

Azathioprine without oral ciclosporin in the long-term maintenance of remission induced by intravenous ciclosporin in severe, steroid-refractory ulcerative colitis.

BACKGROUND: Intravenous ciclosporin is considered to be the only alternative to avoid surgery in severe, steroid-refractory ulcerative colitis. In responders, some authors recommend a switch to oral ciclosporin to act as a 'bridge' until the therapeutic action of azathioprine is achieved for maintenance treatment. AIM: To report the short- and long-term outcome of intravenous ciclosporin-responsive ulcerative colitis patients treated with oral azathioprine without oral ciclosporin. METHODS: The records of all patients treated with intravenous ciclosporin for severe, steroid-refractory ulcerative colitis were reviewed. Responders following treatment with azathioprine but without oral ciclosporin as maintenance therapy were included. Patients with colonic cytomegalovirus infection and/or follow-up of less than 1 year were excluded. RESULTS: Twenty-seven patients were included. Steroids were discontinued in 24 (89%). The median follow-up was 36 months. Eighteen (75%) patients presented mild or moderate relapses, which were easily managed with salicylates or steroids. Cumulative probabilities of relapse were 42%, 72% and 77% at 1, 3 and 5 years, respectively. Eleven (40.7%) patients underwent elective colectomy. Cumulative probabilities of colectomy were 29%, 35% and 42% at 1, 3 and 5 years, respectively. No opportunistic infections were observed. CONCLUSIONS: Oral azathioprine seems to be enough to maintain long-term remission induced by intravenous ciclosporin in patients with steroid-refractory ulcerative colitis. The 'bridging step' with oral ciclosporin may not be necessary in this subset of patients, although a randomized controlled trial is warranted to confirm this hypothesis.