Jorge C. Espinós

Incidence of collagenous and lymphocytic colitis: a 5-year population-based study.

Objective:The incidence of collagenous and lymphocytic colitis is not well known. We sought to assess the incidence of collagenous and lymphocytic colitis in a well-defined population during a 5-yr study period.Methods:From January 1, 1993, to December 31, 1997, all new patients diagnosed with collagenous or lymphocytic colitis living in the catchment area of the Hospital Mútua de Terrassa (Barcelona, Spain) were identified. Since 1993 all patients with chronic diarrhea were referred for a diagnostic colonoscopy. Multiple biopsy sampling of the entire colon was performed when appearance of the colonic mucosa was grossly normal.Results:Twenty-three cases of collagenous colitis and 37 of lymphocytic colitis were diagnosed. The female:male ratios were 4.75:1 and 2.7:1 for collagenous and lymphocytic colitis, respectively. The mean age at onset of symptoms was 53.4 ± 3.2 (range, 29–82) yr for collagenous colitis, and 64.3 ± 2.7 (range, 28–87) yr for lymphocytic colitis (p= 0.012). The mean annual incidence per 100,000 inhabitants based on the year of onset of symptoms was 1.1 (95% confidence interval [CI], 0.4–1.7) for collagenous colitis, and 3.1 (95% CI, 2.0–4.2) for lymphocytic colitis. A peak incidence was observed in older women in both diseases. A rate of microscopic colitis of 9.5 per 100 normal-looking colonoscopies performed in patients with chronic watery diarrhea was observed. Normal rectal biopsies were found in 43% and 8% of patients with collagenous and lymphocytic colitis, respectively.Conclusions:The incidence of lymphocytic colitis is three times higher than that of collagenous colitis. Microscopic colitis should be considered as a major possibility in the work-up of chronic diarrhea in older women.

Drug consumption and the risk of microscopic colitis.

BACKGROUND:Microscopic colitis is a rare disease of unknown etiology. It has been described that some drugs could cause or worsen the disease; however, the scientific evidence is limited.AIM:To investigate the possible association of chronic drug consumption with microscopic colitis.METHODS:This was a case–control study in which groups of cases were Group 1–39 patients with collagenous colitis; Group 2–39 patients with lymphocytic colitis; and Group 3–52 patients with chronic watery diarrhea of functional characteristics. 103 subjects formed the control group. At diagnosis, a drug consumption history of at least 2-wk duration was registered. An age- and sex-adjusted logistic regression analysis was used, and the odds ratio (OR, 95% CI) was calculated.RESULTS:Drug consumption was more frequent in lymphocytic colitis than in the control group (92.3% vs 76.3%, P < 0.05). The mean daily number of drugs by person was also higher in lymphocytic colitis (3.79 ± 0.44 vs 2.13 ± 0.22, P = 0.04). The following associations as compared with the control group were observed: Group 1—Consumption of NSAIDs (46.2% vs 23%, OR 2.9, 1.3–6.4), selective serotonin reuptake inhibitors (SSRIs) (18% vs 1%, OR 21, 2.5–177), specifically, sertraline (15.4% vs 0%, P < 0.0005); Group 2—SSRIs (28% vs 1%, OR 37.7, 4.7–304), beta-blockers (13 vs 3%, OR 4.79, 1.04–20), statins (13% vs 3%, OR 4.6, 1.04–20), biphosphonates (8% vs 0%, P = 0.022); Group 3—SSRIs (15% vs 1%, OR 16.2, 2–135), statins (11.5% vs 3%, OR 5.4, 1.2–24). As compared with the chronic diarrhea group, a significant association with the usage of sertraline in LC (P = 0.005) and a trend for NSAIDs in CC (P = 0.057) were found.CONCLUSIONSDrug consumption increases the risk of microscopic colitis. Some drugs might be trigger factors of colonic inflammation in predisposed hosts, and others might only worsen self-evolving microscopic colitis.

Collagenous and Lymphocytic Colitis: Evaluation of Clinical and Histological Features, Response to Treatment, and Long-Term Follow-Up

OBJECTIVE:Data on collagenous colitis (CC) and lymphocytic colitis (LC) have been based on retrospective studies of registries of patients from multiple hospitals. Such studies may induce a selection of patients with severe forms of the disease, and conclusions about the clinical spectrum of the disease and treatment efficacy are difficult to be drawn. The aim of this study was to compare the clinical features, response to treatment, and long-term follow-up of CC and LC in a large group of patients prospectively diagnosed in a single center.METHODS:A specific program was undertaken to prospectively diagnose all patients with microscopic colitis from those referred for a full colonoscopy because of recurrent or chronic diarrhea. Detailed clinical and histological features, response to treatment, and long-term follow-up were compared in patients with confirmed CC and LC.RESULTS:Thirty-seven patients with CC and 44 with LC were included. Patients with CC were significantly younger and had a significantly longer duration of diarrhea before diagnosis than those with LC. Otherwise, clinical presentation was similar. Drug-induced disease was suspected for ticlopidine, flutamide, gold salts, and bentazepam in LC. Complete resolution of diarrhea was achieved in all patients, spontaneously occurring in nearly 20% of them. Response to salicylates (mainly, mesalazine) was significantly better in LC than in CC (86% vs 42%, p = 0.005). Cholestyramine was highly effective in patients of both groups with concomitant bile acid malabsorption. Patients with CC required prednisone more often than those with LC (30% vs 4.5%, p = 0.005). Both prednisone and budesonide controlled ileal release were highly effective in patients with CC (82% and 89% efficacy). After cessation of diarrhea, 25% of patients with LC and 30% of those with CC relapsed after a mean follow-up of around 3 yr.CONCLUSIONS:CC and LC share a similar clinical picture and have a benign course with long-term cessation of diarrhea in more than 70% of patients. Mesalazine and budesonide seem to be good options as first-line treatment in LC and CC, respectively. Cholestyramine may be a good alternative in patients with concomitant bile acid malabsorption.

Gastric Cancer Susceptibility Is Not Linked to Pro- and Anti-Inflammatory Cytokine Gene Polymorphisms in Whites: A Nationwide Multicenter Study in Spain

BACKGROUND AND AIMS:Recent studies have reported an association between cytokine gene polymorphisms and GC risk. However, results are inconsistent among studies from different geographic regions and ethnic groups. Our goal was to evaluate the influence of Helicobacter pylori (H. pylori) infection and host genetic factors on GC susceptibility in a population of Spanish white GC patients.METHODS: DNA from 404 unrelated patients with GC and 404 sex- and age-matched healthy controls was typed for several functional polymorphisms in pro- (IL-1B, TNFA, LTA, IL-12p40) and anti-inflammatory (IL-4, IL-1RN, IL-10, TGFB1) genes by PCR, RFLP, and TaqMan assays. H. pylori infection and CagA/VacA antibody status were also determined by western blot serology.RESULTS: Logistic regression analysis identified H. pylori infection with cagA strains (OR 2.54, 95% CI 1.77–3.66), smoking habit (OR 1.91, 95% CI 1.25–2.93), and positive family history of GC (OR 3.67, 95% CI 2.01–6.71) as independent risk factors for GC. None of the cytokine gene polymorphisms analyzed in this study were associated with susceptibility to GC development, whether GC patients were analyzed as a group or categorized according to anatomic location or histological subtype. Some simultaneous combinations of proinflammatory genotypes reportedly associated with greater GC risk yielded no significant differences between patients and controls.CONCLUSIONS: Our results show that, at least in some white populations, the contribution of the cytokine gene polymorphisms evaluated in this study (IL-1B, IL-1RN, IL-12p40, LTA, IL-10, IL-4, and TGF-B1) to GC susceptibility may be less relevant than previously reported.

Bile acid malabsorption in microscopic colitis and in previously unexplained functional chronic diarrhea.

Bile acid malabsorption (BAM) has been described in patients with collagenous colitis. There are no similar studies in lymphocytic colitis. The possibility that BAM might not necessarily be part of the microscopic colitis process and that both entities could simply be concomitant has not been evaluated. Our aim was to assess the frequency and severity of BAM in patients with microscopic colitis as well as in patients with previously unexplained functional chronic diarrhea. Likewise, we wanted to investigate the effect of cholestyramine on the induction and maintenance of remission of these conditions. A [75Se]HCAT abdominal retention test was performed in 26 patients with collagenous colitis, 25 with lymphocytic colitis, and 32 with previously unexplained functional chronic diarrhea. Patients with microscopic colitis who had BAM as well as a subgroup of eight collagenous colitis patients without BAM received treatment with cholestyramine. All patients with previously unexplained chronic diarrhea who had BAM were treated with cholestyramine. Twenty-two (43.1%) patients with microscopic colitis and 24 (75%) patients with previously unexplained functional chronic diarrhea presented with BAM. The frequency of BAM was higher in lymphocytic colitis than in collagenous colitis (60% vs 27%; P = 0.025). Cholestyramine induced clinical remission in 19 of 22 patients with microscopic colitis and BAM, none of eight patients with collagenous colitis without BAM, and all patients with previously unexplained chronic diarrhea and BAM. In conclusion, BAM seems to be common in patients with microscopic colitis—mainly in lymphocytic colitis—and in those with previously unexplained functional chronic diarrhea, suggesting that idiopathic BAM and microscopic colitis are often concomitant conditions. In this setting, cholestyramine seems to be highly effective in stopping diarrhea.

Systematic Evaluation of the Causes of Chronic Watery Diarrhea With Functional Characteristics

BACKGROUND AND  AIMS:Causes of chronic watery diarrhea are multiple. There is not definite scientific evidence about which are the recommended explorations to be performed in the diagnostic workup of patients with functional diarrhea. The aim was to assess prospectively the presence of gluten-sensitive enteropathy, bile acid malabsorption, and sugar malabsorption in consecutive patients with chronic watery diarrhea of obscure origin fulfilling Rome II criteria of functional disease.METHODS:A total of 62 patients with chronic watery diarrhea, defined as more than 3 loose or liquid bowel movements a day for at least 4 wk and a stool weight >200 g/day were included. The following tests were performed: (a) HLA-DQ2/DQ8 genotyping, and if positive, endoscopic biopsies from distal duodenum were obtained, and intestinal damage assessed; (b) SeHCAT (Se-homotaurocholate) abdominal retention test; (c) small bowel follow-through; and (d) hydrogen breath test (lactose, fructose + sorbitol). Gluten- or sugar-free diet, or cholestyramine was administered according to results. Functional disease was diagnosed if all tests performed were normal or if either there was no response to specific therapy or diarrhea relapsed during a 12-month follow-up.RESULTS:Bile acid malabsorption was considered to be the cause of diarrhea in 28 (45.2%) patients, sugar malabsorption in 10 (16.1%), gluten-sensitive enteropathy in 10 (16.1%), and both bile acid and sugar malabsorption in 2 patients. Twelve (19.4%) patients remained without a specific diagnosis and were considered as functional bowel disease. Diarrhea stopped in the 50 patients after specific treatment, decreasing the daily stool number from 5.4 ± 0.3 to 1.5 ± 0.1 (P < 0.0005), without relapse after the 12-months follow-up.CONCLUSIONS:The diagnosis of functional disease in patients with chronic watery diarrhea should be performed with caution since in most cases there is an organic cause that justifies diarrhea.

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.

Accuracy of an enzyme immunoassay for the detection of Helicobacter pylori in stool specimens in the diagnosis of infection and posttreatment check-up

OBJECTIVE:The aim of this study was to assess the reliability of a newly developed enzyme immunoassay for Helicobacter pylori-specific antigen detection in stools (HpSA) compared to other standardized diagnostic techniques such as histology (H), rapid urease test (RUT) and 13C-urea breath test (UBT) to diagnose H. pylori infection and to evaluate its usefulness in determining H. pylori status after treatment.METHODS:One hundred eighty-eight patients referred to our department for upper gastrointestinal endoscopy were included. H. pylori infection was confirmed in all patients by HpSA test in stools, RUT, UBT, and H. Patients were defined as positive for H. pylori if RUT and UBT or H were positive. A total of 142 symptomatic patients received eradication treatment and were reassessed 6 wk after therapy; for 70 of these patients, stool samples were also collected at 24 h and 6 months after finishing eradication treatment. In the posttreatment follow-up, UBT was used as gold standard.RESULTS:The sensitivity of HpSA test for the diagnosis of H. pylori infection using a cut-off value of 0.130 was 89.5% and its specificity 77.8%. This specificity was lower than that obtained with UBT, H, and RUT. In the early follow-up the sensitivity of HpSA test was null. At 6 weeks and at 6 months post-treatment its sensitivity was 70.4% and 50% and its specificity was 81.6% and 79.3%, respectively.CONCLUSIONS:The HpSA stool test, using a cut-off value of 0.130, may be useful for the primary diagnosis of H. pylori infection, with sensitivity similar to that obtained with other standard tests, but with less specificity. HpSA test is not useful for early monitoring of treatment efficacy. At 6 wk and at 6 months posttreatment, HpSA test lacks accuracy as compared to UBT for evaluating the outcome of the eradication treatment.

Predisposing HLA-DQ2 and HLA-DQ8 haplotypes of coeliac disease and associated enteropathy in microscopic colitis.

Objective To assess the presence of both genetic and serological markers of coeliac disease in patients with microscopic colitis, and whether there was associated enteropathy. Methods HLA-DQ2, HLA-DQ8, serum immunoglobulin A-antiendomysial and immunoglobulin A-anti-tissue transglutaminase antibodies were investigated in 59 patients with microscopic colitis. Seventy healthy subjects acted as the control group. Endoscopic biopsies from the distal duodenum were obtained in DQ2-positive or DQ8-positive patients. Patients with histological changes compatible with gluten-sensitive enteropathy were started on a gluten-free diet. Results Seventeen of 70 (24.3%) healthy controls were DQ2-positive. Twelve of 25 (48%) patients with lymphocytic colitis (P=0.027 versus controls), and 11 of 34 (32.3%) with collagenous colitis (P=0.38 versus controls) were DQ2-positive. There were no differences in the frequency of DQ8-positivity. The coeliac serology was positive in one patient. Duodenal biopsies were performed in 23 DQ2-positive and/or DQ8-positive patients. None had villous atrophy (Marsh III lesion) (0%; 95% confidence interval, 0–6.1). A Marsh type I lesion was found in four patients. Three of these patients were put on a gluten-free diet with disappearance of diarrhoea. Conclusions The results suggest that there is an association of lymphocytic colitis with HLA-DQ2 genes, which might be relevant in the pathogenesis of this disease. The association of microscopic colitis with Marsh type III coeliac disease seems to be rare, making it unnecessary to routinely screen for coeliac disease in microscopic colitis patients.

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;)