Coeliac disease is a genetically-determined chronic inflammatory intestinal disease induced by an environmental precipitant, gluten. Patients with the disease might have mainly non-gastrointestinal symptoms, and as a result patients present to various medical practitioners. Epidemiological studies have shown that coeliac disease is very common and affects about one in 250 people. The disease is associated with an increased rate of osteoporosis, infertility, autoimmune diseases, and malignant disease, especially lymphomas. The mechanism of the intestinal immune-mediated response is not completely clear, but involves an HLA-DQ2 or HLA-DQ8 restricted T-cell immune reaction in the lamina propria as well as an immune reaction in the intestinal epithelium. An important component of the disease is the intraepithelial lymphocyte that might become clonally expanded in refractory sprue and enteropathy-associated T-cell lymphoma. Study of the mechanism of the immune response in coeliac disease could provide insight into the mechanism of inflammatory and autoimmune responses and lead to innovations in treatment.
Background Celiac disease (CD) is associated with an increased risk of lymphoproliferative malignancy (LPM). It is unknown whether this risk is affected by the results of the follow-up intestinal biopsy, performed to document mucosal healing. Objective To examine the association between mucosal healing in CD and later LPM. Design Population-based cohort study Setting We identified patients with CD from all of Sweden’s 28 pathology departments. Patients Individuals with CD who had a follow-up biopsy after initial diagnosis. Measurements We compared the risk of LPM to that of the general population using expected rates; and through Cox regression we compared the rate of LPM in those with persistent villous atrophy to those with mucosal healing. Results Among 7,625 patients with CD and a follow-up biopsy, persistent villous atrophy was present in 3,308 (43%). The overall risk of LPM was increased compared to the general population (Standardized incidence ratio, SIR 2.81; 95%CI 2.10–3.67), but this increase was greater among those with persistent villous atrophy (SIR 3.78; 95%CI 2.71–5.12) as compared to those with mucosal healing (SIR 1.50; 95%CI 0.77–2.62). Persistent villous atrophy compared to mucosal healing was associated with an increased risk of LPM (Hazard ratio, HR 2.26; 95%CI 1.18–4.34). We found an increased risk of T cell lymphoma (HR 3.51; 95%CI 0.75–16.34), but no excess risk of B cell lymphoma (HR 0.97; 95%CI 0.21–4.49). Limitation We had no data on dietary compliance. Conclusions The increased LPM risk in CD is associated with the results of the follow-up biopsy, with a higher risk among those with persistent villous atrophy. Follow-up biopsy may be a means to effectively stratify CD patients regarding subsequent LPM risk. Primary funding source the National Center for Advancing Translational Sciences, National Institutes of Health, The American Scandinavian Foundation, the Celiac Sprue Association, Örebro University Hospital, Karolinska Institutet, the Swedish Society of Medicine, the Swedish Research Council, and the Swedish Celiac Society.
BACKGROUND AND OBJECTIVES Celiac disease (CD), characterized by the presence of villous atrophy (VA) in the small intestine, is associated with increased mortality, but it is unknown if this excess mortality is influenced by mucosal recovery. We examined overall mortality according to mucosal recovery in CD. METHODS Through biopsy reports from all pathology departments (n=28) in Sweden we identified 7,648 individuals with CD (defined as VA) who had undergone a follow-up biopsy within 5 years following diagnosis. We then used Cox regression to examine overall mortality according mucosal recovery in the follow-up biopsy (persistence of VA vs. recovery). RESULTS The mean age of CD diagnosis was 28.4, 63% were female, and the median follow-up after diagnosis was 11.5 years. Of the 7,648 patients, persistent VA was present in 3,317 (43%). There were 606 (8%) deaths. Patients with persistent VA were not at increased risk of death compared to those with mucosal healing (Hazard Ratio 1.01; 95% Confidence Interval 0.86-1.19). Mortality was not increased in children with persistent VA (HR 1.09 95% CI 0.37-3.16) or adults (HR 1.00 95% CI 0.85-1.18), including adults older than age 50 years (HR 0.96 95% CI 0.80-1.14). CONCLUSION Persistent VA was not associated with increased mortality in CD in this population followed for a median of 11.5 years. While a follow-up biopsy will determine if there is improvement in histology and allow detection of refractory disease in symptomatic patients, our study suggests that early routine follow up biopsies performed within 5 years does not predict long-term mortality risk.
Background Villous atrophy (VA) with intraepithelial lymphocytosis is the histologic hallmark of coeliac disease (CD) but reported rates of mucosal recovery are variable. Aim To determine the impact of age and other demographic variables on the probability of persistent VA on follow-up biopsy. Methods We identified patients with VA on duodenal histology at all 28 Swedish pathology departments during the years spanning 1969–2008. We examined age, gender, calendar period, duration of disease, and educational attainment, to determine predictors of persistent VA. Results Of 7,648 patients with CD who underwent follow-up biopsy, persistent VA was present in 3,317 (43%; 95% CI 42%–44%). The effect of age on persistent VA varied according to time period; among those biopsied in the years spanning 2000–2008, the prevalence of persistent VA was 31%, and increasing age was associated with increasing rates of persistent VA (17% among those younger than 2 years compared to 56% among those ≥70 years). In contrast, persistent VA did not vary widely by age in earlier years. On multivariate analysis (restricted to the calendar period 2000–2008, 2–5 years after CD diagnosis), persistent VA was more common among males (OR 1.43; 95%CI 1.07–1.90) and less common among patients with higher educational attainment (OR for college degree versus <2 years of high school 0.52, 95%CI 0.35–0.78). Conclusions The prevalence of persistent VA has changed over time, with greater rates of healing in recent years. Social differences in persistent VA suggests that access and/or education regarding the gluten-free diet impacts mucosal healing.
Background Lymphocytic gastritis (LG) is an uncommon entity with varying symptoms and endoscopic appearances. This condition, as well as two forms of H. pylori-negative gastritis (chronic active gastritis [CAG] and chronic inactive gastritis [CIG]), appears to be more common in patients with coeliac disease (CD) based on single-center studies. Aim To compare the prevalence of LG, CAG, and CIG among those with normal duodenal histology (or non-specific duodenitis) and those with CD, as defined by villous atrophy (Marsh 3). Methods We analyzed all concurrent gastric and duodenal biopsy specimens submitted to a national pathology laboratory during a six-year period. We performed multiple logistic regression to identify independent predictors of each gastritis subtype. Results Among patients who underwent concurrent gastric and duodenal biopsy (n=287,503), the mean age was 52 and the majority (67%) was female. Compared to patients with normal duodenal histology, LG was more common inpartial villous atrophy (OR 37.66; 95% CI 30.16–47.03), and subtotal/total villous atrophy (OR 78.57; 95% CI 65.37–94.44). CD was also more common in CAG (OR for partial villous atrophy 1.93; 95%CI 1.49–2.51, OR for subtotal/total villous atrophy 2.42; 95%CI 1.90–3.09) and was similarly associated with CIG (OR for partial villous atrophy 2.04; 95%CI 1.76–2.35, OR for subtotal/total villous atrophy 2.96; 95% CI 2.60–3.38). Conclusion LG is strongly associated with CD, with increasing prevalence correlating with more advanced villous atrophy. CAG and CIG are also significantly associated with CD. Future researchshould measure the natural history of these conditions after treatment with a gluten-free diet.
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