The purpose of this clinical practice update is to define key modalities in the diagnosis and monitoring of celiac disease (CD) in adults as well as in children and adolescents.
The recommendations ...outlined in this expert review are based on available published evidence, including cohort and case-control studies of the diagnostic process as well as controlled and descriptive studies of disease management.
Best Practice Advice 1: Serology is a crucial component of the detection and diagnosis of CD, particularly tissue transglutaminase–immunoglobulin A (TG2-IgA), IgA testing, and less frequently, endomysial IgA testing.
Best Practice Advice 2: Thorough histological analysis of duodenal biopsies with Marsh classification, counting of lymphocytes per high-power field, and morphometry is important for diagnosis as well as for differential diagnosis.
Best Practice Advice 2a: TG2-IgA, at high levels (> ×10 upper normal limit) is a reliable and accurate test for diagnosing active CD. When such a strongly positive TG2-IgA is combined with a positive endomysial antibody in a second blood sample, the positive predictive value for CD is virtually 100%. In adults, esophagogastroduodenoscopy (EGD) and duodenal biopsies may then be performed for purposes of differential diagnosis.
Best Practice Advice 3: IgA deficiency is an infrequent but important explanation for why patients with CD may be negative on IgA isotype testing despite strong suspicion. Measuring total IgA levels, IgG deamidated gliadin antibody tests, and TG2-IgG testing in that circumstance is recommended.
Best Practice Advice 4: IgG isotype testing for TG2 antibody is not specific in the absence of IgA deficiency.
Best Practice Advice 5: In patients found to have CD first by intestinal biopsies, celiac-specific serology should be undertaken as a confirmatory test before initiation of a gluten-free diet (GFD).
Best Practice Advice 6: In patients in whom CD is strongly suspected in the face of negative biopsies, TG2-IgA should still be performed and, if positive, repeat biopsies might be considered either at that time or sometime in the future.
Best Practice Advice 7: Reduction or avoidance of gluten before diagnostic testing is discouraged, as it may reduce the sensitivity of both serology and biopsy testing.
Best Practice Advice 8: When patients have already started on a GFD before diagnosis, we suggest that the patient go back on a normal diet with 3 slices of wheat bread daily preferably for 1 to 3 months before repeat determination of TG2-IgA.
Best Practice Advice 9: Determination of HLA-DQ2/DQ8 has a limited role in the diagnosis of CD. Its value is largely related to its negative predictive value to rule out CD in patients who are seronegative in the face of histologic changes, in patients who did not have serologic confirmation at the time of diagnosis, and in those patients with a historic diagnosis of CD; especially as very young children before the introduction of celiac-specific serology.
Best Practice Advice 10: Celiac serology has a guarded role in the detection of continued intestinal injury, in particular as to sensitivity, as negative serology in a treated patient does not guarantee that the intestinal mucosa has healed. Persistently positive serology usually indicates ongoing intestinal damage and gluten exposure. Follow-up serology should be performed 6 and 12 months after diagnosis, and yearly thereafter.
Best Practice Advice 11: Patients with persistent or relapsing symptoms, without other obvious explanations for those symptoms, should undergo endoscopic biopsies to determine healing even in the presence of negative TG2-IgA.
Eosinophilic esophagitis (EoE) is a new disease. It is caused by a T-helper type 2 cell response to food antigens in contact with the esophageal mucosa. Although no single feature defines EoE, a ...constellation of compatible demographic, clinical, endoscopic, and histologic findings establish the diagnosis. Children present with symptoms and endoscopic patterns characteristic of inflammation, whereas adolescents and adults have manifestations of fibrosis and gross esophageal strictures. Clinical and endoscopic scoring systems have helped to standardize diagnosis. There is controversy in EoE research over the optimal endpoint for treatment. Although the most common endpoint is a reduced number of eosinophils in biopsies, changes in symptoms and endoscopic features are becoming important targets of therapy. We should improve our understanding of EoE progression and the need for maintenance therapy, and continue development of diagnostic tools that avoid endoscopy and biopsy analyses to more easily monitor disease activity.
The use of opioid medications on both an acute and chronic basis is ubiquitous in the United States. As opioid receptors densely populate the gastrointestinal tract, symptoms and side effects can be ...expected in these patients. In the esophagus, dysmotility may result, manifesting with dysphagia and a syndrome indistinguishable from primary achalasia. In the stomach, a marked delay in gastric emptying may occur with postprandial nausea and early satiety. Postoperatively, particularly with abdominal surgery, opioid-induced ileus may ensue. In the colon, opioid-induced constipation is common. A unique syndrome termed narcotic bowel syndrome is characterized by chronic abdominal pain often accompanied by nausea and vomiting in the absence of other identifiable causes. With the recognition of the important role of opioids on gastrointestinal function, novel drugs have been developed that use this physiology. These medications include peripheral acting opioid agonists to treat opioid-induced constipation and combination agonist and antagonists used for diarrhea-predominant irritable bowel syndrome. This review summarizes the most recent data in these areas.
Gastroesophageal reflux disease (GERD) is a multifaceted disorder encompassing a family of syndromes attributable to, or exacerbated by, gastroesophageal reflux that impart morbidity, mainly through ...troublesome symptoms. Major GERD phenotypes are non-erosive reflux disease, GERD hypersensitivity, low or high grade esophagitis, Barrett's esophagus, reflux chest pain, laryngopharyngeal reflux, and regurgitation dominant reflux. GERD is common throughout the world, and its epidemiology is linked to the Western lifestyle, obesity, and the demise of
Because of its prevalence and chronicity, GERD is a substantial economic burden measured in physician visits, diagnostics, cancer surveillance protocols, and therapeutics. An individual with typical symptoms has a fivefold risk of developing esophageal adenocarcinoma, but mortality from GERD is otherwise rare. The principles of management are to provide symptomatic relief and to minimize potential health risks through some combination of lifestyle modifications, diagnostic testing, pharmaceuticals (mainly to suppress or counteract gastric acid secretion), and surgery. However, it is usually a chronic recurring condition and management needs to be personalized to each case. While escalating proton pump inhibitor therapy may be pertinent to healing high grade esophagitis, its applicability to other GERD phenotypes wherein the modulating effects of anxiety, motility, hypersensitivity, and non-esophageal factors may dominate is highly questionable.
Esophageal eosinophilia and eosinophilic esophagitis (EoE) are increasingly recognized and prevalent conditions, which now represent common clinical problems encountered by gastroenterologists, ...pathologists, and allergists. The study of EoE has become a dynamic field with an evolving understanding of the pathogenesis, diagnosis, and treatment. Although there are limited data supporting management decisions, clinical parameters are needed to guide the care of patients with eosinophilic-esophageal disorders. In this evidence-based review, recommendations developed by adult and pediatric gastroenterologists are provided for the evaluation and management of these patients. New terminology is emphasized, particularly the concepts of esophageal eosinophilia and proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE) as entities distinct from EoE.
Background & Aims A proportion of patients with Barrett’s esophagus (BE) are diagnosed with esophageal adenocarcinoma (EAC) within 1 year of an endoscopic examination that produced negative findings. ...These cases of missed cancers have not been well studied, despite current surveillance strategies for BE. We performed a systematic review and meta-analysis to determine the magnitude of missed EAC in cohorts of patients with BE. Methods We searched MEDLINE, EMBASE, and Web of Science from their inception to May 31, 2015 to identify cohort studies of adults with BE (baseline nondysplastic BE ± BE with low-grade dysplasia) and at least a 3-year follow-up period, providing data on missed and incident EACs (diagnosed within 1 year and diagnosed more than 1 year after the initial endoscopy in which BE was diagnosed, respectively). The main outcome measure was pooled proportion of missed and incident EACs (of all EACs detected after initial endoscopy) among BE cohorts, using a random effects model. Results In a meta-analysis of 24 studies reporting on 820 missed and incident EACs, 25.3% were classified as missed (95% confidence interval: 16.4%–36.8%) and 74.7% as incident EACs (95% CI: 63.2%–83.6%), although there was substantial heterogeneity among studies (I2 = 74%). When the analysis was restricted to nondysplastic BE cohorts (15 studies), 23.9% of EACs were classified as missed (95% confidence interval: 15.3%–35.4%; I2 = 0%). In a meta-analysis of 10 studies with follow-up periods of ≥5 years (a total of 239 EACs), 22.0% were classified as missed (95% confidence interval: 8.7%–45.5%), with substantial heterogeneity (I2 = 68%). Conclusions Among adults with nondysplastic BE (or BE with low-grade dysplasia) at their index endoscopy and at least a 3-year follow-up period, 25% of EACs are diagnosed within 1 year after the index endoscopy. Additional resources should be allocated to detect missed EAC.