Advances in Celiac Disease, IBS, IBD, and EoE
Advances in Celiac Disease, IBS, IBD, and EoE
Author's Note:
Several important advances in the clinical practice of gastroenterology were addressed during this year's Digestive Disease Week (DDW). This review briefly summarizes the relevant concepts that emerged, and highlights the pace of progress in diagnosing and managing the commonly encountered issues of celiac disease, irritable bowel syndrome, inflammatory bowel disease, and eosinophilic esophagitis.
The standard methods used to diagnose celiac disease rely on serology and duodenal mucosal biopsy. Although current adult guidelines require histologic confirmation of celiac disease, recent pediatric guidelines from the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) have proposed algorithms to reduce the need for biopsy in genetically susceptible symptomatic children.
Efthymakis and colleagues explored the applicability of these somewhat controversial proposed criteria by assessing the accuracy of serology alone in detecting mucosal abnormalities consistent with celiac disease in a prospective cohort of symptomatic adult patients. They reported that anti-tissue transglutaminase (anti-tTG) titers correlated with the degree of villous atrophy. Of 199 adults with elevated anti-tTG titers, epithelial membrane antigen positivity, and genetic susceptibility, 10% showed no villous atrophy, 37% had partial villous atrophy, and 54% had total villous atrophy.
After applying the ESPGHAN criterion of anti-tTG > 10 times the upper limit of normal, the investigators found a sensitivity of 56%, a specificity of 84%, and a positive predictive value of 97%. They concluded that further studies are required to determine the validity of these criteria and optimal serologic cut-off levels.
Mooney and colleagues suggested that obtaining an additional duodenal bulb biopsy may increase the diagnostic yield for celiac disease. However, it is not clear whether patients with villous atrophy detected only in the duodenal bulb have the same phenotype and outcome as those with more diffuse disease. They now report that persons with celiac disease that is manifest only in the duodenal bulb appear to be a subgroup characterized by early-onset disease and lower anti-tTG titers. This may represent a milder form of celiac disease with lower rates of diarrhea and folate deficiency. Long-term follow-up of patients is required to fully characterize this phenotype and assess the long-term impact.
Yang and colleagues evaluated the cost-effectiveness of performing routine duodenal biopsy during esophagogastroduodenoscopy for diagnosing celiac disease in patients with seemingly unrelated gastrointestinal disorders, such as refractory gastroesophageal reflux disease. They concluded that routine duodenal biopsy performed during esophagogastroduodenoscopy to determine the etiology and severity of gastroesophageal reflux disease can detect the majority of cases of celiac disease. However, they emphasized that this strategy will only approach cost-effectiveness thresholds when the prevalence of celiac disease in this population is slightly greater (> 1.8%) than that of the general population.
The standard treatment for celiac disease is lifelong exclusion of gluten. However, this remains challenging because inadvertent gluten exposure is common. The US Food and Drug Administration (FDA) currently labels a food product as "gluten-free" if it has <20 parts per million (ppm) of gluten; does not contain wheat, rye, or barley; and does not contain an ingredient derived from these grains.
At present, the FDA does not regulate dietary supplements and herbal products, although up to 25% of patients with celiac disease report their use, most commonly probiotics. Patients ingesting supplements also reported more celiac disease-related symptoms than those who did not take supplements.
Nazareth and colleagues sought to determine whether gluten was present in 22 popular probiotic preparations, including those that were labeled gluten-free. They found that 55% of them contained gluten. Of these gluten-containing items, 67% were labeled gluten-free. Of the 15 probiotics that were labeled gluten-free, 53% contained gluten, including 13% that contained > 20 ppm. Of the probiotics that were not labeled gluten-free, 57% tested positive for gluten, including 29% that contained > 20 ppm. More than one gluten component (eg, wheat, rye, barley) was detectable in 18% of the probiotics.
Thus, the amount of gluten in probiotics may be significant, especially if one considers the cumulative number of capsules consumed. Because gluten-free labeling does not accurately reflect the gluten content of probiotics, patients with celiac disease should be advised of the potential contamination of probiotics with gluten regardless of labeling.
Nonceliac gluten sensitivity (NCGS), a syndrome characterized by the rapid onset of gastrointestinal symptoms after gluten ingestion, is thought to be present among patients with functional gastrointestinal diseases. However, uniform diagnostic criteria are lacking.
Elli and colleagues reported the results of a prospective, placebo-controlled, double-blind gluten challenge in a multicenter trial of patients reporting symptoms consistent with functional gastrointestinal disorders. Of the patients enrolled (90 of whom were female), 55 had irritable bowel syndrome, 36 had functional dyspepsia, and nine had unspecified functional nonspecific symptoms by Rome III criteria. Celiac disease had been excluded in all patients.
Patients reporting symptomatic improvement after 21 days on the gluten-free diet underwent a 7-day placebo-controlled gluten challenge, in which gluten was administered by capsules. A severe symptomatic relapse after the blind gluten ingestion was reported by 25% of patients; thus, they were classified as having NCGS.
Of note, 56% of enrolled patients who responded to the gluten-free diet did not show symptoms with the gluten double-blind challenge. This group deserves further study.
The authors suggested that a simple dietary challenge may help identify NCGS in patients with functional gastrointestinal disorders and thereby select those who are most likely to respond to a gluten-free diet.
Author's Note:
Several important advances in the clinical practice of gastroenterology were addressed during this year's Digestive Disease Week (DDW). This review briefly summarizes the relevant concepts that emerged, and highlights the pace of progress in diagnosing and managing the commonly encountered issues of celiac disease, irritable bowel syndrome, inflammatory bowel disease, and eosinophilic esophagitis.
Celiac Disease
Diagnosis Using Serology Alone
The standard methods used to diagnose celiac disease rely on serology and duodenal mucosal biopsy. Although current adult guidelines require histologic confirmation of celiac disease, recent pediatric guidelines from the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) have proposed algorithms to reduce the need for biopsy in genetically susceptible symptomatic children.
Efthymakis and colleagues explored the applicability of these somewhat controversial proposed criteria by assessing the accuracy of serology alone in detecting mucosal abnormalities consistent with celiac disease in a prospective cohort of symptomatic adult patients. They reported that anti-tissue transglutaminase (anti-tTG) titers correlated with the degree of villous atrophy. Of 199 adults with elevated anti-tTG titers, epithelial membrane antigen positivity, and genetic susceptibility, 10% showed no villous atrophy, 37% had partial villous atrophy, and 54% had total villous atrophy.
After applying the ESPGHAN criterion of anti-tTG > 10 times the upper limit of normal, the investigators found a sensitivity of 56%, a specificity of 84%, and a positive predictive value of 97%. They concluded that further studies are required to determine the validity of these criteria and optimal serologic cut-off levels.
Celiac Disease Isolated to the Duodenal Bulb
Mooney and colleagues suggested that obtaining an additional duodenal bulb biopsy may increase the diagnostic yield for celiac disease. However, it is not clear whether patients with villous atrophy detected only in the duodenal bulb have the same phenotype and outcome as those with more diffuse disease. They now report that persons with celiac disease that is manifest only in the duodenal bulb appear to be a subgroup characterized by early-onset disease and lower anti-tTG titers. This may represent a milder form of celiac disease with lower rates of diarrhea and folate deficiency. Long-term follow-up of patients is required to fully characterize this phenotype and assess the long-term impact.
Early Diagnosis
Yang and colleagues evaluated the cost-effectiveness of performing routine duodenal biopsy during esophagogastroduodenoscopy for diagnosing celiac disease in patients with seemingly unrelated gastrointestinal disorders, such as refractory gastroesophageal reflux disease. They concluded that routine duodenal biopsy performed during esophagogastroduodenoscopy to determine the etiology and severity of gastroesophageal reflux disease can detect the majority of cases of celiac disease. However, they emphasized that this strategy will only approach cost-effectiveness thresholds when the prevalence of celiac disease in this population is slightly greater (> 1.8%) than that of the general population.
Gluten-Free Products
The standard treatment for celiac disease is lifelong exclusion of gluten. However, this remains challenging because inadvertent gluten exposure is common. The US Food and Drug Administration (FDA) currently labels a food product as "gluten-free" if it has <20 parts per million (ppm) of gluten; does not contain wheat, rye, or barley; and does not contain an ingredient derived from these grains.
At present, the FDA does not regulate dietary supplements and herbal products, although up to 25% of patients with celiac disease report their use, most commonly probiotics. Patients ingesting supplements also reported more celiac disease-related symptoms than those who did not take supplements.
Nazareth and colleagues sought to determine whether gluten was present in 22 popular probiotic preparations, including those that were labeled gluten-free. They found that 55% of them contained gluten. Of these gluten-containing items, 67% were labeled gluten-free. Of the 15 probiotics that were labeled gluten-free, 53% contained gluten, including 13% that contained > 20 ppm. Of the probiotics that were not labeled gluten-free, 57% tested positive for gluten, including 29% that contained > 20 ppm. More than one gluten component (eg, wheat, rye, barley) was detectable in 18% of the probiotics.
Thus, the amount of gluten in probiotics may be significant, especially if one considers the cumulative number of capsules consumed. Because gluten-free labeling does not accurately reflect the gluten content of probiotics, patients with celiac disease should be advised of the potential contamination of probiotics with gluten regardless of labeling.
Nonceliac Gluten Sensitivity
Nonceliac gluten sensitivity (NCGS), a syndrome characterized by the rapid onset of gastrointestinal symptoms after gluten ingestion, is thought to be present among patients with functional gastrointestinal diseases. However, uniform diagnostic criteria are lacking.
Elli and colleagues reported the results of a prospective, placebo-controlled, double-blind gluten challenge in a multicenter trial of patients reporting symptoms consistent with functional gastrointestinal disorders. Of the patients enrolled (90 of whom were female), 55 had irritable bowel syndrome, 36 had functional dyspepsia, and nine had unspecified functional nonspecific symptoms by Rome III criteria. Celiac disease had been excluded in all patients.
Patients reporting symptomatic improvement after 21 days on the gluten-free diet underwent a 7-day placebo-controlled gluten challenge, in which gluten was administered by capsules. A severe symptomatic relapse after the blind gluten ingestion was reported by 25% of patients; thus, they were classified as having NCGS.
Of note, 56% of enrolled patients who responded to the gluten-free diet did not show symptoms with the gluten double-blind challenge. This group deserves further study.
The authors suggested that a simple dietary challenge may help identify NCGS in patients with functional gastrointestinal disorders and thereby select those who are most likely to respond to a gluten-free diet.
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