celiac disease

Chronic diarrhea is defined as loose or watery stools lasting longer than 4 weeks and affects approximately 6% to 7% of adults in the US. More than 90% of patients with chronic diarrhea have a noninfectious etiology.

Observations The most common causes of chronic, noninfectious diarrhea are irritable bowel syndrome with diarrhea (IBS-D) and functional diarrhea. IBS-D typically presents with recurrent abdominal pain relieved or worsened after defecation. Functional diarrhea is a condition in which more than 25% of bowel movements in the preceding 3 months are loose or watery, but it is not associated with significant abdominal pain. Chronic diarrhea due to a small-bowel source, such as celiac disease or small intestinal bacterial overgrowth, is typically associated with large-volume diarrhea and weight loss, with or without steatorrhea. Celiac disease is an autoimmune condition defined by enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals, and small intestinal bacterial overgrowth is characterized by excessive bacteria in the small bowel. Chronic diarrhea due to colon pathology, such as bile acid diarrhea and microscopic colitis, typically presents with frequent, low-volume stools, with or without urgency and excess mucus. Bile acid diarrhea is characterized by excess bile acids in the colon, and microscopic colitis is characterized by chronic inflammation on colon biopsies despite normal endoscopic appearance. Evaluation of chronic diarrhea includes serological testing for celiac disease (tissue transglutaminase immunoglobulin A, along with total immunoglobulin A) and stool testing for fecal calprotectin to evaluate for inflammatory bowel disease. Patients with gastrointestinal bleeding, unexplained weight loss, 45 years or older, nocturnal diarrhea, steatorrhea, and/or iron deficiency anemia should undergo colonoscopy to evaluate for colorectal cancer as well as upper endoscopy. During colonoscopy, random biopsies are recommended to evaluate for microscopic colitis, which affects 13% of patients with chronic diarrhea. If evaluation does not identify a cause of chronic diarrhea, likely diagnoses are IBS-D or functional diarrhea and the patient should be treated with lifestyle modification, such as regularly scheduled meals, exercise, intake of at least 8 cups of noncaffeinated fluids daily, limiting caffeine to 3 cups or fewer daily, and avoiding alcohol and carbonated beverages. For general treatment of chronic diarrhea, dietary modifications, such as consuming a diet low in fermentable oligosaccharides (legumes, wheat, onions, garlic), disaccharides (lactose), and monosaccharides (fructose), and polyols (sorbitol, mannitol), or medications, such as opiate agonists (loperamide), anticholinergics (hyoscyamine, dicyclomine), or 5-hydroxytryptamine 3 receptor (5-HT3) antagonists (ondansetron), can be prescribed. These therapies typically improve diarrhea in 50% to 80% of patients.

Conclusions and Relevance The most common causes of chronic, noninfectious diarrhea include IBS-D and functional diarrhea. Diagnostic testing should include consideration of celiac disease, inflammatory bowel disease, and microscopic colitis. Empiric therapies for chronic diarrhea include lifestyle and dietary modifications and medications, including opiate agonists, anticholinergics, and 5-HT3 antagonists.

Celiac disease is frequently undiagnosed, in part because of its highly variable clinical presentation.

Celiac disease can present with classic gastrointestinal symptoms (e.g., diarrhea, abdominal pain, bloating, weight loss), atypical or extraintestinal manifestations (e.g., anemia, osteoporosis, neurologic symptoms, infertility, fatigue) or asymptomatic presentations detected from screening.

The first-line serologic screening test measures tissue transglutaminase immunoglobulin A and should be conducted while the patient is consuming gluten.

Complications of celiac disease include nutritional deficiencies, osteoporosis, increased risk of viral infections and pneumonia, and, rarely, risk of malignancy.

Adherence to a lifelong, strict gluten-free diet with regular monitoring of disease activity and nutritional status is key for symptom management and to prevent complications.

Guideline title American College of Gastroenterology Guidelines Update: Diagnosis and Management of Celiac Disease

Release date January 2023

Prior version May 2013

Developer and funding source American College of Gastroenterology

Target population Children and adults with celiac disease

Selected recommendations

Screening for celiac disease in asymptomatic people in the general population is not recommended (strong recommendation; low quality of evidence).

Upper endoscopy with multiple (≥4) duodenal biopsies is recommended for diagnostic confirmation in both children and adults who have characteristic signs and symptoms of celiac disease (strong recommendation; moderate quality of evidence).

In symptomatic children, a blood test with high-level tissue transglutaminase antibody (tTG) IgA (>10 times the upper limit of normal) and presence of endomysial antibody (EMA) in a second blood sample are suggested for diagnosis of celiac disease. In symptomatic adults who are unwilling or unable to undergo upper endoscopy, high-level tTG IgA and presence of EMA can be used to establish a diagnosis of likely celiac disease (conditional recommendation; moderate quality of evidence).

A gluten-free diet is required (strong recommendation; moderate quality of evidence) to achieve the treatment goal of resolution of histologic mucosal lesions in adults (conditional recommendation; low quality of evidence).

Objective
To investigate why certain at-risk individuals develop celiac disease, we examined the association of proton pump inhibitors (PPI), histamine-2 receptor antagonist (H2RA), and antibiotic prescriptions in the first six months of life with an early childhood diagnosis of celiac disease.
Study design
A retrospective cohort study was performed using the Military Healthcare System (MHS) database. Children with a birth record from October 1, 2001- September 30, 2013, were identified. Outpatient prescription records were queried for antibiotic, PPI, and H2RA prescriptions in the first 6 months of life. Cox proportional hazards regression was used to calculate the hazard ratio (HR) of developing CD based on medication exposure. ICD-9 codes identified children with an outpatient visit for celiac disease.
Results
968,524 children met inclusion criteria with 1,704 cases of celiac in this group. Median follow up for the cohort was about 4.5 years. PPI’s (HR, 2.23; 95% CI, 1.76-2.83), H2RA’s (HR, 1.94 95% CI, 1.67-2.26) and antibiotics (HR 1.14 95%CI 1.02-1.28) were all associated with an increased hazard of celiac disease.
Conclusion
There is an increased risk of developing celiac disease if antibiotics, PPI’s and H2RA’s are prescribed in the first 6 months of life. Our study highlights modifiable factors such as medication stewardship that may change the childhood risk of CD.