Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 15-27: Malabsorption + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Typical symptoms Weight loss Chronic diarrhea Abdominal distention Growth retardation Atypical symptoms Dermatitis herpetiformis Iron deficiency anemia Osteoporosis Abnormal serologic test results Abnormal small bowel biopsy Clinical improvement on gluten-free diet +++ General Considerations ++ Caused by an immunologic response to gluten that results in diffuse damage to the proximal small intestinal mucosa with malabsorption of nutrients Gluten is a storage protein found in certain grains that is partially digested in the intestinal lumen into glutamine-rich peptides Most cases present in childhood or adulthood, although symptoms may manifest between 6 and 24 months of age +++ Demographics ++ Global prevalence is 1.4% In North America, the prevalence of biopsy-confirmed disease is 0.5% + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ "Classic" symptoms of malabsorption more commonly present in infants (< 2 years) Diarrhea Steatorrhea Weight loss Abdominal distention Weakness Muscle wasting Growth retardation Older children and adults are less likely to manifest signs of serious malabsorption but may report Chronic diarrhea Dyspepsia Flatulence Variable weight loss Many adults have minimal or no gastrointestinal symptoms but present with extraintestinal "atypical" manifestations Fatigue Depression Iron-deficiency anemia Osteoporosis Short stature Delayed puberty Amenorrhea or reduced fertility Physical examination In mild cases: may be normal In more severe cases: may reveal signs of malabsorption, loss of muscle mass or subcutaneous fat, pallor, easy bruising, hyperkeratosis, or bone pain Abdominal examination may reveal distention with hyperactive bowel sounds Dermatitis herpetiformis in < 10% +++ Differential Diagnosis ++ Irritable bowel syndrome Malabsorption due to other causes Lactase deficiency Viral gastroenteritis Eosinophilic gastroenteritis Whipple disease Giardiasis Mucosal damage caused by acid hypersecretion associated with gastrinoma Non-celiac gluten sensitivity Frequency and cause of this entity is debated A large 2013 study found that symptoms improved in gluten-sensitive patients when placed on a FODMAP-restricted diet and worsened to similar degrees when challenged in a double-blind crossover trial with gluten or whey proteins A 2018 double-blind crossover trial in patients self-reporting gluten sensitivity found significantly higher symptom scores during the fructan challenge than during gluten or placebo challenges Finally, a 2019 randomized trial conducted in healthy volunteers found no difference in gastrointestinal symptoms between those given diets with gluten supplements versus placebo These data suggest that self-reported wheat sensitivity is not due to gluten intolerance and that the symptom improvement reported by patients with gluten restriction is due to broader FODMAP elimination + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Obtain complete blood count, prothrombin time, serum albumin, iron or ferritin, calcium, alkaline phosphatase, red cell folate, vitamins B12, A, and D levels Iron deficiency or megaloblastic anemia occurs because of iron or folate or vitamin B12 malabsorption Elevation of prothrombin time occurs due to vitamin K deficiency Other deficiencies may include zinc and vitamin B6 Serologic tests should be performed in all patients IgA transglutaminase-2 (IgA TG2) antibody is recommended; has a 98% sensitivity and 98% specificity for detecting celiac disease Antigliadin antibodies are not recommended because of their lower sensitivity and specificity IgA antiendomysial antibodies are less preferred due to the lack of standardization among laboratories A serum IgA level should be obtained in patients with a negative IgA TG2 antibody when celiac disease is strongly suspected because up to 3% of patients with celiac disease have IgA deficiency A test that measures IgG antibodies to deamidated gliadin peptides (anti-DGP) has excellent sensitivity and specificity and is useful in patients with IgA deficiency and in young children HLA-DQ2/DQ8 testing is sometimes performed in selected cases of diagnostic uncertainty (eg, in patients who initiated a gluten-free diet prior to establishing a formal diagnosis): negative DQ2/DQ8 genotyping excludes the diagnosis Serologic tests become negative (undetectable) 3–12 months after dietary gluten withdrawal +++ Imaging ++ Dual-energy x-ray densitometry scanning for osteoporosis +++ Diagnostic Procedures ++ Mucosal biopsy: endoscopic mucosal biopsy of the proximal duodenum (bulb) or distal duodenum confirms diagnosis + Treatment Download Section PDF Listen +++ ++ Remove all gluten from the diet Most patients with celiac disease also have lactose intolerance either temporarily or permanently and should avoid dairy products until the intestinal symptoms have improved on the gluten-free diet Patients who have acute severe diarrhea with dehydration, electrolyte imbalance, and malnutrition may require total parenteral nutrition and intravenous or oral corticosteroids (prednisone 40 mg or budesonide 9 mg) for 2 or more weeks as a gluten-free diet is initiated +++ Medications ++ Nutrient supplements in initial stages of therapy, as necessary Folate Iron Zinc Calcium Vitamins A, B6, B12, D, and E Calcium, vitamin D, and bisphosphonate therapy for osteoporosis Corticosteroids or immunosuppression with azathioprine or cyclosporine may be helpful in patients with refractory celiac disease who do not have intestinal T cell lymphoma + Outcome Download Section PDF Listen +++ +++ Follow-Up ++ Improvement in symptoms is anticipated within a few weeks on the gluten-free diet +++ Prognosis ++ Excellent prognosis with appropriate diagnosis and treatment Celiac disease that is truly refractory to gluten withdrawal occurs in < 5% and carries a poor prognosis + References Download Section PDF Listen +++ + +Brown NK et al. A clinician's guide to celiac disease HLA genetics. Am J Gastroenterol. 2019 Oct;114(10):1587–92. [PubMed: 31274511] + +Celiac Disease Foundation, 20350 Ventura Blvd, Suite #240, Woodland Hills, CA 91364. https://celiac.org + +Croall ID et al. Gluten does not induce gastrointestinal symptoms in healthy volunteers: a double-blind randomized placebo trial. Gastroenterology. 2019 Sep;157(3):881–3. [PubMed: 31129127] + +Elli L et al. Use of enteroscopy for the detection of malignant and premalignant lesions of the small bowel in complicated celiac disease: a meta-analysis. Gastrointest Endosc. 2017 Aug;86(2):264–73. [PubMed: 28433612] + +Husby S et al. AGA clinical practice update on diagnosis and monitoring of celiac disease—changing utility of serology and histologic measures: expert review. Gastroenterology. 2019 Mar;156(4):885–9. [PubMed: 30578783] + +Leonard MM et al. Celiac disease and nonceliac gluten sensitivity: a review. JAMA. 2017 Aug 15;318(7):647–56. 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