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Celiac disease (Gluten‑sensitive enteropathy…)


Celiac disease, also referred to as celiac sprue or nontropical sprue, is a common condition characterized by a maladaptive immune response to gluten, a protein found in many grains (e.g., wheat). The disease often occurs in patients with other autoimmune illnesses, as both are associated with HLA variants (human leukocyte antigens, which encode immunoregulatory proteins) that cause pathologically increased immune responses. The underlying pathophysiology is believed to be a combination of gluten intolerance, which triggers an autoimmune reaction, and production of autoantibodies that target tissue transglutaminase, specifically within the proximal small intestine. Typical findings include changes in bowel habits and symptoms associated with malabsorption (e.g., fatigue, weight loss, vitamin deficiencies). Diagnostic tests include the detection of various antibodies. To confirm the diagnosis, an endoscopic biopsy from the small intestine is needed. Histopathological findings often include villous atrophy and crypt hyperplasia. A definitive diagnosis is necessary, as therapy involves a lifelong commitment to a gluten-free diet. If patients comply with this diet, the prognosis is generally very good and the increased risk of celiac-associated malignancies (e.g., intestinal lymphoma) is mitigated.


  • Definition: autoimmune disorder characterized by an intestinal hypersensitivity to gluten, a grain protein [1]
  • Synonyms: celiac sprue; gluten-sensitive enteropathy



  • Sex: >
  • Age of onset:
    • The disease can occur at any age.
    • Peak incidence is bimodal:
      • At 8–12 months (or 2–3 months following the first exposure to gluten through diet containing wheat)
      • Third to fourth decade of life
  • Prevalence: in the US ∼ 1:3000
  • More common in individuals of northern European descent


Epidemiological data refers to the US, unless otherwise specified.


  • Genetic predisposition with association to HLA antigens
  • Consuming gliadin from grains such as wheat, rye, and barley leads to an autoimmune reaction within the small intestinal wall.
  • Commonly associated with autoimmune diseases (see “Clinical features” below)



Symptoms manifest when a genetically predisposed individual develops an immunological response to gliadin, an alcohol-soluble fraction of gluten.


Clinical features

Gastrointestinal symptoms

Extraintestinal symptoms and associations

In both children and adults, mild or asymptomatic cases are more common than the classic presentation of the disease.



General principles [6][10][11]

  • Celiac disease is an underdiagnosed condition that requires a high index of suspicion.
  • Diagnosis is based on serology (initial testing) and EGD with duodenal biopsy (confirmation).
    • A gluten-free diet can cause negative test results.
    • HLA-based testing and/or a gluten challenge are options for patients not consuming gluten.
  • Common indications for testing include:

Laboratory studies [6][11]

Routine studies

Additional studies

Endoscopy [6][11]

False-negative serology and histopathology results are possible if patients are already adhering to a gluten-free diet.

Diagnosis without endoscopy [11]

  • Adults: diagnosis without biopsy not recommended.
  • Children: consider diagnosis without biopsy if all of the following criteria are met (controversial) [17][18]

Further evaluation


  • Repeat laboratory studies after 3–6 months and 12 months, then annually [6][11]
    • tTG-IgA or DGP antibodies
    • Nutrient levels if the patient had a deficiency at the time of diagnosis [13]
  • Endoscopy: only if symptoms persist or return in patients adhering to a gluten-free diet [6][13][10]

Differential diagnoses

Tropical sprue

Celiac disease and tropical sprue have similar features (e.g., steatorrhea, abdominal pain, weight loss), but only tropical sprue responds to antibiotics.

Whipple disease

Anyone who CANT appreciate the foamy, PAStoral rivers of England gets Whipped: the most important features of Whipple disease are Cardiac symptoms, Arthralgias, Neurologic symptoms, Trots (diarrhea), and foamy, PAS-positive macrophages on biopsy.

Whipple disease is lethal if left untreated!


The differential diagnoses listed here are not exhaustive.


Diet [6][25]

  • Strict, lifelong gluten-free diet
    • Abstain from products containing wheat, rye, barley, or spelt.
    • Symptoms usually improve quickly [25]
  • Recommended foods: rice, corn, potatoes, soybeans, millet
  • Patients with secondary lactase deficiency: Avoid milk products.


Managing celiac disease mainly consists of maintaining a lifelong gluten-free diet.



We list the most important complications. The selection is not exhaustive.


  • There is no proven measure to prevent celiac disease.
  • With infants, introducing small amounts of wheat (into the supplementary diet) between 4–6 months of age does not increase the risk of developing celiac disease
  • 1. Alaedini A, Green PH. Autoantibodies in celiac disease. Autoimmunity. Autoimmunity. 2008; 41(1): pp. 19–26. pmid: 18176861.
  • 2. Goebel SU. Celiac Disease (Sprue). In: BS Anand. Celiac Disease (Sprue). New York, NY: WebMD. http://emedicine.medscape.com/article/171805. Updated November 20, 2015. Accessed December 23, 2016.
  • 3. Rubio-tapia A, Kyle RA, Kaplan EL, et al. Increased prevalence and mortality in undiagnosed celiac disease. Gastroenterology. 2009; 137(1): pp. 88–93. doi: 10.1053/j.gastro.2009.03.059.
  • 4. Le T, Bhushan V, Sochat M, Petersen M, Micevic G, Kallianos K. First Aid for the USMLE Step 1 2014. McGraw-Hill Medical; 2014.
  • 5. Schuppan D, Dieterich W. Pathogenesis, epidemiology, and clinical manifestations of celiac disease in adults. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/pathogenesis-epidemiology-and-clinical-manifestations-of-celiac-disease-in-adults. Last updated November 8, 2016. Accessed December 23, 2016.
  • 6. Rubio-tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA. ACG clinical guidelines: diagnosis and management of celiac disease. The American Journal of Gastroenterology. 2013; 108(5): pp. 656–76. doi: 10.1038/ajg.2013.79.
  • 7. Lindfors K, Kaukinen K. Contribution of Celiac Disease Autoantibodies to the Disease Process. In: Contribution of Celiac Disease Autoantibodies to the Disease Process. New York, NY: WebMD. http://www.medscape.com/viewarticle/757922. Updated January 1, 2012. Accessed December 25, 2016.
  • 8. Guandalini S. Pediatric Celiac Disease. In: Cuffari C. Pediatric Celiac Disease. New York, NY: WebMD. http://emedicine.medscape.com/article/932104. Updated June 28, 2016. Accessed December 23, 2016.
  • 9. Chin RL, Sander HW, Brannagan TH, et al. Celiac neuropathy. Neurology. 2003; 60(10): pp. 1581–5. pmid: 12771245.
  • 10. Leonard MM, Sapone A, Catassi C, Fasano A. Celiac Disease and Nonceliac Gluten Sensitivity: A Review. JAMA. 2017; 318(7): pp. 647–656. doi: 10.1001/jama.2017.9730.
  • 11. Husby S, Murray JA, Katzka DA. AGA Clinical Practice Update on Diagnosis and Monitoring of Celiac Disease-Changing Utility of Serology and Histologic Measures: Expert Review. Gastroenterology. 2019; 156(4): pp. 885–889. doi: 10.1053/j.gastro.2018.12.010.
  • 12. Hill ID, Fasano A, Guandalini S, et al. NASPGHAN Clinical Report on the Diagnosis and Treatment of Gluten-related Disorders. J Pediatr Gastroenterol Nutr. 2016; 63(1): pp. 156–65. doi: 10.1097/MPG.0000000000001216.
  • 13. Oxentenko AS, Rubio-Tapia A. Celiac Disease. Mayo Clinic proceedings. 2019; 94(12): pp. 2556–2571. doi: 10.1016/j.mayocp.2019.02.019.
  • 14. Hopper AD, Cross SS, Sanders DS. Patchy villous atrophy in adult patients with suspected gluten-sensitive enteropathy: is a multiple duodenal biopsy strategy appropriate?. Endoscopy. 2008; 40(3): pp. 219–24. doi: 10.1055/s-2007-995361.
  • 15. Schiepatti A, Sanders DS, Zuffada M, Luinetti O, Iraqi A, Biagi F. Overview in the clinical management of patients with seronegative villous atrophy. Eur J Gastroenterol Hepatol. 2019; 31(4): pp. 409–417. doi: 10.1097/MEG.0000000000001340.
  • 16. Enns RA, Hookey L, Armstrong D, et al. Clinical Practice Guidelines for the Use of Video Capsule Endoscopy. Gastroenterology. 2017; 152(3): pp. 497–514. doi: 10.1053/j.gastro.2016.12.032.
  • 17. Hill ID, Dirks MH, Liptak GS, et al. Guideline for the Diagnosis and Treatment of Celiac Disease in Children: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2005; 40(1): pp. 1–19. doi: 10.1097/00005176-200501000-00001.
  • 18. Husby S, Koletzko S, Korponay-Szabó IR, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition Guidelines for the Diagnosis of Coeliac Disease. J Pediatr Gastroenterol Nutr. 2012; 54(1): pp. 136–160. doi: 10.1097/mpg.0b013e31821a23d0.
  • 19. Wierdsma NJ, van Bokhorst-de van der Schueren MA, Berkenpas M, Mulder CJ, van Bodegraven AA. Vitamin and mineral deficiencies are highly prevalent in newly diagnosed celiac disease patients. Nutrients. 2013; 5(10): pp. 3975–92. doi: 10.3390/nu5103975.
  • 20. Kreutz JM, Adriaanse MPM, van der Ploeg EMC, Vreugdenhil ACE. Narrative Review: Nutrient Deficiencies in Adults and Children with Treated and Untreated Celiac Disease. Nutrients. 2020; 12(2). doi: 10.3390/nu12020500.
  • 21. Dutly F, Altwegg M. Whipple's Disease and "Tropheryma whippelii". Clin Microbiol Rev. 2001; 14(3): pp. 561–583. doi: 10.1128/cmr.14.3.561-583.2001.
  • 22. Lamont JT. Tropical sprue. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/tropical-sprue. Last updated September 26, 2016. Accessed December 24, 2016.
  • 23. Apstein MD, Schneider T. Whipple's disease. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/whipples-disease. Last updated March 18, 2016. Accessed December 24, 2016.
  • 24. Roberts IM. Whipple Disease. In: Cagir B. Whipple Disease. New York, NY: WebMD. http://emedicine.medscape.com/article/183350. Updated November 20, 2016. Accessed December 24, 2016.
  • 25. Murray JA, Watson T, Clearman B, Mitros F. Effect of a gluten-free diet on gastrointestinal symptoms in celiac disease. Am J Clin Nutr. 2004; 79(4): pp. 669–73. doi: 10.1093/ajcn/79.4.669.
  • 26. Ciclitira PJ. Management of celiac disease in adults. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/management-of-celiac-disease-in-adults#H7. Last updated June 1, 2015. Accessed December 23, 2016.
  • Rampertab SD, Pooran N, Brar P et al. Trends in the presentation of celiac disease. The American Journal of Medicine. 2006; 119(4): pp. 355.e9–14. pmid: 16564784.
last updated 11/17/2020
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