• Clinical science

Celiac disease (Gluten‑sensitive enteropathy…)

Summary

Celiac disease, also referred to as celiac sprue or non-tropical 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 firm 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

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

References:[2][1]

Epidemiology

  • 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

References:[2][3][4]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

  • 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)

References:[5][6]

Pathophysiology

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

References:[5][3][7]

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.

References:[2][8][5][9]

Diagnostics

If celiac disease is suspected (based on the medical history and clinical features), serum antibodies may be tested. Ultimately, the diagnosis should be confirmed via biopsy.

Laboratory tests

Endoscopy with small intestine biopsy

References:[10][11][12][2][8][6][13]

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

  • Definition: :an infectious disease caused by Tropheryma whipplei, an intracellular gram-positive bacteria
  • Epidemiology
    • Very rare
    • Most commonly occurs in males older than 40 years [14]
  • Clinical features
    • Intestinal manifestations
    • Extraintestinal manifestations
      • Enteropathic arthritis (60% of cases)
      • Arthralgias and arthritis, especially sacroiliitis (40% of cases)
      • Fever
      • Polyserositis
      • Lymphadenopathy
      • Cardiac symptoms (e.g., valve insufficiencies)
      • Neurological symptoms (e.g., myoclonia, ataxia, impairment of oculomotor function)
  • Diagnostics
  • Treatment

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!

References:[15][16][17]

The differential diagnoses listed here are not exhaustive.

Treatment

  • Lifelong gluten-free diet
    • Abstain from products containing: wheat, rye, barley, spelt
    • Recommended foods: rice, maize, potatoes, soy beans, millet, potentially oats
    • In ∼ 70% of cases, clinical improvement occurs within two weeks after initiating the diet.
    • Histological improvement occurs within weeks to months after beginning the diet.
  • In case of secondary lactase deficiency: avoid milk products
  • Iron and vitamin substitution
  • Supplementation of calcium and vitamin D to prevent bone loss

Managing celiac disease mainly consists of maintaining a lifelong gluten-free diet!
References:[11][2][18]

Complications

References:[11][2]

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

Prevention

  • 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. N/A. Celiac Disease Antibody Tests. https://labtestsonline.org/understanding/analytes/celiac-disease/tab/test/. Updated February 24, 2015. Accessed December 25, 2016.
  • 11. 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.
  • 12. Rostom A, Murray JA, Kagnoff MF. American Gastroenterological Association (AGA) Institute technical review on the diagnosis and management of celiac disease. Gastroenterology. 2006; 131(6): pp. 1981–2002. doi: 10.1053/j.gastro.2006.10.004.
  • 13. Hill ID. Diagnosis of celiac disease in children. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/diagnosis-of-celiac-disease-in-children. Last updated November 2, 2016. Accessed December 25, 2016.
  • 14. 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.
  • 15. 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.
  • 16. 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.
  • 17. 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.
  • 18. AGA Committee on Osteoporosis in Gastrointestinal Disease. American Gastroenterological Association medical position statement: guidelines on osteoporosis in gastrointestinal diseases. Gastroenterology. 2003; 124(3): pp. 791–4. doi: 10.1053/gast.2003.50107.
  • 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 03/20/2020
{{uncollapseSections(['Qv0u-3', 'Pv0WZR', '4v03ZR', 'kv0mZR', 'lv0vZR', 'Nv0-ZR', 'Mv0M0R', 'Lv0w0R', 'ov00aR', 'Kv0UaR', 'CWcqnY0'])}}