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Celiac Disease

Celiac Disease is a topic covered in the 5-Minute Clinical Consult.

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  • An immune-mediated reaction to dietary gluten (found in wheat, barley, rye) primarily affecting the small intestine in genetically predisposed individuals
  • Presentations
    • Typical
      • Diarrheal illness characterized by villous atrophy with symptoms of malabsorption (steatorrhea, weight loss, vitamin deficiencies, anemia); resolves with a gluten-free diet
      • <50% of adults present with GI symptoms.
    • Atypical
      • Minor GI symptoms, with a myriad of extraintestinal manifestations (e.g., anemia, LFTs, dental enamel defects, neurologic symptoms, infertility)
    • Asymptomatic (silent) disease
      • Found when screening first-degree relatives
      • Positive laboratory tests and genetics, without signs/symptoms and with normal histology on biopsy
  • System(s) affected: gastrointestinal
  • Synonym(s): celiac sprue; gluten enteropathy


  • 1 to 13 per 100,000 worldwide (1)
  • 6.5 per 100,000 in United States (2)
  • Primarily affects those of Northern European ancestry
  • Predominant sex: female > male (3:2)

  • 0.7% in the United States; an estimated 3 million Americans have celiac disease (3).
  • 8 to 204 per 100,000 worldwide and (1)

Etiology and Pathophysiology

Sensitivity to gluten, specifically gliadin protein fraction. Tissue transglutaminase (tTG) modification of the gliadin protein leads to immunologic cross-reactivity, inflammation, and tissue damage (villous atrophy) with subsequent GI symptoms and malabsorption.

Homogenicity for HLA-DQ2/DQ8 increases risk of celiac disease and enteropathy-associated T-cell lymphoma.

Risk Factors

  • First-degree relatives: 5–20% incidence (1)
  • Second-degree relatives

Pediatric Considerations
No other risk factors explain why some susceptible individuals develop celiac, whereas others do not. Topics for investigation include grain processing, genetically modified organisms, hygiene and illness during childhood, breastfeeding, time of introduction of solid foods, pollution, tobacco use, and medication (4).

Commonly Associated Conditions

  • Dermatitis herpetiformis: 85% of patients have celiac disease. All patients should follow gluten-free diet (1).
  • Secondary lactase deficiency
  • Osteopenia and osteoporosis
  • Thyroid disease: Hashimoto thyroiditis
  • Type 1 diabetes: 3–10% of patients with type 1 diabetes also have celiac disease (1).
  • Symptomatic iron deficiency: 10–15% have celiac disease.
  • Elevated AST and ALT (with no direct cause)
  • Hyposplenism
  • Irritable bowel syndrome (IBS)
  • Restless leg syndrome
  • Celiac disease is associated with increased risk for adenocarcinoma and lymphoma of the small bowel.
    • The risk of lymphoproliferative malignancies depends on small intestinal histopathology.
    • Little to no increased risk in latent celiac disease (seropositive but normal biopsy)
  • Associated autoimmune conditions (type 1 diabetes, autoimmune thyroiditis, primary biliary cirrhosis, autoimmune hepatitis, psoriasis, Sjögren disease)
  • Associated genetic conditions (Down syndrome, IgA deficiency, Turner syndrome, Williams syndrome)
Pregnancy Considerations
  • Prevalence of celiac disease: 2.5 to 3.5 times higher in women with unexplained infertility
  • Up to 19% of men with celiac disease have androgen resistance. Semen quality and likelihood of pregnancy increase with gluten-free diet.
  • Higher rates of low birth weight, prematurity, spontaneous abortions, intrauterine growth restriction, and stillbirths

Pediatric Considerations
Children with CD at higher risk for type 1 diabetes, Down syndrome, Turner syndrome, Williams syndrome, IgA deficiency, and autoimmune thyroid disease (5)[C]

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Stephens, Mark B., et al., editors. "Celiac Disease." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116109/all/Celiac_Disease.
Celiac Disease. In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116109/all/Celiac_Disease. Accessed April 19, 2019.
Celiac Disease. (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116109/all/Celiac_Disease
Celiac Disease [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 April 19]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116109/all/Celiac_Disease.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Celiac Disease ID - 116109 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116109/all/Celiac_Disease PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -