Description

• A non–IgE-mediated immune reaction to gliadin, a protein component of dietary gluten (found in wheat, barley, rye, and other grains) 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 (GFD)
    • <50% of adults present with gastrointestinal (GI) symptoms.
  • Atypical
    • Minor GI symptoms, with a myriad of extraintestinal manifestations (e.g., anemia, elevated LFTs, dental enamel defects, neurologic symptoms, infertility)
  • Asymptomatic (silent) disease
    • Found when screening first-degree relatives
    • Positive laboratory tests and genetics, without signs/symptoms; normal histology on biopsy
• System(s) affected: GI
• Synonym(s): celiac sprue; gluten-sensitive enteropathy; nontropical sprue

Epidemiology

Incidence

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

Prevalence

• 0.7% in the United States; an estimated 3 million Americans have celiac disease.
• 1% worldwide (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.

Genetics
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 (e.g., grain processing, genetically modified organisms, hygiene and illness during childhood, breastfeeding, time of introduction of solid foods, pollution, tobacco use, and medication) definitively explain why some susceptible individuals develop celiac disease, whereas others do not.

Commonly Associated Conditions

• Dermatitis herpetiformis (DH): 85% of patients with DH have celiac disease. All patients with DH should follow a GFD (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
• Oral aphthous ulcers
• Irritable bowel syndrome (IBS)
• Restless leg syndrome
• Celiac disease is associated with an 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 GFD.
• Higher rates of low birth weight, prematurity, spontaneous abortions, intrauterine growth restriction, and stillbirths

Pediatric Considerations
Children with type 1 diabetes, Down syndrome, Turner syndrome, Williams syndrome, IgA deficiency, and autoimmune thyroid disease are at risk for celiac disease (3)[C].