Etiology

• Genetic predisposition with association to HLA antigens
  • HLA-DQ2 in 90–95% of patients
  • HLA-DQ8 in 5–10% of patients
• Consuming gliadin from grains such as wheat, rye, and barley leads to an autoimmune reaction within the small intestinal wall.

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Pathophysiology

• Symptoms manifest when a genetically predisposed individual develops an immunological response to gliadin, an alcohol-soluble fraction of gluten.
• Consumption of food containing gluten → tissue transglutaminase is released → modifies gliadin from gluten proteins → pathogenic T cells react to and are activated by modified gliadin → mediate chronic intestinal inflammation → epithelial damage resulting in villous atrophy, crypt hyperplasia, and loss of brush border → impaired resorption of nutrients in the small intestine (especially in the distal duodenum and proximal jejunum) → malabsorption symptoms

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Clinical features

Gastrointestinal symptoms

• Chronic or recurring diarrhea: steatorrhea
• Flatulence, abdominal bloating, and pain

Extraintestinal symptoms and associations

• Malabsorption symptoms: fatigue, weight loss, vitamin deficiency, iron deficiency anemia, osteoporosis, hypocalcemia
• In children: failure to thrive, growth failure, delayed puberty, secondary hyperparathyroidism
• Dermatologic associations: dermatitis herpetiformis
  • Transglutaminases play a role in forming extensively cross-linked proteins (e.g., elastin, coagulation by factor XIII).
• Neuropsychiatric symptoms: peripheral neuropathies (numbness, burning and tingling of the hands and feet) , headache, ataxia, depression, irritability
• Commonly associated with autoimmune diseases

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Diagnostics

Laboratory studies

• IgA tissue transglutaminase antibody (tTG IgA): initial test
• Total IgA
  • Indicated for all patients because of the high prevalence of IgA deficiency in patients with celiac disease (approx. 2–3%)
  • If patients have low IgA, perform further IgG-based testing.
• Deamidated gliadin peptide
  • IgG-based testing: indicated in IgA deficiency or discordant biopsy and serology
    • IgG-tissue transglutaminase (tTG IgG)
    • IgG deamidated gliadin peptide (DGP IgG)
  • IgA-based testing: IgA deamidated gliadin peptide (DGP IgA)
• Anti-endomysial antibody (EMA): Potential second-line confirmatory test (high-specificity)

Endoscopy

• EGD with small intestine biopsy (confirmatory test)
  • Intraepithelial lymphocytic infiltration
  • Crypt hyperplasia
  • Villous atrophy

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Treatment

• Strict, lifelong gluten-free diet
  • Abstain from products containing wheat, rye, barley, or spelt.
  • Symptoms usually improve quickly

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