What is celiac disease?

What is Coeliac Disease?

Coeliac disease is an immune-mediated disorder triggered by gluten ingestion in genetically susceptible individuals, characterized by small intestinal villous atrophy, intraepithelial lymphocytosis, and crypt hyperplasia that improves with strict gluten exclusion. 1

Pathophysiology

Coeliac disease results from a complex interplay between genetic predisposition, environmental triggers, and immune dysregulation. 1

Gluten proteins from wheat, rye, and barley are incompletely digested due to their high proline and glutamine content, leaving large peptides (10-50 amino acids) in the small intestine. 1 These peptides undergo deamidation by tissue transglutaminase (type 2 transglutaminase, TG2), converting glutamine residues to negatively charged glutamic acid. 1

The immune cascade involves these deamidated peptides binding to HLA-DQ2 (present in ~95% of patients) or HLA-DQ8 molecules on antigen-presenting cells, activating pathogenic CD4+ T cells. 1 This triggers both adaptive and innate immune responses, producing anti-TG2 antibodies and pro-inflammatory cytokines that cause lymphocytic infiltration and tissue damage. 1

Genetic susceptibility is essential—nearly 100% of patients with coeliac disease carry HLA-DQ2 and/or HLA-DQ8 alleles, though only a small fraction of carriers develop the disease. 1 First-degree relatives have approximately 10% prevalence, and monozygotic twins show ~75% concordance. 1

Epidemiology

• Prevalence is approximately 1% in the general population, though only 24% of affected individuals are diagnosed, creating a "celiac iceberg" of undiagnosed cases. 1, 2
• Gender distribution shows a 1.5-2:1 female-to-male ratio, though this imbalance may diminish with age. 1
• Age of onset can occur at any point in life, from early childhood through late adulthood. 3, 4

Clinical Manifestations

Classic Gastrointestinal Presentation

The traditional presentation includes diarrhea, steatorrhea, weight loss, abdominal pain, bloating, and malabsorption—though this "classical" pattern now represents a minority of newly diagnosed cases. 1, 2

Non-Classical and Extraintestinal Features

Most adult patients present with non-specific symptoms or extraintestinal manifestations: 2, 4

• Hematologic: Iron deficiency anemia (often resistant to oral supplementation) 2
• Musculoskeletal: Osteoporosis, osteomalacia, bone pain 1
• Neurologic: Peripheral neuropathy, ataxia, depression, inability to concentrate 1, 2
• Reproductive: Infertility, recurrent miscarriages 2
• Dermatologic: Dermatitis herpetiformis (pathognomonic for coeliac disease) 3
• Hepatic: Elevated transaminases 4
• Growth: Failure to thrive and short stature in children 2

High-Risk Populations Requiring Screening

• First-degree relatives (10% prevalence) 1, 2
• Type 1 diabetes (prevalence 1-16% vs 0.3-1% in general population), particularly those with unpredictable glucose control or unexplained hypoglycemia 1, 2
• Autoimmune thyroid disease 2
• Down syndrome 2

Diagnostic Approach

Diagnosis in adults requires both positive serology AND confirmatory small bowel biopsy while the patient is consuming gluten. 1, 5

Serological Testing

• First-line: IgA tissue transglutaminase antibody (tTG-IgA) with 93-96% sensitivity and >95% specificity 1, 5
• Concurrent total IgA measurement is mandatory to identify IgA deficiency (present in 1-3% of coeliac patients vs 1 in 500 in general population), which causes false-negative IgA-based tests 1, 5
• IgA-deficient patients require IgG-based testing (IgG-DGP and IgG-tTG) 5
• Confirmatory serology: IgA endomysial antibodies (EMA) for patients with tTG-IgA >10× upper limit of normal, offering 99.6% specificity 5

Histological Confirmation

Upper endoscopy with multiple biopsies (1-2 from duodenal bulb, ≥4 from distal duodenum) showing villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes using Marsh or Marsh-Oberhuber scoring systems. 1, 5

HLA Typing

HLA-DQ2/DQ8 testing has >99% negative predictive value and is useful when diagnosis is uncertain, serology is equivocal, or patients have already started a gluten-free diet before testing. 1, 5

Critical Diagnostic Pitfalls

• Testing must occur while consuming gluten (at least 10g daily for 6-8 weeks)—starting a gluten-free diet before testing causes false-negative results. 5
• Symptom improvement on gluten-free diet alone has low positive predictive value and should never be used for diagnosis without serological and histological confirmation. 5
• Lymphocytic infiltration without villous atrophy is non-specific and requires consideration of other causes. 5
• Many patients present with non-specific symptoms rather than classic malabsorption, leading to delayed diagnosis. 2

Treatment

A strict, lifelong gluten-free diet is the only effective treatment, requiring complete avoidance of wheat, rye, and barley. 1 Approximately 5% of patients have refractory disease despite strict dietary adherence and require gastroenterology referral for immunosuppressive therapy. 3, 4