What is celiac disease?

Celiac Disease: Definition and Overview

Celiac disease is an immune-mediated small intestinal enteropathy triggered by exposure to dietary gluten in genetically predisposed individuals, characterized by villous atrophy, intraepithelial lymphocytosis, and crypt hyperplasia of the small bowel. 1

Pathophysiology

Celiac disease develops through a complex immunological process:

• Trigger: Gluten, a storage protein found in wheat, rye, and barley, is the environmental trigger 1
• Genetic predisposition: Nearly 100% of patients have HLA-DQ2 and/or HLA-DQ8 genetic markers 1
• Immune response: Gluten peptides are incompletely digested due to their high glutamine and proline content 1
• Autoimmune reaction: Type 2 transglutaminase (TG2) deamidates gliadin peptides, increasing their immunogenicity and facilitating binding to HLA-DQ2/DQ8 molecules 1
• Tissue damage: The immune response leads to formation of anti-TG2 antibodies, pro-inflammatory cytokines, lymphocyte infiltration, and subsequent tissue injury resulting in villous atrophy 1

Epidemiology

• Prevalence: Affects approximately 1% of the global population 1, 2
• Gender distribution: More common in women than men with a ratio of 1.5-2:1 1
• Age: Can occur at any age, not just in childhood as previously thought 1
• Risk in special populations: Higher prevalence (1-16%) in patients with type 1 diabetes compared to 0.3-1% in the general population 1

Clinical Presentation

The clinical presentation of celiac disease has evolved over time and includes:

Classical Symptoms

• Diarrhea
• Steatorrhea
• Weight loss or poor weight gain
• Growth failure (in children)
• Malabsorption 1

Non-Classical Manifestations

• Anemia
• Vague abdominal symptoms (often similar to irritable bowel syndrome)
• Chronic fatigue
• Irritability
• Inability to concentrate
• Neuropathy
• Ataxia
• Depression
• Osteomalacia and osteoporosis
• Liver disease 1

In Patients with Diabetes

• Unpredictable blood glucose levels
• Unexplained hypoglycemia
• Deterioration in glycemic control 1

Asymptomatic Disease

• Often detected through screening of high-risk individuals (first-degree relatives or those with associated disorders) 1

Diagnostic Approach

Serological Testing

• First-line screening: IgA tissue transglutaminase antibodies (tTG-IgA) with 90-96% sensitivity in adults 3
• Confirmatory test: IgA endomysial antibodies (EMA-IgA) with 88% sensitivity and 99.6% specificity in adults 3
• Additional tests: Deamidated gliadin peptide antibodies (DGP) 3
• Important consideration: Patients must maintain regular gluten consumption (1-3 slices of bread daily) for at least 6 weeks prior to testing 3

Histological Confirmation

• Gold standard: Duodenal biopsy with multiple specimens (ideally 6) from the second part of duodenum or beyond 3
• Characteristic findings: Villous atrophy, crypt hyperplasia, increased intraepithelial lymphocytes, and increased lamina propria lymphocytes 3
• Grading system: Marsh or Marsh-Oberhuber score systems are commonly used to describe the severity of small bowel lesions 1

Genetic Testing

• HLA-DQ2/DQ8 typing can be useful in uncertain cases, as absence of these markers virtually excludes celiac disease 3

Management

Gluten-Free Diet

• Primary treatment: Strict, lifelong gluten-free diet under dietitian guidance 1, 3
• Excluded foods: Wheat, rye, barley, and potentially oats 3
• Monitoring: Regular follow-up with serological testing at 6 and 12 months after diagnosis, then yearly 3

Monitoring for Complications

• Regular assessment for nutritional deficiencies
• Screening for associated conditions (osteoporosis, thyroid disorders)
• Vigilance for potential complications like intestinal lymphoma 3, 2

Common Pitfalls and Considerations

• Premature gluten restriction: Can reduce lesion severity and lead to false negative results 3
• IgA deficiency: Present in 1-3% of celiac patients, causing falsely low levels of IgA-based tests 1
• Cross-contamination: Even small amounts of gluten can trigger symptoms; careful food handling practices are essential 4
• Nutritional deficiencies: May persist even on a gluten-free diet, requiring monitoring and supplementation 5
• Persistent symptoms: About 50% of patients may experience persistent inflammation, often due to unintentional gluten ingestion 4

Conclusion

Celiac disease is a complex autoimmune disorder with diverse clinical presentations that requires careful diagnostic workup and lifelong dietary management. Early diagnosis and strict adherence to a gluten-free diet are essential to prevent complications and improve quality of life.