What is celiac disease?

What is Celiac Disease

Celiac disease is an immune-mediated autoimmune disorder of the small intestine triggered by dietary gluten (wheat, rye, barley proteins) in genetically predisposed individuals, causing villous atrophy, malabsorption, and both intestinal and extraintestinal manifestations. 1, 2

Pathophysiology

Celiac disease requires three essential components to develop—all three must be present 3:

• Genetic predisposition: Nearly 100% of patients carry HLA-DQ2 and/or HLA-DQ8 genes, with HLA-DQ2.5 present in approximately 90% of cases 3
• Environmental trigger: Gluten proteins from wheat, rye, and barley are incompletely digested due to high proline and glutamine content 3
• Breakdown of immune tolerance: Factors like gastrointestinal infections, early cereal introduction before 3 months, or large gluten exposure may trigger loss of tolerance 3

The disease mechanism involves tissue transglutaminase (tTG) deamidating gluten peptides, which then bind to HLA-DQ2/DQ8 molecules on antigen-presenting cells, activating pathogenic CD4+ T cells 3. This triggers both humoral (anti-tTG and anti-endomysial antibodies) and cellular immune responses, resulting in lymphocytic infiltration, crypt hyperplasia, and characteristic villous atrophy 3, 4.

Clinical Presentation Spectrum

Classic Gastrointestinal Manifestations

• Diarrhea and steatorrhoea with abdominal pain 1, 5
• Weight loss or failure to thrive in children 1, 5
• Bloating, flatulence, nausea 5
• Malabsorption leading to nutritional deficiencies 5

Non-Classical and Extraintestinal Manifestations

The proportion of patients presenting with classic symptoms has decreased over time, with non-classical presentations now predominating 1:

• Iron deficiency anemia resistant to oral supplementation 5
• Osteomalacia and osteoporosis 1
• Fatigue, weakness, and inability to concentrate 1, 5
• Neuropathy, ataxia, and depression 1
• Reproductive issues including infertility and recurrent miscarriages 5
• Dermatitis herpetiformis (pathognomonic for celiac disease) 2
• Growth failure and short stature in children 1

Special Populations

In patients with type 1 diabetes (prevalence 1-16% vs 0.3-1% in general population), celiac disease may present with 1:

• Unpredictable blood glucose levels despite insulin adherence 1, 5
• Unexplained hypoglycemia episodes 1, 5
• Deterioration in glycemic control without obvious cause 1, 5

Epidemiology and Risk Factors

• Prevalence approximately 0.7-1% in the general population 1, 2
• First-degree relatives have 10% prevalence 3, 5
• Monozygotic twins show 75% concordance 1, 3
• Female-to-male ratio of 1.5-2:1 1
• Can develop at any age 1, 2

High-risk groups requiring screening include first-degree relatives, patients with type 1 diabetes, autoimmune thyroid disease, and Down syndrome 5.

Critical Clinical Pitfalls

Only approximately 24% of those with celiac disease are diagnosed, creating a "celiac iceberg" of undiagnosed cases 5. This occurs because:

• Many patients present with non-specific or extraintestinal symptoms rather than classic gastrointestinal complaints 5
• Symptoms overlap with irritable bowel syndrome, lactose intolerance, or microscopic colitis 5
• Patients who self-initiate gluten-free diets before testing will have false-negative serological and histological results 6
• The vague or non-specific nature of symptoms leads to delayed diagnosis 7

The absence of HLA-DQ2 and HLA-DQ8 genes effectively rules out celiac disease, making genetic testing useful in select instances to exclude the diagnosis 3, 2.