What is Celiac Disease
Celiac disease is an immune-mediated disorder of the small intestine triggered by gluten ingestion in genetically susceptible individuals, characterized by villous atrophy, intraepithelial lymphocytosis, and crypt hyperplasia that improves with gluten exclusion. 1
Pathophysiology
The disease results from a complex interplay between genetics, immunology, and environmental triggers:
Gluten proteins from wheat, rye, and barley are incompletely digested by normal gastrointestinal enzymes due to their high proline and glutamine content, leaving large peptides of 10-50 amino acids. 1
Tissue transglutaminase (tTG) deamidates glutamine residues in these peptides to glutamic acid, increasing their immunogenicity. 1
The modified peptides bind to HLA-DQ2 or HLA-DQ8 molecules on antigen-presenting cells, which are present in nearly 100% of individuals with celiac disease. 1
CD4+ T cells are activated in the intestinal mucosa, leading to production of pro-inflammatory cytokines, lymphocyte infiltration, and tissue injury. 1
The immune response targets both gluten (exogenous antigen) and tTG (autoantigen), making this both an immune-mediated and autoimmune condition. 1, 2
Epidemiology
Prevalence is approximately 1% in the general population, though this varies geographically from <0.25% to >1%. 1
Women are affected 1.5-2 times more frequently than men, though this gender imbalance may diminish with age. 1
First-degree relatives have a 10% prevalence, with monozygotic twins showing approximately 75% concordance. 1, 3
Only about 24% of those with celiac disease are diagnosed, creating a substantial "celiac iceberg" of undiagnosed cases. 3
Clinical Manifestations
Classic Gastrointestinal Presentation
Diarrhea with or without steatorrhea is the most common classic symptom, frequently accompanied by abdominal pain. 1, 3
Weight loss or failure to thrive particularly affects children and reflects chronic malabsorption. 1, 3
Bloating, flatulence, nausea, and vomiting may occur as manifestations of intestinal inflammation. 3
Non-Classical and Extraintestinal Manifestations
Iron deficiency anemia resistant to oral supplementation is a common presenting feature, often occurring without gastrointestinal symptoms. 3, 4
Decreased bone mineral density and osteoporosis result from calcium and vitamin D malabsorption. 4, 2
Neurologic manifestations including neuropathy, ataxia, and inability to concentrate may be the primary presentation. 1, 3
Reproductive issues including infertility and recurrent miscarriages are associated with untreated disease. 3
Chronic fatigue and depression are frequently reported extraintestinal symptoms. 1, 3
Silent or Asymptomatic Disease
Many patients are diagnosed through screening of high-risk groups despite having no overt symptoms. 3
Screening is particularly important in first-degree relatives, patients with type 1 diabetes (prevalence 1-16%), and those with autoimmune thyroid disease. 1, 3
Associated Conditions
Type 1 diabetes patients have a 5.4% prevalence of celiac disease in the United States, compared to 0.3-1% in the general population. 1
Patients with celiac disease and type 1 diabetes may present with unpredictable blood glucose levels, unexplained hypoglycemia, and deteriorating glycemic control. 1, 3
Autoimmune thyroid disease, Down syndrome, and other autoimmune conditions show increased association with celiac disease. 3, 5
Critical Clinical Pitfalls
The majority of patients present with non-specific or extraintestinal symptoms rather than classic diarrhea and malabsorption, leading to significant diagnostic delays. 3
Symptoms overlap substantially with irritable bowel syndrome, lactose intolerance, and microscopic colitis, requiring high clinical suspicion. 3
Patients who have already started a gluten-free diet before testing will have false-negative serological and histological results, making diagnosis impossible without gluten rechallenge. 6
The disease can develop at any age, not just in childhood as historically believed. 1, 4