Pathophysiology
Clinical meaning
Celiac disease is a chronic autoimmune enteropathy triggered by gluten (gliadin fraction of wheat, secalin of rye, hordein of barley) in genetically susceptible individuals carrying HLA-DQ2 or HLA-DQ8. Tissue transglutaminase (tTG) deamidates gliadin peptides, creating neoepitopes that are presented by HLA-DQ2/DQ8 on antigen-presenting cells to CD4+ T cells, triggering an adaptive immune response that destroys enterocytes and flattens intestinal villi. Atypical presentations โ now recognized as more common than classic malabsorptive diarrhea โ include iron-deficiency anemia unresponsive to supplementation, unexplained osteoporosis, dermatitis herpetiformis, elevated transaminases, peripheral neuropathy, infertility, recurrent aphthous stomatitis, and dental enamel defects. The NP must maintain a high index of suspicion for celiac disease in patients with these extraintestinal manifestations, associated autoimmune conditions (type 1 diabetes, autoimmune thyroiditis), or first-degree family members with celiac disease.