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 — now recognized as more common than classic malabsorptive diarrhea — 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.
Diagnosis & workup
Diagnostics & workup: - Serum tTG-IgA (tissue transglutaminase IgA) — first-line screening test with >95% sensitivity and specificity; patient must be consuming gluten at time of testing - Total serum IgA level (2-3% of celiac patients have selective IgA deficiency causing false-negative tTG-IgA) - If IgA deficient: order tTG-IgG or deamidated gliadin peptide IgG (DGP-IgG) - Endomysial antibody (EMA-IgA) — highly specific confirmatory test if tTG-IgA equivocal - Upper endoscopy with duodenal biopsies (gold standard for diagnosis) — obtain at least 4-6 biopsies from distal duodenum and 1-2 from duodenal bulb; findings: villous atrophy, crypt hyperplasia, intraepithelial lymphocytosis (Marsh classification) - CBC (iron-deficiency anemia is the most common atypical presentation), ferritin, folate, B12 - DEXA scan for bone density assessment (osteoporosis/osteopenia from calcium and vitamin D malabsorption) - Hepatic panel (unexplained elevated transaminases in 40% of celiac patients) - HLA-DQ2/DQ8 genotyping (useful to rule OUT celiac if negative — >99% negative predictive value)