celiac sprue

Pathophysiology: Gliadin (a component of gluten) is deamidated by tissue transglutaminase (tTG), enhancing its immunogenicity. The modified peptide binds HLA-DQ2 or HLA-DQ8 on antigen-presenting cells, activating CD4+ T cells in the lamina propria. This triggers a Th1-mediated inflammatory response causing villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis, primarily in the duodenum and proximal jejunum (regions of highest gluten exposure).

Clinical Features: Classic presentation includes chronic diarrhea, steatorrhea, abdominal bloating, weight loss, and failure to thrive in children. Extraintestinal manifestations include iron-deficiency anemia (duodenal malabsorption), dermatitis herpetiformis (pruritic, herpetiform vesicles from IgA deposition), osteoporosis (vitamin D/calcium malabsorption), and neurologic symptoms. Many patients are asymptomatic or have subtle findings (silent celiac disease).

Associations: HLA-DQ2 (95%) and HLA-DQ8; associated with other autoimmune conditions (type 1 diabetes, autoimmune thyroiditis, IgA deficiency). Increased risk of enteropathy-associated T-cell lymphoma and small bowel adenocarcinoma with long-standing disease.

Diagnosis: Serologic testing with IgA anti-tTG antibodies (first-line; check total IgA to rule out deficiency), anti-endomysial antibodies, and anti-deamidated gliadin peptide antibodies. Confirmatory duodenal biopsy shows villous blunting, crypt hyperplasia, and increased intraepithelial lymphocytes (Marsh classification). Findings improve on gluten-free diet.

Treatment: Strict, lifelong gluten-free diet (avoid wheat, barley, rye). Nutritional supplementation as needed (iron, calcium, vitamin D, folate). Monitor serology to assess dietary compliance.

High-Yield Points: Distinguish from tropical sprue (responds to antibiotics, affects entire small bowel, seen in tropical regions) and Whipple disease (PAS-positive macrophages, Tropheryma whipplei, associated with arthralgias and CNS symptoms).