Expansion
Immune-mediated villous atrophy in the proximal small bowel
Expansion
Mechanism
- Gliadin peptides are deamidated by tissue transglutaminase
- Presented by HLA-DQ2 or DQ8 to T cells
- T cell response causes villous atrophy, crypt hyperplasia and increased intraepithelial lymphocytes
Consequences
- Loss of absorptive surface area and of brush border enzymes, including lactase
- Disease is worst proximally and lessens distally, matching the gluten concentration
The proximal predominance predicts the deficiencies:
- Iron and folate deficiency are common, since both are absorbed proximally
- B12 is often normal, since the terminal ileum is usually spared
- Fat-soluble vitamin deficiency and osteomalacia with severe disease
- Secondary lactose intolerance from loss of brush border lactase, which resolves as the mucosa recovers
Diagnosis requires serology while on gluten (IgA tissue transglutaminase, with total IgA to exclude deficiency) and duodenal biopsy. Hyposplenism is an associated finding, so vaccination is advised.