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Celiac disease (gluten-sensitive enteropathy)

Rheumatic manifestations in patients with celiac disease (gluten-sensitive enteropathy):

  • Arthritis (4% to 26%)—symmetric, nonerosive polyarthritis involving predominantly large joints (knees and ankles > hips and shoulders). May precede enteropathic symptoms in 50% of cases. Notably, oligoarthritis and sacroiliitis have also been reported. The arthritis responds to a gluten-free diet in 40% to 60% of cases.
  • Osteomalacia due to steatorrhea from severe enteropathy causing vitamin D deficiency. Some of these patients are mistakenly diagnosed as fibromyalgia with irritable bowel syndrome.
  • Dermatitis herpetiformis.

Celiac disease is an enteropathy resulting from an autoimmune reaction to wheat gluten/gliadin by T lymphocytes in the gut in genetically predisposed individuals. It is a relatively common disease (1:300) in white individuals and can occur at any age.

HLA-DQ2 and/or HLA-DQ8 (usually in linkage with HLA-DR3) are seen in 99% of celiac disease patients compared with 40% of the normal population. Dietary gluten is partly digested by gastric enzymes to form a 33-amino acid peptide that is deaminated by tissue transglutaminase increasing its immunogenicity. The immunogenic gliadin peptide is then presented in the context of HLA-DQ2 or HLA-DQ8 to CD4+ T cells, resulting in interferon-γ release and inflammation, altered gut permeability, and villous atrophy. Only 66% have characteristic bowel symptoms, whereas others will present with arthritis, vitamin D or vitamin B12 deficiency, iron deficiency anemia, cerebellar disease, infertility, or peripheral neuropathy. It is more likely to occur in patients with other HLA-DR3-associated autoimmune diseases such as Sjögren’s syndrome, type I diabetes mellitus, autoimmune thyroid disease, or autoimmune liver disease.


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