Human leukocyte antigen genetics and clinical features of self-treated patients on a gluten-free diet.

Background and Aims: Increasingly, people start a gluten-free diet (GFD) without a clear celiac disease (CD) diagnosis. Human leukocyte antigen (HLA) genotyping is useful in ruling out CD in patients with equivocal results of serologic testing or small-bowel biopsy (SBB), but its utility and the clinical features of patients on self-treated GFD (ST-GFD) are largely unknown. Methods: Retrospective study of single tertiary care center cohort compared 137 patients on ST-GFD and 443 patients with well-defined CD. We compared HLA genotype, symptoms, serologic and SBB results, and response to GFD between the 2 groups. Analysis used univariate logistic regression modeling, adjusted for age and sex. Results: Patients with ST-GFD presented more often with diarrhea (P < 0.001), abdominal distention (P < 0.001), flatulence (P = 0.002), cramping (P = 0.02), itchy skin (P = 0.02), oral inflammation (P = 0.04), and constipation (P = 0.01) and less often with anemia (P < 0.001) or malaise (P = 0.02) than CD patients. In addition, 41% did not carry DQ2.5 and DQ8 versus 6% of CD patients (P < 0.001). Only 2% of ST-GFD patients had SBB clearly consistent with CD. Family history of CD showed no difference between groups (P = 0.77). Although CD patients had a statistically higher rate of GFD benefit, both groups had a high responsiveness rate (98% vs. 94%; P = 0.03). Conclusions: HLA genotyping is useful in evaluating patients on an ST-GFD. Although confirmed CD is rare in self-treated patients, most still report benefit from GFD regardless of DQ2 and DQ8 status. Nonceliac gluten sensitivity may play a role.