Refractory functional dyspepsia (RFD) is characterized by symptoms persistence in spite of medical treatment or H. pylori eradication. No study has yet investigated the presence of gluten-dependent RFD as a clinical presentation of Non-Celiac Gluten Sensitivity (NCGS). Patients with RFD, in whom celiac disease, wheat allergy and H. pylori infection had been ruled out, followed a six weeks long gluten-free diet (GFD). Symptoms were evaluated by means of visual analogue scales; patients with ≥30% improvement in at least one of the reported symptoms after GFD underwent a double-blind placebo controlled gluten challenge. Subjects were randomly divided in two groups and symptoms were evaluated after the gluten/placebo challenge. GFD responders were further followed on for 3 months to evaluate the relationship between symptoms and gluten consumption. Out of 77 patients with RFD, 50 (65%) did not respond to GFD; 27 (35%) cases showed gastrointestinal symptoms improvement while on GFD; after blind gluten ingestion, symptoms recurred in 5 cases (6.4% of patients with RFD, 18% of GFD responders) suggesting the presence of NCGS. Furthermore, such extra-intestinal symptoms as fatigue and weakness (P = 0.000), musculo-skeletal pain (P = 0.000) and headache (P = 0.002) improved in NCGS patients on GFD. Because of the high prevalence of NCGS among patients with RFD, a diagnostic/therapeutic roadmap evaluating the effect of GFD in patients with RFD seems a reasonable (and simple) approach.
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