Abstract
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.
Highlights
Because of the lack of data investigating the presence of Non-celiac gluten sensitivity (NCGS) in patients with Refractory FD (RFD), we performed a double-blind placebo-controlled gluten-challenge trial in Iranian patients with RFD with the aim to evaluate any presence of gluten-related dyspepsia
452 patients aged between 18 and 55 years (36.5 ± 7.3 years) with dyspepsia were evaluated: 259 were excluded because of the presence of an underlying disorder related to the clinical picture (16 patients with drug-related dyspepsia, 2 with celiac disease, 28 with Irritable bowel syndrome (IBS), 19 with GERD, 268 with H. pylori infection and 4 with other diseases). 115 patients were left with no apparent causes and 78 patients with positive H. pylori test reported symptoms permanence despite H. pylori eradication; these subjects were defined as affected by FD (n = 193)
193 FD patients were treated with proton pump inhibitors (PPIs) for at least 8 weeks ± Tricyclic anti-depressants (TCAs) and prokinetics for 12 weeks. 116 patients presented symptoms relief after medical treatment and were excluded; 77 patients had persistent symptoms despite H. pylori eradication and medical therapy and were defined as RFD (Fig. 1)
Summary
Upper endoscopy with biopsies should be performed, and psychological therapy should be considered as well[16,17,18,19,20]. Refractory FD (RFD) is defined as FD presenting symptoms continuing for at least 6 months, unresponsive to at least two medical treatments such as PPIs, prokinetics, or H. pylori eradication[21]. Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by gastrointestinal and extra-intestinal symptoms related to the ingestion of gluten-containing products, in patients without wheat allergy (WA) or celiac disease (CD)[22,23]. According to the Salerno criteria, the diagnosis of NCGS should be considered in patients with persistent intestinal (e.g. dyspepsia) and/or extra-intestinal symptoms triggered by the ingestion of gluten-containing food[35]. Because of the lack of data investigating the presence of NCGS in patients with RFD, we performed a double-blind placebo-controlled gluten-challenge trial in Iranian patients with RFD with the aim to evaluate any presence of gluten-related dyspepsia
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