Background: Non-celiac gluten sensitivity (NCGS) is a recently recognized disorder, characterized by the occurrence of symptoms following gluten ingestion. It is often self-diagnosed by the patient, but should be confirmed by the response to a gluten-free diet, followed by a gluten challenge. Celiac disease (CD) and wheat allergy (WA) must first be ruled out. Aims: (1) to determine the frequency of visits performed for symptoms self-perceived as gluten-related; (2) to assess in this cohort, the proportion of patients satisfying the diagnostic criteria for NCGS. Methods: A two-year prospective study including all consecutive patients complaining of gluten-related symptoms. NCGS was diagnosed on the basis of the disappearance of the symptoms within 6 months of a gluten-free diet, followed by their reappearance with the reintroduction of gluten in the diet for 1 month. Results: Three hundred and ninety two patients complaining of gluten-related symptoms were enrolled; 26 of these (6.63%) were affected by CD, 2 (0.51%) by WA and 27 were diagnosed with NCGS (6.88%). The remaining 337 patients (85.96%) did not experience any change of symptoms with a gluten-free diet. The PPV of the gluten-related symptom was found to be 7%. Conclusion: Eighty six percent of patients reporting gluten-related symptoms have neither NCGS, nor CD, nor WA. Self-perceived gluten-related symptoms are rarely indicative of the presence of NCGS.

Journal Section:
Original Paper
Keywords:
Non-celiac gluten sensitivity, Gluten, Celiac disease, Wheat allergy, Gluten-related disorders, Gluten-free diet
1.
Catassi C, Bai JC, Bonaz B, Bouma G, Calabrò A, Carroccio A, Castillejo G, Ciacci C, Cristofori F, Dolinsek J, Francavilla R, Elli L, Green P, Holtmeier W, Koehler P, Koletzko S, Meinhold C, Sanders D, Schumann M, Schuppan D, Ullrich R, Vécsei A, Volta U, Zevallos V, Sapone A, Fasano A: Non-celiac gluten sensitivity: the new frontier of gluten related disorders. Nutrients 2013;5:3839-3853.
2.
Digiacomo DV, Tennyson CA, Green PH, Demmer RT: Prevalence of gluten-free diet adherence among individuals without celiac disease in the USA: results from the continuous national health and nutrition examination survey 2009-2010. Scand J Gastroenterol 2013;48:921-925.
3.
Volta U, Caio G, Tovoli F, De Giorgio R: Non-celiac gluten sensitivity: questions still to be answered despite increasing awareness. Cell Mol Immunol 2013;10:383-392.
4.
Sapone A, Bai JC, Ciacci C, Dolinsek J, Green PH, Hadjivassiliou M, Kaukinen K, Rostami K, Sanders DS, Schumann M, Ullrich R, Villalta D, Volta U, Catassi C, Fasano A: Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med 2012;10:13.
5.
Cooper BT, Holmes GK, Ferguson R, Thompson RA, Allan RN, Cooke WT: Gluten-sensitive diarrhea without evidence of celiac disease. Gastroenterology 1980;79:801-806.
6.
Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH, Hadjivassiliou M, Kaukinen K, Kelly CP, Leonard JN, Lundin KE, Murray JA, Sanders DS, Walker MM, Zingone F, Ciacci C: The Oslo definitions for coeliac disease and related terms. Gut 2013;62:43-52.
7.
Sanders DS, Aziz I: Non-celiac wheat sensitivity: separating the wheat from the chat! Am J Gastroenterol 2012;107:1908-1912.
8.
Volta U, Bardella MT, Calabrò A, Troncone R, Corazza GR; Study Group for Non-Celiac Gluten Sensitivity: An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity. BMC Med 2014;12:85.
9.
Brown AC: Gluten sensitivity: problems of an emerging condition separate from celiac disease. Expert Rev Gastroenterol Hepatol 2012;6:43-55.
10.
Di Sabatino A, Corazza GR: Nonceliac gluten sensitivity: sense or sensibility? Ann Intern Med 2012;156:309-311.
11.
Oberhuber G, Granditsch G, Vogelsang H: The histopathology of coeliac disease: time for a standardized report scheme for pathologists. Eur J Gastroenterol Hepatol 1999;11:1185-1194.
12.
Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC: Functional bowel disorders. Gastroenterology 2006;130:1480-1491.
13.
Molina-Infante J, Santolaria S, Sanders DS, Fernández-Bañares F: Systematic review: noncoeliac gluten sensitivity. Aliment Pharmacol Ther 2015;41:807-820.
14.
Volta U, De Giorgio R: New understanding of gluten sensitivity. Nat Rev Gastroenterol Hepatol 2012;9:295-299.
15.
Aziz I, Lewis NR, Hadjivassiliou M, Winfield SN, Rugg N, Kelsall A, Newrick L, Sanders DS: A UK study assessing the population prevalence of selfreported gluten sensitivity and referral characteristics to secondary care. Eur J Gastroenterol Hepatol 2014;26:33-39.
16.
Leonard MM, Vasagar B: US perspective on gluten-related diseases. Clin Exp Gastroenterol 2014;7:25-37.
17.
Carroccio A, Mansueto P, Iacono G, Soresi M, D'Alcamo A, Cavataio F, Brusca I, Florena AM, Ambrosiano G, Seidita A, Pirrone G, Rini GB: Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity. Am J Gastroenterol 2012;107:1898-1906; quiz 1907.
18.
Singh VV, Toskes PP: Small bowel bacterial overgrowth: presentation, diagnosis, and treatment. Curr Treat Options Gastroenterol 2004;7:19-28.
19.
Fernández-Bañares F, Esteve M, Viver JM: Fructose-sorbitol malabsorption. Curr Gastroenterol Rep 2009;11:368-374.
20.
Misselwitz B, Pohl D, Frühauf H, Fried M, Vavricka SR, Fox M: Lactose malabsorption and intolerance: pathogenesis, diagnosis and treatment. United European Gastroenterol J 2013;1:151-159.
21.
Mansueto P, Seidita A, D'Alcamo A, Carroccio A: Role of FODMAPs in patients with irritable bowel syndrome: a review. Nutr Clin Pract 2015;pii:0884533615569886.
22.
Ohlsson B: New insights and challenges in microscopic colitis. Therap Adv Gastroenterol 2015;8:37-47.
23.
Cojocaru M, Cojocaru IM, Silosi I, Vrabie CD: Gastrointestinal manifestations in systemic autoimmune diseases. Maedica (Buchar) 2011;6:45-51.
24.
Biesiekierski JR, Newnham ED, Irving PM, Barrett JS, Haines M, Doecke JD, Shepherd SJ, Muir JG, Gibson PR: Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Am J Gastroenterol 2011;106:508-514; quiz 515.
25.
Biesiekierski JR, Peters SL, Newnham ED, Rosella O, Muir JG, Gibson PR: No effects of gluten in patients with self-reported non-celiac gluten sensitivity after following dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates. Gastroenterology 2013;145:320-328.e1-e3.
26.
Peters SL, Biesiekierski JR, Yelland GW, Muir JG, Gibson PR: Randomised clinical trial: gluten may cause depression in subjects with non-coeliac gluten sensitivity - anexploratory clinical study. Aliment Pharmacol Ther 2014;39:1104-1112.
27.
Fasano A, Sapone A, Zevallos V, Schuppan D: Nonceliac gluten sensitivity. Gastroenterology 2015;148:1195-1204.
28.
Sapone A, Lammers KM, Casolaro V, Cammarota M, Giuliano MT, De Rosa M, Stefanile R, Mazzarella G, Tolone C, Russo MI, Esposito P, Ferraraccio F, Cartenì M, Riegler G, de Magistris L, Fasano A: Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity. BMC Med 2011;9:23.
29.
Brottveit M, Beitnes AC, Tollefsen S, Bratlie JE, Jahnsen FL, Johansen FE, Sollid LM, Lundin KEA: Mucosal cytokine response after short-term gluten challenge in celiac disease and non-celiac gluten sensitivity. Am J Gastroenterol 2013;108:842-850.
30.
Czaja-Bulsa G: Non coeliac gluten sensitivity - a new disease with gluten intolerance. Clin Nutr 2015;34:189-194.
31.
Hollon J, Puppa EL, Greenwald B, Goldberg E, Guerrerio A, Fasano A: Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity. Nutrients 2015;7:1565-1576.
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