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Non-Celiac Wheat Sensitivity Diagnosed by Double-Blind Placebo-Controlled Challenge: Exploring a New Clinical Entity

Carroccio, Antonio MD1; Mansueto, Pasquale MD2; Iacono, Giuseppe MD3; Soresi, Maurizio MD2; D'Alcamo, Alberto MD2; Cavataio, Francesca MD3; Brusca, Ignazio MD4; Florena, Ada M MD5; Ambrosiano, Giuseppe MD2; Seidita, Aurelio MD2; Pirrone, Giuseppe MD2; Rini, Giovanni Battista MD2

American Journal of Gastroenterology: December 2012 - Volume 107 - Issue 12 - p 1898–1906
doi: 10.1038/ajg.2012.236

OBJECTIVES: Non-celiac wheat sensitivity (WS) is considered a new clinical entity. An increasing percentage of the general population avoids gluten ingestion. However, the real existence of this condition is debated and specific markers are lacking. Our aim was thus to demonstrate the existence of WS and define its clinical, serologic, and histological markers.

METHODS: We reviewed the clinical charts of all subjects with an irritable bowel syndrome (IBS)-like presentation who had been diagnosed with WS using a double-blind placebo-controlled (DBPC) challenge in the years 2001–2011. One hundred celiac disease (CD) patients and fifty IBS patients served as controls.

RESULTS: Two hundred and seventy-six patients with WS, as diagnosed by DBPC challenge, were included. Two groups showing distinct clinical characteristics were identified: WS alone (group 1) and WS associated with multiple food hypersensitivity (group 2). As a whole group, the WS patients showed a higher frequency of anemia, weight loss, self-reported wheat intolerance, coexistent atopy, and food allergy in infancy than the IBS controls. There was also a higher frequency of positive serum assays for IgG/IgA anti-gliadin and cytometric basophil activation in “in vitro” assay. The main histology characteristic of WS patients was eosinophil infiltration of the duodenal and colon mucosa. Patients with WS alone were characterized by clinical features very similar to those found in CD patients. Patients with multiple food sensitivity were characterized by clinical features similar to those found in allergic patients.

CONCLUSIONS: Our data confirm the existence of non-celiac WS as a distinct clinical condition. We also suggest the existence of two distinct populations of subjects with WS: one with characteristics more similar to CD and the other with characteristics pointing to food allergy.

1 Division of Internal Medicine, Hospital of Sciacca, ASP, Agrigento, Italy

2 Division of Internal Medicine, Policlinico University Hospital of Palermo, Palermo, Italy

3 Division of Pediatric Gastroenterology, “Di Cristina” Hospital, Palermo, Italy

4 Department of Clinical Chemistry, Buccheri-La Ferla Hospital, Palermo, Italy

5 Department of Pathology, Policlinico University Hospital of Palermo, Palermo, Italy

Correspondence: Antonio Carroccio, MD, Medicina Interna, Hospital of Sciacca, ASP, Agrigento, Italy. E-mail: or

SUPPLEMENTARY MATERIAL accompanies this paper at

Received 25 December 2011; accepted 26 June 2012

published online 24 July 2012

© The American College of Gastroenterology 2012. All Rights Reserved.
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