Original Contribution | Published:

Colon/Small Bowel

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

The American Journal of Gastroenterology volume 107, pages 18981906 (2012) | Download Citation



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.


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.


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.


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.

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We thank Ms Carole Greenall for her precious help in revising the English. We also thank other physicians who recruited and followed up the patients during the study period, in particular Dr Lidia Di Prima.

Author information


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

    • Antonio Carroccio
  2. Division of Internal Medicine, Policlinico University Hospital of Palermo, Palermo, Italy

    • Pasquale Mansueto
    • , Maurizio Soresi
    • , Alberto D'Alcamo
    • , Giuseppe Ambrosiano
    • , Aurelio Seidita
    • , Giuseppe Pirrone
    •  & Giovanni Battista Rini
  3. Division of Pediatric Gastroenterology, “Di Cristina” Hospital, Palermo, Italy

    • Giuseppe Iacono
    •  & Francesca Cavataio
  4. Department of Clinical Chemistry, Buccheri-La Ferla Hospital, Palermo, Italy

    • Ignazio Brusca
  5. Department of Pathology, Policlinico University Hospital of Palermo, Palermo, Italy

    • Ada M Florena


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Competing interests

Guarantor of the article: Antonio Carroccio, MD.

Specific author contributions: Study design, patient recruitment and follow-up, data collection and interpretation, and writing the manuscript: Antonio Carroccio; patient recruitment and follow-up, data collection and interpretation, and revising the manuscript: Pasquale Mansueto; data interpretation and revising the manuscript: Giuseppe Iacono and Giovanni B Rini; histology study, data collection and interpretation: Ada M Florena; patient recruitment and follow-up, data collection and interpretation: Alberto D’Alcamo, Francesca Cavataio, Aurelio Seidita, and Giuseppe Pirrone; immunology assays, data collection, and interpretation: Ignazio Brusca; statistics, data collection, and interpretation: Maurizio Soresi; patient recruitment and follow-up, data collection: Giuseppe Ambrosiano.

Financial support: This study was supported by a Grant from the University of Palermo (MIUR-Ricerca Scientifica di Ateneo, ex quota 60%, years 2006–7).

Potential competing interests: None.

Corresponding author

Correspondence to Antonio Carroccio.

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