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World J Gastroenterol. Apr 14, 2018; 24(14): 1521-1530
Published online Apr 14, 2018. doi: 10.3748/wjg.v24.i14.1521
Extra-intestinal manifestations of non-celiac gluten sensitivity: An expanding paradigm
Giuseppe Losurdo, Mariabeatrice Principi, Andrea Iannone, Annacinzia Amoruso, Enzo Ierardi, Alfredo Di Leo, Michele Barone
Giuseppe Losurdo, Mariabeatrice Principi, Andrea Iannone, Annacinzia Amoruso, Enzo Ierardi, Alfredo Di Leo, Michele Barone, Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, Bari 70124, Italy
Author contributions: Losurdo G, Barone M and Di Leo A planned the study; Principi M, Iannone A, Amoruso A and Barone M collected the data; Losurdo G and Ierardi E wrote the paper; Barone M and Di Leo A revised the article; Losurdo G and Principi M contributed equally and are co-first authors.
Conflict-of-interest statement: None declared.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Giuseppe Losurdo, MD, Doctor, Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, Piazza Giulio Cesare 11, Bari 70124, Italy. giuseppelos@alice.it
Telephone: +39-80-5593452 Fax: +39-80-5593088
Received: March 8, 2018
Peer-review started: March 9, 2018
First decision: March 14, 2018
Revised: March 27, 2018
Accepted: March 31, 2018
Article in press: March 31, 2018
Published online: April 14, 2018
Processing time: 34 Days and 0.1 Hours
Abstract

Non celiac gluten sensitivity (NCGS) is a syndrome characterized by a cohort of symptoms related to the ingestion of gluten-containing food in subjects who are not affected by celiac disease (CD) or wheat allergy. The possibility of systemic manifestations in this condition has been suggested by some reports. In most cases they are characterized by vague symptoms such as ‘foggy mind’, headache, fatigue, joint and muscle pain, leg or arm numbness even if more specific complaints have been described. NCGS has an immune-related background. Indeed there is a strong evidence that a selective activation of innate immunity may be the trigger for NCGS inflammatory response. The most commonly autoimmune disorders associated to NCGS are Hashimoto thyroiditis, dermatitis herpetiformis, psoriasis and rheumatologic diseases. The predominance of Hashimoto thyroiditis represents an interesting finding, since it has been indirectly confirmed by an Italian study, showing that autoimmune thyroid disease is a risk factor for the evolution towards NCGS in a group of patients with minimal duodenal inflammation. On these bases, an autoimmune stigma in NCGS is strongly supported; it could be a characteristic feature that could help the diagnosis and be simultaneously managed. A possible neurological involvement has been underlined by NCGS association with gluten ataxia, gluten neuropathy and gluten encephalopathy. NCGS patients may show even psychiatric diseases such as depression, anxiety and psychosis. Finally, a link with functional disorders (irritable bowel syndrome and fibromyalgia) is a topic under discussion. In conclusion, the novelty of this matter has generated an expansion of literature data with the unavoidable consequence that some reports are often based on low levels of evidence. Therefore, only studies performed on large samples with the inclusion of control groups will be able to clearly establish whether the large information from the literature regarding extra-intestinal NCGS manifestations could be supported by evidence-based agreements.

Keywords: Non celiac gluten sensitivity; Celiac disease; Gluten; Gluten ataxia; Autoimmunity; Gluten-related disorders; Thyroiditis; Extra-intestinal

Core tip: Non celiac gluten sensitivity is an expanding field of investigation within gluten-related disorders. Similarly to celiac disease, it shows a systemic involvement, therefore several extra-intestinal manifestations have been hypothesized and investigated in many studies. They may involve many districts and have neurological/psychiatric, dermatological, rheumatologic and nutritional implications. Moreover, the possibility of association with other autoimmune diseases should not be underestimated. However, the large data amount from the literature often requires to be supported by evidence-based agreements.