Non-celiac gluten sensitivity

Celiac disease is but one consequence of autoimmunity or autoinflammation triggered by gluten among a host of others better characterized by the term non-celiac gluten sensitivity (NCGS). The lack of standardization in terminology has obscured this fact, so two recent papers that help to clear the air are welcome. The authors of a study in published in The American Journal of Gastroenterology state:

"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."

They focused on irritable bowel syndrome (IBS), and examined data for subjects who had been diagnosed with WS using a double-blind placebo-controlled (DBPC) challenge over a ten year period. For controls they used one hundred celiac disease (CD) and fifty IBS patients. Their data showed that wheat exposure could trigger allergic reactions different from celiac disease:

"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."

This alerts those not already aware of the fact that gluten/wheat sensitivity can derange the gastrointestinal mucosa without necessarily being characterized as celiac disease. The authors conclude:

"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."

The authors of another paper recently published in GUT (An International Journal of Gastroenterology and Hepatology) cast a wider net to encompass more of the autoimmune disorders associated with gluten sensitivity and further clarify the distinction between celiac disease and non-celiac gluten sensitivity. The authors recognize that...

"CD and related diseases are now common chronic diseases in children and adults, and increased diagnosis has led to a proliferation of research activities. As with many other chronic conditions, the boundaries of CD are not always clear, with the consequence that there is considerable confusion and a lack of consensus regarding diagnostic criteria of CD and related conditions...the scientific community has come to recognise that there is a spectrum of disorders related to gluten ingestion."

This range of disorders has not been defined by a settled nomenclature, so...

"Due to a lack of common definitions for the spectrum of terms and disorders related to CD, a multidisciplinary task force of 16 physicians from seven countries with particular expertise in diagnosis and treatment of CD proposes the following definitions for the variety of vague and often confusing terms currently in use in the literature. These definitions are based on thorough literature reviews, a discussion in Oslo at the 14th International Coeliac Disease Symposium in June 2011, and agreement on consensus statements by a web survey and phone conferences. We refer to our definitions as the ‘Oslo definitions’."

Disorders associated with gluten sensitivity span a wide spectrum...

"In addition to ‘CD’, the following descriptors of CD were evaluated (in alphabetical order): asymptomatic, atypical, classical, latent, non-classical, overt, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, dermatitis herpetiformis, gluten, gluten ataxia, gluten intolerance, gluten sensitivity and gliadin-specific antibodies."

The authors suggest the term gluten sensitivity be replaced by non-celiac gluten sensitivity:

"In some papers the term gluten sensitivity is used synonymously with CD. Other papers used the concept of gluten sensitivity as an umbrella term to include CD and other conditions related to gluten ingestion, such as DH [dermatitis herpetiformis], gluten ataxia and NCGS. Most recently several authors employed the term gluten sensitivity to describe a condition in which symptoms are triggered by gluten ingestion, in the absence of TTG or EMA antibodies and enteropathy, with variable HLA status and variable anti-gliadin (AGA) presence. It is important to distinguish CD from less well characterised diseases related to gluten ingestion. We therefore recommend that the term gluten sensitivity should not be used and that NCGS [Non-celiac gluten sensitivity] be used instead."

Further defining non-celiac gluten sensitivity...

"The term NCGS relates to one or more of a variety of immunological, morphological or symptomatic manifestations that are precipitated by the ingestion of gluten in people in whom CD has been excluded...NCGS is a condition in which gluten ingestion leads to morphological or symptomatic manifestations despite the absence of CD. As opposed to CD, NCGS may show signs of an activated innate immune response but without the enteropathy, elevations in tTG, EMA or DGP antibodies, and increased mucosal permeability characteristic of CD. Recently, in a double-blind randomised trial, Biesiekierski et al showed that patients with NCGS truly develop symptoms when eating gluten."

Clincial note: Practitioners must bear in mind that the absence of celiac disease does not rule out an autoimmune or autoinflammatory disorder triggered by gluten consumption.