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Review
, 10, 13

Spectrum of Gluten-Related Disorders: Consensus on New Nomenclature and Classification

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Review

Spectrum of Gluten-Related Disorders: Consensus on New Nomenclature and Classification

Anna Sapone et al. BMC Med.

Abstract

A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide. Now we are observing another interesting phenomenon that is generating great confusion among health care professionals. The number of individuals embracing a gluten-free diet (GFD) appears much higher than the projected number of celiac disease patients, fueling a global market of gluten-free products approaching $2.5 billion (US) in global sales in 2010. This trend is supported by the notion that, along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns. This review will summarize our current knowledge about the three main forms of gluten reactions: allergic (wheat allergy), autoimmune (celiac disease, dermatitis herpetiformis and gluten ataxia) and possibly immune-mediated (gluten sensitivity), and also outline pathogenic, clinical and epidemiological differences and propose new nomenclature and classifications.

Figures

Figure 1
Figure 1
Proposed new nomenclature and classification of gluten-related disorders.
Figure 2
Figure 2
Mapping of α-gliadin motifs. Those exerting cytotoxic activity are shown in red, immunomodulatory activity in yellow, zonulin release and gut permeating activity in blue, and CXCR3-dependent IL-8 release in celiac disease patients in dark green. Partially modified from [60].
Figure 3
Figure 3
Trend of three different diets (low carbohydrate diet, fat-free diet, and gluten-free diet), in the USA during the period 2004 to 2011. For the American general population, adopting a gluten-free diet is becoming an increasingly popular option. The market for gluten-free food and beverage products grew at a compound annual growth rate of 28% from 2004 to 2011, eclipsing the low carbohydrate diet and the fat-free diet in 2008, to finish with almost $1.6 billion in retail sales in 2010. By 2012 the market is expected to reach about $2.6 billion in sales. The fact that approximately three million Americans suffer from celiac disease and only a fraction of these patients have been diagnosed implies that patients suffering other forms of proven gluten reaction, including gluten sensitivity and wheat allergy, contribute to this market growth. The rest of the market is filled either by people who undertake the diet as occasional consumers (no medical necessity) or by individuals affected by maladies that have been claimed to be affected by gluten exposure, including autism spectrum disorder, attention deficit hyperactivity disorder, multiple sclerosis and irritable bowel syndrome, but for which there is no evidence of the effectiveness of the diet.
Figure 4
Figure 4
Proposed algorithm for the differential diagnosis of gluten-related disorders, including celiac disease, gluten sensitivity and wheat allergy.

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