View source for Gluten-related disorders

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==Overview==
'''Gluten-related disorders''' is the umbrella term for all diseases triggered by [[gluten]].<ref name="pmid22345659">{{cite journal |author=Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH, Hadjivassiliou M, Kaukinen K, Kelly CP, Leonard JN, Lundin KE, Murray JA, Sanders DS, Walker MM, Zingone F, Ciacci C |title=The Oslo definitions for coeliac disease and related terms |journal=Gut |volume=62 |issue=1 |pages=43–52 | date=January  2013 |pmid=22345659 |pmc=3440559 |doi=10.1136/gutjnl-2011-301346 |url=}}</ref><ref name="sapone-etal-2010-b" /> Gluten-related disorders include [[celiac disease]] and [[non-celiac gluten sensitivity]] (NCGS). Formerly, also ''gluten intolerance'' has been used as umbrella term, and the expression ''gluten sensitivity'' has been used either as umbrella term or for NCGS. 

Symptoms include bloating, abdominal discomfort or pain, diarrhea, constipation, muscular disturbances, headaches, migraines, severe acne, fatigue, and bone or joint pain.<ref name="sapone-etal-2010-a">{{cite journal |author=Sapone A, Lammers KM, Mazzarella G, et al. |title=Differential mucosal IL-17 expression in two gliadin-induced disorders: gluten sensitivity and the autoimmune enteropathy celiac disease |journal=Int. Arch. Allergy Immunol. |volume=152 |issue=1 |pages=75–80 |year=2010 |pmid=19940509 |pmc=2956008 |doi=10.1159/000260087 |type=Research Support, N.I.H., Extramural}}</ref><ref name="ReferenceB">{{cite journal |author=Hadjivassiliou M, Chattopadhyay AK, Grünewald RA, et al. |title=Myopathy associated with gluten sensitivity |journal=Muscle Nerve |volume=35 |issue=4 |pages=443–50 | date=April  2007 |pmid=17143894 |doi=10.1002/mus.20709 |type=Research Support, Non-U.S. Gov't}}</ref>

Also other substances of wheat other than gluten have been found to contribute to symptoms, casting doubt on the role of gluten in [[functional bowel disorder]]s like [[irritable bowel syndrome]].<ref name="ReferenceC">{{cite journal |author=Biesiekierski JR, Peters SL, Newnham ED, Rosella O, Muir JG, Gibson PR |title=No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates |journal=Gastroenterology |volume=145 |issue=2 |pages=320–8.e1–3 | date=August  2013 |pmid=23648697 |doi=10.1053/j.gastro.2013.04.051 |type=Randomized Controlled Trial}}</ref>

Gluten, named from the Latin ''gluten'' meaning ''glue'',<ref>"Gluten" def. 3. ''Oxford English Dictionary'' Second Edition on CD-ROM (v. 4.0) © Oxford University Press 2009</ref> is a substance that gives elasticity to [[dough]] helping it to rise and to keep its shape. It is found in many [[staple food]]s in the [[Western diet]]. 

== Types ==
The following classification of gluten-related disorders was announced 2011 by an expert's panel in London, published 2012 and further expanded on later that year:<ref name="Czaja-Bulsa-2014-section9-figure2">{{cite journal |author=Czaja-Bulsa G |title=Non coeliac gluten sensitivity - A new disease with gluten intolerance |journal=Clinical Nutrition (Edinburgh, Scotland) |volume= 34|issue= |pages= 189–194| date=August  2014 |pmid=25245857 |doi=10.1016/j.clnu.2014.08.012 |type=Review}} See section 9 and Figure 2: Classification of gluten-dependent disorders.</ref>
* [[Autoimmunity|Autoimmune]] disorders: [[celiac disease]], [[dermatitis herpetiformis]], [[gluten ataxia]]
* Non-autoimmune, non-allergic: disorder with unknown cause, likely immune-modulated: [[non-celiac gluten sensitivity]] (NCGS)
* [[Allergy|Allergic]]: [[food allergy]] (IgE-mediated and non-IgE-mediated), [[Wheat allergy#Exercise-induced anaphylaxis|wheat dependent exercise induced anaphylaxis]] (WDEIA), [[baker's asthma]], [[contact dermatitis]].

=== Autoimmune disorders ===
[[Autoimmunity|Autoimmune]] conditions related to gluten include [[celiac disease]], [[dermatitis herpetiformis]], and [[gluten ataxia]]. There is research showing that in certain patients with [[gluten ataxia]] early diagnosis and treatment with a gluten-free diet can improve ataxia and prevent its progression.<ref>{{cite journal |author=Hadjivassiliou M, Sanders DS, Woodroofe N, Williamson C, Grünewald RA |title=Gluten ataxia |journal=Cerebellum |volume=7 |issue=3 |pages=494–8 |year=2008 |pmid=18787912 |doi=10.1007/s12311-008-0052-x |type=Review}}</ref> The population of patients with gluten ataxia and other neurological conditions appears to have a different HLA distribution, in particular more [[HLA-DQ1]], compared to the population of typical celiac disease patients.<ref>{{cite journal |author=Troncone R, Jabri B |title=Coeliac disease and gluten sensitivity |journal=Journal of Internal Medicine |volume=269 |issue=6 |pages=582–90 | date=June  2011 |pmid=21481018 |doi=10.1111/j.1365-2796.2011.02385.x |type=Review}}</ref>

=== Non-celiac gluten sensitivity ===
In a 2009 paper, Verdu et al. defined gluten sensitivity as "one or more of a variety of immunological, morphological or symptomatic manifestations that may also be shared by celiac disease and [[irritable bowel syndrome]] (IBS)".<ref>{{cite journal |author=Verdu EF, Armstrong D, Murray JA |title=Between celiac disease and irritable bowel syndrome: the "no man's land" of gluten sensitivity |journal=Am. J. Gastroenterol. |volume=104 |issue=6 |pages=1587–94 |date=June 2009  |pmid=19455131 |pmc=3480312 |doi=10.1038/ajg.2009.188 |type=Review}}</ref> In cases where there is reactivity to gluten, yet celiac disease and wheat allergy are eliminated as possibilities, NCGS may be considered. While the general clinical picture for NCGS is similar to celiac disease in particular, it is usually less severe and neither anti-tissue transglutaminase antibodies nor autoimmune comorbidities are found.

However, in 2013, Biesiekierski JR et al. concluded that NCGS, as currently defined, might not be a discrete entity (or its effects might be confounded by [[FODMAP]] restriction), and that gluten might not cause functional gut symptoms once dietary FODMAPs are reduced.<ref name="ReferenceC"/> An editorial in Gastroenterology calls into question the existence of NCGS as a discrete entity.<ref>{{cite journal |author=Vanga R, Leffler DA |title=Gluten sensitivity: not celiac and not certain |journal=Gastroenterology |volume=145 |issue=2 |pages=276–9 |date=August 2013 |pmid=23806541 |doi=10.1053/j.gastro.2013.06.027 |type=Comment}}</ref>
The authors suggest that reduction of FODMAPs, rather than gluten or other wheat proteins, might be mechanism by which low-gluten diets improve gastrointestinal symptoms. These findings suggest that gluten sensitivity may not play a significant role in the etiology of [[functional gastrointestinal disorders]] like [[irritable bowel syndrome]].

NCGS, which is possibly immune-mediated, now appears to be more common than celiac disease.<ref name="Hogg-Collars-2014">{{cite journal |author=Hogg-Kollars S, Al Dulaimi D, Tait K, Rostami K |title=Type 1 diabetes mellitus and gluten induced disorders |journal=Gastroenterology and Hepatology from Bed to Bench |volume=7 |issue=4 |pages=189–97 |year=2014 |pmid=25289132 |pmc=4185872 |doi= |type=Review}}</ref>

=== Other conditions ===
{{Primary sources|section|date=January 2015|reason=Updated secondary sources (e.g. review articles) are needed; also, the 1991 reference comes from a period when testing for subclinical CD was undeveloped.}}
[[Anti-gliadin antibodies|Antibodies to α-gliadin]] have been significantly increased in non-celiacs individuals with [[oral ulceration]].<ref name="pmid1753350">{{cite journal | author = O'Farrelly C, O'Mahony C, Graeme-Cook F, Feighery C, McCartan BE, Weir DG | title = Gliadin antibodies identify gluten-sensitive oral ulceration in the absence of villous atrophy | journal = J. Oral Pathol. Med. | volume = 20 | issue = 10 | pages = 476–8 | year = 1991 | pmid = 1753350 | doi =10.1111/j.1600-0714.1991.tb00407.x }}</ref> Anti-α-gliadin antibodies are frequently found in celiac disease (CD), to a lesser degree [[wikt:subclinical|subclinical]] CD, but are also found in a subset who do not have the disease. Of people with [[pseudo-exfoliation syndrome]], 25% showed increased levels of anti-gliadin IgA.<ref name="pmid7656149">{{cite journal | author = Ringvold A, Overgaard RG | title = Increased IgA antibodies to gluten and gliadin in serum of persons with ocular pseudo-exfoliation | journal = Acta ophthalmologica Scandinavica | volume = 73 | issue = 2 | pages = 171–2 | year = 1995 | pmid = 7656149 | doi =10.1111/j.1600-0420.1995.tb00662.x | type=Comparative Study}}</ref> One fourth of people with Sjögren's syndrome had responses to gluten, of 5 that had positive response to gluten, only one could be confirmed as CD and another was potentially {{clarify|text=GSE|reason=Is GSE (gluten-sensitive enteropathy) meant to stand for coeliac disease, or for what else? see http://www.aafp.org/afp/2002/1215/p2259.html|date=December 2014}}, the remaining 3 appear to be gluten-sensitive. All were HLA-DQ2 and/or DQ8-positive.<ref name="pmid17613926">{{cite journal | author = Lidén M, Kristjánsson G, Valtýsdóttir S, Hällgren R | title = Gluten sensitivity in patients with primary Sjögren's syndrome | journal = Scand. J. Gastroenterol. | volume = 42 | issue = 8 | pages = 962–7 | year = 2007 | pmid = 17613926 | doi = 10.1080/00365520701195345|type=Research Support, Non-U.S. Gov't}}</ref>

== Symptoms ==
More than 250 symptoms of gluten sensitivity have been reported, including bloating, abdominal discomfort or pain, constipation and diarrhea. <ref name="Korn">Korn, Danna. ''Living gluten-free for dummies''. Hoboken, NJ: Wiley Pub., 2006. 14, 27-31. Print.</ref> Sensitivity may also present with extraintestinal symptoms, including headache, "brain fog", tingling and/or numbness in hands and feet, fatigue, as well as muscular disturbances and bone or joint pain;<ref name="sapone-etal-2010-a"/><ref name="ReferenceB"/><ref name="nijeboer-etal-2013">{{cite journal |author=Nijeboer P, Bontkes HJ, Mulder CJ, Bouma G |title=Non-celiac gluten sensitivity. Is it in the gluten or the grain? |journal=Journal of Gastrointestinal and Liver Diseases : JGLD |volume=22 |issue=4 |pages=435–40 | date=December  2013 |pmid=24369326 |doi= |type=Review}}</ref> also neuropsychiatric manifestations ("[[gluten-sensitive idiopathic neuropathies]]") have been reported on.<ref name="GenuisLobo2014">{{cite journal|author=Genuis S, Lobo RA|title=Gluten Sensitivity Presenting as a Neuropsychiatric Disorder|journal=Gastroenterology Research and Practice|volume=2014|year=2014|pages=1–6|issn=1687-6121|doi=10.1155/2014/293206|pmid=24693281|type=Review}}</ref>

== Etiology ==
When enteropathy develops in early childhood, symptomatic disease is more rapidly evident. A survey of geriatrics with celiac disease in Finland revealed that the incidence of disease was much higher than the general population.<ref>{{cite journal |author=Vilppula A, Collin P, Mäki M, et al. |title=Undetected coeliac disease in the elderly: a biopsy-proven population-based study |journal=Dig Liver Dis |volume=40 |issue=10 |pages=809–13 | date=October  2008 |pmid=18467196 |doi=10.1016/j.dld.2008.03.013 |type=Research Support, Non-U.S. Gov't}}</ref> Allergic disease may rise or fall with age; certain evidence points to the increased or daily use of non-steroidal anti-inflammatory factors (aspirin, ibuprofen) as an increased risk factor for [[urticaria]] or [[anaphylaxis]], and the sensitizing dose may include low-dose aspirin therapy used in the treatment of heart disease. NCGS may be a late-onset condition: in a prospective study performed among adults of 18 to 80 years, the median age of disease onset was found to be 55 years, with a six times higher prevalence in females than in males.<ref name="Volta-etal-2013">{{cite journal |author=Volta U, Caio G, Tovoli F, De Giorgio R |title=Non-celiac gluten sensitivity: questions still to be answered despite increasing awareness |journal=Cellular & Molecular Immunology |volume=10 |issue=5 |pages=383–92 | date=September  2013 |pmid=23934026 |pmc=4003198 |doi=10.1038/cmi.2013.28 |type=Review}}</ref>

A double-blind placebo-controlled trial found that gluten caused significantly worse pain, tiredness, bloating and stool consistency than a placebo diet in [[irritable bowel syndrome|IBS]] patients. There was no difference in celiac or gliadin antibodies between the gluten and control groups.<ref>{{cite journal | author = Biesiekierski, Jessica R et al | title=Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease: A Double-Blind Randomized Placebo-Controlled Trial|journal=Am J Gastroenterol | volume=106 | issue=3 |pages=508–514 |date=March 2011 | doi=10.1038/ajg.2010.487|url= | pmid = 21224837|type=Controlled Clinical Trial}}</ref> However a more detailed follow-up trial by the same authors found no difference between gluten or placebo groups.<ref name="ReferenceC"/>

== Causes of gluten sensitivity ==

=== Immunochemistry of glutens ===
[[Triticeae glutens|''Triticeae'' glutens]] are important factors in several inflammatory diseases. The immunochemistry can be subdivided into innate responses (direct stimulation of immune system), [[MHC class II|class II]] mediated presentation ([[HLA-DQ]]), [[MHC class I|class I]] mediated stimulation of [[killer cells]], and [[antibody]] recognition. The responses to [[gluten]] proteins and [[polypeptide]] regions differs according to the type of gluten sensitivity. The response is also dependent on the genetic makeup of the [[human leukocyte antigen]] genes. In enteropathy, there are at least 3 types of recognition, [[innate immunity]] (a form of cellular immunity priming), HLA-DQ and antibody recognition of gliadin and transglutaminase.<ref name="pmid16766754">{{cite journal |author=van Heel DA, West J |title=Recent advances in coeliac disease |journal=Gut |volume=55 |issue=7 |pages=1037–46 |date=July 2006 |pmid=16766754 |pmc=1856316 |doi=10.1136/gut.2005.075119 |type=Review}}</ref> In NCGS, there is high [[Anti-gliadin antibodies#Anti-gliadin IgG|AGA IgG]] in more than half of the cases.<ref>{{cite journal|author=Catassi C, Bai J, Bonaz B, Bouma G, Calabrò A, Carroccio A, Castillejo G, Ciacci C, Cristofori F, Dolinsek J, Francavilla R, Elli L, Green P, Holtmeier W, Koehler P, Koletzko S, Meinhold C, Sanders D, Schumann M, [[Detlef Schuppan|Schuppan D]], Ullrich R, Vécsei A, Volta U, Zevallos V, Sapone A, [[Alessio Fasano|Fasano A]]|title=Non-celiac gluten sensitivity: the new frontier of gluten related disorders|journal=Nutrients|volume=5|issue=10|year=2013|pages=3839–3853|issn=2072-6643|doi=10.3390/nu5103839|pmid=24077239|type=Review}}</ref> In [[wheat allergy]], there appears to be an innate component and the response pathways are mediated through IgE against gliadin and other wheat proteins.<ref name="pmid18036646">{{cite journal |author=Bittner C, Grassau B, Frenzel K, Baur X |title=Identification of wheat gliadins as an allergen family related to baker's asthma|issue=3 |pages=744–9 |date=March 2008 |pmid=18036646 |doi=10.1016/j.jaci.2007.09.051 |type=Research Support, Non-U.S. Gov't |volume=121 |journal=Journal of Allergy and Clinical Immunology}}</ref><ref name="pmid18186814">{{cite journal |author=Matsuo H, Dahlström J, Tanaka A, et al. |title=Sensitivity and specificity of recombinant omega-5 gliadin-specific IgE measurement for the diagnosis of wheat-dependent exercise-induced anaphylaxis |journal=Allergy |volume=63 |issue=2 |pages=233–6 |date=February 2008 |pmid=18186814 |doi=10.1111/j.1398-9995.2007.01504.x|type=Evaluation Studies}}</ref><ref name="pmid17655322">{{cite journal |author=Akagawa M, Handoyo T, Ishii T, Kumazawa S, Morita N, Suyama K |title=Proteomic analysis of wheat flour allergens |journal=Journal of Agricultural and Food Chemistry |volume=55 |issue=17 |pages=6863–70 |date=August 2007 |pmid=17655322 |doi=10.1021/jf070843a |type=Research Support, Non-U.S. Gov't}}</ref>

== Pathophysiology ==
Compared to the [[Coeliac disease#Pathophysiology|pathophysiology of celiac disease]], the pathophysiology of NCGS is far less understood.

A literature review of 2014 found that patients suffering from NCGS "are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis and clinical history, and, probably, clinical course".<ref name="mansueto-etal-2014">{{cite journal|author=Mansueto P, Seidita A, D’Alcamo A, Carroccio A|title=Non-Celiac Gluten Sensitivity: Literature Review|journal=Journal of the American College of Nutrition|volume=33|issue=1|year=2014|pages=39–54|issn=0731-5724|doi=10.1080/07315724.2014.869996|pmid=24533607|type=Review}}</ref>

=== Genetics ===
Celiac disease (CD) and NCGS are closely linked with [[human leukocyte antigen]] (HLA) class II genes, [[HLA-DQ2]] and [[HLA-DQ8]], located on [[Chromosome 6 (human)#p-arm|chromosome 6p21]].<ref name="sapone-etal-2010-b">{{cite journal |author=Sapone A, Bai JC, Ciacci C, Dolinsek J, Green PH, Hadjivassiliou M, Kaukinen K, Rostami K, Sanders DS, Schumann M, Ullrich R, Villalta D, Volta U, Catassi C, Fasano A |title=Spectrum of gluten-related disorders: consensus on new nomenclature and classification |journal=BMC Medicine |volume=10 |issue= |pages=13 |year=2012 |pmid=22313950 |pmc=3292448 |doi=10.1186/1741-7015-10-13 |type=Review}}</ref> Nearly all CD patients are NLA-DQ2/HLA-DQ8 positive,<ref name="sestak-etal-2013">{{cite journal |author=Sestak K, Fortgang I |title=Celiac and Non-Celiac Forms of Gluten Sensitivity: Shifting Paradigms of an Old Disease |journal=British Microbiology Research Journal |volume=3 |issue=4 |pages=585–589 | date=October  2013 |pmid=25383340 |pmc=4224078 |doi=10.9734/BMRJ/2013/6083 |type=Review}}</ref> with 95% HLA-DQ2 and the rest usually HLA-DQ8 (which is carried by 30% of Caucasians).<ref name="sapone-etal-2010-b"/> However, the [[Sensitivity and specificity|specificity]] of HLA-DQ2 and/or HLA-DQ8 for CD is low, with estimates ranging from 36% to 53%. In NCGS patients, the HLA-DQ2 and/or HLA-DQ8 alleles are present in only about 50%, which is still a greater proportion than in the general population.<ref name="sapone-etal-2010-b"/><ref name="sestak-etal-2013"/>

=== Complications ===
{{Primary sources|section|date=December 2014|reason=Updated secondary sources (e.g. review articles) are needed.}}
Studies using [[anti-gliadin antibodies]] (AGA) reveal that {{clarify|text=diagnosed or untreated|reason=Diagnosed/untreated for what?|date=December 2014}} individuals with AGA have an increasing risk for lymphoid cancers and decreased risk for other conditions associated with affluence.<ref name="pmid17206762">{{cite journal | author = Anderson LA, McMillan SA, Watson RG, et al. | title = Malignancy and mortality in a population-based cohort of patients with coeliac disease or "gluten sensitivity" | journal = World J. Gastroenterol. | volume = 13 | issue = 1 | pages = 146–51 | year = 2007 | pmid = 17206762 | doi = 10.3748/wjg.v13.i1.146 | type=Retrospective Studies}}</ref>

== Diagnosis ==
A literature review of 2014 found that non-coeliac gluten sensitivity diagnosis can be reached only by excluding celiac disease (CD) and [[wheat allergy]].<ref name="mansueto-etal-2014"/>

Persons suspected of having celiac disease may undergo [[serological]] testing for IgA anti-tissue transglutaminase antibodies (abbreviated anti-tTG antibodies or anti-TG2 antibodies) and anti-[[endomysium|endomysial]] antibodies (abbreviated EMA) provided the IgA-level is high, and if IgA is low, testing for certain IgG antibodies; in case of positive serological indication, a [[Biopsy#Gastrointestinal tract|duodenal biopsy]] may [[Coeliac disease#Diagnosis|confirm active celiac disease]].<ref name="Tonutti-etal-2014">{{cite journal |author=Tonutti E, Bizzaro N |title=Diagnosis and classification of celiac disease and gluten sensitivity |journal=Autoimmunity Reviews |volume=13 |issue=4-5 |pages=472–6 |year=2014 |pmid=24440147 |doi=10.1016/j.autrev.2014.01.043 |type=Review}}</ref>

Eliminating the possibility of CD can generally also be done by adding [[HLA-DQ]] typing. The absence of HLA-DQ2 and HLA-DQ8 has a very high negative predictive value for CD,<ref name="sapone-etal-2010-b"/><ref name="LebwohlGreen2012">Lundin KEA, Alaedini A, ''Non-celiac Gluten Sensitivity''. In: {{cite book|author=Lebwohl B, Green PHR|title=Celiac Disease, An Issue of Gastrointestinal Endoscopy Clinics|url=http://books.google.com/books?id=mWBFEpD2TrQC|date=1 November 2012|publisher=Elsevier Health Sciences|isbn=1-4557-4735-1|pages=}}</ref> and the predictive value can be further enhanced by including [[HLA-DQ7#DQ7.5|HLA-DQ7.5]] (HLA-DQ2 and HLA-DQ8 are found in coeliac disease 98% of the time in Caucasians, HLA-DQ7.5 present in the remaining 1.6% and only 0.4% of Caucasians are missed with the combination of these 3).{{citationneeded|date=January 2015}} Without serological or HLA-DQ2/8 positivity, celiac disease is likely not present. HLA-DQ typing has a practical advantage in that it is the only diagnostic test that allows to exclude CD when a patient is already on a gluten-free diet; however, as not only celiacs are HLA-DQ2/HLA-DQ8 positive, this method has a higher false positive rate than anti-TG2 and EMA antibody testing.

A four-of-five rule was proposed 2010 for confirming celiac disease, with the disease confirmed if at least four of the following five criteria are satisfied:<ref name="sapone-etal-2010-b"/><ref name="pmid20670718">{{cite journal |author=Catassi C, Fasano A |title=Celiac disease diagnosis: simple rules are better than complicated algorithms |journal=The American Journal of Medicine |volume=123 |issue=8 |pages=691–3 | date=August  2010 |pmid=20670718 |doi=10.1016/j.amjmed.2010.02.019 |type=Research Support, Non-U.S. Gov't}}</ref>
*typical symptoms of celiac disease;
*positivity of serum celiac disease immunoglobulin, A class autoantibodies at high titer;
*human leukocyte antigen (HLA)-DQ2 or DQ8 genotypes;
*celiac enteropathy at the small bowel biopsy; and
*response to the gluten-free diet.

== Treatment ==
For patients with celiac disease, a lifelong strict gluten-free diet is the only effective treatment to date;<ref name="LamacchiaCamarca2014">{{cite journal |author=Lamacchia C, Camarca A, Picascia S, Di Luccia A, Gianfrani C |title=Cereal-based gluten-free food: how to reconcile nutritional and technological properties of wheat proteins with safety for celiac disease patients |journal=Nutrients |volume=6 |issue=2 |pages=575–90 |year=2014 |pmid=24481131 |pmc=3942718 |doi=10.3390/nu6020575 |type=Review}}</ref><ref name="Czaja-Bulsa-2014-table2">{{cite journal |author=Czaja-Bulsa G |title=Non coeliac gluten sensitivity - A new disease with gluten intolerance |journal=Clinical Nutrition (Edinburgh, Scotland) |volume= 34|issue= |pages= 189–194| date=August  2014 |pmid=25245857 |doi=10.1016/j.clnu.2014.08.012 |type=Review}} See [http://www.clinicalnutritionjournal.com/article/S0261-5614%2814%2900218-0/fulltext#tbl2 Table 2: Characteristics of gluten-dependent disorders].</ref> for patients diagnosed with NCGS, there are still open questions concerning for example the duration of such a diet; for patients with [[wheat allergy]], the individual average is 6 years of gluten-free diet with exception for persons with anaphylaxis for whom the diet is to be wheat-free for life.<ref name="Czaja-Bulsa-2014-table2"/>

A gluten-free diet should not be started before the tests for excluding celiac disease have been performed, for the reason that the serological and biopsy tests for celiac disease are reliable only if the patient is consuming gluten.

Preferably, newly diagnosed celiacs seek the help of a dietician to receive support for identifying hidden sources of gluten, planning balanced meals, reading labels, food shopping, dining out, and dining during travel.<ref name="pmid24444577">{{cite journal |author=Pelkowski TD, Viera AJ |title=Celiac disease: diagnosis and management |journal=American Family Physician |volume=89 |issue=2 |pages=99–105 | date=January  2014 |pmid=24444577 |doi= |url=}}</ref> Knowledge of hidden sources of gluten is important for celiac disease patients as they need to be very strict on eating only gluten-free food; for NCGS patients, it is not certain how strict the diet needs to be.<ref>{{cite journal|author=Cristofori F, Arezzo F, Gentile A, Francavilla R|title=Gluten Sensitivity in Pediatrics: A Clinical Conundrum|journal=Current Pediatrics Reports|date=September 2014|volume=2|issue=3|pages=204–210|url=http://link.springer.com/article/10.1007/s40124-014-0053-9|doi=10.1007/s40124-014-0053-9}}</ref> Balanced eating is important because, [[Gluten-free diet#Risks|unless particular care is taken]], a gluten-free diet can be lacking in vitamins, minerals and fiber and too high in fat and calories.<ref>{{cite article|author=Capili B, Chang M, Anastasi JK|url=http://www.sciencedirect.com/science/article/pii/S1555415514005224|title=A Clinical Update: Nonceliac Gluten Sensitivity—Is It Really the Gluten?|journal=The Journal for Nurse Practitioners. Special Focus: Legal Matters|volume=10|issue=9|date=October 2014|pages=666–673}}</ref>

Gluten-free oats can provide a valuable source of fiber, vitamin B, iron, zinc and complex carbohydrates.<ref name="pmid12844381">{{cite journal |author=Størsrud S, Hulthén LR, Lenner RA |title=Beneficial effects of oats in the gluten-free diet of adults with special reference to nutrient status, symptoms and subjective experiences |journal=Br. J. Nutr. |volume=90 |issue=1 |pages=101–7 |date=July 2003 |pmid=12844381 |doi= 10.1079/BJN2003872|type=Research Support, Non-U.S. Gov't}}</ref> Recent studies show that gluten-sensitive individuals on a gluten-free diet often get too much simple carbohydrate, too little fiber and vitamin B. Currently most guidelines do not include oats in a gluten-free diet. While this is likely to change, oats are not recommended within a year of diagnosis because of the risk of [[Oat sensitivity#Avenin-sensitive enteropathy|avenin-sensitive enteropathy]] (ASE), the desire to establish a clinical baseline and complexity of the contamination issue.<ref name="Rashid">{{cite web
| title=Guidelines for Consumption of Pure and Uncontaminated Oats by Individuals with Celiac Disease
| last=Rashid| first=Mohsin
| date=2007-06-08
| url=http://www.celiac.ca/Articles/PABoatsguidelines2007June.html
| publisher=Professional Advisory Board of Canadian Celiac Association
| accessdate=2008-08-14
}}</ref> Consuming oats when anti-gliadin antibodies or gliadin are present increases anti-avenin antibodies and may promote ASE, therefore duodenal biopsy may be recommended after oat consumption is initiated; the DQ phenotype of all 3 ASE individuals studied so far indicated DQ2 homozygotes are at risk for ASE.{{citationneeded|date=January 2015}} Guidelines are also available for the introduction of pure, uncontaminated oats into the gluten-free diet.<ref>{{cite journal |author=Rashid M, Butzner D, Burrows V, et al. |title=Consumption of pure oats by individuals with celiac disease: a position statement by the Canadian Celiac Association |journal=Can. J. Gastroenterol. |volume=21 |issue=10 |pages=649–51 | date=October  2007 |pmid=17948135 |pmc=2658132 |doi= |type=Guideline}}</ref>

== Epidemiology ==
The incidence of celiac disease and of wheat allergy is estimated each to lie at around 1% of the population. The incidence of NCGS is unknown; estimates range from 0.6% to 6%.<ref name="Czaja-Bulsa-2014-table2"/>

In Europe, the average consumption of gluten is 10g to 20g per day, with parts of the population reaching 50g or more per day.<ref name="sapone-etal-2010-b"/>

== Society and culture ==
[[File:Espiga barrada.jpg|thumb|right|Crossed-grain symbol of the Association Of European Coeliac Societies (AOECS)]]
In various countries, [[Gluten-free diet#Regulation and labels|regulations and labelling requirements for gluten-free food products]] have been implemented.

For Europe, the ''Commission Regulation (EC) No. 41/2009 of 20 January 2009 concerning the composition and labelling of foodstuffs suitable for people intolerant to gluten'' has laid down harmonised rules on the content and labelling of these foodstuffs, setting out the conditions under which foods may be labelled as "gluten-free" or "very low gluten".<ref>{{cite web|url=http://eur-lex.europa.eu/legal-content/EN/TXT/?qid=1420391798410&uri=URISERV:sa0024|title=Gluten-free foodstuffs|publisher=EUR-Lex|date=22 February 2011|accessdate=4 January 2015}}</ref> Having entered into force on 10 February 2009 and taken effect on 1 January 2012, these rules have been repealed with effect as of 20 July 2016. The background is that, in line with the ''Regulation (EU) No 609/2013 on food for specific groups'', gluten-free foods shall, in future, be legislated for under the EU Food Information for Consumers Regulation ([[Regulation (EU) No. 1169/2011]]). Furthermore, the ''Commission Implementing Regulation (EU) No 828/2014 of 30 July 2014 on the requirements for the provision of information to consumers on the absence or reduced presence of gluten in food'' extends the rules of Regulation (EC) 41/2009 on "gluten-free" and "very low gluten" statements also to non pre-packed foods such as those served in restaurants. The implementing regulation also clarifies how consumers are to be informed of the difference between foods that are naturally free of gluten and products that are specially formulated for gluten-intolerant persons.<ref>{{cite web|url=http://ec.europa.eu/food/food/labellingnutrition/glutten-free-foods/index_en.htm|title=Foods for people intolerant to gluten (gluten-free foods)|publisher=European Commission|accessdate=4 January 2015}}</ref>

Recognition of gluten-free packaged foods is facilitated by the crossed-grain symbol, representing a crossed [[Ear (botany)|ear]] of wheat. The symbol is used as a logo that facilitates food shopping for patients with CD and other gluten-related disorders. The symbol, which is protected as a trademark in Europe and the United States and is covered by worldwide copyright, can be represented in any colour.<ref>{{cite web|url=http://www.coeliac.org.uk/food-industry-professionals/the-crossed-grain-symbol/|title=The Crossed Grain Symbol|publisher=Coeliac UK|accessdate=12 January 2015}}</ref><ref>{{cite web|url=http://www.aoecs.org/?id=-31|title=Licensing the Crossed Grain symbol|publisher=Association of European Coeliac Societies (AOECS)|accessdate=12 January 2015}}</ref>

== See also ==
* [[List of allergies]]
* [[Vomitoxin]], a [[mycotoxin]] which currently occurs abundantly in grains in [[Norway]] due to [[climate change]].<ref>http://www.vkm.no/dav/eee04d10c4.pdf</ref> It might give rise to somewhat comparable symptoms.

== References ==
{{reflist|2}}

{{Gluten sensitivity}}

{{DEFAULTSORT:Gluten Sensitivity}}
[[Category:Immune system disorders]]
[[Category:Wheat]]
[[Category:Sensitivities]]

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