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	Coeliac disease is a featured article; it (or a previous version of it) has been identified as one of the best articles produced by the Misplaced Pages community. Even so, if you can update or improve it, please do so.
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Ideal sources for Misplaced Pages's health content are defined in the guideline Misplaced Pages:Identifying reliable sources (medicine) and are typically review articles. Here are links to possibly useful sources of information about Coeliac disease. PubMed provides review articles from the past five years (limit to free review articles) The TRIP database provides clinical publications about evidence-based medicine. Other potential sources include: Centre for Reviews and Dissemination and CDC

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Coeliac/Celiac: Please read prior discussions regarding the name of this article at /Archive 1#Requested move.

This article was the subject of an educational assignment in 2013 Q3. Further details were available on the "Education Program:Case Western Reserve University/ANTH 302 Darwinian Medicine (Fall 2013)" page, which is now unavailable on the wiki.

Archives

/Archive 1 /Archive 2 /Archive - oat controversy /Archive 3 /Archive 4

Terminology

... has been reviewed in an international forum doi:10.1136/gutjnl-2011-301346 JFW | T@lk 21:31, 11 December 2012 (UTC)

NEJM review

doi:10.1056/NEJMcp1113994 ("Clinical practice") JFW | T@lk 11:28, 21 December 2012 (UTC)

RfC: Claims of link between medical conditions and WP:WEIGHT

Does a simple (single sentence) claim of a link between medical conditions, in a large article, need to be "fully established" or "definitive" to not run afoul of WP:WEIGHT or any other policy? (Assuming it meets the requirements of WP:MEDRS.) Int21h (talk) 05:17, 9 June 2013 (UTC)

• Coeliac disease has been associated with a very large number of conditions. Int21h has decided to emphasise one (atopic dermatitis) of many associated skin conditions in their edits. I don't think that is the right way of going about it. The only classically associated skin condition is dermatitis herpetiformis. JFW | T@lk 22:12, 10 June 2013 (UTC)
  • So am I to understand you assert an association must be a "classic association" to be mentioned on Misplaced Pages? Int21h (talk) 04:17, 11 June 2013 (UTC)
    • You are twisting my words. Please don't do that. JFW | T@lk 20:48, 24 June 2013 (UTC)

• if a link between conditions is to be mentioned, then there must be a good reason why other linked conditions are *not* mentioned. So if there are multiple conditions of at least as certain association as the one currently mentioned, we should either mention all or none. Quantum Burrito (talk) 23:21, 20 June 2013 (UTC)
  • What other conditions? Int21h (talk) 07:53, 21 June 2013 (UTC)
    • doi:10.1155/2012/952753 mentions psoriasis, alopecia areata etc. Do they not count? JFW | T@lk 20:48, 24 June 2013 (UTC)

This is a tentative link at best as discussed above. Maybe if we had a subpage these less significant details could be discussed there. Doc James (talk · contribs · email) (if I write on your page reply on mine) 20:53, 24 June 2013 (UTC)

• If this article can get into very technical details about tissue transglutaminase and epitopes which go way over the head of over 99.9% of readers, I don't see why it can't discuss things which are much more relevant to the average reader such as associated medical conditions. The proposed edit adds stuff about eczema; however, the cited review by Caproni et al 2012 discusses psoriasis after DH and says "among the inflammatory skin diseases improved by gluten-free diet, psoriasis is one of the most important". It follows with overviews of alopecia areata, chronic uticaria, hereditary angioneurotic edema, cutaneous vasculitis, and finally atopic dermatitis. I suggest citing Caproni et al with a more balanced overview of the skin conditions the reviewers feel are noteworthy. At the same time, Misplaced Pages articles improve iteratively. For example, someone probably didn't try to keep out the details on prolamins on the basis that, say, the diet section lacked details. II | (t - c) 03:32, 25 June 2013 (UTC)

The article is in need of simplification. Doc James (talk · contribs · email) (if I write on your page reply on mine) 05:38, 19 August 2013 (UTC)

2013 clinical guideline

http://www.ncbi.nlm.nih.gov/pubmed/23609613?dopt=Abstract Doc James (talk · contribs · email) (if I write on your page reply on mine) 05:38, 19 August 2013 (UTC)

doi:10.1038/ajg.2013.79 is the DOI. It's behind a paywall on the Am J Gastroenterol website, always a great idea with guidelines. JFW | T@lk 08:37, 26 August 2013 (UTC)

External links

I don't know where to put this comment so I'll put it here. In the history section there's a brief reference to the diet proposed in 1924 by Sydney Haas with the comment: "This diet remained in vogue until the actual cause of coeliac disease was determined." But the diet is still very much 'in vogue' in a more developed form referred to by Haas as the Specific Carbohydrate Diet. It was presented by Haas in 1951 in his medical textbook 'The Management of Celiac Disease'. So I'm suggesting that a link should be provided to the Wiki article 'Specifi Carbohydrate Diet' which discusses this form of the diet and also discusses a 1987 book for laypeople which is still in print and which lists thirteen web sites devoted to the issue. This 1987 book had been translated as of 2005 into seven languages, a good indication that many people have found the diet useful. In fact the diet addresses a whole range of digestive problems, not just coeliac disease.

Until recently, the article had several useful external links to reliable, professionally-written websites with relevant extra information that could be useful to interested readers and future editors (e.g. the US NIH). This has been removed and replaced with a link to "DMOZ", which appears to be a vague web directory of oddly chosen non-professional websites. I tried to restore the professional medical links, but they were removed and the DMOZ link replaced, with the claim that this is in line with WPMED consensus. Can someone enlighten me as to where WPMED stipulates we must replace reliable medical resources with strange web directories? Arripay (talk) 00:48, 22 September 2013 (UTC)

WP:NOT states we are not a collection of external links. The great think about DMOZ is that one can go there and help improve the links they have if you deem they are not professional. Doc James (talk · contribs · email) (if I write on your page reply on mine) 11:35, 22 September 2013 (UTC)

Let me get this straight - this is not a collection of external links, so we should link to a collection of external links. We can then edit the other site's collection of links, but we can't do that directly on wikipedia - the website on which I am actually an editor. Nope, still making no sense to me I'm afraid. The manual of style for medicine-related pages says of external links: "Disease-related organisations and government health departments sometimes produce web pages containing substantial information that would be of interest to readers wishing to further study the topic. Such links are chosen for the information content, not because the organisation is particularly worthy or helpful." This perfectly describes the links that were there (NIH etc). That's been changed to link to a bunch of irrelevant stuff. It baffles me that anyone could see that as an improvement. Arripay (talk) 23:27, 22 September 2013 (UTC)

None of the links really contains anything our article does not already discuss. Doc James (talk · contribs · email) (if I write on your page reply on mine) 12:31, 23 September 2013 (UTC)

May as well delete all of them, then. Arripay (talk) 19:21, 24 September 2013 (UTC)

Updates in Genetics in reference to Evolutionary History

I would like to make the following changes to the final paragraph in the Genetics subsection so the paragraph reads:

The prevalence of CD genotypes in the modern population is not completely understood. Given the characteristics of the disease and its apparent strong heritability, it would normally be expected that the genotypes would undergo negative selection and to be absent in societies where agriculture has been practised the longest (compare with a similar condition, Lactose intolerance, which has been negatively selected so strongly that its prevalence went from ~100% in ancestral populations to less than 5% in some European countries). This expectation was first proposed by Simoons (1981). By now, however, it is apparent that this is not the case; on the contrary, there is evidence of positive selection in CD genotypes. The DQ2.5 haplotype, in certain tests did not show a preference for positive selection but, 4 out of the network of 40 CD related genes showed a positive selection. The four genes are also risk factors for other diseases such as Crohn’s, Type 1 diabetes, and other autoimmune/inflammatory diseases. It is suspected that some of them may have been beneficial by providing protection against bacterial infections. One particular loci, SH2B3 when in a homozygous patient, allows for a higher concentration of cytokines responsible for inflammatory responses. This observation further suggests that the four loci with a positive selection may play a role in fighting infection but makes individuals more susceptible to autoimmune diseases like coeliac.

End of edit

My reasoning for this change is to update the proposed cause of coeliac. What was present in the article wasn't completely correct and I believe this expands on why this disease is still prevalent despite its negative effects. Please let me know what changes you would suggest either here or on my talk page. Thanks.

Note: The reference numbers should changed once the edit is made. If I messed that up, please let me know.

Tcs46 (talk) 02:04, 31 October 2013 (UTC)

Per WP:MEDRS we typically use secondary sources rather than primary sources. This is a primary source ]. Can you make these changes? Thanks Doc James (talk · contribs · email) (if I write on your page reply on mine) 12:42, 31 October 2013 (UTC)

The article you linked to is already present in the article and was not added by me. Tcs46 (talk) 15:14, 31 October 2013 (UTC)

I'm not finding it. It would be helpful if you would use PMIDs (and add them to your suggested text to make it easier to review your sources). For example, I do not see PMID 19805228 in the current article. SandyGeorgia (Talk) 19:03, 31 October 2013 (UTC)

OK, I found and tried to fix the problem, and failed so I archived the old sections. That primary source was not in the article-- but it was being pulled into the ref list here on talk because it was discussed elsewhere on this talk page. I fixed it by changing the reflist parameter in this talk section and archiving the old talk sections. There is a reference template that will pull only from the current section on talk, but I don't know where to find it-- perhaps someone else will fix it. SandyGeorgia (Talk) 19:16, 31 October 2013 (UTC)

Proposed change

So, you've included the entire current para above with your changes. Is it correct that your proposed change is adding these two sentences (for which I have corrected your citation of Abadie to the style used in the article):

• The DQ2.5 haplotype, in certain tests did not show a preference for positive selection but, 4 out of the network of 40 CD related genes showed a positive selection. The four genes are also risk factors for other diseases such as Crohn’s, Type 1 diabetes, and other autoimmune/inflammatory diseases.
• One particular loci, SH2B3 when in a homozygous patient, allows for a higher concentration of cytokines responsible for inflammatory responses. This observation further suggests that the four loci with a positive selection may play a role in fighting infection but makes individuals more susceptible to autoimmune diseases like coeliac.

References

1. Walcher, Dwain N. and Kretchmer, Norman (1981). Food, nutrition, and evolution: food as an environmental factor in the genesis of human variability. Papers presented at the International Congress of the International Organization for the Study of Human Development, Masson Pub. USA. pp. 179–199. ISBN 0893521582.{{cite book}}: CS1 maint: multiple names: authors list (link)
2. ^ , PMC 21219178.
3. Catassi, Carlo (2005). "Where Is Celiac Disease Coming From and Why?". Journal of Pediatric Gastroenterology & Nutrition. 40 (3): 279. doi:10.1097/01.MPG.0000151650.03929.D5.
4. Zhernakova A; et al. (2010). "Evolutionary and Functional Analysis of Celiac Risk Loci Reveals SH2B3 as a Protective Factor against Bacterial Infection". The American Journal of Human Genetics. 86 (6): 970. doi:10.1016/j.ajhg.2010.05.004. {{cite journal}}: Explicit use of et al. in: |author= (help)
5. ^ Abadie V, Sollid L, Barreiro L, Jabri B (2011). "Integration of genetic and immunological insights into a model of Celiac Disease pathogenesis". Annual Review of Immunology: 493–525. doi:10.1146/annurev-immunol-040210-092915. PMID 21219178.{{cite journal}}: CS1 maint: multiple names: authors list (link)

I am not following why you want to add these two sentences, but perhaps DocJames or Jdfwolff will. SandyGeorgia (Talk) 19:31, 31 October 2013 (UTC)

They add clarification to the genetic history. The paragraph before the change made it seem that the haplotype was positively selected for. This is incorrect. 4 other genes within the network are positively selected for and this change gives an example to show their significance in other diseases related to coeliac. Tcs46 (talk) 18:46, 1 November 2013 (UTC)

If clarification was the intent, perhaps one of the other editors here can reword in such a way that that is achieved. SandyGeorgia (Talk) 18:48, 1 November 2013 (UTC)

Selenium and thyroid disease

3AlarmLampscooter added a discussion about doi:10.4415/ANN_10_04_06. This seems to pose a number of theories about why autoimmune thyroiditis is linked with coeliac disease, and places hyposelenaemia at the centre of the hypothesis. As SandyGeorgia suggests, this is not something that has made its way into the major reviews on coeliac disease. The theory is probably too obscure to discuss here with such certainty (WP:WEIGHT is the relevant policy). If stronger sources can be provided, this can be revisited. JFW | T@lk 20:50, 17 December 2013 (UTC)

• The link between coeliac disease and low selenium levels was published in the BMJ all the way back in 1985. Nature Endocrinology published a review last year calling selenium deficiency "likely to constitute a risk factor for a feedforward derangement of the immune system". While benefits of actually supplementing selenium in either case is still a very controversial topic and perhaps should be left out, I think it's pretty clear selenium is a legitimate factor in the diseases, and all the explained pathways between selenium, coeliac and thyroiditis in the 2010 review I cited checked out fine to me. 3AlarmLampscooter (talk) 14:13, 18 December 2013 (UTC)

PMID 22009156 is a recent review; Jfdwolff may have better information about the journal. SandyGeorgia (Talk) 17:36, 18 December 2013 (UTC)

My concern is that the recent reviews don't mention this link directly. The only source that unequivocally claims that in coeliac disease, the predisposition to thyroid disease is mediated by hyposelenaemia is the obscure review in Ann Ist Super Sanità. Selenium status may be abnormal in coeliac disease, but can we say with confidence that it is a causal relationship? I think the fact that this hypothesis is not followed by any other reviewer is sufficient to exclude it from this very broad article.

Unfortunately I have no access to the Nat Rev Endocr review (doi:10.1038/nrendo.2011.174), but if it does not mention coeliac disease explicitly I don't think it's going to help us much. JFW | T@lk 19:30, 18 December 2013 (UTC)

Funny how fast things can progress, the new version of Clinical Gastroenterology just came out a few days ago, now citing the Stazi and Trinti paper on the link to autoimmune thyroiditis. Highlights include "Micronutrient screening for zinc, copper, and selenium should be performed at least annually and sooner, if deficiency is suspected" and "CD patients deficient in selenium may complain of generalized fatigue and muscle weakness. Physical exam and labwork may reveal low serum selenium levels, hypertension, cardiomyopathy, elevated transaminases, autoimmune thyroid disease, and perhaps even psychiatric manifestations (schizophrenia)". I'd say at this point we should update the article to reflect this. Any objections 3AlarmLampscooter (talk) 17:17, 20 December 2013 (UTC)

I am happy to mention selenium deficiency with doi:10.1007/978-1-4614-8560-5_11 as a reference, but it doesn't seem that this source says that hyposelenaemia is the cause of the thyroid disease, so I don't think I can support any claims to that effect. JFW | T@lk 23:14, 21 December 2013 (UTC)

I've re-added the content with some more reserved wording on possible causation versus correlation, in addition to copper and zinc deficiency. Other evidence of selenium's beneficial effects for some patients continues to grow: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003098 3AlarmLampscooter (talk) 20:21, 24 October 2014 (UTC)

3AlarmLampscooter The points about trace element deficiencies are reasonable and the source is good, but the fringe theory about the association with thyroid disease needs to stay out. We would need a much stronger source than what you've presented so far. JFW | T@lk 22:00, 26 October 2014 (UTC)

Incidence of Selenium deficiency in thyroid disease, Celiac Disease and Autoimmune Thyroid Disease. 3AlarmLampscooter (talk) 20:47, 1 December 2014 (UTC)

Hwp1 proposed to be included in the transglutaminase section

Hwp1 should be added to the Coeliac Disease transglutaminase section page.

I think Hwp1 (Candida Albicans protein) is as required to be cited in the Coeliac Disease page of Misplaced Pages as VP7 (Rotavirus protein). VP7 is greatly related to Coeliac disease, but Hwp1 too.

VP7 is cited in the Coeliac Disease Misplaced Pages page and Hwp1 is not.

Moreover, VP7 is cited in the transglutaminase section when VP7 is NOT so far defined as a transglutaminase substrate. Hwp1 has been proven as a transglutaminase substrate, It has also been clearly associated with celiac disease by the homology between Hwp1 and gliadin.

The three references below has been considered by Doc James as Not suitable to allow Hwp1 to be included.

1) Staab JF, et al. (1999) Adhesive and mammalian transglutaminase substrate properties of Candida albicans Hwp1. Science 283:1535-1538

2) Nieuwenhuizen WF, et al. (2003) Is Candida albicans a trigger in the onset of coeliac disease?. Lancet 361: 2152–54

3) Sakly W, Thomas V, Quash G, El AS. 2006. A role for tissue transglutaminase in alpha-gliadin peptide cytotoxicity. Clin. Exp. Immunol. 146:550–558

But these three references show that:

1) Hwp1 is a transglutaminase substrate.

2) Hwp1 share homology in primary sequence with gliadin.

3) Gliadin is a transglutaminase substrate.

4) Hwp1 and gliadin enter human body by the same route: oral route and transglutaminase acts on both gliadin and Hwp1 being this transglutaminase action related to associated diseases (Coeliac Disease and Candidiasis respectively)

5) Hwp1 and gliadin are cause of diseases in human oro-esapho-gastro-intestinal system.

6) Hwp1 (Candidiasis) and gliadin (Coeliac disease) related diseases share histophatological tissue damage characteristics.

7) Hwp1 is a Candida Albicans virulence factor in Candididasis disease and gliadin is the causative agent of coeliac disease.

8) Removing of Hwp1 (hwp1 knockout mice experiments) is related with significantly reduced virulence and removing of gluten

I think that the eight proven facts above do Hwp1 inclusion in the transglutaminase section of Coeliac Disease page of WIkipedia neccesary to have a complete understanding of the relationships in this disease.

The truth is I still do not understand why these references are invalid having been published in prestigious publications like Science or Lancet.

--FOTGCREN (talk) 13:47, 18 February 2014 (UTC)

The edit in question is this one were the primary sources were removed and the review left.

This is a primary source

This is a primary source

And this is a primary source

Per WP:MEDRS we should be using secondary sources such as review articles Doc James (talk · contribs · email) (if I write on your page reply on mine) 14:19, 18 February 2014 (UTC)

Indented line

--Ok. Thanks for the clarifications. I now can understand that my references are primary sources and they are not allowed as references in this type of medical pages of Misplaced Pages. I need Misplaced Pages reliable sources that acomplish with Misplaced Pages policies. I´ll try to find them. I request anybody to help me to do it. I think Hwp1 must be included in transglutaminase section of Coeliac Disease page. --FOTGCREN (talk) 15:12, 18 February 2014 (UTC)

Hello FOTGCREN, I think I need to clarify why I reverted your edit despite your use of secondary sources. I think you might be falling foul of WP:NOR/WP:SYNTH, suggesting an association that can only be supported by sources if you extrapolate stuff from them. If I search PubMed with MeSH "MAJR" headings "celiac disease" and "candida albicans" only a single paper comes up (PMID 12826451). When I review citations to this paper in Scopus, it has received some citations but not in the core reviews of coeliac disease in any of the major journals. I think it is a theory that has not been sufficiently investigated to be suitable for inclusion on this page.

I am not at all clear whether "Alternative Medicine Review" is a WP:MEDRS, by the way. JFW | T@lk 11:43, 28 February 2014 (UTC)

Oh, and FOTGCREN, your personal website seems to concede that this is still a hypothesis. It's not common for encyclopedia articles to discuss hypotheses that are awaiting proof, unless the proof has been elusive and the hypothesis has received extremely widespread attention (e.g. the Higgs boson). JFW | T@lk 11:54, 28 February 2014 (UTC)

First of all, thanks for the clarifications. I agree with almost everything you say. Anyway, there is a fact, two proteins, Hwp1 and gliadin, its primary sequences are available in UNIPROT. http://www.uniprot.org/uniprot/P46593, http://www.uniprot.org/uniprot/Q9ZP09, http://www.uniprot.org/uniprot/P08079. It is simple. Compare them. Protein structure define protein function and enzyme substrate ability. Primary sequence has its role in building structure of proteins. It is not a definitive proof but it is very suspicious. Maybe not so suspicious as the fact that after Nieuwenhuizen, research on these issues does not exist. Maybe does not interest that were to conclude that the cereals couln´t be a human food. I´ll try one last editting trying to accomplish all requirements about "WP:NOR" and "WP:PRIMARY" — Preceding unsigned comment added by FOTGCREN (talk • contribs) 13:38, 28 February 2014 (UTC)

Oh, and maybe the Higgs boson hypothesis, like searching what is the exactly number of stars in the universe be an hypothesis that has received extremely widespread attention. To me it has no interest compared with the minimun possibility of knowing how any food you eats everyday could be the cause of any disease that affects you in the future. Thats is important to me. Not the Higgs Bosson. I suppose I'm a rare guy. Thanks anyway for your time.

--FOTGCREN (talk) 17:41, 28 February 2014 (UTC)

Have reverted these edits as:

1) This line was copied and pasted from this source "Nieuwenhuizen et al.9 demonstrated that the virulent factor of Candida albicans—hyphal wall protein 1—shares similar sequence homology of amino acids with gliadin." 2) This source does not mention the disease in question Doc James (talk · contribs · email) (if I write on your page reply on mine) 19:38, 28 February 2014 (UTC)

And this one? There were three paragraphs deleted.

The Candida albicans hyphal wall protein 1 (Hwp1) is homologous to T cell epitopes involved in celiac disease.

Wagner (2005) "Innate and Adaptive Immunity against Candida spp. Infections in the Gastrointestinal Tract". Fungal Immunology: 303–321.

--FOTGCREN (talk) 21:20, 28 February 2014 (UTC)

Yes you copied and pasted from this source to. Doc James (talk · contribs · email) (if I write on your page reply on mine) 21:41, 28 February 2014 (UTC)

Ok. Its true but there are few ways of saying the same. Last attempt in this Coeliac Disease page. I´ll try to do my best. Thanks. — Preceding unsigned comment added by FOTGCREN (talk • contribs) 22:51, 28 February 2014 (UTC)

Well, I better thought that I am going to leave the decission of adding these two references on you Doc,do what you think is best;

It was shown by the dutch Ph.D. Willem Nieuwenhuizen in the year 2003 that gliadin has homologous sequences of amino acids when it is compared to Candida albicans hyphal wall protein 1 (hwp1). This is indicated in the review: “New Insights in Celiac Disease”.

Branski D. New Insights in Celiac Disease. RMMJ 2012;3 (1):e0006. doi:10.5041/RMMJ.10073

T cell epitopes related to celiac disease were shown having homologies with aminoacids into the sequence of the Candida albicans hyphal wall protein 1 (hwp1). This is indicated in the review: “Innate and Adaptive Immunity against Candida spp. Infections in the Gastrointestinal Tract”

Wagner (2005). "Innate and Adaptive Immunity against Candida spp. Infections in the Gastrointestinal Tract". Fungal :Immunology: 303–321.

Put these links or not say it did not seem right not to add them with reference to the review of Williams 2013 indicating that Hwp1 is a substrate of transglutaminase.

Hyphal wall protein 1 (Hwp1; encoded for by the HWP1 gene) is a protein involved in Candida Albicans adhesion to epithelial cells and this protein is perhaps the most widely studied adhesin of C. albicans. Glutamine residues in the N-terminal domain of Hwp1 can be cross-linked to unidentified host proteins by host transglutaminase activity and this leads to covalent attachment of the yeast to host epithelial cells. This interaction has been shown to be important for Candida albicans colonisation within the oral cavity

Williams DW, Jordan RP, Wei XQ, Alves CT, Wise MP, Wilson MJ, Lewis MA (2013)."Interactions of Candida albicans with host epithelial surfaces". J Oral Microbiol.doi:10.3402/jom.v5i0.22434.

Yet when VP7 is not a transglutaminase substrate proved (to date). And VP7 is broadly cited in this page.

Thanks for all.

--FOTGCREN (talk) 23:56, 28 February 2014 (UTC)

FDA issued final regulation for gluten free

The FDA issued final regulation for gluten free last year . The article should be updated to reflect that.Jasonhein1 (talk) 23:25, 20 February 2014 (UTC)

I have updated the citations for the final rule and added a citation to the codified regulations. The mention of the (proposed) regulations was already in the #Diet section next to the Codex Alimentarius mention. Int21h (talk) 17:34, 21 February 2014 (UTC)

I should also note that the Food Allergen Labeling and Consumer Protection Act of 2004 (the law requiring regulation of the term "gluten-free") also requires wheat to be identified prominently on labeling. The European Union also has some analogous regulations, somewhat explained here and here, which discusses the background of Commission Delegated Regulation (EU) No 1155/2013, which was published November 2013 and amends Regulation (EU) No 1169/2011, with implementing regulations to come later; "gluten-free" had been regulated in the EU since 2009 with Commission Regulation (EC) No 41/2009, which will be repealed by Regulation (EU) No 609/2013 effective July 2016. Int21h (talk) 19:26, 21 February 2014 (UTC)

Those are some interesting links. There should be more coverage on gluten-free labeling in the US given the market size for the product. Also, FALCPA said that gluten-free should have been finalized by 2008, but wasn't which perturbed the celiac community. Also, there's no mention of the CSA certification seal, or GFCO's GF seal.Jasonhein1 (talk) 22:27, 21 February 2014 (UTC)

Increasing incidence?

The article suggests that there may not be a real rise in prevalence, it was simply underdiagnosed in the past: Historically, coeliac disease was thought to be rare, with a prevalence of about 0.02%. Recent increases in the number of reported cases may be due to changes in diagnostic practice.
Recent studies seem to contradict that view.

• http://www.ncbi.nlm.nih.gov/pubmed/23511460 The incidence of CD has continued to increase in the past decade in a North-American population.
• http://pediatrics.aappublications.org/content/early/2013/09/04/peds.2013-0932.abstract The incidence of pediatric CD increased 6.4-fold over the 20 years. This study demonstrates that this rise is significant for classic CD, indicating a true rise in the incidence of pediatric CD.
• http://www.gastrojournal.org/article/S0016-5085%2809%2900523-X/abstract During 45 years of follow-up, undiagnosed CD was associated with a nearly 4-fold increased risk of death. The prevalence of undiagnosed CD seems to have increased dramatically in the United States during the past 50 years. Ssscienccce (talk) 15:00, 23 February 2014 (UTC)

How can you ensure that these are not the results of increased testing? JFW | T@lk 21:33, 23 February 2014 (UTC)

No studies quite "ensure" that yet that I know of, but the sources that Ssscienccce offered above are certainly reputable, and these more recent papers do speak directly to the question of underdiagnosis vs. real evidence for a real rise. The italicized portions included above are quoted from the "Conclusions" sections of the abstracts of these papers, and specifically use the terms "prevalence" and "incidence" to mean actual occurrence of CD -- as opposed to just a rise in number of diagnoses from better screening methods. Here are a few more related sources corroborating the involvement of external factors:

• http://www.mayo.edu/research/discoverys-edge/celiac-disease-rise

"'This tells us that whatever has happened with celiac disease has happened since 1950,' Dr. Murray says. 'This increase has affected young and old people. It suggests something has happened in a pervasive fashion from the environmental perspective.'"

• http://www.celiac.nih.gov/prevalence.aspx

“'Consumption of wheat has increased steadily over the past 50 years, but it still is less than what it was a century ago, so the issue is not simple consumption,' Murray noted. 'It more likely involves the wheat itself, which has undergone extensive hybridization as a crop and undergoes dramatic changes during processing that involves oxidizers, new methods of yeasting, and other chemical processes. We have no idea what effect these changes may have on the immune system.'”

• http://time.com/3511235/gluten-free-celiac-disease/

"Dr. Alessio Fasano, MD, director of the Center for Celiac Research and chief of the division of pediatric gastroenterology and nutrition at Mass General Hospital for Children, was a co-author of that recent study about breast-feeding and timing of gluten introduction. He says he found the 'major, unpredictable results shocking. The lesson learned from these studies is that there is something other than gluten in the environment that can eventually tilt these people from tolerant to the immune response in gluten to developing celiac disease...We’ve been radically changing our lifestyle, particularly the way that we eat, too fast for our genes to adapt.'"

In any case, I think it's worth updating the article to mention the fact that more recent studies have provided strong evidence that the increase in CD incidence can't simply be explained by better screening methods. If no objections, I will do this. Dalfet (talk) 09:07, 18 October 2015 (UTC)

Found a BMJ review that says their is a 4.5 fold increase (despite taking into account changing diagnostic criteria). Have updated with that review. Doc James (talk · contribs · email) 09:06, 19 October 2015 (UTC)

Change to lead

Hi, people, as this is a featured article I feel the need to get consensus on a change to the lead I would like to make. The change I would like to make is the following; the first sentence currently reads:
"Coeliac disease (/ˈsiːli.æk/; celiac disease in the United States and often celiac sprue) is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward."

I think the article would benefit if I was to change this sentence to:
"Coeliac disease (/ˈsiːli.æk/; celiac disease in the United States and often celiac sprue) is an autoimmune disorder of the small intestine that occurs in genetically-predisposed people of all ages in response to dietary consumption of gluten."

As I think it's important to get to the crux of the disease in the first sentence and part of this is the fact that gluten is the precipitating factor in CD sufferers. Plus I may not be an English teacher but I'm pretty sure in British English we're meant to use hyphens when two words are woven together in the sentence. I am Australian so British English is meant to be second nature to me. Thoughts? Fuse809 (talk) 03:19, 20 March 2014 (UTC)

Remission

I had celiac and a very restricted diet as a small child. It was explained to me later by a relative (chief of staff at a major hospital) that children often outgrow celiac or at least its symptoms. Indeed, I have observed no diet restrictions for decades since early childhood, eat great quantities of wheat products, and as far as I know have no symptoms of the condition whatsoever. I think remission should be discussed in the article. — Preceding unsigned comment added by Econprof (talk • contribs) 04:35, 13 April 2014 (UTC)

Hello Econprof. Current thinking is that people who are rechallenged with gluten will usually relapsed. If you believe that it can be "outgrown", I suggest you present a high-quality secondary source here (see WP:MEDRS) to support that assertion. Thanks! JFW | T@lk 19:50, 13 April 2014 (UTC)

Being asymptomatic isn't necessarily the same as being in remission (ask any cancer patient). Have you had negative antibody tests as an adult? 3AlarmLampscooter (talk) 19:50, 24 October 2014 (UTC)

Other pathological findings

Humpath added content based on doi:10.1309/AJCPE89ZPVJTSPWL. This is unfortunately a primary source. There are several recent secondary sources specifically about coeliac disease pathology (doi:10.5858/arpa.2011-0572-RA and doi:10.1016/j.giec.2012.07.001) that might be better sources. JFW | T@lk 17:37, 27 April 2014 (UTC)

Cross-reaction between gliadin and different foods

A subgroup of coeliac disease patients continues to experience symptoms even on a gluten-free diet. The list of foods which can cause coeliac symptoms is long and includes: rice, corn, yeast, dairy and many other popular gluten-free products. I heard that coeliac disease patients are advised to remove all of them from their diet.

I think there should be a significant section in the article or even a separate article on that issue. I'm not an expert and I can't do that myself, so I ask all more competent people to consider my suggestion. Thanks. — Preceding unsigned comment added by Agnes86 (talk • contribs) 19:22, 3 June 2014 (UTC)

doi:10.4236/fns.2013.41005 is a weak primary source that does not demonstrate whether exclusion of further foods actually improved the symptoms. There is a real risk of losing out on important micronutrients and I cannot support a significant section on something dubious like this. Many times, contamination is the real issue. JFW | T@lk 21:27, 8 June 2014 (UTC)

Avitaminosis

I added a link from "vitamin deficiencies" to Avitaminosis. If that's not an appropriate link, then could someone suggest a different one? Rissa, copy editor (talk) 19:04, 25 June 2014 (UTC)

Inaccurate schematic of mucosal immunopathology

The schematic of mucosal immunopathology shows the crypts of Lieberkühn inaccurately. In the current schematic, they are shown running perpendicular under the villi wherein reality they are positioned at the base of villi in parallel shafts.

It's an otherwise nice diagram of the Marsh score, but it needs to be either corrected to show the crypts properly or else removed. AcrossThePond (talk) 16:16, 2 July 2014 (UTC)

WikipedianProlific, the creator of the image, is not active anymore. Do you think you could modify the image yourself and upload a corrected version, AcrossThePond? JFW | T@lk 20:10, 2 July 2014 (UTC)

Gut flora in CD

doi:10.1128/CMR.00106-13 JFW | T@lk 21:33, 6 July 2014 (UTC)

Guideline

The British Society of Gastroenterology has (finally!) issued a consensus guideline. doi:10.1136/gutjnl-2013-306578. The article will require updating. JFW | T@lk 14:56, 8 July 2014 (UTC)

Confusing prevalence

The text says:

The prevalence amongst adult blood donors in Iran, Israel, Saudi Arabia and Turkey is 0.60%, 0.64%, 1.61%, 1.15% and 1.0%, respectively.

That's confusing. There are 5 percentages and 4 countries. Which corresponds to which? --pgimeno (talk) 15:28, 31 August 2014 (UTC)

Fixed. In the source the numbers pertained to "Iran, Israel, Syria, Turkey and Anatolia" which is confusing as Anatolia not a country but a region that overlaps to a large extent with Turkey. I removed the last number and also fixed Syria's transformation into Saudi Arabia. Kattfisk (talk) 12:58, 4 October 2014 (UTC)

Clarification requested

The article text reads "One region of α-gliadin stimulates membrane cells, enterocytes, of the intestine to allow larger molecules around the sealant between cells." It is unclear to me what it actually allows (does it for example allow larger molecules to reach the area around the sealant, or for example to stay around the sealant?) and how it "allows" this (by increasing the membrane permeability?). Similarly, two sentences later the text reads "Membrane leaking permits peptides of gliadin that stimulate two levels of immune response, the innate response and the adaptive (T-helper cell mediated) response." In which sense does it permit the peptides (does it for example permit peptides to stimate two levels, or for example permit peptides to cross the membrane?) and how does it "permit" this? Surely it's just a question of wording. --Chris Howard (talk) 16:35, 12 December 2014 (UTC)

It would be nice if someone could clarify this. --Chris Howard (talk) 19:00, 23 December 2014 (UTC)

Talk page references

1. "Small Intestine - Normal mucosa".
2. "The Histology Guide - University of Leeds".

Capsule endoscopy

There is no mention of whether capsule endoscopy (CE) can be used for diagnosing coeliac disease or not. As addition to the "Endoscopy" section, I propose:

Capsule endoscopy (CE) allows to identify typical mucosal changes observed in coeliac disease but has a lower sensitivity compared to regular endoscopy and histology. CE is therefore not the primary diagnostic tool for coeliac disease. However, CE can be used for diagnosing T-cell lymphoma, ulcerative jejunoileitis and adenocarcinoma in refractory or complicated celiac disease.(inline reference: PMID 25400450)

Please approve this change or propose modifications. --Chris Howard (talk) 21:58, 28 December 2014 (UTC)

Seems reasonable. JFW | T@lk 22:52, 28 December 2014 (UTC)

Thanks for your feedback. Done. --Chris Howard (talk) 22:57, 28 December 2014 (UTC)

Celiac Disease deaths.

This is the only allusion to death due to CD that I see in the article and it pops up at the very end, out of the blue: "Dicke noticed that the shortage of bread led to a significant drop in the death rate among children affected by CD from greater than 35% to essentially zero. He also reported that once wheat was again available after the conflict, the mortality rate soared to previous levels."

Shouldn't the death of some celiacs to the disease be mentioned specifically somewhere in the article? I would think a "prognosis" section would be a good place for it, except there's no such section. Is there no information on prognosis available? Thank you, Wordreader (talk) 04:52, 4 January 2015 (UTC)

We need some proper refs first. Have you come across any? Doc James (talk · contribs · email) 12:33, 4 January 2015 (UTC)

Wordreader Dicke's data was from war-torn Holland where food supplies were limited and there was genuine starvation. It is impossible to generalise to the present day. In fact, one can not really speak of death from coeliac disease alone because it is not independently known to cause death without some other illness contributing.

As James says, one can only write a "prognosis" section if there is discussion on prognosis in the relevant secondary sources. What kind of outcomes would one expect to use? Clearly not death (apart perhaps in a population sense), but improvement of symptoms, rate of complications? JFW | T@lk 13:40, 4 January 2015 (UTC)

Some refs:

In a population sense, a 2012 review article (PMID 23083988) states that "patients with diagnosed CD are at increased risk of mortality" and that regarding adherence to a gluten-free diet (GFD) "the evidence that a GFD reduces the risk of mortality is weak, but there is some evidence suggesting that a GFD may reduce the risk of lymphoproliferative malignancy"; a 2008 review article (PMID 19096486) concludes: "Coeliac disease causes a certain increased risk of cancer and early death" and states that a GFD "is at least partly protective."

In terms of specific risks, a 2013 review article (PMID 21621350) speaks of invasive T lymphoma occurring in one celiac patient in 1000, stating that GFD is protective.

--Chris Howard (talk) 16:46, 4 January 2015 (UTC)

P.S.: There's another one along similar lines:

See the section 4. "Enteropathy-Associated T-cell Lymphoma and Celiac Disease" of this 2013 review article (PMID 23984314).

--Chris Howard (talk) 00:09, 5 January 2015 (UTC)

That is not the same as death caused directly by coeliac disease; statistical association does not prove causation. EATL is a complication, which can be lethal. JFW | T@lk 00:16, 5 January 2015 (UTC)

Certainly correlation does not prove causation. The 2008 review article says it "causes" an increased risk, but the full text is Norwegian so we are not sure what they meant. Your wording on EATL surely makes sense. An interesting point may be whether GFD makes a difference or not.

Anyway, this is not what Wordreader cited Dicke for, in terms of a drop from greater than 35% to essentially zero in children affected by CD. --Chris Howard (talk) 11:29, 5 January 2015 (UTC)

Fractures

Are more common in clinically diagnosed disease but the data in undiagnosed coeliac disease is more contradictory: doi:10.1210/jc.2014-1858 JFW | T@lk 15:28, 6 January 2015 (UTC)

Cause

I looked at the Cause section and found this:

"Coeliac disease is caused by a reaction to gliadin"

But what causes an individual to have a reaction? Does it just happen randomly, or what?

Then I read the lead again. So one inherits a predisposition, and when somebody with this predisposition consumes gliadin, that person from that point forward has the disease. Is this correct?

Moreover, the Cause section looks like a mixture of two things: the causes of coeliac disease itself, and what triggers symptoms in people who have the disease. The latter should really be in a separate section, leaving the main Cause section to concentrate on explaining the causes (both genetic and environmental) of a person having the condition in the first place. Does anybody who knows more about it than I do fancy a stab at it? — Smjg (talk) 23:05, 20 January 2015 (UTC)

Proposed addition to "Research" section

There is a 2015 review paper that gives some structure and overview with regard to research on new approaches for treating CD. As addition to the "Research" section, I propose to introduce the following sentence as overview (after the first sentence of the section "Research"):

Three main approaches have been proposed as new therapeutic modalities for celiac disease: gluten detoxification, modulation of the intestinal permeability, and modulation of the immune response.(inline reference: Castillo NE, Theethira TG, Leffler DA (2015). "The present and the future in the diagnosis and management of celiac disease". Gastroenterology Report (Review). 3 (1): 3–11. doi:10.1093/gastro/gou065. PMC 4324867. PMID 25326000.)

and then to add a further paragraph at the end of that section:

Attempts to modulate the immune response with regard to celiac disease are mostly still in phase I of clinical testing; one agent (CCX282-B) has been evaluated in a phase II clinical trial on the basis of small-intestinal biopsies taken from celiac disease patients before and after gluten exposure. (same inline reference)

Please approve this or propose other changes. --Chris Howard (talk) 09:10, 5 March 2015 (UTC)

I intend to introduce the proposed change if no objection is raised in the next, say, 24h. --Chris Howard (talk) 18:10, 7 March 2015 (UTC)

Done. --Chris Howard (talk) 18:32, 9 March 2015 (UTC)

Coeliac vs Celiac

I was studying up on Celiac (as it's spelled in my country) and but dove to a section about the origins and didn't realize until then, that the usage of "Coeliac" and "Celiac" are plentiful. At first what I thought was a typo turned into a research into the etymology of the word and now I'm wondering if we should have some formalized spelling for the Misplaced Pages page. While reading, it's frustrating going back and forth as with the words "diarrhoea" and "diarrhea". Should we make the spelling uniform, even if it's the omission of a single letter. I know that English sources are preferred on English articles, but what do we say about UK vs US spelling? Frankly, I don't care if it's all the UK spelling or all US spelling, but I'd like to see us as editors stick to one at least on a page to page basis. Let me know you're thoughts. I'll be watching the page. Complete turing (talk) 16:57, 8 March 2015 (UTC)

Complete turing In this article all spellings should be British English, per WP:ENGVAR. If you find American spellings feel free to correct them. JFW | T@lk 19:49, 8 March 2015 (UTC)

Coeliac disease video

I do not agree with the inclusion of this video:

.

It is very interactive and nice, but it does not reflect the current knowledge about the EC. These "old ideas" are the reason that most celiacs remain unrecognized, undiagnosed and untreated, and exposed to the risk of long-term complications, including malignancies such as intestinal lymphoma and greater mortality. And most patients suffer severe disease symptoms and extensive investigations for many years, before a proper diagnosis is achieved.

This video says that serological markers are "98% specific and sensitive" and that they are "super effective!" (minute 6:38), but many patients are seronegative. Yes, they are "super effective!", but only when they are present…

Also, it says that celiac disease leads to villous atrophy (destroyed villi, "flattened villi", minute 7:10), but the reality is that it only occurs in a minority of cases. Most patients (especially older than 2 years) have minor mucosal lesions, without atrophy of the intestinal villi.

This video only talk about diarrhea, failure to thrive and abdominal distension in children ("classical symptoms") and chronic diarrhea, bloating, but "symptoms vary", in adults (minute 7:48). However, people with these manifestations are only a little, little minority! Currently, this is the least common presentation form of the disease, which affects predominantly to small children generally younger than two years of age. Coeliac disease with “non-classic symptoms”, with mild or absent gastrointestinal symptoms but a wide variety of systemic manifestations, or even completely asymptomatic, is the most common clinical found type in people of all ages (children, adolescents and adults). In this video, there is no mention to non-gastrointestinal symptoms, nor associated diseases.

I repeat, these "old ideas" are “very dangerous” and the reason which most celiacs remain unrecognized, undiagnosed and untreated. So I removed this video.

Best regards. --BallenaBlanca (talk) 21:59, 8 March 2016 (UTC)

You state "Coeliac disease with “non-classic symptoms”, with mild or absent gastrointestinal symptoms but a wide variety of systemic manifestations, or even completely asymptomatic, is the most common clinical found type in people of all ages (children, adolescents and adults)."

While the ref states "The classical presentation in children occurs at age under 2 years with symptoms of malabsorption and poor growth.31–33This typically occurs after introduction of gluten in the diet. There is, however, a trend toward fewer patients presenting with symptomatic CD characterized by diarrhea and a significant shift toward more patients presenting with milder symptoms or as asymptomatic adults detected at screening.34"

This does not mean that non classic symptoms are most common just that they are less common than they used to be. Doc James (talk · contribs · email) 22:12, 8 March 2016 (UTC)

Hi, Doc James. No problem, there are a lot of literature that reflects this reality. For example:

Gastroenterol Hepatol Bed Bench. 2011 Summer;4(3):102-8. Subclinical celiac disease and gluten sensitivity. Rostami Nejad M, Hogg-Kollars S, Ishaq S, Rostami K (Review) PMID: 24834166 PMC: 4017418

Atypical presentation is the most common form of celiac disease (CD). (atypical --> non-classical symptoms)

CD is a common disorder in children as well as in adults. The spectrum of clinical presentations is wide, and currently extraintestinal manifestations (eg, anemia or short stature) are more common than the classic malabsorption symptoms. A high degree of awareness among health care professionals and a liberal use of serologic CD tests can help to identify many of the nonclassic cases. (..) Associated Conditions. An increasing number of studies have shown that many CD-associated problems, which originally were described mostly in adults, can indeed be observed in children or adolescents.

Autoimmun Rev. 2014 Apr-May;13(4-5):472-6. doi: 10.1016/j.autrev.2014.01.043. Epub 2014 Jan 15. Diagnosis and classification of celiac disease and gluten sensitivity. Tonutti E, Bizzaro N. PMID: 24440147

Clinical manifestations. CD is characterized by multiple clinical expressions. An ESPGHAN (European Society for Paediatric Gastroenterology, Hepatology and Nutrition) working group has recently developed new guidelines for the diagnosis of CD based on scientific and technical developments using an evidence-based approach . The ESPGHAN working group decided to revise the classification, also taking into consideration signs and symptoms that had not been considered in the previous classification. In particular, it was deemed advisable to eliminate the distinction between classic and atypical CD based on symptoms, as atypical signs and symptoms (e.g. anemia, neuropathy, reduced bone density) may be considerably more common than classic symptoms (e.g. chronic diarrhea).

Sci Am. 2009 Aug;301(2):54-61. Surprises from celiac disease. Fasano A. PMID: 19634568

Because CD often presents in an atypical fashion, many cases still go undiagnosed. This new ability to recognize the disease in all its conseforms at an early stage allows gluten to be removed from the diet before more serious complications develop.

Best regards. --BallenaBlanca (talk) 23:16, 8 March 2016 (UTC)

Thanks lets see if they are willing to update the video based on the concerns you have raised. Doc James (talk · contribs · email) 20:20, 9 March 2016 (UTC)

Thank you very much, Doc James, you are very kind. Best regards. --BallenaBlanca (talk) 09:01, 10 March 2016 (UTC)

Hi BallenaBlanca. Thanks for your feedback. Here are our thoughts: - "Yes, they are "super effective!", but only when they are present…" At 6:38 we state 1-2% of patients do not have IgA antibodies and require IgG testing. Does that statement address your concern? If so I don't think we need to change that part of the video. - We can state most patients (in particular over the age of 2 years) have minor mucosal lesions without atrophy of the intestinal villi. In some cases, celiac disease destroys the villi causing the villi to flatten out. - We can state celiac disease can have a wide variety of symptoms, and many people of any age are asymptomatic or have very mild gastrointestinal symptoms. What non-gastrointestinal symptoms and associated diseases would you recommend we highlight?

Are there any other issues you noticed? OsmoseIt (talk) 22:28, 9 March 2016 (UTC)

Hi, OsmoseIt Thank you very much for your kindness.

First, I want to congratulate you for your work!

I'll try to answer as best I can:

"At 6:38 we state 1-2% of patients do not have IgA antibodies and require IgG testing. Does that statement address your concern?" No, it is not enough. There is an important confusion about sensitivity of antibodies: they are high sensitivity only for diagnosis typical (=classical, the least common forms) celiac disease, when there is villous atrophy, and show a marked decrease in sensitivity (of the order of 40-50%) in cases with mild villous atrophy or minimal changes (currently, the more common forms of the CD), but this fact is widely unknown.

Aliment Pharmacol Ther. 2006 Jul 1;24(1):47-54. Systematic review: the use of serology to exclude or diagnose coeliac disease (a comparison of the endomysial and tissue transglutaminase antibody tests). Lewis NR1, Scott BB. PMID 16803602

Results. Both the endomysial antibody and tissue transglutaminase antibody have very high sensitivities (93% for both) and specificities (>99% and >98% respectively) for the diagnosis of typical coeliac disease with villous atrophy. (...) Thirty-four studies fulfilled our criteria and the details are shown in Table 1. The histological criterion for diagnosing coeliac disease was partial or more severe villous atrophy in the majority. (...) As the detection of at least partial villous atrophy was used to make a diagnosis of coeliac disease in the vast majority of studies, we can't assume that the same LRs apply to coeliac patients with lesser abnormality such as an increase in intraepithelial lymphocytes or electron-microscopic changes only. In fact, if such lesser abnormalities were used as criteria for diagnosing (and excluding) coeliac disease, the sensitivity of the tests could be lower (i.e. more false negatives), especially since a number of studies suggest that the EMA and tTG antibody tests are less sensitive with lesser degrees of mucosal abnormality.41–43 "

Med Clin (Barc). 2008 Sep 6;131(7):264-70. Celiac disease. Article in Spanish. Rodrigo L, Garrote JA, Vivas S PMID 18775218

La TG-t es el antígeno principal frente al que reaccionan los AEM, y es posible que haya otros antígenos menores localizados también en el endomisio. Posiblemente ésta sea la razón por la que los resultados de la determinación de los AEM y de la TG-t no sean del todo concordantes. En general puede decirse que los AEM son más específicos y los TG-t, más sensibles, en especial con el empleo del antígeno recombinante humano. Estos marcadores presentan en general una elevada sensibilidad y especificidad (cercanas al 90%) en presencia de atrofia marcada de las vellosidades intestinales. Sin embargo, muestran una notable disminución de la sensibilidad (del orden del 40-50%) en casos con atrofia vellositaria leve o cambios mínimos. En contraposición, también es posible que estos marcadores sean positivos en casos con mucosa normal o con cambios mínimos16,17. (tTG is the major antigen against which react EMA, and there may be other minor antigens also located in the endomysium. This is probably the reason why the results of the determination of EMA and tTG are not entirely consistent. In general it can be said that the EMA are more specific and tTG more sensitive, especially with the use of recombinant human antigen. These markers generally have high sensitivity and specificity (around 90%) in the presence of marked atrophy of the villi. However, they show a marked decrease in sensitivity (of the order of 40-50%) in cases with mild villous atrophy or minimal changes. In contrast, it is also possible that these markers are positive in cases with normal mucosa or with minimal changes16,17)

There is a diagnosis protocol, published by the Ministerio de Sanidad de la Nación (Argentina) which reflects this issue:

GUÍA DE PRÁCTICA CLÍNICA SOBRE DIAGNÓSTICO Y TRATAMIENTO DE LA ENFERMEDAD CELÍACA

La tasa de falsos negativos de las pruebas serológicas varía de acuerdo a la edad de los pacientes (mayor en adultos) y al grado de la lesión histológica. El anticuerpo antitransglutaminasa es positivo en sólo el 7,69%, 33,33% y 55,55 % de las lesiones en estadío Marsh I, II y IIIa respectivamente, mientras que la positividad asciende al 83,87% y 95,83% en las lesiones Marsh IIIb y IIIc respectivamente. Existe un riesgo manifiesto de no diagnosticar correctamente una proporción de pacientes con daño histológico leve a moderado si no se recurre a la biopsia confirmatoria.73 (The false negative rate of serological tests varies according to the age of patients (higher in adults) and the degree of histological injury. The transglutaminase antibody is positive in only 7.69%, 33.33% and 55.55% of lesions in Marsh stage I, II and IIIa respectively, whereas positivity amounts to 83.87% and 95.83% Marsh lesions IIIb and IIIc respectively. There is a clear risk of not properly diagnose a proportion of patients with mild to moderate histological damage if confirmatory biopsy was not undertaken)

It seems that people with minor mucosal lesions in fact develop antibodies, but they do not pass into the blood and remain in the intestinal mucosa:

Aliment Pharmacol Ther. 2015 May;41(9):807-20. doi: 10.1111/apt.13155. Epub 2015 Mar 6. Systematic review: noncoeliac gluten sensitivity. Molina-Infante J1, Santolaria S, Sanders DS, Fernández-Bañares F PMID 25753138

This recognition and differentiation becomes difficult in patients with negative coeliac disease serology and histological findings (Marsh 1 lesions or LE) not diagnostic for coeliac disease. In this regard, consensus guidelines from the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) state that a high count of cd cells (or cd/CD3 ratio) in immunohistochemical assessment of biopsies or the presence of IgA anti-TG2 intestinal deposits might be specific for CD in patients with LE.22 (LE: lymphocytic enteritis)

And also, probably is better to say that the rates of IgA deficiency are 2%:

Aliment Pharmacol Ther. 2006 Jul 1;24(1):47-54. Systematic review: the use of serology to exclude or diagnose coeliac disease (a comparison of the endomysial and tissue transglutaminase antibody tests). Lewis NR1, Scott BB. PMID 16803602

Another complicating factor is immunoglobulin (Ig) A deficiency which is found in 2% of coeliacs and 0.2% of the general population. Since the usual serology tests (tTG antibody and EMA) are for IgA antibodies, there will be more false negatives thus slightly reducing the sensitivity.

It is also very important saying that excluding CD is not the end of the diagnosis protocol, because patient may have indeed non-celiac gluten sensitivity, whom diagnosis is made based on exclusion of celiac disease and wheat allergy and evaluating the response to gluten free diet.

Gastroenterol Hepatol Bed Bench. 2011 Summer;4(3):102-8. Subclinical celiac disease and gluten sensitivity. Rostami Nejad M, Hogg-Kollars S, Ishaq S, Rostami K (Review) PMID: 24834166 PMC: 4017418

Villous atrophy is not mandatory any longer to qualify a patient for GFD. In fact a large number of patients present with non-celiac gluten sensitivity with completely normal biopsy and negative serology. They also seem to benefit from a GFD. (GFD: gluten-free diet)

The list of possible extra-gastrointestinal manifestations of untreated CD is immense! It is important to say that there is no single pattern but wide variations between patients and also in the same patient at different times of life, as the waves that come and go, even with completely asymptomatic periods. It is also important to say that gastrointestinal symptoms, when present, are not distinguishable to those of irritable bowel syndrome, and that many patients are diagnosed of IBS by years before diagnosis of CD. Constipation may appear even in very small children, and may be severe.

SIGNS: Pale skin and mucosas. Short stature. Weightloss. Overweight. Dermatitis (such as dermatitis herpetiformis, atopic dermatitis, urticaria, follicular keratosis). Various tissue disease. Aphthous stomatitis. Enamel defects. Peripheral polyneuropathy. Proximal myopathy. Muscular weakness. Generalized bone pain. Polyarthritis localized or diffuse. Maleolares edemas. Tetany crisis. Multiple spontaneous hematoma, etc.

SYMPTOMS: Often asymptomatic. Recurrent upper respiratory processes of immuno-allergic nature (such as rhinitis, pharyngitis, tonsillitis, otitis, sinusitis, recurrent bronchitis, asthma crisis). Delayed menarche. Menstrual irregularities. Reproductive disorders (sucha as amenorrhea, menorrhagia, early menopause, spontaneous abortions, infertility, impotence, increased neonatal morbidity). Dyspnea middle efforts. Recurrent headaches, migraines. Tetany crisis. Muscle cramps. Fibromyalgia like symptoms. Bone and/or joint pain. History of repeat fractures (for trivial injuries). Paresthesia. Tingling. Hair loss. Brittle nails. Neuropsychiatric symptoms (such as irritability, apathy, introversion, sadness, asthenia, anxiety, depression, restless legs, muscle cramps, sleep disorders -insomnia, hypersomnia-). Fibromyalgia. Attention deficit hyperactivity disorder. Autism, etc.

RISK GROUPS AND RELATED DISEASES:

• Relatives of first and second degree.
• Down's Syndrome.
• Williams syndrome.
• Turner syndrome.
• Autoimmune diseases and other immunopathies, sucha as selective IgA Deficiency, inflammatory bowel disease, systemic lupus erythematosus, IgA nephropathy.
• Endocrine diseases, such as diabetes mellitus type I, hypothyroidism, hyperthyroidism, autoimmune thyroiditis, Addison's disease. :*Neurological and psychiatric disorders, such as cerebellar ataxia, epilepsy with or without cerebral calcifications, polyneuropathy, multiple sclerosis, progressive encephalopathy, cerebellar syndromes, dementia with brain atrophy, leukoencephalopathy, schizophrenia, depression, anxiety.
• Liver diseases, such as primary biliary cirrhosis, autoimmune hepatitis, autoimmune cholangitis, idiopathic chronic hypertransaminasemia.
• Rheumatic diseases, such as Sjögren's syndrome, ankylosing spondylitis, rheumatoid arthritis, other arthritis.
• Heart diseases, such as dilated cardiomyopathy, recurring myocarditis, autoimmune pericarditis.
• Skin diseases, such as dermatitis herpetiformis, psoriasis, vitiligo, alopecia areata.
• Other associations: iron deficiency anemia, osteoporosis/osteopenia, Hartnup's disease, cystinuria, microscopic colitis, cardiomyopathy, fibromyalgia, chronic fatigue syndrome, scleroderma.
• Certain cancers, such as non-Hodgkin’s lymphoma, small intestinal adenocarcinoma, squamous cell carcinoma of the pharynx and mouth .
• etc...

Gastroenterol Hepatol Bed Bench. 2011 Summer;4(3):102-8. Subclinical celiac disease and gluten sensitivity. Rostami Nejad M, Hogg-Kollars S, Ishaq S, Rostami K (Review) PMID: 24834166 PMC: 4017418

More and more diseases are proven to be associated with CD. In these conditions, screening is strongly recommended.

In fact, celiac disease is known as the "great imitator":

Duggan JM (May 17, 2004). "Coeliac disease: the great imitator" (PDF). Med J Aust (Review) 180 (10): 524–6. PMID 15139831

Eur Ann Allergy Clin Immunol. 2004 Mar;36(3):96-100. A great imitator for the allergologist: intolerance to gluten. Article in French. Rousset H. PMID 15137480

Finally, in my humble opinion, I think that if the video is intended for the general public, it is better to talk less about the pathophysiology, because it is difficult to understand and of little use. It is more useful to talk about practical aspects on how to recognize the disease and know that most cases are undiagnosed due to a general lack of update on the disease. Unfortunately, most physicians only know the classic disease...

I hope I've helped you!

Best regards. --BallenaBlanca (talk) 11:29, 10 March 2016 (UTC)

Hi BallenaBlanca,

Thanks for your detailed feedback. Here are our proposed changes:

1) We'll state antibodies are high sensitivity only for diagnosis typical (the least common forms) celiac disease, when there is villous atrophy, and show a marked decrease in sensitivity (of the order of 40-50%) in cases with mild villous atrophy or minimal changes (currently, the more common forms of the CD), but this fact is widely unknown.

2) We'll briefly discuss non-celiac gluten sensitivity, specifically that diagnosis is made based on exclusion of celiac disease and wheat allergy and evaluating the response to gluten free diet

3) We'll state the rates of IgA deficiency is 2%.

4) We'll state there is no single pattern of symptoms but wide variations between patients and also in the same patient at different times of life, as the waves that come and go, even with completely asymptomatic periods.

5) We'll state gastrointestinal symptoms, when present, are not distinguishable to those of irritable bowel syndrome, and that many patients can be diagnosed of IBS by years before diagnosis of CD.

6) We'll state most patients (in particular over the age of 2 years) have minor mucosal lesions without atrophy of the intestinal villi. In some cases, celiac disease destroys the villi causing the villi to flatten out.

Let me know if you feel those changes are sufficient. The target audience of our videos is for medical students, and the videos are to serve as supplementary materials rather than comprehensive references. That's why we choose to highlight specific content. I'd also like to invite you to our WikiProject Medicine page where we post scripts to our upcoming videos. We greatly appreciate your input, especially if you can help us address issues like this before we create the video. OsmoseIt (talk) 23:47, 14 March 2016 (UTC)

References

1. Ciccocioppo R, Kruzliak P, Cangemi GC, Pohanka M, Betti E, Lauret E, Rodrigo L (Oct 22, 2015). "The Spectrum of Differences between Childhood and Adulthood Celiac Disease". Nutrients (Review). 7 (10): 8733–51. doi:10.3390/nu7105426. PMC 4632446. PMID 26506381.{{cite journal}}: CS1 maint: unflagged free DOI (link)
2. Elli L, Branchi F, Tomba C, Villalta D, Norsa L, Ferretti F, Roncoroni L, Bardella MT (Jun 21, 2015). "Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity". World J Gastroenterol (Review). 21 (23): 7110–9. doi:10.3748/wjg.v21.i23.7110. PMC 4476872. PMID 26109797.{{cite journal}}: CS1 maint: unflagged free DOI (link)
3. Lebwohl B, Ludvigsson JF, Green PH (Oct 2015). "Celiac disease and non-celiac gluten sensitivity". BMJ (Review). 5: 351:h4347. doi:10.1136/bmj.h4347. PMC 4596973. PMID 26438584. Celiac disease occurs in about 1% of the population worldwide, although most people with the condition are undiagnosed. It can cause a wide variety of symptoms, both intestinal and extra-intestinal because it is a systemic autoimmune disease that is triggered by dietary gluten. Patients with celiac disease are at increased risk of cancer, including a twofold to fourfold increased risk of non-Hodgkin's lymphoma and a more than 30-fold increased risk of small intestinal adenocarcinoma, and they have a 1.4-fold increased risk of death.
4. Levy J, Bernstein L, Silber N (Dec 2014). "Celiac disease: an immune dysregulation syndrome". Curr Probl Pediatr Adolesc Health Care (Review). 44 (11): 324–7. doi:10.1016/j.cppeds.2014.10.002. PMID 25499458.
5. ^ Ludvigsson JF, Card T, Ciclitira PJ, Swift GL, Nasr I, Sanders DS, Ciacci C (Apr 2015). "Support for patients with celiac disease: A literature review". United European Gastroenterol J (Review). 3 (2): 146–59. doi:10.1177/2050640614562599. PMC 4406900. PMID 25922674.
6. Fasano, A; Catassi, C (Dec 20, 2012). "Clinical practice. Celiac disease". The New England Journal of Medicine (Review). 367 (25): 2419–26. doi:10.1056/NEJMcp1113994. PMID 23252527.
7. Bold J, Rostami K (2011). "Gluten tolerance; potential challenges in treatment strategies". Gastroenterol Hepatol Bed Bench (Review). 4 (2): 53–7. PMC 4017406. PMID 24834157.
8. ^ Fasano A (Apr 2005). "Clinical presentation of celiac disease in the pediatric population". Gastroenterology (Review). 128 (4 Suppl 1): S68-73. doi:10.1053/j.gastro.2005.02.015. PMID 15825129.

Update

Linking with the previous conversation, I think that is the time to update the page, beginning with the introduction, which must reflect a brief summary of the current knowledge and issues of coeliac disease.

I propose this text, whith updates that are already on other pages and have been revised (Gluten-related disorders#Coeliac disease and Gluten#Coeliac disease):

Coeliac disease - Introduction

Best regards. --BallenaBlanca (talk) 20:09, 9 March 2016 (UTC)

Leads should be 4 paragraphs generally. And we should try to use easier to understand language. Doc James (talk · contribs · email) 20:22, 9 March 2016 (UTC)

Simplified it some. Doc James (talk · contribs · email) 20:30, 9 March 2016 (UTC)

Thanks, Doc James, I really appreciate your help!

I completed treatment, added some sources and an important clarification. Do you agree with this version?

Best regards. --BallenaBlanca (talk) 21:33, 10 March 2016 (UTC)

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