Talk:Coeliac disease

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

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 Wikipedia? 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, Wikipedia 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 [1]]. 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

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 Wikipedia as VP7 (Rotavirus protein). VP7 is greatly related to Coeliac disease, but Hwp1 too.

VP7 is cited in the Coeliac Disease Wikipedia 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 [2] were the primary sources were removed and the review left.

This [3] is a primary source

This [4] is a primary source

And this [5] 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 Wikipedia. I need Wikipedia reliable sources that acomplish with Wikipedia 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[6] 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[7] 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 [8] 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." [9] 2) This source does not mention the disease in question [10] 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 [11]. 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%.[88] Recent increases in the number of reported cases may be due to changes in diagnostic practice.[89]
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^[1] 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^[1] 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.[11]

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)

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 Wikipedia 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:

Video explanation of celiac disease

.

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 [10]. 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)

Hi, OsmoseIt

1) In my opinion, these other rates have more accuracy: GUÍA DE PRÁCTICA CLÍNICA SOBRE DIAGNÓSTICO Y TRATAMIENTO DE LA ENFERMEDAD CELÍACA 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.

4) And may develop associated diseases (see list above).

5) In a little proportion of cases, specially in children younger than 2 years, may be a classical presentation of CD with diarrea and malabsortion. However, in these very young children also presents frequently with non-classical symptoms. For example, some babies present a marked constipation.

It is important to state that the majority of cases (about 85%) remain unrecognized and undiagnosed, and exposed to the risk of serious long-term complications, such as lymphomas and greater mortality. Untreated celiac disease may affect any organ of the body.

Finally, saying that gluten-free diet improves symptoms and related conditions, and prevents complications.

Best regards. --BallenaBlanca (talk) 13:10, 16 March 2016 (UTC)

Thanks BallenaBlanca. We'll implement your feedback in our next revision of the video. OsmoseIt (talk) 16:56, 16 March 2016 (UTC)

Hi BallenaBlanca. I just reviewed your suggestions with the rest of my team. We are trying to keep our videos short and concise, so we won't be able to expand the scope of the video. We will however address the scientific errors you mentioned. Thanks! OsmoseIt (talk) 20:29, 21 March 2016 (UTC)

References

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? [12]

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

Sorry to butt in, but I have tried to improve the comprehensibility of the lede. BallenaBlanca's source seems perfectly good, but it is written in long complicated sentences. Apart from any copyright issues, we do need to write in simple language wherever possible. I hope that this edit is useful. Richard Keatinge (talk) 11:34, 16 March 2016 (UTC)

Thank you for your help and kindness, Richard Keatinge I'll keep that in mind. Best regards. --BallenaBlanca (talk) 12:22, 16 March 2016 (UTC)

Well, there are no more comments. I will edit the lead. Also, I will calmly continue updating the other sections. Best regards. --BallenaBlanca (talk) 13:25, 17 March 2016 (UTC)

Have worked on it a little further to simplify and organized the lead such that it follows the layout of the body of the article. Best Doc James (talk · contribs · email) 00:32, 18 March 2016 (UTC)

Very thanks, Doc James. You made a good work simplifying. Nevertheless, there are some ambiguities to improve.

It is very important to properly reflect that "contrary to the past when it was thought that celiac disease was a disorder predominantly affecting childhood and characterized by a malabsorption syndrome, nowadays it is well recognized that it affects also adult and elderly people with an impressive variability of clinical presentation." Another widespread misconception is that there is always atrophy of intestinal villi. Now, reading the text, I see that these issues are no clear.

I will do edits to clarify.

Thank you very much again for your help. It's a good way to work together!

Best regards. --BallenaBlanca (talk) 10:47, 18 March 2016 (UTC)

I have never heard the rumor that this only affects kids. I had always heard it was life long and affected people of all ages.

We mention that there may be minor histological changes and negative serology. Doc James (talk · contribs · email) 00:40, 19 March 2016 (UTC)

References

Ah found the ref which say "In fact, contrary to the past when it was thought that celiac disease was a disorder predominantly affecting childhood and characterized by a malabsorption syndrome"

So adjusted it to "In the past it was considered a digestive disease of mostly child"

Doc James (talk · contribs · email) 01:21, 19 March 2016 (UTC)

"I have never heard the rumor that this only affects kids." Then you are very young! "I had always heard it was life long and affected people of all ages." If begins in childhood and is life long, it is clear that "affects all ages". The key point of the question is "when is developed". For a few years it is known that can appear at any age.

The sentence is okay. Nevertheless, is better to move it to understand why it talks about "classic symptoms" and "non-classic symptoms" (the reason is the change in understanding celiac disease).

You're right, it was repeated "it may affects any organ of the body". To avoid this duplication, is a good solution stating that it is a systemic disease, with wikilink, which is also explained below.

Best regards. --BallenaBlanca (talk) 03:14, 19 March 2016 (UTC)

I will adjust "Non-classic symptoms are the most common, especially in older children and adults":

• PMID 22197856: European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. 2012 "Several classifications of CD have been used, most important with distinctions drawn among classical, atypical, asymptomatic, latent, and potential CD. Because atypical symptoms may be considerably more common than classic symptoms, the ESPGHAN working group decided to use the following nomenclature: gastrointestinal symptoms and signs (eg, chronic diarrhea) and extraintestinal symptoms and signs (eg, anaemia, neuropathy, decreased bone density, increased risk of fractures)."
• PMID 24834166: "Atypical presentation is the most common form of celiac disease (CD)."

NOTE: Atypical = non-classical. There is a good explanation on this source: The Oslo definitions for coeliac disease and related terms. PMID 22345659

Best regards. --BallenaBlanca (talk) 04:11, 19 March 2016 (UTC)

I hope we can continue to keep this reasonably simple, with appropriate secondary sources in high impact journals including multiple international expert consensus statements PMID 22345659 and recent high quality guidelines PMID 26333593 . Please be careful when picking which of the 900+ Pubmed reviews to include. Recent edits have duplicated other reviews and have not necessarily added anything new. Is there any support for branching out and creating new related articles? Jrfw51 (talk) 14:16, 18 March 2016 (UTC)

Doc James, I agree with you. I hope we can keep this reasonably simple... but without losing clarity. There is no disease comparable to celiac disease, due to the amount of complications it produces that affect any organ or tissue of the body, with a so complicated diagnosis in the majority of the patients and with rates of underdiagnosis so alarmingly high. However, there is very little knowledge among physicians and the general population.

"Is there any support for branching out and creating new related articles?" Not for the moment. I think the first thing is to update existing information and then we'll see.

On this edition, you removed "and many people may have minor mucosal lesions, without atrophy of the intestinal villi." because "(do not see were it says may)" and removed the references that supported the text: PMID 24834166 PMC 4017418 and PMID 24834157 PMC 4017406. These two sources state Marsh scale that classifies histological findings compatible with the EC, which is a fact reflected currently in diagnostic protocols:

• minor mucosal lesions: Marsh I (intestinal-intraepithelial lymphocyte or IEL) and Marsh II (lymphocyte infiltration and crypt hyperplasia)
• macroscopic enteritis with villous atrophy: Marsh IIIa (partial villous atrophy), Marsh IIIb (subtotal villous atrophy) and Marsh IIIb (total atrophy)

That is to say that when a person presents Marsh I or II (that are lesions compatible with CD) implies that has not villous atrophy. It is important to clarify this for the public that reads us, it is a fact widely ignored. Traditional and desfasdas ideas remain in most minds: celiac = atrophy of intestinal villi. Nevertheless, currently is the less common form of the disease. We could use any other reference, such as those you mentioned above (PMID 22345659 or PMID 26333593), but to avoid future confusion, I will use another more literal reference, already present (this quotation was also already present): 2015 source published on Aliment Pharmacol Ther, which have an impact factor of 5.727, ranked 9/76

Furthermore, seronegativity is more common in coeliac disease patients without villous atrophy (Marsh 1-2 lesions), but these ‘minor’ forms of coeliac disease may have similar clinical manifestations to those with villous atrophy16–18 and may show similar clinical–histological remission with reversal of haematological or biochemical disturbances on a gluten-free diet (GFD).

Best regards. --BallenaBlanca (talk) 19:48, 18 March 2016 (UTC)

We want to write the lead so it is more or less understandable by someone in grade 8. The body can get more complicated. I would disagree with the statement that "in most minds celiac = atrophy of villi"

Change it from "without atrophy of the intestinal villi" to "normal villi" as atrophy is a complicated word and we link to villa to make it easier. I felt that "minor mucosal lesions" was enough to mean that no villi atrophy was present.

We state that some tests maybe normal, that 85% of cases in the developing world are not diagnosed, and that "People may have severe symptoms and be investigations for years before a diagnosis is achieved"

This "It is often very difficult so that most cases are diagnosed with great delay." is basically saying that again so I have moved it to the body to reduce duplication in the lead. Doc James (talk · contribs · email) 01:21, 19 March 2016 (UTC)

Wording

"Systemic disease" is technical terminology, this means "may involve any organ in the body". We do not need to say both in the first paragraph and we already say the latter.

We also already state that it can involved young children, older children, and adults in the first paragraph. Why do we need to say it as "however, it may develop at any age" in the first paragraph aswell? The first paragraph should not repeat the same thing with different wording. Doc James (talk · contribs · email) 04:09, 19 March 2016 (UTC)

Let me think about it, please. Now I have not more time. We will continue talking. Thanks. Best regards. --BallenaBlanca (talk) 04:17, 19 March 2016 (UTC)

Also IMO adolescents are simply older children and the latter is simpler so not sure we need both. Doc James (talk · contribs · email) 04:20, 19 March 2016 (UTC)

Well, well... You have mentioned a very important issue! If saying "older children" makes people to understand "adolescents", then we must to clarify. "Older children" in this context must be "children older than 2-3 years"

Best regards. --BallenaBlanca (talk) 10:55, 19 March 2016 (UTC)

See my comment at User talk:BallenaBlanca. Jrfw51 (talk) 12:19, 19 March 2016 (UTC)

Do we need to have 4 references for a single point in the lead? Typically we just have the one or two best sources? Doc James (talk · contribs · email) 02:48, 20 March 2016 (UTC)

• "duodenal lymphocytosis" is a complicated entity that IMO does not need to be discussed in the lead and therefore I have moved it to the body of the text. Doc James (talk · contribs · email) 03:04, 20 March 2016 (UTC)

I agree. I think that is okay moving detailed text to Pathology section and let on the lead a brief explanation. Only one detail. I miss "may be only minor mucosal lesions", or better to understand it, "may be only minor intestinal lesions". --BallenaBlanca (talk) 09:10, 20 March 2016 (UTC)

Yes minor intestinal changes is better IMO. Doc James (talk · contribs · email) 17:28, 20 March 2016 (UTC)

Oats

"Oats may be a problem in some people with coeliac but moderate quantities are often okay. This may be depend on the type consumed, or cross contamination with other gluten-containing grains."

• The first ref says "Studies have demonstrated that when consumed in moderation, oats free from cross-contamination are well tolerated by most children [44,45]. Under the nutritional point of view, oats represent a good source of iron, dietary fiber, thiamin and zinc and, in addition, have a good palatability [46]. A study conducted by Størsund et al. in CD children suggests that oats may improve the nutritional value of GFD and, in view of the good palatability, may also help increase compliance [47]. Recently, Lee et al. demonstrated that adding three servings of gluten-free alternative grains, including oats, positively impacts the nutrient profile (fiber, thiamin, riboflavin, niacin, folate and iron) of the grain portion of the gluten-free diet [48]."

• The second ref says "Inclusion of oats in a gluten-free diet might be valuable due to their nutritional and health benefits, and several countries currently permit oats to be included as an ingredient in such diets. However, it is extremely important to remember that in vitro studies have shown that the immunogenicity of oats varies depending on the cultivar used."

Based on this text I think we can say "moderate quantities are often okay". What are other peoples thoughts? Doc James (talk · contribs · email) 02:56, 20 March 2016 (UTC)

It is an important issue and because of the severe complications that untreated CD (or incorrectly treated, it is the same thing) can develop, I think that we must be very cautious. "are well tolerated by most children" means that some children can't tolerate it. These people can't consume it, even in small amounts. There is a lot of confusion. It is not enough tolerating it "symptomatically", nor if serology is "normal", nor if "there is not villous atrophy". If there are "only" intraepithelial lymphocytes, it means that disease is active. It is not known the long-term effects of a diet containing oats. Actually, 10–30% of patients with celiac disease are non-responders and have persistent symptoms despite being on a gluten-free diet. Non-responsive celiac disease is largely caused by inadvertent exposure to gluten that accounts for 35–50% of persistent symptoms in patients with celiac disease. Consumption of toxic oats (although it is free of contamination) may play an important role. We need to stay it well specified.

Take a look at this paper:

PMID 17068278 2006 Coeliac disease and oats: a systematic review.

A systematic review of the literature related to the inclusion of oats in the gluten-free diet for patients with coeliac disease to assess whether oats can be recommended. A computerised literature review of multiple databases was carried out, identifying 17 primary studies, 6 of which met the criteria for inclusion in this review. None of the six studies found any significant difference in the serology between the oats and control groups. Two studies, however, identified a significant difference (p<0.001; p = 0.039) in intraepithelial lymphocyte counts between the oats and control groups. Oats can be symptomatically tolerated by most patients with coeliac disease; however, the long-term effects of a diet containing oats remain unknown. Patients with coeliac disease wishing to consume a diet containing oats should therefore receive regular follow-up, including small bowel biopsy at a specialist clinic for life.

I will edit to do a little correction that improves understanding, but I let on your hands completing it.

Best regards. --BallenaBlanca (talk) 08:29, 20 March 2016 (UTC)

We also need to be careful about not excluding too much food or some people may not get enough nutrients. YEs agree that oats are controversial.

The two reviews I used above are newer than 2006. 2006 is getting a little old. Doc James (talk · contribs · email) 17:22, 20 March 2016 (UTC)

I agree with the current text.

Just a comment. The priority for people with CD is avoiding diet transgressions, the complications may be so severe and cannot be compared. The general recommendation we give to patients to correctly do GFD is: "If in doubt, do not consume it". Oat is not essential and is easily replaced, as in the case of wheat, barley and rye. The grains of pseudocereals, which are gluten free, (such as quinoa, amaranth and buckwheat) and other minor cereals, are rich in proteins with higher biological value.

Best regards. --BallenaBlanca (talk) 19:30, 20 March 2016 (UTC)

I am thinking that for those in the developing world who have lack of variety of food than "If in doubt, do not consume it" might not be appropriate. Doc James (talk · contribs · email) 20:31, 20 March 2016 (UTC)

References

Death

We state "If untreated it may result in cancers such as intestinal lymphoma and a slight increased risk of early death."

The may applies to both cancers and the slight increased risk of early death. Therefore not sure "possibly" is needed.

And the source is more definitive saying "they have a 1.4-fold increased risk of death"[13]

Doc James (talk · contribs · email) 03:30, 20 March 2016 (UTC

The source is more nuanced in the actual text rather than this bold statement in the Introduction. We have lots of "mays" and "possibly" is a bit different! Jrfw51 (talk) 18:32, 20 March 2016 (UTC)

We are only specifically saying that without treatment it increases the risk of death, I do not think that needs a "possibly". I agree the possibly would apply for those with proper treatment Doc James (talk · contribs · email) 19:19, 20 March 2016 (UTC)

I agree with Doc James. IMO the currently text is okay. Best regards. --BallenaBlanca (talk) 19:37, 20 March 2016 (UTC)

Old and modern ideas: a very important issue

I apologies for being persistent, but it is necessary to state clearly the issue about "old and modern ideas" about coeliac disease. This is certainly the most, most important thing we must let clear to our readers. It is the starting point to understand coeliac disease. And now, I believe that there are confusions.

Classic symptoms include gastrointestinal problems such as chronic diarrhoea, abdominal distention, malabsorption, loss of appetite, and among children failure to grow normally. This often begins between six months and two years of age.[2] Non-classic symptoms are the most common, especially in children older than two years and adults.[3][4][5] There may be mild or absent gastrointestinal symptoms, a wide number of symptoms that may involve any organ of the body, or no obvious symptoms.[6][2]

In my experience talking with patients, it is not easy to understand. People who read it may understand (and in fact often understand) that is a "evolution" of disease symptoms and that disease always develop between six months and two years. As I stated on other comments, in most minds remain old, and difficult to remove, ideas (children disease with malabsorption and villous atrophy). Unfortunately, this covers general population and also a large majority of physicians.

Classic symptoms? Non-classic symptoms? What are these? If there is not a previous explanation, it is not correctly understood. So I think that is essential an explanation with this brief sentence: In the past it was considered a digestive disease of childhood; however, it is a systemic disease which may develop at any age. Saying systemic disease and after "a wide number of symptoms that may involve any organ of the body", in my opinion, is not a duplication but an explanation for lego readers. Wikipedia policies state that is important understanding information without the need to navigate to other pages. I think that in this case is a perfect form to make easy to understand it.

So I will edit again. I hope you'll agree.

Best regards. --BallenaBlanca (talk) 10:06, 20 March 2016 (UTC)

"Old and new" are relative terms and I do not agree this is the most important thing to state. Yes coeliac disease is usually undiagnosed and can present at any age and this needs to be clear. Samuel Gee in the 1880 did describe it in children. But Adult coeliac disease has been known for decades with multiple publications from the start of Pubmed. And the Systemic nature is also difficult: anaemia produces all sorts of systemic features but as a complication of haematinic malabsorption. Skin (DH), cerebellar gluten ataxia and other gluten sensitvity are only debatably coeliac disease. I'll make a few changes. Jrfw51 (talk) 10:49, 20 March 2016 (UTC)

Yes, it is true that since years it is published that it affects adults, this aspect is generally known today, but is also true that it was not easy that knowledge of these ideas became widespread. Perhaps I have not explained well, the most important is the advancement of knowledge of the clinical picture and diagnosis. And about systemic nature of coeliac disease, there seems no doubt now. Most pubications and guideliness state that CD is a systemic disease, for example:

ESPGHAN Gastroenterology Committee; European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (Jan 2012). "European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease" (PDF). J Pediatr Gastroenterol Nutr (Practice Guideline) 54 (1): 136–60. doi:10.1097/MPG.0b013e31821a23d0. PMID 22197856

INTRODUCTION AND STRUCTURE. ESPGHAN guidelines for the diagnosis of CD were last published in 1990 (1) and at that time represented a significant improvement in both the diagnosis and management of CD. Since 1990, the understanding of the pathological processes of CD has increased enormously, leading to a change in the clinical paradigm of CD from a chronic, gluten-dependent enteropathy of childhood to a systemic disease with chronic immune features affecting different organ systems. Although CD may occur at any age (2), these guidelines focus on childhood and adolescence.

One interesant paper about autoimmunity in CD:

Nat Rev Gastroenterol Hepatol. 2015 Sep;12(9):507-15. doi: 10.1038/nrgastro.2015.136. Epub 2015 Aug 25. Coeliac disease and autoimmune disease-genetic overlap and screening. Lundin KE, Wijmenga C2. PMID 26303674

Associated autoimmune diseases. The abnormal immunological response elicited by gluten-derived proteins can lead to the production of several different autoantibodies, which affect different systems. The most prominent autoantibodies target members of the TG family, notably IgA-class antibodies against TG2 in coeliac disease,29 TG2 and TG3 in dermatitis herpetiformis and TG6 in gluten ataxia.29–31 The levels of these antibodies are influenced by the gluten intake of patients with coeliac disease.32,33 Antibodies against coagulation factor XIII, another member of the TG family, have also been described.34 Whether this finding implicates an underlying autoimmune aspect of bleeding disorders is unclear. Antibodies to a range of other autoantigens have been reported, particularly actin, calreticulin, gangliosides, collagens, synapsin, zonulin, cardiolipin, ATP synthase subunit β and enolase.35 Interestingly, autoantibodies typically seen in general autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematous are rarely seen in coeliac disease.35 A number of organ-specific autoimmune disorders and conditions are influenced by and associated with coeliac disease (Figure 1), but only a selection is discussed in this Review.3,36,37 Moreover, accurate, unbiased population-based data on disease prevalence are generally lacking and the published results are mainly derived from studies performed on patients who have been referred to secondary or tertiary care.

Best regards. --BallenaBlanca (talk) 11:44, 20 March 2016 (UTC)

This is simply English "a wide number of symptoms that may involve any organ of the body". Stating it is a "systemic disease" is basically stating the same thing in more complicated language that most people will not understand. IMO that belongs in the body of the text. We state what the classic symptoms are right after we use the term. Doc James (talk · contribs · email) 17:36, 20 March 2016 (UTC)

Thanks for making it simple -- too easy to go into medical jargon! Jrfw51 (talk) 17:40, 20 March 2016 (UTC)

I have linked "symptoms that may involve any organ of the body" to systemic disease of which it is basically the definition. Doc James (talk · contribs · email) 17:42, 20 March 2016 (UTC)

I agree with the current text, with a brief sentence about age of presentation after symptoms description. The link to systemic disease is an excellent idea.

I don't agree with mentioning anaemia as frequently found on this first paragraph, or not with only mentioning anaemia. Why? Anaemia is common, but is "only" present in about 15% of adults and in about 3% of children younger than 18 years. Perhaps you'd be surprised for the number of doctors that rule out coeliac disease in the absence of anaemia, and so they don't make any other evaluation nor derive patient to specialist (so people have severe symptoms and are investigated for many years before a CD diagnosis is achieved...) And because if we mention anaemia, we must mention the other most common extraintestinal manifestations to balance the information, which include reduced bone density, arthritis, peripheral neuropathy, short stature and hepatitis, among others. But after, we say that the symptoms may affect any part of the body, so IMO is best to let it into Signs and symptoms section. I find interesting to take a look at the causes of these common manifestations:

	Pathophysiology
Anaemia	Nutritional deficiencies: iron most frequently followed by folate and vitamin B12. Chronic inflammation
Reduced bone density	Nutritional, inflammatory, autoimmune
Arthritis	Inflammatory and/or autoinmune
Peripheral neuropathy	Autoimmune, inflammatory
Short stature	Nutritional, hormonal, Inflammatory
Hepatitis	Inflammatory, autoimmune

I will remove anaemia of the lead. I hope you agree.

Best regards. --BallenaBlanca (talk) 21:10, 20 March 2016 (UTC)

Yes do not need a mention of anemia in the lead Doc James (talk · contribs · email) 21:16, 20 March 2016 (UTC)

I disagree. This is one of the commonest presenting features leading to diagnosis in adult patients. In the reference you give below, it is described as "...the second most frequent mode of presentation in adults..." and although you correctly quote the figure of 15% here, this is rather a low estimate taken from two papers, and in the subsequent section, they review papers with figures of 20% and 25%. More recent series give figures of 30% [PMID 26452305], 32% [PMID 24084055], 48% [PMID 20670066] for instance. Pediatric GI experts might care to review this paper showing differences in anemia presentation in children and adults [PMID 21619387]. Failure to correctly investigate anemia in adults seems to be a major reason for diagnostic delay [PMID 24892255]. Anemia as a feature of the disease is much more important to include in the lead, especially when compared to the rare associations with autoimmune phenomena such as thyroiditis (8%) or complications like lymphoma! While making the point that there are many undiagnosed celiacs (which I am happy to include), we must not miss out on the mainstream features. Jrfw51 (talk) 15:28, 21 March 2016 (UTC)

Excellent point. And what was the most common presentation? Doc James (talk · contribs · email) 17:51, 21 March 2016 (UTC)

"In adults, the most common symptom upon presentation is diarrhoea, which develops in ~40% of patients, although some of these patients can have anaemia as well." Jrfw51 (talk) 19:03, 21 March 2016 (UTC)

It is a good paper, but in this issue is not right. It all depends on the patient selection criteria. And unfortunately, most studies are still choosing only, or mostly, patients with villous atrophy, who may more frequently present diarrhea. This paper states this issue:

Lewis NR, Scott BB (Jul 1, 2006). "Systematic review: the use of serology to exclude or diagnose coeliac disease (a comparison of the endomysial and tissue transglutaminase antibody tests)". Aliment Pharmacol Ther (Review) 24 (1): 47–54. doi:10.1111/j.1365-2036.2006.02967.x. PMID 16803602.

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. In four, total villous atrophy was required, 10, 24, 29, 38 and in two 9, 17 an abnormality ranging from an increase in intraepithelial lymphocytes alone to total villous atrophy was allowed. Two studies 32, 35 were vague simply saying that the diagnosis was histologically proven and therefore some degree of villous atrophy was assumed.

These are the old ideas about CD, still thinking in patients with diarrhea and villous atrophy, and are the main reasons why 85% of people remain unrecognized and undiagnosed.

Best regards. --BallenaBlanca (talk) 19:36, 21 March 2016 (UTC)

The Leffler Nat Rev Gastro Hep paper I just quoted from to answer Doc James is a high standard review which you have been quoting too. The experience of adult and paediatric gastroenterologists is different and hence this statement. As WP editors, I think we have no clear view on why 85% of the presumed cases are undiagnosed. What about family and population screening? These approaches seem to find lower Hb values too. But I think this is too detailed and specialist for the lead! Thanks for all you have done to improve it. Jrfw51 (talk) 20:25, 21 March 2016 (UTC)

Dear Jrfw51. I agree your new edition. First, I apologize if I cannot express properly in English. Written communication is difficult, many nuances are lost, and more if it is not in your own language.

"This is one of the commonest presenting features leading to diagnosis in adult patients." I agree, of course. I disagreed letting it alone among extraintestinal manifestations because the main problem is that CD is like a chameleon and the possible presentations are enormous. We must reflect that idea so we must avoid "closing the clinical picture", to avoid people think "I don´t have anemia, I cannot have celiac disease." Of course, we must draw attention to the anemia caused by undiagnosed CD, as you say it is a serious issue, even most serious in women because it tend not to evaluate them, It blames the menses and closed issue. For this reason, I agreed to include anaemia among non-classical symptoms, but as I said only if we include some more of the most common. Let's take a look:

Case finding is now becoming more common and is conducted in a wide range of clinical situations ranging from the presence of gastrointestinal symptoms (diarrhea, abdominal pain and distension), failure to thrive in children [4, 5] , prolonged fatigue [6] , unexpected weight loss, recurrent aphthous stomatitis, anemia [7] , increased liver transaminases [8] and unexplained neuropsychiatric disorder [9]

Table 1. Extraintestinal manifestations of CD (extracted the most common ones)

• Anemia ~50% * Most commonly secondary to iron deficiency but may be multifactorial in etiology; low serum levels of folate and vitamin B12 without anemia are frequently seen * NOTE: yes, here more elevated rates ;-)
• Thrombocytosis up to 60% Possibly secondary to iron deficiency or hyposplenism
• Bones Osteopenia/osteoporosis ~50% Affects 50% of nontreated CD; multifactorial etiology: malabsorption, inflammation, immunology and autoimmunity
• Fractures ~50% Multifactorial etiology; CD clinical presentation and gender influence
• Neurologic Peripheral neuropathy 49% Most common neurologic affection in CD
• Migraines ~50%
• Depression ~50%

These signs are haematological (anemia of various types, hyper platelets by hyposplenism, haemorrhagic signs) cutaneous (herpetiform dermatitis, cutaneous vasculitis) mucosal (aphtose), hepatic (cytolysis), neurophysical (fatigue, troubles of behaviour, cerebral syndrome, neuropathy) and osteo-articulitis (osteopenia, arthralgias, diffuse pains). The association of certain auto-immune illnesses must be emphasized (diabetes, Hashimoto thyroiditis, Gougerot disease, primitive biliary cirrhosis).

Coeliac disease has a variable presentation in many different settings of health care. Recently, and in view of the recognition of the increased prevalence of the disease, guidelines from the National Institute of Clinical Excellence (NICE) published in 200913 recommend offering or considering offering serological testing in many and varied clinical settings. These include persistent gastrointestinal symptoms, malaise, unexplained anaemias, autoimmune and neurological disease, metabolic bone disease with low mineral density, gynaecological symptoms and lymphoma. Recent genome-wide association studies have shown that chronic inflammatory and autoimmune diseases are linked genetically to coeliac disease; for example, type 1 diabetes mellitus, Grave’s disease and Crohn’s disease. 21–23 If present, these should prompt concurrent

Coeliac disease can present with a wide range of clinical features, both gastrointestinal (such as indigestion, diarrhoea, abdominal pain, bloating, distension or constipation) and non-gastrointestinal (such as fatigue, dermatitis herpetiformis, anaemia, osteoporosis, reproductive problems, short stature, neuropathy, ataxia or delayed puberty). Although some people present with typical symptoms, others have few or no symptoms. People with autoimmune conditions such as type 1 diabetes and autoimmune thyroid disease, or people with a first-degree family history of coeliac disease, have an increased likelihood of coeliac disease

The spectrum of clinical presentations is wide, and currently extraintestinal manifestations (eg, anemia or short stature) are more common than the classic malabsorption symptoms.

Best regards. --BallenaBlanca (talk) 18:20, 21 March 2016 (UTC)

I was writing when you write, Doc James. Perhaps my previous message serve to answer you. Best regards. --BallenaBlanca (talk) 18:23, 21 March 2016 (UTC)

And more, and more... an endless list. Other examples:

Typical (classical) signs and symptoms (this is the less common presentation):

• Abdominal distension
• Abdominal pain
• Anorexia
• Bulky, sticky and pale stools
• Diarrhea
• Flatulence
• Failure to thrive
• Muscle wasting
• Steatorrhea
• Vomiting
• weight loss

Atypical (non-classical) signs and symptoms (the more common presentation):

• Alopecia areata
• Anemia (iron deficiency)
• Aphthous stomatitis
• Arthritis
• Behavioral changes
• Cerebellar ataxia
• Chronic fatigue
• Constipation
• Dental enamel hypoplasia
• Dermatitis herpetiformis
• Epilepsy
• Esophageal reflux
• Hepatic steatosis
• infertility, recurrent abortions
• isolated hypertransaminasemia
• Late-onset puberty
• Myelopathy
• Obesity
• Osteoporosis/osteopenia
• Peripheral neuropathy
• recurrent abdominal pain
• Short stature

Associated diseases:

• Addison disease
• Atrophic gastritis
• Autoimmune hepatitis
• Autoimmune pituitaritis
• Autoimmune thyroiditis
• Behçet disease
• Dermatomyositis
• inflammatory arthritis
• Myasthenia gravis
• Primary biliary cirrhosis
• Primary sclerosing cholangitis
• Psoriasis
• Sjögren disease
• Type 1 diabetes mellitus
• Vitiligo

Table 1. Who to test?

• Gastrointestinal:
• Chronic or intermittent diarrhoea
• Persistent or unexplained gastrointestinal symptoms including nausea and vomiting recurrent abdominal pain, cramping or distension sudden or unexpected weight loss
• Irritable bowel syndrome
• Microscopic colitis
• Persistent or unexplained constipation
• Persistently raised liver enzymes with unknown cause
• Aphthous stomatitis (mouth ulcers)
• Dental enamel defects
• Malaise:
• Prolonged fatigue (‘tired all the time’)
• Failure to thrive or faltering growth (in children)
• Haematological:
• Unexplained iron-deficiency anaemia, or other unspecified anaemia
• Immunological ⁄ autoimmune disease:
• Type 1 diabetes mellitus Addison’s disease
• Autoimmune thyroid disease
• Autoimmune myocarditis
• Autoimmune liver conditions
• Chronic thrombocytopenia purpura
• Sjögren’s syndrome
• Neurological:
• Ataxia Polyneuropathy
• Epilepsy
• Depression or bipolar disorder
• Metabolic bone disease – low mineral density:
• Vitamin D deficiency Low-trauma fracture
• Reduced bone mineral density
• Metabolic bone disease (such as rickets or osteomalacia)
• Gynaecological:
• Recurrent miscarriage
• Turner’s syndrome
• Unexplained subfertility
• Amenorrhoea
• Dermatological:
• Dermatitis herpetiformis
• Unexplained alopecia
• Associated conditions:
• Sarcoidosis
• Down’s syndrome
• Malignancy:
• Lymphoma
• Small bowel adenocarcinoma

--BallenaBlanca (talk) 18:41, 21 March 2016 (UTC)

References

Duodenal lymphocytosis

I have created an article on duodenal lymphocytosis which we previously did not have. Please take a look and add to it. Pictures and links would be useful which I haven't had the time to find! I think it would be better for the coeliac disease entry if we moved some of the detailed discussion we have been adding here to other pages such as this. I looked at the Spanish WP entry (which BallenaBlanca has added a great deal of information to), and although there is much information of great relevance there, I feel to duplicate that here would make it excessive. We could write multiple academic reviews, and indeed books, based on all the systematic reviews in the literature, but it would have the drawback of making it less easy to understand for the average reader. We want something accessible to the patient who has just been told "I think you might have coeliac disease". Even the medical student told to write up a case of coeliac disease only needs to find the headings of issues here and should then go to the academic literature.Jrfw51 (talk)

Agree that subarticles are a great idea. Would be nice to summarize the pathophysiology section as 4 or 5 paragraphs and then move the rest to a subarticle were things could be gone into in greater depth. Doc James (talk · contribs · email) 17:34, 20 March 2016 (UTC)

Do not worry, it has never been my intention to duplicate all here.

We want something accessible to the patient who has just been told "I think you might have coeliac disease" but it is even more important for people with compatible symptoms or related diseases who has just been told "You can not have coeliac disease" or simply never has been told they may have coeliac disease, but they have related diseases and / or symptoms (up to 85% of coeliac people remain undiagnosed because of multiple diagnosis pitfalls...) ;-) Best regards. --BallenaBlanca (talk) 22:07, 20 March 2016 (UTC)

"a wide number of symptoms involving any part of the body"

We state this in the first paragraph.

Therefore trimmed "and have many different features" also in the first paragraph and "which can affect different organs and tissues of the body" from the second paragraph as these are basically saying the same thing with different words.

Doc James (talk · contribs · email) 17:32, 20 March 2016 (UTC)

Well, but if we remove "Upon exposure to gluten, it develops an abnormal immunological response which may lead to the production of several different autoantibodies, which can affect different organs and tissues of the body", is better to clarify in the first paragraph. I made this edition, with a brief sentence, supported by a 2015 source PMID 26260366, published on Nat Rev Gastro Hepat (12.61 impact factor, ranked 3/76.).

Best regards. --BallenaBlanca (talk) 22:19, 20 March 2016 (UTC)

I have moved this here "These manifestations are consequences of autoimmune reactions, inflammation and/or incorrect absorption of nutrients."

Because in the next paragraph we already state "Upon exposure to gluten, an abnormal immune response may lead to the production of several different autoantibodies.[11][12] In the small-bowel this causes an inflammatory reaction and may produce shortening of the villi lining the small intestine (villous atrophy).[1][13] This affects the absorption of nutrients.[9]"

I do not understand why we would say it twice in the lead?

The first paragraph even says it is an autoimmune disorder in the first sentence. So we already say twice that it is an autoimmune reaction. We should not be saying it three times. Doc James (talk · contribs · email) 01:07, 21 March 2016 (UTC)

This issue is currently not clear for most readers (lay or non-lay readers).

In the first paragraph we state: "is an autoimmune disorder affecting primarily the small intestine." Small intestine. "a wide number of symptoms involving any part of the body". It is no clear after read previous text that autoimmune reactions may affect other organs. And currently almost everybody thinks that these symptoms are caused by malabsorption or incorrect absorption, even after explanations, because there is great resistance to admit it (that includes most physicians). I have seen this for years. With all my respect, we have a recent example in this Wikipedia:

• BallenaBlanca, I'm not seeing any reason to believe that mainstream medicine believes any such "growing evidences" of any "connection between gluten and a variety of neurological symptoms" exist, outside of celiac disease and its occasional complications (e.g., nutritional deficiencies because your intestines are so wrecked that they can't absorb nutrients).;
• And I repeat from our earlier exchange: Mainstream medicine (not just neurologists, not just autism experts) does not appear to believe that gluten-free diets affect neurology (unless celiac is so severe that the patient is vitamin-deficient).

NOTE: Pathophysiology of gluten ataxia: Autoimmune. The autoimmune reaction in gluten ataxia is mediated by antibody crossreactivity between Purkinje cells and gluten proteins and a widespread perivascular deposition of TG2 antibodies in the brain. Antibodies against TG6, a TG primarily expressed in the brain, have been detected in patients with gluten ataxia. In addition, serum from patients with gluten ataxia and anti-TG immunoglobulins, which were derived using phage display technology, can trigger ataxia when injected intraventricularly into mice. After having been diagnosed with gluten ataxia, patients are advised to adhere to a gluten-free diet. However, the improvement of ataxia symptoms can be variable and depends on the duration of the disease, as loss of Purkinje cells and detectable atrophy are not reversible. Early diagnosis and prompt treatment are therefore important to minimize harmful consequences and prevent the progression of the disease. (TG: transglutaminase) Pathophysiology of peripheral neuropathy: Autoimmune, inflammatory.

In addition, those who know something about coeliac antibodies, basically know only antibodies affecting the intestine. When reading "Upon exposure to gluten, an abnormal immune response may lead to the production of several different autoantibodies" It's not clear that they are antibodies that affect different organs. In the best case, they will think in IgA / IgG anti-transglutaminase (TG2), anti-endomysial, anti-gliadin and anti-reticulin antibodies, which are "several different autoantibodies". But there are other antibodies that may develop [14] which affect different systems, and not only small intestine.

If we do not put an information in the first paragraph, we have to put it in the second. In one of the two, but we have to put it. IMO, this brief sentence in the first paragraph: "These manifestations are consequences of autoimmune reactions, inflammation and/or incorrect absorption of nutrients." because it is more complete and easy to understand. And also, let clear that inflammation affects other organs. The second paragraph talks only about small intestine (in the small-bowel this causes an inflammatory reaction). It is not enough and is not the same as duplicate information.

Best regards. --BallenaBlanca (talk) 03:50, 21 March 2016 (UTC)

"any part of the body" means "other organs"

I have expended the sentence on pathophysiology in the second paragraph to "Upon exposure to gluten, an abnormal immune response may lead to the production of several different autoantibodies that can affect a number of different organs." Doc James (talk · contribs · email) 05:09, 21 March 2016 (UTC)

I agree. Best regards. --BallenaBlanca (talk) 12:40, 21 March 2016 (UTC)

References

Lead... finished?

Doc James and Jrfw51. I want to thank you again. It is a pleasure working with you. I think the lead is running really well and IMO possibly already be finished. Best regards. --BallenaBlanca (talk) 12:51, 21 March 2016 (UTC)