Tag Archives: Non celiac gluten sensitivity

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Dr. Fasano’s Gift of Gluten Freedom

Dr. Alessio Fasano, founder and director of the Center for Celiac Research at Massachusetts General Hospital, is one of the world’s leading experts in celiac disease and non-celiac gluten sensitivity. Without his dedication and research, there’s a good chance that many of us with celiac disease would still be walking around undiagnosed and chronically ill. As I have stated before, he is one of my heroes.

I had the fortune to read Dr. Fasano’s brand new book, Gluten Freedom, as I sat at O’Hare airport earlier this week due to a flight delay.   It made for one of the most fascinating flight delay experiences of my life.

Gluten Freedom explains the history of celiac disease, celiac disease awareness in the medical community, and the amazing leaps in celiac research over the past two decades.  Most significant research findings related to celiac disease are discussed and summarized in an easy to read manner. Dr. Fasano shows how celiac disease can have effects on all areas of the body, not just the digestive system, and discusses new research on the neurological and psychiatric/behavioral effects of gluten.  Non-celiac gluten sensitivity is discussed in depth as well, and Dr. Fasano makes it clear that non-celiac gluten sensitivity is a separate diagnosis from celiac disease that occurs in up to 6% of Americans. In addition, Dr. Fasano paints us a picture of why not all of us are successful on the gluten free diet, and justifies the need for additional medical treatment options for celiac disease.

My favorite part of the book was Part 3, in which the chapters deal with living with celiac disease during specific phases of life, including pregnancy, childhood, college, and the elderly years. A lot of the questions I have had others ask about me about being gluten free during pregnancy are discussed in this book.

One of my favorite quotes was Dr. Fasano’s discussion of what happens at the time of diagnosis. He states, “As a physician, I’m very sympathetic with this complex combination of emotions.  I never minimize the feelings of someone who has just realized that his or her life has been changed forever by this restriction on one of the most enjoyable activities of humankind, that is, eating.” He truly “gets it” like I wish other doctors would.

Although I’d love to be able provide a summary of the entire book for you, like I often do for journal and research articles, I cannot, as my post would end up being about 500 pages long!  If possible, I urge you to read this book on your own.  No matter what age you are, or where you are in your gluten-free journey, you will be helped by the information in it and will gain a better understanding of your medical condition.

Although the hardcover version of Gluten Freedom will not be available until April 29th, the Kindle version is already available on Amazon.com for $11.99. If you can swing it, it is money well spent, I promise.

And Dr. Fasano, if you (or one of your representatives) ever do read my post, thank you for all you’ve done and continue to do for all of us with gluten-related disorders.  We truly appreciate it!

 

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Non-celiac gluten sensitivity in children

I was thrilled to come across a paper about non-celiac gluten sensitivity in children in the Journal of Pediatrics, one of the main pediatric journals. Many of my pediatrician colleagues read this journal on a regular basis. In this article, a group of Italian researchers have described the symptoms and lab test results in 15 children with gluten sensitivity (GS) compared to 15 children with active celiac disease and 15 controls (children with IBS-type symptoms that have no correlation with gluten intake). None of the children included in the GS group had an IgE-mediated wheat allergy causing symptoms. Most of the children in the study were between 8 and 10 years old.

Here is a brief overview of the research study:

  • The main symptoms in the gluten sensitive group included abdominal pain, chronic diarrhea, bloating, failure to thrive (poor growth), vomiting, and constipation. These symptoms were similar to those seen in the group of children with active celiac disease. The “control” group of children with functional (IBS-type symptoms) had only abdominal pain and indigestion as symptoms.
  • The gluten sensitive children had “extraintestinal” symptoms of tiredness, headaches, and limb pains. Interestingly, these were not seen in children with active celiac disease. The celiac group of children had anemia and elevated liver function enzymes but the gluten sensitive children did not.
  • Two thirds of the gluten sensitive children had abnormally high antigliadin IgG antibodies (this is an older antibody that was used in the past to assess for celiac disease, but is no longer used because it is non-specific for celiac disease). None of the gluten sensitive children had elevated celiac antibodies (TTG IgA and endomysial IgA). All of the children with active celiac disease had abnormally high TTG IgA and endomysial IgA levels and 13/15 with celiac disease had elevated antigliadin antibodies. The control group kiddos with functional abdominal pain were negative for all antibodies (antigliadin, TTG, and endomysial).
  • Seven of the 15 children with GS had one of the celiac genes (DQ2/8) and 8 did not. The 8 gluten sensitive children who were DQ2/8 negative all had some combination of HLA DQ1, DQ5, and DQ7.
  • Eleven of the 15 GS children had an intestinal biopsy while on a gluten-containing diet. All of those with GS had normal to mildly inflamed intestinal mucosa, corresponding to Marsh stage 0 to 1.

In summary, the authors provide findings that support the existence of gluten sensitivity in children as a distinct problem from celiac disease. Children with gluten sensitivity have celiac-like symptoms that resolve on a gluten free diet and return when gluten is reintroduced. Although gluten sensitive children often have elevated antigliadin IgG levels, they have normal TTG IgA and endomysial IgA levels, at least in this study. Their small bowel biopsies show no evidence of villous blunting and, in the majority of cases, the biopsies are normal. In addition, these children’s symptoms are not as a result of being allergic to wheat. Although this is a small study, it is a step in the right direction toward the recognition of non-celiac gluten sensitivity in the pediatric population, and I am thankful that there is finally a research study to support its existence. I am looking forward to being able to read and share similar articles with you.

Reference:

Francavilla, R., Cristofori, F., Castellaneta, S., et al. Clinical, serologic, and histologic features of gluten sensitivity in children. Journal of Pediatrics. E-pub ahead of print. Nov. 16, 2013.

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“Celiac Disease Now”

Note: This is part 2 of several posts summarizing information discussed at the International Celiac Disease Symposium (ICDS) 2013 in Chicago 9/23-9/25. 

The introductory lecture of the clinical forum of the International Celiac Disease Symposium (ICDS) 2013 in Chicago last week was entitled “Celiac Disease Today: An Overview” given by Drs. Alessio Fasano and Peter Green.

Although the official slides and presentations from the symposium are not yet available for purchase, based on my notes the following topics were addressed during this opening session:

Celiac Disease involves both an innate and an adaptive immune system response to gluten. 1 in 133 Americans have Celiac Disease. The risk of Celiac Disease in 1st degree relatives of Celiac patients (parents, siblings, and children) is 1 in 22. The risk in 2nd degree relatives (aunts and uncles and grandparents) is 1 in 39.  Research has shown that the true prevalence of Celiac Disease has increased by 15% in the last few decades.  Most people with Celiac Disease (83%) are unaware that they have it…

Although the current “gold standard” for diagnosing Celiac Disease is to perform an endoscopy and small intestinal biopsy, Dr. Fasano did bring up the concept of the “4 out of 5” rule, in which some have proposed that Celiac Disease can be diagnosed if a patient meets at least 4 of the following 5 criteria:

  1. Adverse symptoms when gluten is ingested
  2. Elevated Celiac antibodies on serology (blood tests)
  3. An improvement in symptoms when gluten is removed from the diet
  4. Genetic markers (HLA DQ2 and/or 8, although he did mention that 1-2% of Celiacs are DQ2 and DQ8 negative)
  5. Abnormal small intestinal (duodenal) biopsy

Anti-TTG IgA antibodies are greater than 95% sensitive and 95% specific for Celiac Disease.  The DGP IgA antibodies have a sensitivity and specificity of greater than 90%.

No one is born with Celiac Disease and it can develop at any age. Celiac Disease involves a shift from gluten tolerance to an immune (autoimmune) response to gluten.  The current thinking is that in order to develop Celiac Disease, one must have a genetic predisposition, ingest gluten, and be exposed to a (yet to be defined) environmental factor. In order to figure out exactly what the environmental factor(s) are, researchers will need to follow a large cohort of children from birth and monitor them for the development of Celiac Disease.  We did learn later during the conference that this is actually being done as part of the “Prevent Celiac Disease Study” in Europe, which I will discuss in a later post (www.preventCD.com).

It is now believed that a change in the gut microbiome (bacteria) is involved in the pathogenesis and development of Celiac Disease.  Although our gut microbiomes are inherited from our mothers,  the composition of our gut bacteria is continually changing.  There has been some recent research showing that birth by c-section increases a child’s risk of Celiac Disease by 2-3x. During a normal vaginal delivery newborns’ digestive tracts are colonized by bacteria that they pick up from their mothers’ bodies during labor and delivery.  During a c-section this mother to infant transfer of bacteria does not take place.

There are over 70 clinical trials of Celiac Disease going on right now, many of which are currently enrolling subjects.  You can check out www.clinicaltrials.gov and search for “celiac disease” for more information.

Dr. Green stated that currently recognized gluten related disorders include Celiac Disease, gluten ataxia, dermatitis herpetiformis, wheat allergy, and non celiac gluten sensitivity (NCGS).  NCGS was discussed at the ICDS pre-conference (see my previous post for more details).  Celiac Disease can be differentiated from these disorders by the presence of intestinal inflammation and villous atrophy.  Based on a 2012 publication, only 17% of people with Celiac Disease have actually been diagnosed. Young men in the age range of 20-30 have the lowest rates of diagnosis.

Currently recognized risk factors for Celiac Disease include formula feeding, being introduced to gluten before 4 months of life or after 7 months of life, being born during the winter months, PPI (proton pump inhibitor, a type a reflux medication) use, and frequent respiratory infections during infancy.  Much of this information comes from Sweden, where there was an epidemic of Celiac Disease in children during the 1980s and 1990s which triggered much research and analysis.

We were cautioned of a few pitfalls in the diagnosis of Celiac Disease, many of which I will describe in more detail in future posts.  Some of the researchers have found that TTG (tissue transglutaminase) antibody testing from certain labs can be unreliable.  Likewise, some research has shown that only 35% of the biopsies performed during evaluations for Celiac Disease are done correctly. Most GI docs take only 2 samples of small bowel, despite the current recommendations that 4-6 samples be taken.

Although Celiac Disease is often associated with digestive symptoms, many patients do not have any symptoms at all (i.e. they are picked up because they are screened due to having a family member with Celiac).  Some of the most severe cases of Celiac Disease have been found in patients whose only symptom is anemia (low red blood cell count).  On the flip side, a 2009 study showed that only 51% of patients with symptoms of Celiac Disease were actually screened.

A few sort of depressing stats:

-only 20% of patients with Celiac Disease have adequate follow-up after diagnosis

-the average U.S. medical student learns about Celiac Disease for one hour during medical school (I can personally relate to this one!)

And things that I think everyone should know:

-If a patient has dermatitis herpertiformis (DH), then they have Celiac Disease. Dr. Green stated that if one has DH, there is no need for a small bowel biopsy.

-1st degree family members of Celiac Disease patients should be screened every 5 years.

-The Celiac Center at Beth Israel Deaconess Medical Center in Boston has a great new website called “Celiac Now.” Check it out here.

More ICDS information to come soon…Also, any questions are welcome in the meantime!

 

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Recap of Non Celiac Gluten Sensitivity ICDS Pre-Conference 9.22.2013

I was fortunate to be able to attend the International Celiac Disease Symposium (ICDS) in Chicago last week, during which I was able to hear lectures given by world expert doctors, researchers, and nutritionists.  Although I got home 3 days ago, my mind is still spinning from all of the information that I learned and tried to absorb during the 22 hours of lectures.  I was also fortunate to meet some awesome people from the Celiac internet community, including Erica from Celiac and the Beast, Rebecca from Pretty Little Celiac, G-Free Laura, and The Gluten-Free Professor. Although I was not one of the official bloggers from the conference, I did learn some information that I’d like to share with you.

Over the next few weeks I plan to summarize much of the information that I learned about both Celiac Disease and Non Celiac Gluten Sensitivity (NCGS) at the symposium, as well as to try to convince you to attend the next ICDS in Prague in 2015 with me, as my dear husband has already declined.

On Sunday night there was a pre-conference on NCGS with a panel of speakers who are world’s experts on NCGS.  I am very interested in this topic as I have several family members who have NCGS and I am amazed by the lack of awareness of this condition in the medical community. There are many doctors who believe that you cannot get sick from gluten unless you have Celiac Disease (intestinal damage) and as you may already know, this is not true!

The experts who presented information about NCGS included Drs. Fasano, Green, Kelly, Mooney, Volta, Schuppan, and Leffler. Below is a summary of some of the information that was shared with the audience:

Patients with NCGS experience adverse symptoms after ingesting gluten but they do not meet the criteria for getting diagnosed with Celiac Disease (namely, they do not have the findings of Celiac Disease on small bowel biopsy).  NCGS is a “diagnosis of exclusion” meaning that, ideally, Celiac Disease is ruled out before a diagnosis of NCGS is given. Despite this, many with NCGS are self-diagnosed.

Between 0.5 to 6% of U.S. population has NCGS, depending on which study is referenced.  The average age of diagnosis is around 40 years, but the research on NCGS is really still in its infancy. Some patients with NCGS have abnormally high antibodies that are associated with Celiac Disease, such as TTG IgA and/or anti-gliadin antibodies, and others do not. About half of patients with NCGS have one of the two main Celiac genes (HLA-DQ2 and/or DQ8) and half do not.  There are currently no biomarkers for NCGS, which plays a large part in the difficulty of diagnosis.

In a large Italian survey, the most common symptoms associated with NCGS included abdominal pain, bloating, diarrhea, fatigue, headache, anxiety, and a “foggy mind.” This mirrors the symptoms that have been described in previous studies.

Dr. Green introduced the acronym PWAWG which stands for People Who Avoid Wheat and Gluten.  According to Dr. Green, not all PWAWGs have NCGS, and many have other problems such as small intestinal bacterial overgrowth (SIBO) and fructose intolerance.  In one recent study, which has gotten a lot of attention, many NCGS patients’ reactions to gluten totally disappear when FODMAPs are also removed from the diet (see link to paper in references below).  However, the researchers only looked for a resolution of abdominal and digestive symptoms and we do not know if other symptoms of NCGS, such as headaches and anxiety, also improved when FODMAPs were removed.  More research is needed in this area. Although I will discuss FODMAPs more in the upcoming weeks, you can refer to Stanford’s website for more information on the low FODMAP diet if interested.

I learned that both autism and schizophrenia have been associated with anti-gliadin antibodies. There was a publication in 2011 that showed that there is subset of autistic children whose symptoms improve on a gluten free and casein free diet.  There are also ongoing clinical trials to see if the GF diet can help improve symptoms associated with schizophrenia.  The tissue transglutaminase antibody (TTG) type 6 looks to be a marker of neuroinflammation and is a possible biomarker for schizophrenia. TTG type 2 antibodies are what are currently measured in blood tests for Celiac Disease.

The pathogenesis of NCGS appears to involve the innate immune system and it is possible that wheat amylase trypsin inhibitors (ATIs), a totally different portion of wheat than the gluten proteins, may be involved. I wrote about this a bit last winter (see link) and the article referenced can be found in the references below.

During the panel discussion, we were reminded that the only way that a NCGS individual who is already GF can find out if he or she has Celiac Disease is to undergo a “gluten challenge.”

One of the last questions to the panel was, “Who should be avoiding gluten?” The answer given was patients with Celiac Disease, NCGS, and possibly autism and schizophrenia.

I also learned that Dr. Fasano recently published a book called “A Clinical Guide to Gluten-Related Disorders,” which I plan to purchase a copy of ASAP. It is available on Amazon.com (see here).

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Dr. Fasano reminded us that there is currently more confusion than understanding of NCGS, and that it is similar where we were with understanding Celiac Disease 20 to 30 years ago. The great thing is NCGS is finally being recognized and properly studied!

For a great overview of NCGS, please check out the following abstract from PubMed by Dr. Volta, who was one of the experts on NCGS at the symposium:

Volta U, Caio G, Tovoli F, De Giorgio R.Cell Mol Immunol. Non-celiac gluten sensitivity: questions still to be answered despite increasing awareness.  2013 Sep;10(5):383-92. doi: 10.1038/cmi.2013.28. Epub 2013 Aug 10.

Recently, the increasing number of patients worldwide who are sensitive to dietary gluten without evidence of celiac disease or wheat allergy has contributed to the identification of a new gluten-related syndrome defined as non-celiac gluten sensitivity. Our knowledge regarding this syndrome is still lacking, and many aspects of this syndrome remain unknown. Its pathogenesis is heterogeneous, with a recognized pivotal role for innate immunity; many other factors also contribute, including low-grade intestinal inflammation, increased intestinal barrier function and changes in the intestinal microbiota. Gluten and other wheat proteins, such as amylase trypsin inhibitors, are the primary triggers of this syndrome, but it has also been hypothesized that a diet rich in fermentable monosaccharides and polyols may elicit its functional gastrointestinal symptoms. The epidemiology of this condition is far from established; its prevalence in the general population is highly variable, ranging from 0.63% to 6%. From a clinical point of view, non-celiac gluten sensitivity is characterized by a wide array of gastrointestinal and extraintestinal symptoms that occur shortly after the ingestion of gluten and improve or disappear when gluten is withdrawn from the diet. These symptoms recur when gluten is reintroduced. Because diagnostic biomarkers have not yet been identified, a double-blind placebo-controlled gluten challenge is currently the diagnostic method with the highest accuracy. Future research is needed to generate more knowledge regarding non-celiac gluten sensitivity, a condition that has global acceptance but has only a few certainties and many unresolved issues.

Additional References from ICDS pre-conference:

1. DiGiacomo, et al. Prevalence of gluten-free diet adherence among individuals without celiac disease in the USA: results from the Continuous National Health and Nutrition Examination Survey 2009-2010. Scand Journal Gastroenterol. 2013 Aug;48(8):921-5. doi: 10.3109/00365521.2013.809598. Epub 2013 Jul 8.

2. Biesiekierski JR, Newnham ED, Irving PM, Barrett JS, Haines M, Doecke JD, et al. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Am J Gastroenterol 2011;106:508–14.

3. Biesiekierski JR., et al. No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates. Gastroenterology. 2013 Aug;145(2):320-8.e1-3. doi: 10.1053/j.gastro.2013.04.051. Epub 2013 May 4.

4. Junker, et al. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. J Exp Med. 2012 Dec 17;209(13):2395-408. doi: 10.1084/jem.20102660. Epub 2012 Dec 3.