Tag Archives: icds 2013

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2013 International Celiac Disease Symposium Poster Highlights

Although I did not allot enough time to check out all of the posters of abstracts that were on display at the International Celiac Disease Symposium (ICDS) in person, all of us received a spiral bound book that contained the hundreds of scientific posters that were presented. Abstracts are summaries of new research studies, and in many cases, they have not yet been published in a journal. I have started to review the book of abstracts that I received from the ICDS and there are some abstracts that are truly fascinating. We’ll hopefully hear more about these studies in the future as they get published in journals.

Here is a brief synopsis of five of the most interesting studies that I’ve been reading about:

1. “Nine years of follow-up of potential celiac disease in children.” A group of researchers from Naples, Italy (Aurrichio, et al) followed 156 with potential celiac disease who were not on a GF diet. Potential celiac disease, as I discussed here, is when a patient has abnormally high celiac antibodies on blood screening, and often symptoms, but a normal intestinal biopsy. The management is currently controversial. In this study, over a 5-year period, 46.8% of the children with potential celiac disease developed full-blown celiac disease.

2. “Celiac disease detection in asymptomatic children of 2 and 11 years old in a primary care health center using a transglutaminase antibodies quick test.” A Spanish team (Vallejo, et al) screened groups of 2 and 11 year olds for celiac disease in an outpatient clinic using rapid tests. 2% of the 2 year olds had confirmed celiac disease, and 1.5% of the 11 years had celiac disease. The overall rate of celiac disease in their population was 1.7%, which is higher than previously described.

3. “Absence of HLA-DQ2 and HLA-DQ8 does not exclude celiac disease in Brazilian patients.” HLA DQ2 and DQ8 are the 2 main celiac disease genes and are the ones that are currently tested for by most U.S. laboratories. In this study, a Brazilian team (Kotze, et al) performed gene tests on 101 patients with biopsy confirmed celiac disease. They found that 9 (8.9%) of their patients with celiac disease were DQ2 and DQ8 negative. They suspect that this is related to having such an ethnically diverse population in Brazil.

4. “Neurological dysfunction in patients with newly diagnosed celiac disease: a large prospective study.” Dr. Hadjivassiliou and team from the UK performed neurological evaluations on 73 patients with newly diagnosed celiac disease. 63% complained of neurologic symptoms; the most common were frequent headaches, problems with balance, and sensory symptoms. 32% had abnormal white matter lesions on MRI scanning and 43% had abnormal spectroscopy of the vermis of the cerebellum. The cerebellum is the part of the brain involved in balance and posture.

5. “Potential or definite celiac disease: push enteroscopy changes the diagnosis.” A celiac research team from the UK, lead by Dr. Eross, evaluated 16 patients with “potential” celiac disease. Potential celiac disease, as discussed above, is the term for when a patient has abnormally elevated celiac antibodies but no evidence of celiac disease on small bowel biopsy. They found that when their original duodenal biopsies were re-reviewed and biopsies of the jejunum (2nd part of the small intestine that is not typically biopsied when a patient is evaluated for celiac disease) were performed that 15 of the 16 patients actually did have celiac disease. They recommend that a diagnosis of potential celiac disease can only be made if the jejunum has been evaluated by biopsy.

Please let me know if you are interested in reading more about the abstracts that were presented at the ICDS poster session, as there are literally hundreds more that I can summarize for you. Also, I would love to hear about any interesting research that you have stumbled upon!

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ICDS 2013: The Celiac Iceberg Revisited

The second to last session on day one of the 2013 International Celiac Disease Symposium (ICDS) was a talk entitled, “Melting the Celiac Iceberg-potential, latent, silent: to treat or not to treat?” I was very confused about these terms when I first came across them in the Celiac medical and research literature a few years ago.

“Silent” Celiac Disease refers to patients who have Celiac Disease (elevated Celiac antibodies on blood testing and abnormal small bowel mucosa on endoscopy and biopsy) but no outward symptoms (or at least, do not appreciate any abnormal symptoms). Many silent Celiacs are picked up when they are screened for Celiac Disease due to having a family member with Celiac Disease and/or being in a high risk category for Celiac Disease, i.e. having Type 1 Diabetes.

“Latent” or “Potential” Celiac Disease is the term for when a patient has abnormally high Celiac antibodies on blood testing but either normal, or almost normal, small bowel mucosa on endoscopy. Many with potential Celiac Disease have abnormal symptoms. Some patients with this problem are told they are gluten sensitive, some have been told that they may have “early” or “pre” Celiac Disease, some are told by their doctors that they can continue to eat gluten, and others are advised by their doctors to go gluten free. My understanding is that, in recent years, the word “potential” is preferred over the word “latent” to describe this group.

Dr. Daniel Leffler, from the Celiac Center at Beth Israel Deaconess in Boston, presented the case for the GF diet in patients with potential and silent Celiac Disease, while Dr. Riccardo Troncone, from Naples, Italy, presented the case against the GF diet in these populations. Here are some interesting points that were brought up during both sides of the debate:

Children with first-degree relatives with Celiac Disease (parents and/or siblings) should be screened for Celiac Disease every 2-3 years in the absence of outward symptoms. Many “silent” Celiacs who think they feel “fine” prior to diagnosis will notice improvement on the GF diet. The presenters reminded us that 60% of newly diagnosed Celiacs have atypical symptoms.

There are many types of tissue transglutaminase (TTG) antibodies. Type 2 TTG antibodies can attack the placentas of pregnant women, type 3 cause the skin problem of dermatitis herpetiformis, and type 6 can attack the brain and nervous system. As an aside (from another talk during the ICDS), the commercially available assays in the U.S. test for Type 2 only!

There is conflicting information of the risks to silent Celiacs who do not go gluten free. One study in 2006 (Metzger, et al.) showed that untreated silent Celiacs have an increased risk of mortality and cancer over a 10 year period. But another study in 2009 (Lohi, et al) did not show an increase in cancer for this group. As with many areas, more research is necessary.

According to Dr. Troncone, it is not known if untreated silent Celiac Disease is associated with the development of other autoimmune diseases. He did state that going GF does not improve blood glucose control in patients who have both silent Celiac Disease and Type 1 diabetes.

Dr. Leffler presented research that shows that up to 50% of potential Celiacs will develop full blown Celiac Disease over a 5 year period and reminded us that TTG antibodies can cause harm even if there are no intestinal changes. He also stated that in order to be diagnosed with “potential” Celiac Disease that one must have an abnormally high TTG antibody level on at least 2 separate occasions (this is to rule out a false positive on the initial test).

I felt that the take home message from this lecture/debate was that those with silent and potential Celiac Disease should be on the GF diet, but that much more research is needed. Per my notes, they recommended that silent Celiacs should be GF, but it was not explicitly stated that potential Celiacs need to be GF. My concern is that many potential Celiacs may actually have full blown Celiac Disease that was not picked up on biopsy (see my previous ICDS post for information on how biopsies can be done incorrectly and that the damage from Celiac Disease can be missed). I will update all of my ICDS posts once I can get my hands on the power point presentations from the lectures, which I hope is soon! We were unable to take photos of the slides and although I tried to write as quickly as I could, I will add in key information that I may have missed.

Also, as a total aside, I am thankful to the anonymous reader who has nominated me for the WEGO Health “Geek Health Activist” of the year award. I have never been so proud to be called a geek in my entire life!

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Updates on Celiac Disease Screening and Testing from the 2013 International Celiac Disease Symposium

It’s been a busy three weeks since I attended the 2013 International Celiac Disease Symposium (ICDS) in Chicago and I have dedicated only two posts to the symposium thus far (as I was reminded by my friend last night). So, here is some more information for you. This will be post #3 of about 9 or 10 total.

On the first day of the conference, Dr. Benjamin Lebwohl from Columbia gave a lecture entitled “The Correct Diagnostic Approach.” Some of his bullet points on the diagnosis of Celiac Disease included the following:

  • At the current time, most algorithms for diagnosis use both blood tests (serology) and a small bowel biopsy.
  • The TTG IgA antibody is the blood test that is the most sensitive and specific for Celiac Disease. If a patient has a selective IgA deficiency (occurs in about 3% of the population), the deamidated gliadin peptide IgG (DGP IgG) can be useful for screening. The DGP IgA antibody is also more sensitive than the TTG IgA antibody in children under the age of 2.
  • The Celiac antibody tests are imperfect. In approximately 10% of Celiac patients, at time of diagnosis the antibody tests will be negative (normal) but there is still damage seen on biopsy. If these patients had only blood tests performed, their cases of Celiac Disease would be missed.
  • All patients with Irritable Bowel Syndrome (IBS) should be tested for Celiac Disease.
  • It is not feasible to screen all people for Celiac Disease because the positive predictive value (PPV) of the Celiac tests is too low. PPV refers to the percentage of patients with a positive test result who actually have a disease. He stated that if all people were screened, 2/3 of people with abnormal Celiac antibodies would actually not have Celiac Disease (too many false positives) .
  • Lastly, he reminded us that it is crucial that 4 to 6 biopsies be taken during endoscopy, as the damage from Celiac Disease can be missed if too few biopsies are taken. There are many people walking around who have Celiac Disease but were told that their small bowel biopsies were normal because not enough biopsies were taken. If you are interested in reading more about this, I discussed this in a recent post.

Later in the day, Dr. Enzo Bravi from Europe discussed rapid “point of care” tests for Celiac Disease.  There are several tests on the market that require only a few drops of blood and can give results in 5 to 10 minutes.  Simtomax and Biocard are two examples that are used in Europe and other parts of the world.  All of the rapid tests look for some combination of antibodies (TTG IgA, total IgA, DGP IgA and IgG, etc).  There are hopes that these tests will be especially useful in pediatric populations and in developing countries.  Dr. Bravi is currently researching if these tests can be used to assess compliance with the GF diet in Celiac patients who are already GF.   He emphasized that these tests are not intended to be used for the final diagnosis of Celiac Disease.  For more on the Simtomax tests, please see link.  I had an opportunity to briefly speak with Dr. Bravi during one of the breaks and learned that none of these tests are FDA approved for use in the U.S.  If/when they are approved,  I would love to be able to use them in a clinical research study!

Session 4 of the ICDS focused on the pathology of Celiac Disease.  The speakers were Drs. Marsh, Hart, and Bhagat.  We were reminded that small intestinal (duodenal) tissue biopsies are graded from Marsh Type 0 (normal) to Type 3 (villous atrophy and destruction).  Types 1 and 2, the intermediate lesions, have infiltration of tissues with white blood cells, which is called intraepithelial lymphocytosis (IEL). Type 2 also includes tissue hyperplasia, or thickening.

Type 1 lesions, with IEL only, can be seen in IBS and other causes of malabsorption.  If a patient has a Marsh Type 1 lesion in the duodenum and positive TTG antibodies, the diagnosis is either Celiac Disease or Crohn’s Disease.  If anti-endomysial antibodies are present, it is Celiac Disease, and if they are absent, it is Crohn’s Disease.

There are several other diseases that can cause villous blunting that is similar to that seen in Celiac Disease.  They include the following:

  1. Olmesartan associated enteropathy
  2. Common variable immunodeficiency (CVID)
  3. Crohn’s Disease
  4. Giardia infection
  5. Tropical sprue
  6. Autoimmune enterocolitis

CVID, an immunodeficiency, has a mean age of diagnosis of 35.  Two thirds of patients with CVID have increased IEL +/- villous atrophy on their biopsies.  Celiac antibody tests are often negative.  Patients with CVID have no improvement on the gluten free diet. This is one of the biggest red flags that CVID is a possibility for a patient.  CVID needs to be ruled out in cases of refractory (non-responsive) Celiac Disease.

Olmesartan is a medication used for high blood pressure (hypertension) that is in a category of drugs called ACE inhibitors. It can cause duodenal damage that is almost identical to that seen in Celiac Disease. Colchicine is another drug that can cause similar bowel changes.

The speakers emphasized that in patients with refractory Celiac Disease (that do not respond to the gluten free diet), #1-6 need to be excluded.

More information from ICDS to come, including what to do for those with “potential” Celiac Disease and nutrional aspects of Celiac Disease.  Thank you for both reading and being patient with me!

For additional information from the conference, please check out recent posts from both The Savvy Celiac  and Pretty Little Celiac who were official ICDS bloggers.

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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!