Tag Archives: celiac disease

Goldilocks and Gluten

Posted on by

A recent study (CA Aronsson et al. Clin Gastroenterol Hepatol 2016; 14: 403-09, editorial 410-12) suggests that how much gluten is given may be another important factor rather than looking at the timing with regard to the development of celiac disease (CD).

In this 1-to-3 nested case-control study with 146 cases of CD and 436 controls, the authors indicate that a larger intake of gluten than controls increased the likelihood of celiac disease.  Specifically, children receiving large amounts of gluten (>5 g/day) during their first 24 months had a 2.6-fold increased risk of CD compared to those who consumed lower quantities.

The associated editorial notes that the total amount of gluten intake was only marginally increased in CD cases versus all control patients (OR 1.05) and that the association was decreased when individuals with first-degree relatives with CD were excluded.  In addition, this high consumption increased the risk after the first 2 years of life, rather than during this period of high consumption.

Does this make sense? Not to me.  These findings need to be replicated in other studies to determine if gluten exposure is like Goldilocks: too little, too much –>just right.

My take: For now, I think sticking with the timing of gluten exposure (recommended at 4-6 months) rather than the quantity is worthwhile.

Related blog posts:

Celiac Studies

Posted on by

Three reports on celiac disease:

  • KM Simmons et al. J Pediatr 2016; 169: 44-8.
  • NR Reilly et al. J Pediatr 2016; 169: 40-54
  • MMS Wessels et al. J Pediatr 2016; 169: 55-60.

In the first study, the authors examined bone mineral density (BMD), glycemic control with hemoglobin A1c, and celiac autoimmunity in children with type 1 diabetes (T1D).  This was a cross-sectional study of 252 children with T1D; 123 had positive serology were anti-tissue transglutaminase (tTG) antibody.  In addition, another cohort (n=141) of children without T1D were examined who carried HLD-DR, DQ genotypes with (n=71) and without (n=70) tTG.  Key findings:

  • Children with T1D: those positive for tTG had significantly worse BMD L1-L4 (-0.45 ± 1.22 vs 0.09 ± 1.10, P= .0003).  Higher tTG and higher HgbA1c were independent predictors of lower BMI.
  • In children without T1D: no differences in BMD were found based on tTG status.
  • The authors concluded that celiac autoimmunity and hyperglycemia had synergistic effects on low BMD.

In the second study, the researchers used a population-based cohort study and compared 958 individuals with both T1D and celiac disease (CD) to 4598 similar individuals with T1D alone. Key finding: Over a 13 year period, 12 patients with both T1D and CD had a fracture (1 osteoporotic fracture). CD did not influence the risk of any fracture (aHR 0.77) in patients with T1D.  The researches concluded: “CD does not seem to influence fracture risk in young patients with T1D.”

My take: Looking at these studies in juxtaposition shows how important it is to consider multiple studies and how frequent discrepant results occur.  While the second study does not show a significant fracture risk, the preponderance of evidence does show an association between celiac disease and low BMD particularly in adults. In addition, a gluten free diet has been shown to reverse low BMD in those with CD.

Relevant studies:

  1. Gastroenterology 2010; 139: 763.
  2. Aliment Pharmacol Ther 2000; 14: 35-43.
  3. JPGN 2003; 37: 434-6.
  4. Gut 1996; 38: 322-7.

In the third study, the investigators looked at “complementary” investigation in children with CD.  These included tests like hemoglobin, ferritin, folate, vitamin B12, calcium, vitamin D, and thyroid assays.  Between 2009-2014, 182 children were evaluated included 119 with new diagnosis. Key findings:

  • At time of diagnosis: Iron deficiency (28%), iron deficiency anemia (9%), folate deficiency (14%), vitamin B12 (1%), and vitamin D deficiency (27%) were identified. No hypocalcemia or thyroid dysfunction was found.
  • At followup: iron deficiency (8%), iron deficiency anemia (2%), folate (3%), vitamin D (25%) were identified and no other abnormalities were evident.
  • The investigators concluded that these complementary tests “are relevant at the time of diagnosis of CD but have little diagnostic yield during followup-visits” after institution of gluten-free diet.

My take: Particularly at followup, identification of nutrient deficiencies is typically similar to the general population.

Related posts:

Castillo San Felipe del Morro, San Juan

Castillo San Felipe del Morro, San Juan

Systematic Review of Gluten Introduction

Posted on by

A recent systematic review/meta-analysis (MI Pinto-Sanchez et al. J Pediatr 2016; 168: 132-43) identified 15 eligible studies among an initial search of 1982 studies.

Key findings:

  • There was a 25% increase in celiac disease risk with late (>6 months) vs recommended (4-6 months) gluten introduction.
  • There was no significant effect of breastfeeding or not breastfeeding.

The authors state there is no evidence on whether early introduction (<4 months) of gluten would affect the risk of celiac disease.  Late introduction (>6 months) is associated with increase risk of celiac disease.

Related blog posts:

Isla Verde, San Juan

Isla Verde, San Juan

Should Patients with IBS be Screened for Celiac Disease?

Posted on by

Despite widespread expert opinion that those with irritable bowel syndrome (IBS) should be screened for celiac disease, whether it is a good idea is not settled.  A recent study (RS Choung et al. Clin Gastroenterol Hepatol 2015; 13: 1937-43) showed that celiac disease has a low prevalence in US patients (mean age 61 yrs in this cohort) with IBS.

Here’s an excerpt of a summary of this report from the AGA Blog: “Should all Patients with IBS be Screened for Celiac Disease?”

Rok Seon Choung et al investigated whether subjects with positive results from serologic tests for celiac disease are frequently diagnosed with IBS or other functional gastrointestinal disorders (FGIDs).

They sent self-report bowel disease questionnaires to 7217 residents of Olmsted County, Minnesota, to collect data on symptoms compatible with functional GI disorders, including IBS, collecting data on symptoms compatible with functional GI disorders, including IBS. These symptom data were linked to surveys of undiagnosed celiac disease conducted among more than 47,000 individuals from the same region, based on results of tests for immunoglobulin A tissue transglutaminase and then endomysial antibody.

Among the 3202 subjects who completed the questionnaires and had their serum sample analyzed, 13.6% had IBS and 55.2% had some gastrointestinal symptoms.

The prevalence of celiac disease, based on serologic markers, was 1.0%. However, whereas 3% of patients with celiac disease met the criteria for IBS, 14% of patients without celiac disease met the criteria for IBS.

Abdominal pain, constipation, weight loss, and dyspepsia were the most frequent symptoms reported by subjects who tested positive for celiac disease, but none of the gastrointestinal symptoms or disorders were significantly associated with results of serologic test for celiac disease.

My take: This study along with others show that celiac disease is infrequent in patients with IBS.  Since the symptoms of celiac disease overlap with IBS, I doubt this study will dissuade practitioners from screening for celiac despite the low yield.

Also, this fall I posted several blogs on GMOs.  An interesting article (from Vox/Grist) on this subject explains how GMOs are a lot like pornography: It’s practically impossible to define “GMOs”

Leaving Work

Atlanta Sky

Zonulin –Possible Biomarker for Gluten Sensitivity?

Posted on by

A recent abstract indicated that there are high levels of zonulin in patients with gluten sensitivity as well as in patients with celiac disease.  These results are preliminary but could indicate a potential biomarker for this condition.  Here is a link to a review of these findings from NPR which includes commentary from Alessio Fasano: A Protein In The Gut May Explain Why Some Can’t Stomach Gluten

An excerpt:

Zonulin is an inflammatory protein first discovered by Fasano and his team in 2000. It helps regulate leakiness in the gut by opening and closing the spaces or “junctions” between cells in the lining of the digestive tract…

Giovanni Barbara and a team of researchers at the University of Bologna measured blood levels of zonulin in four groups of individuals: those with celiac disease, those with irritable bowel syndrome marked by diarrhea, those with self-diagnosed gluten sensitivity and healthy volunteers. Both celiacs and gluten sensitives turned up with remarkably high levels of zonulin in their blood. Those with IBS had elevated levels but less than half of celiacs or gluten sensitive individuals. Healthy volunteers had negligible blood levels of zonulin.

The results were presented in October as an abstract at the 23rd United European Gastroenterology Week in Barcelona, Spain.

Related blog posts:

“To biopsy or not to biopsy” –that is the question (for Celiac disease)

Posted on by

First off -thanks to Ben Gold for the following reference and the blog title as well.

  • CM Trovato et al. Am J Gastroenterol 2015; 110: 1485-89.

In this retrospective study (alluded to in a previous post:Celiac Update September 2015 | gutsandgrowth), the researchers examined whether “biopsy-sparing” protocols for symptomatic children with high titers of serum anti-transglutaminase (anti-TTG) antibody levels (>10 times upper limit of normal [ULN]) would be suitable for asymptomatic patients.

Background: In 2012, the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) published guidelines that it is possible to omit endoscopic biopsies for celiac disease if patients older than 2 years of age had high anti-TTG titers (>10 times ULN), positivity for EMA, compatible HLA DQ2 or HLA DQ8 and were symptomatic.

Findings:

  • Among 196 patients, the 40 who were asymptomatic had severe Marsh lesions (3a, 3b, or 3c) in 92% compared with 91% of 156 who were symptomatic. In both groups, the remaining patients had either Marsh 1 or 2 lesions.
  • 94.4% of patients had improved serology during followup along with symptomatic improvement (in those with symptoms)

Bottomline:  Whether symptomatic or not, those with high antiTTG titers who meet all of the other ESPGHAN criteria have a very high probability of celiac disease.

Briefly noted: K Marild et al. Am J Gastroenterol 2015; 110: 1475-84. This study, based on a large prospective Norwegian cohort (72,921 children) that frequent infections (>10) in the first 18 months of life increased the risk of celiac disease with an adjusted odds ratio of 1.32 (highest infection quartile compared to lowest infection quartile).  However, alternative explanations, including surveillance bias and reverse causation, cannot be excluded.

Related blog posts:

 

Milder Celiac Disease Being Diagnosed Now

Posted on by

A study (Kivela L et al. J Pediatr 2015; 167: 1109-15) over a period of 48 years from Finland provides some hard data regarding the changing presentation of celiac disease.

Here are the key points;

  • Age at diagnosis has increased from a median of 4.3 years before 1980 to 7.6 years and 9.0 years in later periods.
  • Poor growth has decreased.  Among the 46 children diagnosed prior to 1980, poor growth occurred in 66% whereas 2010-2013: 23% had poor growth (had 14% were overweight or obese)
  • Severity of small-bowel mucosal damage was milder (Figure 1 D).  Among those with gastrointestinal presentation, total villous atrophy also declined from “61-62% to 18-22% (P=.001).”

Why is the presentation changing? There are increased “proportions of screen-detected and asymptomatic children…[this has] increased over 6-fold and simultaneously gastrointestinal symptoms …decreased.”  While there are improved diagnostic methods and increased knowledge, there has also been a “well-defined increase in the true prevalence of celiac disease.”

Related blog posts:

Nutrition Symposium Georgia AAP (Part 2)

Posted on by

Last week I summarized an excellent talk by Ronald Kleinman.  For me, I had never heard such a concise and definitive rebuttal of the claims of those fearful of food biotechnology.  There were three other lectures at the symposium.  These three lectures covered areas that are well-known to pediatric gastroenterologists but less familiar to general pediatricians.  The full set of slides are available at the Georgia AAP Symposium Website.

Jeff Lewis had an excellent lecture that tied together gluten and our microbiome: Gluten – Eat not, suffer not and Microbiome 101: Waste Not, Want Not

After reviewing celiac disease and other wheat-related disorders (eg. wheat intolerance syndrome, and wheat allergy), he summarized a great deal of information regarding the human microbiome and which factors influence this. In addition, he had the opportunity to briefly present data from his research on fecal microbiota transplantation (for C diff) and its influence on the microbiome over time. Here are a couple of slides from his talk:

 

Screen Shot 2015-11-13 at 5.51.40 PM

Screen Shot 2015-11-13 at 5.50.12 PM

Screen Shot 2015-11-13 at 5.49.18 PM

Key points:

  • “It is hard to communicate science to families. It is a huge challenge for us.”
  • Dermatitis herpetiformis (rare in kids), a rash associated with celiac disease, can be treated with Dapsone. This rash has caused such severe itching that there are cases of suicide that have been reported.
  • For celiac disease, Dr. Lewis recommends testing of 1st degree relatives but this needs to be after gluten exposure and before gluten-free diet.
  • Wheat allergy reviewed. Skin test positivity does not prove that you are allergic to food. IgG based testing is worthless –it means you have been exposed to a food, but is not an indication of food allergy.
  • Nonceliac gluten sensitivity (aka. wheat intolerance syndrome): need to test for celiac first. No tests/biomarker that can confirm this diagnostic. This appears to be a true disease; there is a small subset of patients who develop symptoms with a double-blind challenge.
  • Microbiome –more bacterial DNA in us than human DNA. New organisms –archaea kingdom.  Now a specimen of a person’s microbiome can be run for <$50.
  • Microbiome terms: Richness, Diversity, and Dysbiosis. Many diseases are associated with dysbiosis (obesity, IBD), but there is a ‘chicken and the egg’ problem. Is dysbiosis a causal factor or a secondary factor?
  • Xyloglucans (in lettuce) –not broken down by humans and affected by gut bacteria.
  • Mice given stool from fat mice or fat person become heavy.

Celiac Update September 2015

Posted on by

A useful review (CP Kelly et al. Gastroenterol 2015; 148: 1175-86) summarizes the ‘state of the art” information regarding celiac disease presentation and management. The review notes that some expert organization consensus state that intestinal biopsy is mandatory whereas some do not under certain conditions.

According to ESPGHAN, if anti-TTG >10-fold elevated, anti-EMA positive in separate sample, and +HLA typing, then a biopsy may not be required.  For the WGO (World Gastroenterologic Organization), the exception focuses on available local resources.

The article recommends the following for monitoring:

  • Clinical evaluation -annually or if recurrent symptoms
  • Serology & Nutritional evaluation -every 3-6 months until normal, then every 1-2 years.  Common nutrient deficiencies: iron, vitamin D, vitamin B12, folate, and zinc
  • Bone density -once within first 2 years.  (Some recommend checking after 1 year on gluten free diet)
  • Liver transaminase levels & Thyroid function tests -at diagnosis, then every 1-2 years.  Autoimmune thyroid disorders are “found in approximately 15-20% of adults with celiac disease”

A second retrospective indicates that ESPGHAN criteria for avoiding biopsy in children and adolescents with high titers for anti-TTG (>10-fold) along with positive EMA, and HLA-DQ2/DQ8.are reasonable.  Here’s the abstract:

Are ESPGHAN “Biopsy-Sparing” Guidelines for Celiac Disease also Suitable for Asymptomatic Patients?

CM Trovato, et al.The American Journal of Gastroenterology , (15 September 2015) | doi:10.1038/ajg.2015.285

OBJECTIVES:

In 2012, European Society of Pediatric Gastroenterology, Hepatology, and Nutrition published novel guidelines on celiac disease (CD) diagnosis. Symptomatic children with serum anti-transglutaminase (anti-tTG) antibody levels ≥10 times upper limit of normal (ULN) could avoid duodenal biopsies after positive HLA test and serum anti-endomysial antibodies (EMAs). So far, both asymptomatic and symptomatic patients with anti-tTG titer <10 times ULN should undergo upper endoscopy with duodenal biopsies to confirm diagnosis. The aim of this study was to assess the accuracy of serological tests to diagnose CD in asymptomatic patients.

METHODS:

We retrospectively reviewed data of 286 patients (age range: 10 months to 17 years) with CD diagnosis based on elevated titer of anti-tTG, EMA positivity, and histology. All patients were distinguished between symptomatic and asymptomatic; histological lesions were graded according to the Marsh–Oberhuber (MO) criteria. Fisher exact test was applied to analyze both groups in terms of diagnostic reliability of serological markers.

RESULTS:

A total of 196 patients (68.53%) had anti-tTG titers ≥10 times ULN. Among them, a group of 156 patients (79.59%) also had symptoms suggestive of CD (“high-titer” symptomatic); of these, 142 patients (91.02%) showed severe lesion degree (3a, 3b, 3c MO). Conversely, 40 out of 196 patients (20.40%) were asymptomatic (“high-titer” asymptomatic) and 37 patients (92.5%) of them showed severe lesion degree (3a, 3b, 3c MO). No difference in histological damage was found between “high-titer” symptomatic and “high-titer” asymptomatic children (Fisher exact test, P=1.000).

CONCLUSIONS:

If confirmed in large multicenter prospective studies, the “biopsy-sparing” protocol seems to be applicable to both symptomatic and asymptomatic patients with anti-tTG titer ≥10 times ULN, positive EMA, and HLA-DQ2/DQ8.

Related blog posts: