Tag Archives: celiac disease

How to Protect Children From Celiac Disease

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While many parents have asked what they can do to protect their children from celiac disease, the new answer will be more limited than in the past.  Two recent studies from NEJM indicate that timing of gluten introduction and breastfeeding do not appear to significantly influence the development of celiac disease.

Here are the links:

1st Study: Introduction of Gluten (6 months vs 12 months)

  • Results: (n=707) At 5 years of age, the between-group differences were no longer significant for autoimmunity (21% in group A and 20% in group B, P=0.59) or overt disease (16% and 16%, P=0.78 by the log-rank test).
  • CONCLUSIONS: Neither the delayed introduction of gluten nor breast-feeding modified the risk of celiac disease among at-risk infants, although the later introduction of gluten was associated with a delayed onset of disease. A high-risk HLA genotype was an important predictor of disease.

2nd Study: Gluten 16-24 weeks or Delayed  n=944

  • CONCLUSIONS As compared with placebo, the introduction of small quantities of gluten at 16 to 24 weeks of age did not reduce the risk of celiac disease by 3 years of age in this group of high-risk children.

Here’s a story from Boston Globe summarizing findings: Tactics to Prevent Celiac

Bottomline: These well-designed studies argue persuasively against the previously held views that breastfeeding and timing of gluten introduction influence the development of celiac disease.

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NASPGHAN Educational materials for medical professionals –NASPGHAN Celiac Link

Another Look at Gluten-free Diet for Asymptomatic Celiac

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Previously, a blog entry (Benefits of Gluten-Free Diet for “Asymptomatic” Celiac …) reviewed the abstract (available early online) from Gastroenterol 2014; 147: 610-17.  With the publication of the printed version, some useful commentary (Gastroenterol 2014; 147: 557-59) provides perspective.

Study limitations: small number (20 assigned to gluten-free diet, 20 regular diet).

Key points from editorialists:

  • “This study provides some of the strongest data yet supporting celiac disease screening of family members of patients with celiac disease.  However, important issues must be addressed before screening is widely adopted.”
  • “This [study] leaves us in the uncomfortable position of offering a diagnosis that may improve gastrointestinal symptoms, but simultaneously worsen socialization, offer limited overall change in health-related quality of life, and for which the long-term risk-to-benefit ratios are unknown.”
  • This “makes the cost of a gluten-free loaf of bread for all with asymptomatic celiac disease too high, unless and until additional more substantial benefits can be demonstrated.”

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How Accurate is Serology at Predicting Mucosal Healing in Pediatric Celiac Disease?

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A recent study (Am J Gastroenterol doi: 10.1038/ajg.2014.200) shows that in children, unlike adults, that normalization of celiac disease (CD) serology correlates well with mucosal healing.

In this study, 150 children with biopsy-proven CD were prospectively evaluated with duodenal biopsies, tissue transglutaminase (tTG) IgA serology, and deamidated gliadin peptide (DPG) IgG serology.  After maintaining a gluten-free diet (GFD) for at least 1 year, participants underwent followup evaluation.

  • Of the 97 with normalization of their serology, 91 had normal biopsies (Marsh 0) and 6 had slight abnormalities (Marsh 1).
  • Of the 27 with positive serology, only 6 had Marsh 3 changes.
  • Overall, 124 (82.7%) had normalization of duodenal mucosal biopsies irregardless of serology.

Higher rates of mucosal healing are possible with longer duration of GFD.

On the other hand, a recent retrospective study (JPGN 2014; 59: 229-31) notes that among 40 children who underwent followup endoscopic evaluation (>4 months after GFD, median 24 months), most of whom were symptomatic, only 25 had complete healing. Though among those with adherence to a GFD, only five had persistent villous atrophy (Marsh 3 lesion) . Serological correlation was not provided.

Take-home message: Followup biopsies are not needed in children with normalization of their serology (tTG IgA and DGP IgG).  That is, serology correlates well with mucosal healing in children with celiac disease on a GFD >12 months. However, it is certainly reasonable to consider followup endoscopy in those who are symptomatic, especially if serology is abnormal.
In a related matter, the new requirements regarding gluten-free labeling have been implemented -here’s a link from the LA Times: Celiac Regulations or First federal gluten–free regulation takes effect

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Nutrient Deficiencies with Celiac Disease

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A recent study (JPGN 2014; 59: 225-28) examined fat-soluble vitamin deficiencies in pediatric patients with newly diagonosed Celiac disease (CD).

Of the 83 patients analyzed between 1995-2012 at the Mayo clinic, the key findings:

  • No patients had vitamin A deficiency
  • Two patients had vitamin E deficiency.  Both of these patients had complete villous atrophy along with a malabsorptive presentation.
  • Nine patients had mild-to-moderate vitamin D deficiency (less than the reported frequency in the general pediatric population)
  • All of these vitamin deficiencies corrected with gluten-free diet and vitamin supplements.

A limitation of the study was a selection bias as not all children underwent vitamin level measurements.

Take-home message (from authors): “fat-soluble deficiencies are uncommon in children with a new diagnosis of CD.  Routine measuring of fat-soluble vitamin levels may not be necessary.”

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Drug Therapy for Celiac Disease

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While a life-long gluten-free diet (GFD) is effective in most individuals with Celiac disease (CD), it is not effective in some. This could be related to cross contamination of food products, improper/inaccurate labeling and perhaps other factors as well.  As a consequence, there is a rationale for the development of medical therapy.  A recent study (Gastroenterol 2014; 146: 1649-58) has shown the ability of ALV003, a mixture of 2 recombinant gluten-specific proteases administered orally, to protect patients with celiac disease from gluten-induced mucosal injury in a phase 2 trial.

Methods: In a 6-week challenge study, adults with biopsy-proven celiac disease were divided into a treatment group with ALV003 (n=20) or a placebo group (n=21).  The 2.0 g gluten dose (equivalent to 1/2 slice of bread) for the study was determined after an optimization study (using 1.5 g, 3.0 g or 6.0 g of gluten (bread crumbs) in three divided doses).  Biopsies were taken before and after the gluten challenge.

Key finding:

  • No significant mucosal deterioration was observed in biopsies from the ALV003 group based on biopsies after the challenge period.  In contrast, the placebo group did have evidence of mucosal injury.

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Celiac Disease Risk -TEDDY Study

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“The Environmental Determinants of Diabetes in the Young (TEDDY) is a multinational study that follows children at high genetic risk for type 1 diabetes, with the development of celiac disease as a secondary outcome.”  A recent publication provides excellent data with regard to the longitudinal risk of developing celiac disease (CD) (NEJM 2014; 371: 42-9).

Methods: 424,788 newborns were screened for at-risk HLA genotypes (from 2004 to 2010) in four countries (U.S, Finland, Germany, and Sweden).  21,589 had one of nine HLA genotypes of interest to the investigators –>8677 infants were enrolled in the study; 6403 of this group had one of the four HLA genotypes reported in this study:

  1. DR3-DQ2 homozygotes
  2. DR3-DQ2/DR4-DQ8
  3. DR4-DQ8 homozygotes
  4. DR4-DQ8/DR8-DQ4

Median follow-up: 60 months

Definitions for study:

  • Celiac autoimmunity: presence of tTG antibodies on two consecutive tests at least 3 months apart
  • Celiac disease: CD diagnosis based on biopsy (Marsh 2 or higher) or persistently high tTG (≥100 units) on at least two tests at least 3 months apart

Key findings:

  • Overall 786 children developed celiac autoimmunity (12%) and 291 had confirmed CD.
  • Children with DR3-DQ2 homozygosity had more than 5 times the risk of CD than the lowest-risk groups; in addition, the risk was 2.5 times more than the risk for a heterozygote (single DR3-DQ2) haplotype.
  • By 5 years of age, celiac autoimmunity developed in 26% and 12% respectively among children with DR3-DQ2 homozygosity  and in 11% and 3% of those children with DR3-DQ2 heterozygosity.
  • Residence in Sweden increased risk for CD with hazard ratio of 1.9.  The fact that residents with same genetic haplotypes had increased risk suggests that an environmental factor is playing a role.  It was noted that these children were given gluten-containing cereals at the earliest age.
  • CD was more common in females with HR of 2.16 (P<0.001) and in those with family history of CD HR 2.95 (P<0.001)

Take-home message: This prospective TEDDY study is providing useful information about how likely an individual with a genetic predisposition will develop CD and how quickly this develops.

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Change the Name: “Functional” is Lousy

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A recent commentary explains why “functional” pain is such a lousy term (JAMA Pediatr. Published online June 02, 2014. doi:10.1001/jamapediatrics.2014.530 –thanks to Ben Gold for this reference).  In pediatric GI practice, functional gastrointestinal disorders (FGIDs) constitute a large part of clinical work.

The author, Neil Schechter from the Chronic Pain Program in Boston, makes several important observations:

  • “There is general dissatisfaction with the terminology.”  This stems from the fact that “in common parlance today, functional disorders are typically assumed to be a product of psychological distress.” Yet, parents/patients are “not ready to accept a strictly psychological explanation.”
  • The idea that functional pain is solely a psychological disturbance is inaccurate.  Though, anxiety and depression are common associated problems which often contribute to symptoms.  He states that “hyperexcitability” of the nervous system is “the core biological link and final common pathway for the creation of functional pain disorders.”
  • This category should be labeled dysfunctional pain.  “In effect, calling pain ‘functional’ is like calling disease, ‘ease.'”
  • These disorders frequently respond to centrally acting therapies including antidepressants, anticonvulsants, exercise, cognitive behavioral therapy, and acupuncture.
  • “The search for an appropriate term for these pain problems is far more than semantic…[a patient’s] understanding of their illness is clearly linked to their compliance with medical advice…it may stem their desire for additional costly investigation.”
  • Dr. Schechter proposes the term “primary pain disorder.”  “Unlike Shakespeare’s rose, functional pain would benefit from a new name.”

Take-home message: I wish I had written this commentary.  Explaining “functional” pain and “irritable bowel syndrome” are Sisyphean tasks.  Better nomenclature could ease the burden.  Join me in abandoning the use of the word “functional.”

In the same issue, an editorial on the “Role of Celiac Disease Screening for Children with Functional Gastrointestinal Disorders” (JAMA Pediatr. 2014;168(6):514-515. doi:10.1001/jamapediatrics.2013.5418) comments on a study (JAMA Pediatr. 2014; 168(6):555-60) in the same issue which reports a 4-fold higher prevalence of celiac disease among children who meet clinical criteria for irritable bowel syndrome.  The study reports the results from a cohort of 992 children identified with recurrent abdominal pain in a primary care setting.  In the editorial, the authors note:  “When grouped together, the prevalence rate of celiac disease among all children with FGIDs (IBS included) approaches 2%.  Celiac disease screening in this population would result in a positive tTG-IgA test result in 4%…However, 53% of all positive test results would be falsely elevated.”  As such the editorial advocates in favor of screening for celiac disease in children with IBS but not all FGIDs.

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Benefits of Gluten-Free Diet for “Asymptomatic” Celiac

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Here’s a link to the abstract: gastrojournal.org/article/S0016-…

Methods: “We performed a prospective trial of 3031 individuals at risk for celiac disease based on screens for EmA. Of 148 seropositive individuals, 40 fulfilled inclusion criteria and were randomly assigned to groups placed on a GFD or gluten-containing diets.”

Results: “The GFD group also had reduced indigestion (P=.006), reflux (P=.05), and anxiety (P=.025), and better health, based on the visual analog scale (P=.017), than the gluten-containing diet group.”

Take-home message: A gluten free diet improves symptoms (even in “asymptomatic” patients) with celiac disease

AJG Celiac Practice Guidelines 2013 -Useful Link

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This full-text link to AJG Practice Guidelines for Celiac Disease 2013 (Am J Gastroenterol 2013; 108:656–676; doi:10.1038/ajg.2013.79) provides 45 evidence-based recommendations for diagnosis and management of celiac disease along with 264 references.  

Table of Contents for Article

Table of Contents for Article

Topics of particular interest

  • Whether to test first-degree relatives.  The article recommends testing in symptomatic individuals and consideration of testing in asymptomatic individuals
  • When to perform genetic testing
  • When to use tests besides tissue transglutaminase antibody (TTG IgA) (mainly in children less than 2 years)
  • Recommends against use of stool or salivary testing
  • How to approach refractory celiac disease
  • The limited circumstances which justify followup endoscopy

Potential Reasons for Genetic Testing:

Potential Reasons for Genetic Testing

Celiac vs. Gluten Sensitivity:

Celiac vs. Gluten Sensitivity

Bottomline: This practice guideline covers most of the issues dealing with celiac and gluten sensitivity –it is a useful reference.

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