Tag Archives: celiac disease

Wheat Intolerance Syndrome?

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Even though we’ve lived in our house for many years, some of our neighbors refer to our house as the ‘Walden’ house; the Waldens lived here for a long time before we did. Probably when we move, our neighbors will call our present home the “Hochman” house, regardless of who resides there.

I think nomenclature in medicine has a similar reluctance to adopt new terms.  A recent medical progress report (Guandalini S, Polanco I. J Pediatr 2015; 166: 805-10) suggests dropping the term “Nonceliac gluten sensitivity” (NCGS) in favor of “Wheat Intolerance Syndrome.”

It’s probably a good idea and their arguments are sound. Two key points:

  • “There is no proof that gluten is causing NCGS.”
  • It is likely that the majority of patients considered NCGS have not even eliminated celiac disease before instituting a gluten-free diet.

With regard to the first point, the authors note that recent studies have suggested that a “FODMAP” (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet is likely the culprit in many cases of so-called NCGS.  They review a pivotal double-blind study (see related blog post: An Unexpected Twist for “Gluten Sensitivity” | gutsandgrowth) there was no role for gluten “at least in these patients with IBS-like NCGS.”  In addition, other studies have demonstrated a strong role for a placebo/nocebo effect of dietary elimination.  “It is quite conceivable that a portion of patients with NCGS, and arguably a substantial one, fall in this category.”

With regard to the second point, it is not a good idea to initiate a gluten-free diet before excluding the diagnosis of celiac disease (hence the prior term: “nonceliac” gluten sensitivity).  A related comment from the authors is that a “Grade 1 [Marsh] intestinal lesion has traditionally been considered of a very low specificity for celiac disease.”  More testing in this circumstance can help determine if celiac disease is the reason, including checking the levels of ϒδ T-cell receptors in intraepithelial lymphocytes (very specific for celiac disease) and/or detection of IgA anti-tissue transglutaminase antibody deposits in intestinal mucosa.

Other pointers:

  • Genetic testing for HLA-DQ2 and/or HLA-DQ8 genotypes (which are nearly 100% in celiac disease) are present in about 40% of NCGS which does not differ from the general population
  • “Estimating the prevalence of NCGS is impossible.”  Estimates have ranged from 0.6% of the U.S. population to as high as 50% according to some websites.

Bottomline: While “Wheat Intolerance Syndrome” works fine for me, I think the term nonceliac gluten sensitivity is going to be around for a while.  Hopefully, more families and care providers will exclude celiac disease before contemplating this label and consider other foods as potential contributors to the symptomatology.

Related Reference: “Coeliac Disease and Noncoeliac Gluten Sensitivity” Meijer CR, Shamir R, Mearin ML. JPGN 2015; 60: 429-32.  This reference covers much of the same territory.  The Table 1 in this article nicely summarizes the relevant literature/studies from 2008-2014.

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How Likely is Celiac Disease if My TTG Test Is Only a Little Bit Abnormal?

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A terrific celiac serology study (Gidrewicz D, et al.Am J Gastroenterol 2015; -advanced online publication doi: 10.1038/ajg.2015.87) helps answer questions about the utility of serology in making diagnostic decisions. (Thanks to corresponding author J Decker Butzner for sharing reference.)

Using consecutive samples in a laboratory database with 17,505 patients, the authors retrospectively examined the performance of the tissue transglutaminase (TTG), endomysial antibody (EMA) tests and the ESPGHAN celiac guidelines for nonbiopsy diagnosis of celiac disease.  Among this large cohort, 775 with positive TTG and 574 with a negative TTG were biopsied.

Key findings:

  • If the TTG >10-fold the upper limit of normal (ULN) along with a positive EMA and symptoms were present, 98.2% had biopsies consistent with celiac disease.
  • If the TTG was 3-10-fold-ULN along with positive EMA, then 75.7% had biopsies consistent with celiac disease.  The histology of celiac disease (CD) was present in only 40% of the TTG 3-10-fold ULN if EMA was negative.
  • If the TTG was 1-3-fold-ULN along with positive EMA, 52.2% had CD-positive histology, whereas CD-positive histology was evident in only 13.3% of TTG 1-3-ULN if EMA was negative.
  • IgA deficiency is common in CD (“1in 60 vs 1 in 700” in general population)

Implications & Take-home points:

  • The researchers note that the positive predictive value of TTG drops when the prevalence of CD in the testing population is lower.  Thus, in their population and most clinical practice where the prevalence is below 35-40%, the PPV of the TTG-based tests drops to <80%.
  • While TTG-based tests have high specificity, there are multiple medical conditions that can cause a false positive (additional reference below), including autoimmune diseases like diabetes mellitus, inflammatory bowel diseases as well as infections, and liver disorders.
  • Asymptomatic patients with low TTG titers and negative EMA may benefit from following celiac serology rather than proceeding immediately to intestinal biopsy.
  • Using ESPGHAN nonbiopsy criteria (symptomatic child, TTG ≥10 ULN, positive EMA, positive HLA typing), there were four patients whose initial biopsies were not consistent with CD.  Thus these criteria identified 98.2% accurately who did not need an intestinal biopsy.  One of these four developed CD subsequently.  To achieve 100% PPV for non biopsy, the authors note that one would need an EMA titer ≥1:80.
  • Study limitations: retrospective study, lack of standardization between TTG assays

Bottomline: EMA improves the PPV of TTG testing, especially when low titer elevations are noted.  TTG alone is a highly sensitive test “with a 99.4% negative predictive value” in this study.

Related study: “Serum Anti-Tissue Transglutaminase Antibodies Detected during Febrile Illness May Not be Produced by the Intestinal Mucosa” J Pediatr 2015; 166: 761-3.  This case report describes two children with abnormal TTG (one more than 20-fold ULN)) both were EMA-negative. No mucosal anti-TTG was identified using two immunoassays.

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Taking One ‘Bite’ At A Time -For Celiac Diagnosis

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A small study (reference from KT Park’s Twitter feed –Gastrointestinal Endoscopy DOI: http://dx.doi.org/10.1016/j.gie.2014.10.024) suggests that taking a single biopsy per pass rather than two biopsies per pass results in better quality specimens:

Link: Endoscopic Biopsy Technique in the Diagnosis of Celiac Disease

Here are the results and conclusion of the abstract:

Results

Patients (N = 86) were enrolled, 47% with known celiac disease, 36% with suspected celiac disease, and 17% with an unknown celiac disease status. Well-oriented biopsy specimens were noted in 66% of patients with the single-biopsy technique and 42% of patients with the double-biopsy technique (P < .01). Analysis of matched pairs showed improved orientation with the single-biopsy technique (odds ratio 3.1; 95% confidence interval, 1.5-7.1; P < .01). This persisted in subgroup analysis of patients with known celiac disease (P = .02), villous atrophy (P = .02), and a final diagnosis of celiac disease (P < .01).

Conclusion

The single-biopsy technique improves the yield of well-oriented duodenal biopsy specimens. Endoscopists should consider taking only 1 biopsy specimen per pass of the forceps in patients undergoing biopsies of the duodenal mucosa.

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I'm the one on the right

I’m the one on the right

Can an Altered Microbiome Explain Persistent Symptoms in Treated Celiac Disease?

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A recent study (Am J Gastroenterol dii:10.1038/ajg.2014.355) from Helsinki examined 177 patients with celiac disease.  Their goal was to investigate whether altered intestinal microbiota may be associated with persisting gastrointestinal symptoms in celiac patients who had been following a strict gluten-free diet (GFD) for at least 3 years.

After administering a questionnaire (Gastrointestinal Symptom Rating Scale or GSRS) to those with negative celiac antibodies and normal small bowel mucosa (n=164), the researchers identified the 18 subjects with the highest total score (persistent symptom group) and compared them to the 18 subjects with the lowest total score.  Three duodenal biopsies during endoscopy had been frozen and were subsequently analyzed for their microbial DNA.  In each group, one microbial profile was unsuccessful.

Key findings:

  • In the persistent symptom group, there was lower relative abundance of Bacteroidetes (15% vs. 25%, P=0.01), lower Firmicutes (33% vs 46%, P=0.05) and higher relative abundance of Proteobacteria (40% vs 21%, P=0.04).
  • The “microbial richness,” measured as a number of detected genera or operational taxonomic units (OTUs), was reduced in patients with persistent symptoms.  On average, patients with persistent symptoms had 32 genera and 72 OTUs per sample; in contrast, those without symptoms, on average had 37 genera and 106 OTUs.

Some of the strengths of this study include the normal villous architecture for all of the patients; this helps exclude refractory celiac disease as an etiology for the persistent symptoms.  In the discussion, the authors note that the “intestinal microbiota composition in healthy adults is relatively stable and can tolerate normal stress in the intestine caused by, e.g. daily changes in diet.” The speculate that long-term untreated celiac disease “may disrupt a stable intestinal microbiota community that, in some patients, could then reform in a dysbiotic state.”

The limitations of this study include the difficulty of excluding small intestinal bacterial overgrowth which could be related and the difficulty of excluding coexisting irritable bowel syndrome.  Like most studies regarding the micro biome, this study cannot “show causality or distinguish the effects of different bacteria to the persistent symptoms.”

Bottomline: Treated celiac patients with persistent symptoms have a different duodenal microbiome compared to treated celiac patients whose symptoms resolved with a gluten-free diet.

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Family Feud with Allergies and Celiac Disease

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A recent article in Allergic Living highlights the common phenomenon of other family members not believing or not willing to make changes in the face of food allergies and celiac disease.

Here’s an excerpt:

Every day, adults and kids are diagnosed with food allergies or celiac disease, and they naturally expect that the people closest to them will take the most care – as they would with any serious health condition. After all, you should be able to trust your mom to keep gluten out of her gravy, and assume that, when your brother babysits your peanut-allergic daughter, he carefully reads the ingredients on that chocolate bar, right?

For too many living with food allergies and celiac disease, sadly the answer is no. In the fall of 2010, Allergic Living sent out a request for anecdotes of family experiences (both good and bad), and within days we were inundated with responses…

In the end, there is no magic cure that will work for every family because complex problems cannot be solved with simple solutions – and, as they say, you don’t choose your family. But clear and calm communication is vital, as is the ability for those living with allergies to put themselves in their relatives’ shoes.

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Save a life with free allergy education | gutsandgrowth

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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