Gluten Intake and Development of Celiac Disease -Two Studies

  • NA Lund-Blix et al. Am J Gastroenterol 2019; 114: 1299-1306.
  • K Marild et al. Am J Gastroenterol 2019; 114: 1307-14.

Thanks to Ben Gold for these references.

In the first study, the authors used an observational prospective nationwide cohort study, the Norwegian Mother and Child Cohort Study (MoBa) with 67,608 children born between 2000-2009 and with a mean followup of 11.5 years.

Key findings:

  • Celiac disease (CD) was diagnosed in 738 children (1.1%)
  • The adjusted relative risk of CD was 1.1 per standard deviation increase in daily gluten amount at age 18 months.
  • Compared to children in the lowest quartile of gluten ingestion, those in the upper quartile had an adjusted relative risk of 1.29.
  • Timing of gluten introduction, ≥6 months or before 4 months, was also an independent risk factor for CD. In those before 4 months the aRR was 1.45 and for those ≥6 months the aRR was 1.34

In the second study, the authors used the prospective Diabetes Autoimmunity Study in the Young cohort with 1875 at-risk children.

Key findings:

  • Children in the highest tertile of gluten intake between ages of 1 and 2 had a 2-fold greater hazard of developing CD autoimmunity (positive tTG antibodies) (aHR 2.17) than those in the lowest tertile.
  • The risk of CDA increased by 5% per daily gram increase in gluten intake in 1 year olds.

My take: Taken together, these studies indicate that higher gluten exposure (between 1-2 years) is associated with a modestly-higher risk of CD; in addition, early (<4 months) and late exposure (>6 months) may increase the risk as well.

Related blog posts:

Spoiler alert: This case study by A Fasano et al. NEJM 2020; 382: 180-9. describes a presentation of celiac disease and Addision’s disease. I recently had a teenager present with similar symptoms who had Addison’s alone (clues were fatigue, low sodium and hyperpigmentation)

How helpful is a pH-Impedance Study in Identifying Reflux-Induced Symptoms?

In both kids and adults, individuals presenting with complaints of reflux more often have other problems like functional heartburn or reflux hypersensitivity (see posts below).  A recent prospective, cross-sectional study (LB Mahoney et al. JPGN 2020; 70: 31-36) provides data that further shows that abnormal pH-impedance (pH-MII) testing does NOT predict reduced quality of life (QOL) in children with reflux symptoms (n=82).

Key findings:

  • 38% had abnormal pH-MII testing; however, there were no significant differences in QOL scores on any of the tested questionairres between those with normal or abnormal pH-MII studies.
  • Subjects with gross esophagitis on EGD reported significantly worse QOL scores. Microscopic esophagitis was not associate with differences in QOL scores.

The implication of this study is that reflux without esophagitis is NOT a driver of abnormal QOL parameters; instead, functional GI disorders are likely more important.

My take: This study makes it clear that gross endoscopic findings are much more consequential than abnormal pH-MII studies.

Related blog posts:

Highlights in IBD from Two 2019 Meetings: American College of Gastroenterology and United European Gastroenterology Week

Gastroenterology & Hepatology. December 2019 – Volume 15, Issue 12, Supplement 5

Excerpts from William Sandborn Commentary which are at the end of this supplement along with references:

Vedolizumab

In the VARSITY study (An Efficacy and Safety Study of Vedolizumab Intravenous [IV] Compared to Adalimumab Subcutaneous [SC] in Participants With Ulcerative Colitis), 769 patients with ulcerative colitis were randomized to a year of therapy with either adalimumab at the US Food and Drug Administration (FDA)-approved dose or vedolizumab at the FDA-approved dose…This shows that the idea that vedolizumab (and anti-integrin therapy) is slower-acting than anti-TNF therapy is not correct, and that both of these classes of drugs can work fairly quickly in a number of patients.

Dr Brian Bressler and colleagues looked at the effectiveness of anti-TNF therapy in the real world when used second line after failing first-line biologic therapy with vedolizumab…The study conducted by Dr Bressler and colleagues, which included both Crohn’s disease patients and ulcerative colitis patients, found that the results were fairly similar whether patients received first-line biologic therapy with an anti-TNF agent or whether patients received first-line therapy with vedolizumab… It is generally thought that vedolizumab is a safer therapy than anti-TNF therapy, so with the finding from this study, a reasonable treatment approach could be to start with vedolizumab and see if it works

Dr Christina Chambers and colleagues identified outcomes for pregnancy in 223 women, 53 of whom received vedolizumab. The researchers found that there were no major structural birth defects reported in the vedolizumab group, compared to 5.7% and 5.3% in the disease-matched group and healthy control group, respectively. Thus, there seemed to be no signal for an increased malformation risk in patients who were undergoing treatment with vedolizumab and became pregnant.

Adalimumab

The SERENE trials are a set of head-to-head trials, one for ulcerative colitis and one for Crohn’s disease, comparing standard-dose adalimumab to a more intensive induction regimen of adalimumab…

For both ulcerative colitis and Crohn’s disease, the SERENE trials showed that the current FDA-approved dosing regimen is effective and that more intensive induction therapy does not improve outcomes over time. Thus, there is no utility in giving high induction doses. 

Tofacitinib

Over 1000 patients who had been treated with tofacitinib were examined…during induction and maintenance of the placebo-controlled portion of the tofacitinib clinical trials, there were a total of 5 deep vein thrombosis and pulmonary emboli events. All 5 occurred in patients who were receiving placebo; none of these events occurred in patients who were receiving tofacitinib…[And] There was a total of 5 deep vein thrombosis and pulmonary emboli events during this long-term extension…Looking at the ulcerative colitis clinical trial data that I presented, it is somewhat reassuring that we did not see the same elevation in risk for deep vein thrombosis and pulmonary emboli that was seen in the high-risk rheumatoid arthritis patient population.

Mont Royal (Montreal)

ESPGHAN Guidelines for Diagnosing Coeliac Disease 2020

Briefly noted: S Husby et al. JPGN 2020; 70: 141-56.

Link to document: ESPGHAN Guidelines for Diagnosing Coeliac Disease 2020

Key recommendations for diagnosing celiac disease (CD):

  • If CD is suspected, measurement of total serum IgA and IgA-antibodies against transglutaminase 2 (TGA-IgA) is superior to other combinations
  • We recommend against deamidated gliadin peptide antibodies (DGP-IgG/IgA) for initial testing
  • Only if total IgA is low/undetectable, an IgG-based test is indicated
  • If TGA-IgA is ≥10 times the upper limit of normal (10× ULN) and the family agrees, the no-biopsy diagnosis may be applied, provided endomysial antibodies (EMA-IgA) will test positive in a second blood sample. HLA DQ2-/DQ8 determination and symptoms are not obligatory criteria
  • In children with positive TGA-IgA <10× ULN at least 4 biopsies from the distal duodenum and at least 1 from the bulb should be taken

Related blog posts:

 

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Development of Primary Sclerosing Cholangitis in Pediatric Patients with Inflammatory Bowel Disease

A recent study (A Chandrakumar et al. J Pediatr 2019; 215: 144-51) followed 190 children with inflammatory bowel disease from 2011 to 2018 in a longitudinal population-based cohort in Manitoba and examined the development of primary sclerosing cholangitis (PSC).  The diagnosis of PSC was made on discretion of the treating physician; thus, only a subset of patients underwent extensive evaluations for PSC.

Key findings:

  • 9 developed PSC-UC (9/95) and overall 11 developed PSC-IBD (11/190)
  • Among children with PSC-UC, 8 had high GGT (>50) at baseline and only 1 had a normal GGT at baseline.
  • All UC patients who developed PSC were diagnosed withing 6 months of their UC diagnosis.
  • At baseline, 22 patients with UC had an elevated GGT and 73 had a normal GGT.  Thus, about one-third of patients with an elevated GGT developed PSC (possibly more as all patients were not subjected to extensive testing)

My view: This study reinforces two concepts: 1) GGT is valuable as a screening test 2) PSC (often asymptomatic) is fairly common in UC and needs to be considered especially in the first year of diagnosis.  What this study does not do is help us figure out what should be done about children with asymptomatic PSC as there are no proven therapies.

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Do You Need Separate Cookware for Celiac Disease?

Maybe.  A recent abstract at 2019 NASPGHAN meeting addressing this issue was highlighted in Gastroenterology and Endoscopy News.

Link: Recommendations for Children With Celiac Disease Need Update

An excerpt:

In two related experiments, researchers from the celiac disease program at Children’s National Medical Center in Washington D.C., looked at whether, and how much, gluten could be transferred from contaminated cafeteria foods and school supplies to children’s hands, work tables and gluten-free food (abstract 656). The researchers also analyzed how effective different washing methods were at removing gluten contamination…

Ms. Weisbrod said she and her colleagues were surprised that using a shared toaster for both gluten-free and gluten-containing bread transferred minimal gluten (<5 parts per million [ppm] in most samples), as did playing with Play-Doh (median, 1.25 ppm). Both exposures were well below the 20-ppm threshold the FDA uses to consider an item gluten-free.

My take: The NASPGHAN meeting also featured a lecture by Alessio Fasano indicating that ~30%of patients with celiac disease had persistent disease due to poor adherence with a gluten-free diet and about 10% of patients with celiac disease are exquisitely sensitive to gluten.  So, while this small study indicates that gluten exposure may be lower than gluten threshold in many cases when sharing toasters, etc, I think more attention should be directed at strict gluten avoidance rather than trying to discern if some level of cross contamination may be acceptable.

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