Northern Latitudes -Higher Prevalence of Celiac Disease and Gluten Avoidance

A recent study (A Unalp-Arida et al. Gastroenterol 2017; 152: 1922-32) examines the relationship of latitude and the prevalence of celiac disease and gluten avoidance.

Using the NHANES 2009-2014 survey with 22,277 participants (6 years and older), the authors identified persons with celiac disease (based on serology) along with those who avoided gluten without a diagnosis of celiac disease.

Key findings:

  • 0.7% of participants had celiac disease and 1.1% avoided gluten without celiac disease
  • Celiac disease was more common among individuals who lived at latitudes of above 35 degrees and more common with higher socioeconomic status. Figure 2 map provides latitude lines. In the eastern U.S. the Georgia-Tennessee border corresponds to this latitude line and in the western U.S. the southern tip of Nevada lies on this line.
  • From 35 degrees to 39 degrees the odds ratio was 3.2, whereas the odds ratio was 5.4 for those above 40 degrees.  These odds ratios were independent of race, ethnicity, socioeconomic status and body mass index.
  • Similarly, the prevalence of gluten avoidance without celiac disease was twice as common among persons living north of 40 degrees compared with those residing at latitudes <35 degrees.
  • The findings on latitude were heavily influenced by the increased rate of celiac and gluten avoidance in the Northeast region (more so than in the West)

In their discussion, the authors note that “a North-South gradient in disease occurrence in genetically similar populations has been shown in studies of autoimmune diseases, including inflammatory bowel disease, multiple sclerosis, and rheumatoid arthritis.” Potential environmental factors could include lack of sunshine/vitamin D deficiency, hygiene, and infections.  A study comparing similar populations in Finland and Russia suggested a lower economic status/less hygiene increased the risk of celiac disease despite similar gluten exposure.  The authors note that there was NOT an increased risk in Northern Sweden compared to Southern Sweden.  In fact, this study of children found a higher rate of celiac disease in Southern Sweden (Arch Dis Child 2016; 101: 1114-18).

My take: This is another intriguing study regarding celiac disease epidemiology which strongly points to environmental factors accounting for marked variation in celiac disease prevalence.

More information on this topic from AGA Blog: Do More People Have Celiac Disease in the North vs the South?

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Is there a link between Eosinophilic Esophagitis and Celiac Disease?

Probably most pediatric gastroenterologists have seen patients who underwent endoscopy for celiac disease and found out that the patient had both celiac disease and esophageal eosinophilia.  Whether the esophageal eosinophilia should be classified as eosinophilic esophagitis (EoE) is based in part on whether one concludes that the EoE is a separate disorder and unrelated to the celiac disease.

One useful retrospective study on this topic (S Hommeida et al. JPGN 2017; 65: 58-63) examines the association between celiac disease and EoE.   Key findings:

  • Among a cohort of 10,201 children seen at the Mayo clinic, 595 were considered to have EoE and 546 had celiac disease.
  • Only 10 patients had both celiac disease and EoE.
  • The risk of EoE was not increased in children with celiac disease compared to those without celiac disease (odds ratio 0.29).  The prevalence of EoE in children with celiac disease was 1.8% whereas the prevalence among all children undergoing endoscopy was 5.8%.
  • 4 of 10 children treated only with GFD clinically improved (no followup histology)

Limitations:

  • The diagnosis of EoE was not clear in this study.  As noted in the associated editorial (pg 1-2), “the use of a high-dose proton pump inhibitor at the time of initial diagnosis is not mentioned.”
  • Overall, the number of patients with both EoE and celiac disease was small.  Thus, a much larger study could be necessary to prove the lack of an association.

My take: This study suggests that there is not an association between EoE and celiac disease. Some patients with both disorders will respond to a gluten free diet, whereas some will require additional treatment directed at EoE.

Related study: T Wallach et al. JPGN 2017; 65: 64-8. This retrospective study showed poor adherence to biopsy guidelines in EoE and celiac disease.  Among 9171 children, 8% were biopsied in accordance with 2007 AGA EoE consensus recommendations and 35% in accordance with  2006 AGA celiac guidelines.  Higher detection rates were observed among patients who had higher adherence to diagnostic guidelines. With both diseases, obtaining sufficient number of biopsies is key; and with celiac disease, obtaining biopsies from duodenal bulb as well as distal duodenum is recommended.

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Professional Resources: Gastric Feeds, Celiac Disease

Many of our patients use Farrell bags to help with their enteral feedings; though, this decompression system is often used incorrectly.  The following is a link to the company’s instructions on how to use this product correctly. Halyard Health: Farrell System

Note: I do not have commercial ties.

From NASPGHAN -Celiac resource: NASPGHAN Clinical Guide For Celiac Disease

I reviewed this website.  Overall, this is a useful resource.  There are multiple links that address some of the nuances with celiac disease.  Interestingly, the website is not entirely consistent in its recommendations. For example, under the link “my parent/child has celiac” recommendations for screening family member are for TTG IgA and IgA (if asymptomatic) whereas under the health professional area, after diagnosis, the website recommends much more extensive testing of family members: HLA DQ2/DQ8 genetics, TTG IgA, IgA, and anti-DGP IgG testing

 

Celiac Disease Epidemic?

A recent prospective study (E Liu et al. Gastroenterol 2017; 152: 1329-36) reports a very high rate of celiac disease in Denver.

The authors collected data on HAL-DR, DQ genotypes in 31,766 infants.  Among the various genotypes, a total of 1339 were followed .for 20 years (starting in 1993). The key outcomes were development of celiac disease autoimmunity (CDA) indicated by persistence of anti-TTG IgA antibody for at least 3 months or development of celiac disease (CD) with biopsies showing at least Marsh 2 histologic lesions.  The authors weighted the genotypes based on their frequency in the population to develop estimates for the entire Denver population.

Key findings:

  • 66 (of 1339) developed both CD and CDA. Another 46 developed only CDA. In this group of 46, seropositivity reverted to normal in 21 (46%).
  • Cumulative incidence for CDA at 5, 10 and 15 yrs of age: 2.4%, 4.3%, and 5.1% respectively
  • Cumulative incidence for CD at 5, 10 and 15 yrs of age: 1.6%, 2.8%, and 3.1% respectively

In their discussion, the authors note that “the 3.1% cumulative incidence of CD in Denver by age 15 is the highest to date in North America and is consistent with the 3% prevalence reported in Sweden for 12 year olds born during an ‘epidemic’ thought to be the result of early introduction…of gluten.” This theory about the epidemic is has been discounted: “timing of gluten introduction is not likely a factor” though the quantity could be a factor.

My take: These rates of CD and CDA are very high; ongoing data to determine the frequency in other parts of the country are needed.  This high rate of CD is clearly bad news for a lot of people, excepting those with commercial interests in gluten free products.

 

For 1-3 year old, AAP recommendation for maximum of 4 oz./day of 100% juice, and for 4-6 year olds a maximum of 6 oz/day.  For 7 years and older, AAP recommends a maximum of 8 oz/day

NPR: Banana Diet for Celiac Disease

A recent report from NPR highlights a previous diet for celiac disease -the banana diet. While celiac disease had been discovered in the 1890s by Dr. Samuel Gee, the role of gluten was not understood until WWII.

NPR: Doctors Once Thought Bananas Cured Celiac Disease

Here’s an excerpt:

a high-calorie, banana-based diet [was] invented by Dr. Sidney Haas in 1924. The diet forbade starches but included numerous daily bananas, along with milk, cottage cheese, meat and vegetables…

Haas arrived at his banana diet through an honest error — one that, unfortunately, had serious repercussions for people with celiac disease. In his 1924 paper, he wrote of a town in Puerto Rico where “dwellers who eat much bread suffer from [celiac] sprue while the farmers who live largely on bananas never.”

Haas skipped over the role of wheat and focused instead on the exotic bananas, which he thought held curative powers…

But Haas’ honest error led to serious consequences. As the children recovered, wheat was reintroduced.

It was a Dutch pediatrician, Willem Karel Dicke, who first realized that wheat might be linked to celiac disease. He noticed that in the last few years of World War II, when bread was unavailable in the Netherlands, the mortality rate from celiac disease dropped to zero. In 1952, Dicke and his colleagues identified gluten as the trigger for celiac disease, and the gluten-free diet was born.

 

Vaccine for Celiac Disease

A recent study (KM Kemppainen et al. Clin Gastroenterol Hepatol 2017; 15: 694-702, editorial 703-5) showed that gastrointestinal infections can trigger celiac disease (CD) and that immunization with the rotavirus vaccine was protective against developing CD.

This study is part of the TEDDY study: The Environmental Determinants of Diabetes in the Young.  The TEDDY cohort involves more than 8000 children who are part of an international prospective cohort who carry genes (HLA-DR-DQ genotypes) with increased risk for diabetes and CD. In this particular group, the authors identified 6327 children who were 4 yrs old by March 2015.

Key Definition: CD autoimmunity (CDA) -children who tested positive for tTG IgA at their annual visit and remained persistently positive 3 months later

Key Findings:

  • Gastointestinal infections (n=13,881) but not respiratory infections (n=79,816) were associated with an increased risk of CDA.  CDA risk was increased within the 3 months of the GI infection.
  • 732 of 6327 (11.6%) developed CDA.  In this cohort, 318 underwent duodenal biopsy and 283 (90%) had biopsy indicative of CD (Marsh score >1). Thus, in their cohort, there is variability in the onset of CD from the onset of CDA.
  • Risk of CDA was reduced in children vaccinated against rotavirus and introduced to gluten before age 6 months (HR =0.57).
  • The exact risk depending on interaction with multiple factors including breastfeeding, HLA genotype, seasonality of birth, and timing of gluten introduction. Timing of infection plays a role as well, as earlier exposure to GI infections earlier in life was associated with a decreased risk of celiac disease.

This reference should be kept handy for vaccine advocates.  Not only can vaccines prevent infections, but they have now been shown to prevent an autoimmune disease (CD).  In addition, previous studies have shown that vaccines can prevent cancers, including hepatocellular carcinoma and cervical cancer.

My take (modified from editorial): This study “demonstrates the power of rigorously conducted prospective studies to reveal complex interactions among genetic and environmental factors.” In addition, this study shows that preventing rotavirus infection with vaccination lowers the risk of celiac disease.

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SuperPoopers CCFA Team 2017

Celiac Disease and Mode of Delivery -Perhaps Not Very Consequential

Briefly noted:

A recent study (E Lionetti et al. J Pediatr 2017; 184: 81-6) did NOT find an association between mode of delivery and the development of celiac disease (CD).

After a telephone interview to confirm mode of delivery, the authors identified 431 children at high risk for CD and compared the rates of celiac autoimmunity (serology-positive) and overt CD that developed by age 5 years:

  • CD autoimmunity –cesarean vs vaginal:  24% and 19% (P=.2)
  • Overt CD –cesarean vs vaginal:  19% and 14% (P=.2)

While neither reached statistical significance, there was a higher rate in those born by cesarean mode.  The lack of a statistical association could be a reflection on sample size or the specific population that was studied.  However, more likely, this suggests that “the role of intestinal microbiota at birth in the pathogenesis of immune mediated disorders has been overestimated.”

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La Source, Jean Auguste Dominque Ingres, Musee d’ Orsay