Celiac Disease and Rheumatologic Disorders in Children: Is There an Association?

By: Lewis First, MD, MS; Editor-in-Chief  
 

Dep. of Foreign Affairs

   While autoimmune mechanisms may play a role in the pathophysiology of celiac disease, we do not often think of celiac disease as being associated with the common rheumatologic signs and symptoms we encounter in our patients. 

     Yet Sherman et al. (doi: 10.1542/peds.2014-2379) did think about a possible association and report it out in a study we are releasing this week.  The authors looked at more than 2100 new patients presenting to a pediatric rheumatology program over 7 ½ years and screened these children for celiac disease as part of their initial serologic evaluation.  36 new cases were found—all of which improved with resolution of their myalgias, arthralgias and rashes after initiation of a gluten-free diet. 

     Have you thought about celiac disease in your patients with a variety of aches and pains?  Have you gotten the same positive resolution once their celiac disease was being treated?

      Share with us your experience with unusual presentations of celiac disease by responding to this blog, an e-letter, or posting on our Facebook and Twitter websites.

Related Links

• Clinical Features of Celiac Disease: A Prospective Birth Cohort
• Prevalence of Childhood Celiac Disease and Changes in Infant Feeding

Let Them Eat Cake: Gluten Free Diets In Response To Celiac Disease

By: Joann Schulte  DO, MPH; Editorial Board Member

Public Health Image Library (PHIL)

     Gluten-free dining and groceries are a growth industry these days.   Multiple restaurants, both of   Some charge a higher price for gluten-free items that can include everything from pizza to Mongolian beef to the flourless chocolate cake.  Such items have to be prepared carefully so there’s no cross-contamination in the kitchen from wheat or barley. There’s even a class-action lawsuit that’s been filed in California, claiming that the extra charges and higher prices are a violation of the Americans with Disabilities Act the gourmet type and the chain variety, spout their gluten-free menus.

      The availability of such diets and grocery choices is good news for patients with celiac disease (CD), including the children who are often diagnosed after prolonged complaints of abdominal pain, diarrhea, failure to thrive and nutritional deficiencies.  About 1% of the US population is estimated to have celiac disease, and new research published this month in Pediatrics documents risk factors associated with the disease among a birth cohort followed in six clinical centers located in four countries. 

     Agardh et al. (doi:10.1542/peds.2014-3675) followed a group of 6,706 children who were positive for HLA-DR3-DQ2 and/or DR4-DQ8.  Those HLA types have been associated with a higher risk of celiac disease.  The children were screened annually for tissue transglutaminase antibodies (tTGA) and screened for symptoms via questionnaires.  Those questionnaires include an assessment of abdominal discomfort, anemia, chronic constipation, loose stools, vomiting and poor growth.  The researchers also collected information about children’s height, weight and body mass index. The researchers found a 5% incidence of CD among children with HLA types linked to the disorder.

      Among the screened children, 914 developed persistent positive tTGA, 406 underwent intestinal biopsies and 304 were diagnosed with CD.  The researchers compared their pediatric subjects with age-matched children who were tTGA negative.  The children who were persistently positive were more likely to have symptoms at ages 2 and 3 years and to have higher levels of tTGA at seroconversion.  The levels of tTGA correlated with the severity of mucosal lesions in both symptomatic and asymptomatic children.

      In a related commentary, Dr. Richard Noel (doi:10.1542/peds.2015-0209) suggests that the study offers a tiered approach to CD diagnosis.  The 2-tiered approach of early genetic screening for genetic susceptibility and later screening for the celiac antibodies has been proposed.   Currently an individual physician must undertake the testing.  The study suggests a possible case-finding strategy in a disease that may be more easily managed given the attention it is getting both from medicine and the food industry.

Related Links:

• Prevalence of Childhood Celiac Disease and Changes in Infant Feeding  

•  Hospital Pediatrics: A Formula for Success

Gluten Diets In Infants and Links to Celiac Disease

 Courtesy of NormalltyRellief @Flickr

Editorial Board Member Terrill Bravender, MD, MPH  

     While cooking breakfast recently, I noticed that the bacon I had just opened carried a splashy label on the front of the package touting it as being a “gluten-free food.” I found this amusing.  I remember the same brand of bacon carried a label touting it as being a “low-carb food.” While some might view our cultural concerns regarding gluten on par with the low-carb obsessions of a few years ago, gluten sensitivity is no fad, as we have seen increases in the rates of celiac disease in western countries. What is driving this increase is not entirely clear, but the idea that the timing of infant exposure to gluten plays a role makes intuitive sense. A number of small studies have born this out, and many investigators believe that early exposure (e.g., consuming gluten prior to 4 months of age) as well as later exposure (e.g., not eating gluten until after 8 months of age) may be risk factors for the development of gluten sensitivity. Intriguingly, other researchers have reported that breastfeeding during the introduction of gluten to infants’ diets may be protective.

     In the month’s Pediatrics, though, a large study by Aronsson et al. (doi:10.1542/peds.2014-1787) calls these prior assumptions into question. Their paper reports findings from the Environmental Determinants of Diabetes in the Young data in which over six thousand newborn infants with high-risk HLA genotypes for celiac disease were screened for tissue transglutaminase (tTG) antibodies, a commonly used marker for celiac disease. While the authors found that babies in different countries tended to be fed gluten at different ages (for example, Swedish infants were fed gluten-containing cereals at an average age of 22 weeks, Finish infants at 26 weeks, and American and German infants at 30 weeks), they found no differences in the risk for the development of tTG antibodies or celiac disease based on the timing of gluten exposure. It is worth noting that children in Sweden had almost twice the risk of developing celiac disease than those from other countries in the study, but the early dietary gluten introduction seen in Sweden was not predictive of this risk.

     The most controversial finding of the study, though, is that breastfeeding at the time of the introduction of dietary gluten was a risk factor for the development of tTG antibodies, though not for the eventual development of celiac disease. The clinical significance of this finding is not clear, particularly since other studies have found breastfeeding to lower the risk of celiac disease.

     These results should not change our current recommendations regarding infant feeding practices, but they may help advance our understanding of the development of celiac disease, as well as perhaps alleviating a bit of parental anxiety about the introduction of solid foods to their infants. While the “gluten-free” marketing of bacon might be a fad, the need for a better understanding of the increasing rates of celiac disease, as well as proper dietary management options for those with celiac disease are more important than ever. 

Related Links:

• Peds In Review: Celiac Disease
• Rethinking Strategies to Screen for Celiac Disease
• Clinical, Serologic, and Histologic Features of Gluten Sensitivity in Children

Celiac Disease: How Well Does a Symptom-Based Screening Questionnaire Detect It?

We recognize that the definitive test for celiac disease is an intestinal biopsy, but who needs that test, and can those who might benefit the most be identified simply by their symptoms?

Photo by Samir via Wikimedia Commons

Rosen et al. (doi: 10.1542/peds.2012-3765) investigated this question by looking at the frequency of symptoms and associated conditions unique to those with biopsy confirmed celiac disease and those without the disease. The authors used a population-based screening of 12-year-olds, who along with their parents, filled out a questionnaire asking about celiac disease-associated conditions.

Unfortunately, the sensitivity and specificity of symptoms for those who screened positive leaves much more to be desired—suggesting that the ability to diagnose celiac purely by symptomatology is not the gold standard and will miss a number of patients who also have this disorder without the classic symptoms.

The study results are tough to digest if one has previously considered celiac screening solely on the basis of classic symptoms and raise the question of whether or not a different set of questions might be needed to not miss as many cases as were missed in this study by the use of the questionnaire. Learn more about diagnosing children with celiac disease by reading this article.

Related Readings:

• Pediatrics: Questionnaire-Based Case Finding of Celiac Disease in a Population of 8- to 9-Year-Old Children
• Pediatrics: Clinical Features of Children With Screening-Identified Evidence of Celiac Disease

A Gut Check on the Rising Incidence of Celiac Disease

Every so often we receive an article noting the increasing incidence of celiac disease, and this week we are sharing a most convincing one that helps sort out whether the increased incidence is a result of improved case ascertainment or a true rise in cases.  White et al. (doi: 10.1542/peds.2013-0932) reviewed all new cases of celiac disease in southeast Scotland over a 20 year period (1990-2009) to determine if cases were diagnosed due to a classical presentation, non-classical presentation, or simply due to targeted screening.  The results are interesting in all three diagnostic categories and seal the deal on suggesting that there is a true rise occurring with this disorder.

You really need to read this study to absorb all it has to offer. In turn, perhaps, you may consider celiac even higher in your differential diagnostic compendium for a variety of symptom complaints.