the patient celiac

Celiac Disease: More Common Yet “Atypical” than Previously Thought

8 comments February 24, 2016

I recently wrote this paper for an online pediatric journal and thought it might be of interest to some of you. Please feel free to repost and share (as long as you credit me). Thank you! -Jess

"Celiac disease, an autoimmune enteropathy triggered by the consumption of gluten, can develop in genetically predisposed children (HLA DQ2 and/or DQ8 positive) at any point from 9 months of age through adulthood. Although the incidence of celiac disease in both North America and the bulk of Europe is approximately 1 in 100, patients with a first-degree relative with celiac disease are at a much higher risk of development. For example, up to 25% of children who are homozygous for HLA- DQ2 will develop evidence of celiac autoimmunity by age 6. Additional risk factors for the development of celiac disease include type 1 diabetes, autoimmune thyroid disease, Trisomy 21, Turner syndrome, William’s syndrome, and selective IgA deficiency. The celiac genes (HLA-DQ2 and DQ8) contribute 40% of the risk of developing celiac. Environmental risk factors for celiac disease include infant feeding patterns, early infections, gut microbiota, receiving multiple doses of antibiotics during early life and the amount and timing of initial gluten exposure.

Although the “classic” symptoms of pediatric celiac disease include abdominal pain and distension, diarrhea, and failure to thrive there has been increased recognition over the last decade that many children with celiac disease present with “atypical” symptoms. These atypical symptoms include fatigue, iron deficiency anemia, dermatitis herpetiformis, dental enamel defects, aphthous ulcers, arthritis and arthralgias, low bone mineral density, elevated liver enzymes, short stature and delayed puberty. Neurologic and psychiatric symptoms of celiac disease in children include cerebellar ataxia, recurring headaches, peripheral neuropathy, seizures, anxiety, panic attacks, and depression. In addition, many children with celiac disease are asymptomatic. Hence, the need for celiac screening in high-risk groups, including those with affected family members, as well as children with any of the aforementioned atypical symptoms of celiac disease.

A basic celiac disease screening panel should include both a serum IgA level and a TTG (tissue transglutaminase) IgA. In children who are younger than age 4 years of age, as well as those with a selective IgA deficiency, a DGP (deamidated gliadin peptide) IgG can be tested. The anti-gliadin IgA is no longer considered to be an adequate celiac screening test due to having low specificity. Children need to be consuming gluten at the time of testing, as it takes only 2 weeks on a gluten-free diet to make the results of a patient’s celiac disease testing unreliable. Confirmatory testing for celiac disease consists of endoscopy with small bowel biopsy. At least 4 to 6 tissue samples should be obtained for histologic analysis, including at least one sample from the duodenal bulb, as the villous blunting in celiac disease can be confined to solely this area.

The only current treatment for celiac disease is strict adherence to the gluten free diet for life; however, there are multiple therapies in development to augment the gluten-free diet and to help prevent symptoms from inadvertent gluten ingestion via cross-contamination. It is crucial for parents and children diagnosed with celiac disease to meet with dieticians who are well versed in celiac and the gluten free diet as the most common cause of persistent symptoms is accidental gluten ingestion. In addition children with celiac disease may have multiple vitamin and mineral deficiencies at the time of diagnosis that may need to be corrected, including low levels of Vitamin D, folate, and zinc.

In conclusion, celiac disease is a relatively common autoimmune disease with a myriad of presenting symptoms that can develop at any point during life. Early diagnosis and treatment of celiac disease can lead to an improved quality of life and decrease in complications and also presents an opportunity for at-risk family members to be periodically screened."


1. Liu E, Lee HS, Aronsson CA, et al. TEDDY Study Group. Risk of pediatric celiac disease according to HLA haplotype and country. N Engl J Med. 2014 Jul 3;371(1):42-9.

2. Guandalini S, Assiri A. Celiac Disease: A Review. JAMA Pediatr. 2014 Jan 6. doi: 10.1001/jamapediatrics.2013.3858.

3. Lebwohl, B, Ludvigsson, JF, Green, PHR. The unfolding story of celiac disease risk factors. Clinical Gastroenterology and Hepatology (2013), doi: 10.1016/j.cgh.2013.10.031.

4. Hadjivassiliou, M, Sanders, D, Grubewald, R, et al. Gluten sensitivity: from gut to brain. The Lancet. March 2010. 9: 318-330.

5. Aggarwal, S., Lebwohl, B, and Green, P. Screening for celiac disease in average-risk and high-risk populations. Therap Adv Gastroenterol. Jan 2012; 5 (1): 37-47.

6. Castillo, N., Thimmaiah, G., Leffler, D. The present and the future in the diagnosis and management of celiac disease. Gastroenterology Report. 2014, 1-9.

In reply to Shauna B.
Hi Shauna,

I am sorry that I have taken so long reply. I do not know of any references regarding how to proceed with gluten challenges when severe symptoms erupt in the pediatric population, but I know that many of the adult celiac docs believe that a gluten challenge should be stopped if a patient gets too sick and that testing should then happen (even if the duration of the challenge has not been as long as planned. The rationale behind this is that if that significant of symptoms are occurring that there should be some evidence of inflammation on intestinal biopsy.

I hope this helps. This was discussed at the preceptorship that I did at the U of Chicago in 2014.

7/19/2016 4:57:36 PM
In reply to Julie.
Hi Julie,

You’re welcome. Thanks so much for reading. I am TWO months behind in replying to comments, but I always love seeing you post on here. Hope you are having a great spring!

7/19/2016 4:57:16 PM
Shauna B
My 4 year old son and I are both Celiac and we are in the process of diagnosing my almost 2 year old daughter. We are a gluten free house, so she’s only exposed to it when we are out (snacks at church, friends houses, restaurant, etc.) We had the blood panel done last year after a cruise where she ate gluten every meal for a week. The results were abnormal but not conclusive. We are now at a point where we need to retest. However, she gets sick (vomits) after major gluten ingestion and gets diarrhea and rash after minor gluten ingestion. But i know only consistent exposure will help her get a diagnosis. I’m at a loss for what to do. Do you have any articles or resources you could send my way? I know you have studied the testing of at risk kids extensively. Thanks in advance!
7/19/2016 4:56:53 PM
Great article! Finally, all the information in one well written article. A must read for anyone needing the up to date facts on celiac disease. Now, we need a dietitian to write a comparable article with the facts and needed information for celiacs from their specialty. Thanks for writing this, Jess.
7/19/2016 4:56:22 PM
In reply to Peg.
Hi Peg,
Yes, if a person has serum total IgA levels that are too low, testing for celiac using the TTG IgA test is meaningless–someone with celiac will show up as being negative. In cases of serum IgA deficiency DGP-IgG testing should thus be done.
I hope this helps. Please let me know if you have more questions.
7/19/2016 4:55:56 PM
In reply to christine.
Hi Christine,
It’s good to hear from you.
There are a small percentage of patients with celiac who are DQ2/DQ8 negative. From the studies I’ve seen DQ7 appears to be the culprit in these cases. There is a fair amount of work regarding other genetic variants associated with celiac, like MYO9B…if you search PubMed you’ll be able to find some of the studies.
You can also check out this link for more info.
7/19/2016 4:55:23 PM
Could the tTG IgA give a false negative if total IGA is below normal range ( total IGA wasn’t checked at the time of the test but was later found to be below normal)?
7/19/2016 4:54:57 PM
Are there any other Genetic markers for Celiac Disease besides the genes HLA-DQ2 and DQ8?

Good article..thank you for sharing.
7/19/2016 4:53:53 PM
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