Celiac Disease Diagnosis: ESPGHAN vs. NASPGHAN Guidelines
Michelle Pietzak Children’s Hospital of Los Angeles
This lecture started with a succinct history of celiac disease, including discussion of the banana diet and the observation that wheat deprivation during World War II was associated with improvement in children with celiac disease. The sequential diagnostic recommendations of ESPGAN and NASPGHAN were reviewed.
ESPGHAN 2012 guidelines separated children in two groups: symptomatic and asymptomatic. The guidelines indicated that symptomatic children with high titer serology (TTG IgA >10-fold ULN and positive EMA) could be diagnosed without an intestinal biopsy.
ACG 2013 Guidelines: TTG IgA preferred serologic test if over age 2 years, TTG IgA along with deamidated gliadin (IgG and IgA) recommend if younger than 2 years. Even if negative serology, a biopsy was recommended if significant suspicion of diagnosis.
NASPGHAN, AGA, ACG all recommend small bowel biopsy to confirm this lifelong condition
The speaker did not critically discuss the Leonard et al study suggesting that 19% of individuals had persisting enteropathy on a gluten fee diet (see previous posts below)
Jimmy Fallon: “10% of the population is allergic to gluten and 90% are tired of hearing about it”
Fad Diets: The Good, the Bad, and the Just Plain Ugly
Mark Corkins University of Tennessee Health Science Center
Fad diets driven in part by obesity
Gluten-free diet is the most trendy, ~30% of U.S. adults are ‘limiting’ gluten, though most do not understand what gluten is. “Wheat Belly” book by Dr. William Davis has been influential despite lack of data.
According to marketing report, 35% who consumer gluten limited diet have no reason for this, 26% for ‘healthier option,’, 19% for ‘digestive health,’, 13% for weight loss, 8% for gluten sensitivity
Recommends: choosemyplate.gov. These feeding guidelines have been developed by nutrition experts.
Update on H pylori
Nicola Jones Hospital for Sick Children (Toronto)
Reviewed current recommendations based on ESPGHAN/NASPGHAN 2016 recommendations.
The speaker indicates that upper endoscopy is recommended for initial diagnosis of H pylori but testing is not recommended for functional abdominal pain. The lecture did not address the issue that there can be an overlap in the presentations of these disorders.
Adherence is crucial for adequate eradication
Newer studies show improved eradication rates for quadruple therapy (bismuth-based) & in U.S. this is recommended as first-line treatment unless resistance patterns are known (which could allow for triple therapy)
Another large study (KJ Werkstetter et al. Gastroenterol 2017; 153: 924-35) shows a high accuracy of diagnosing celiac disease (CD) without a biopsy when very high celiac titers are identified in symptomatic patients. A previous study (n=898) this year also showed similar findings: The Non-Biopsy Diagnosis of Pediatric Celiac Disease
The current study (2001-2014) identified 743 consecutive pediatric patients with positive celiac serology (TTG-IgA). Key findings:
If TTG-IgA was higher than 10-fold the upper limit of normal and a separate sample tested positive for endomysial antibodies, then non-biopsy approach had a positive predictive value >99.6%. The authors utilized a variety of TTG-IgA assays.
The authors noted that HLA-DQ2/DQ8 typing did not improve the accuracy of CD diagnosis. “Negative results for HLA-DQ2/DQ8 in patients with TGA or EMA positivity are most likely false negative …or due to very rare risk-allele combinations not recognized by the test systems.”
“At least 50% of affected children in clinical practice will benefit from this nonbiopsy approach, which reduces burden and risks of endoscopy and anesthesia” and is more cost-effective.
The authors’ conclusion: “allowing omission of biopsies enables a correct diagnosis of CD in symptomatic children if TTG-IgA exceed 10xULN and positive EMA-IgA confirms celiac disease autoimmunity in a second blood sample. If one of these criteria is not fulfilled, biopsy should be performed to confirm the diagnosis.”
My take: This study provides convincing data that CD diagnosis does NOT require an intestinal biopsy under specific conditions.
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.
Apparently a great number of celiac disease (CD) experts took exception to the authors’ conclusion that “neither the presence of symptoms nor positive serology were predictive of a patient’s histology at the time of repeat biopsy. These findings suggest a revisitation of monitoring and management criteria of celiac disease in childhood.”
A recent commentary (S Koletzko et al. JPGN 2017; 65: 267-9) from the CD working group of ESPGHAN critiques the limitations of the study. Limitations included the following:
Selection bias -70% of patients in this retrospective study had repeat endoscopy were symptomatic
Including children with admitted non-adherence to gluten-free diet (GFD)
Including ~25% of children who were rebiopsied within 17 months of starting GFD
Lack of standardized tTG testing
Lack of blinding of pathologist
“We do not think that the data..give sufficient support…that routine biopsies should be performed in all children at diagnosis and after the initiation of GFD.”
“The CD working group of ESPGHAN strongly advises against regular rebiopsy in children on a GFD…Re-endoscopy should be reserved for symptomatic patients–in particular when seronegative.”
The authors of the initial study (MM Leonard, A Fasano. JPGN 2017; 65: 270-1) were given an opportunity to defend their conclusions. Their commentary was much less provocative in my view, and titled: “Zero, One, or Two Endoscopies to Diagnosis and Monitor Pediatric Celiac Disease? The Jury is Still Out”
They note that there is a lack of data to know whether there are “no real clinical consequences” of persistent enteropathy, as stated by S Koletzko et al. They state that until further research is completed a “personalized approach to follow-up care is needed.” It is encouraging that they have started a prospective study to address the limitations of their retrospective study.
For patients with CD who are strictly-adherent, asymptomatic and with normal serology, repeat endoscopy is of questionable benefit. If there are abnormalities in the histology, what is the appropriate intervention?
There has been a study (Gastroenterology 2010; 139: 763) which showed that mortality was NOT worsened in undiagnosed CD (identified by review of serology) in Olmstead County. In this population, the main long-term detrimental effect was reduced bone density. My inference is that for CD patients who are asymptomatic, particularly those with normalized serology, they are unlikely to have easily-identifiable adverse effects noted, even if their histology is abnormal.
My take (unchanged from last year): I think it is premature to recommend routine followup biopsies in asymptomatic patients with normal serology.
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.
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.
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)
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: TWallach 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.
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
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