The overall prevalence of celiac disease in the entire cohort was 0.6%. Of those with functional constipation, 1 (0.5%) was diagnosed with celiac disease, and 3 (0.7%) of the control patients
The authors note that some prior publications (references 11 and 12) have found a slight increase risk of celiac disease in children with constipation.
My take: In children with functional constipation, the yield from testing for celiac disease is very low and probably not significantly greater than the general population. In children with irritable bowel syndrome (which is often confused with constipation), the yield is probably a bit higher.
Beginning at 1 year after a diagnosis of CD, 29 patients (0.06%) received a diagnosis of small bowel adenocarcinoma vs 45 reference individuals (0.02%).
HRs were small bowel adenocarcinoma 3.05, carcinoids 0.59, and adenomas 5.73.).
Overall, there was 1 extra case of small bowel adenocarcinoma in every 2944 patients with CD followed for 10 years.
There was an inverse association between mucosal healing risk of future small bowel adenocarcinoma (HR, 0.18; 95% CI, 0.02–1.61), although the HR failed to attain statistical significance.
It is important to note that lymphoma is much more common malignancy than adenocarcinoma in celiacdisease. The authors, in their discussion, state: “compared with lymphomas, small bowel adenocarcinomas were approximately 10 times less common in patients with CD.” At the same time, with the discovery of milder cases of Celiac disease, lymphoma risk is not nearly as high as previously suggested. A large cohort study (Clinical Gastroenterology and Hepatology 2012; 10: 30-36) of ~45,000 did not see an increased risk of GI cancers beyond the first year after diagnosis. In addition, another study (Gastroenterology 2010; 139: 763), found that mortality NOT worsened in undiagnosed celiac disease (identified by review of serology) in Olmstead County, though bone density decreased. n=129 of 16,847. (?milder cases undiagnosed). Related post: Good News For Celiac Disease
My take (mostly borrowed from authors): There is a tiny increase in risk of “small bowel adenomas and adenocarcinomas in patients with diagnosed CD, but only a very marginal increase in terms of absolute risk. Our results do not imply a need for surveillance but celiac individuals with signs or symptoms of malignancy should merit further investigation for small bowel adenocarcinoma. Mucosal healing was strongly associated with lower risk of small bowel adenocarcinoma, although the association failed to reach statistical significance.’ Lymphoma is a more common malignancy associated with CD but the absolute risk remains low.
Methods: The authors identified 65 relevant studies after searching databases including MEDLINE, EMBASE, CENTRAL, Web of Science, CINAHL, DARE, and SIGLE through June 25, 2019 for studies assessing the risk of CeD in patients with IBD, and IBD in patients with CeD
Among patients with celiac disease, there was an increased risk of IBD vs controls (RR 9.88; 95% CI 4.03–24.21); the risk was greater for Crohn’s disease than ulcerative colitis
Among patients with inflammatory bowel disease, there was an increased risk of celiac disease vs controls (risk ratio [RR] 3.96; 95% confidence interval [CI] 2.23–7.02); however, this finding needs to be interpreted with a lot more caution.
The population-based studies that identified this risk relied on ICD codes.
Celiac diagnosis is much more difficult in patients with IBD. Overdiagnosis is possible due to increased surveillance, and misinterpretation of serology (eg. false positive serology). In addition, the pooled prevalence in this study of 0.75%, while greater than the controls of 0.3%, remains lower that the current worldwide prevalence of approximately 1%.
Only more prospective cohort studies will prove a definitive increase in risk.
My take: In patients with either IBD or celiac disease, clinicians should consider additional diagnoses in patients with ongoing symptoms.
In some patients with celiac disease, institution of a gluten-free diet may be detrimental without good dietary counseling as a highly-processed diet can increase the risk of adverse cardiovascular events.
In total dietary surveys were completed for 100 children with celiac disease. Key findings:
77% consumed processed gluten-free (GF) foods multiple times per day
20% ate exclusively processed GF foods
The main reasons for processed GF foods were convenience and taste
Patients and families interest in dietary counseling diminished with time. In children <1 year from diagnosis, 35% were interested in dietary feedback, compared to 18% 2-3 years after diagnosis, 15% 4-6 years after diagnosis, and 11% at 7+ years from diagnosis
The authors speculate that highly-processed foods are leading to obesity which is increasingly reported in pediatric celiac disease.
The greatest opportunity for dietary counseling is at the time of the diagnosis.
Children with celiac disease commonly consume an unhealthy diet and are at risk for the same types of outcomes as children without celiac disease who also frequently consume an unhealthy diet
“In this largest genetic study of CC to date with histologically confirmed diagnosis, we strongly implicated the HLA locus and proposed potential non-HLA mechanisms in disease pathogenesis. We also detected a shared genetic risk between CC, celiac disease, CD, and UC.”
Background: The prevalence of CD among patients with T1DM is between 3-10%
Using a retrospective observational cohort with 63 children, the authors recommend raising the cut-off from performing biopsies from 3 times the ULN to 11 times ULN.
This change in increases the specificity from 36% to 73% while reducing sensitivity from 96% to 87%. In addition, this improves the positive predictive value from 88% to 94%, but lowered negative predictive value from 67% to 53%. Overall, this leads to a reduction in “unnecessary biopsies.”
The authors note that while the serology sensitivity is reduced, it is still acceptable and justified because “normalization of elevated TG2A can occur in up to one-third of patients.”
Another finding from this cohort was that 55% of children with Marsh 0 or 1 histology were symptomatic, indicating that symptoms are not specific for CD.
While the authors have recommended a higher threshold and advocated for repeating serology ~3 months later in those with lower titers, the associated editorial by Stefano Guandalini makes the following points:
Raising the titer threshold would leave 13% of patients with celiac disease undiagnosed (or at least with a delay in diagnosis)
“For lower titers, the physician will have to apply his or her knowledge and conscience in each individual case…we must be mindful of the serious risk of missing too many patients with celiac disease by applying a high threshold, a risk probably outweighing that of an unnecessary biopsy.”
My take: This study shows that in children with T1DM who have abnormal lower-value celiac serology, a careful discussion with parents is needed about the merits of endoscopy or deferring until persistent positivity.
Briefly noted: L Waters et al. Annals Int Med 2020; doi:10.7326/L20-0497. Celiac Disease Remission With Tofacitinib
The authors describe a male with a well-documented case of celiac disease and alopecia areata. He was placed on tofacitinib off-label for his alopecia areata and it was discovered that his celiac disease had developed “complete histologic and serologic remission…while he was still on a gluten-containing diet.” Prior to medication, he had confirmation of both severe histologic changes and high tTG IgA titers.
The authors note that tofacitinib inhibits CD8+ T-cell mediated enteropathy in a transgenic mouse model.
My take (borrowed from authors): Tofacitinib has many potential adverse effects but may considered for further study, especially in refractory celiac disease.
Table –From Annals of Internal Medicine Twitter Feed
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