Tag Archives: celiac disease

Safety Net for Celiac Disease?

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JA Murray, JA Syage et al.Gastroenterol 2022; 163: 1510-1521. Open access! Latiglutenase Protects the Mucosa and Attenuates Symptom Severity in Patients With Celiac Disease Exposed to a Gluten Challenge

Background: Latiglutenase (IMGX003) is an investigational dual-enzyme drug candidate that acts to degrade gluten in vivo when consumed with a meal. The authors note that “despite strict adherence to a GFD, about half of CD patients show evidence of persistent small intestinal mucosal injury (Marsh grades II–III);’ thus, there is a need to improve treatment with other measures in addition to diet.

Methods: 43 patients (IMGX003, n = 21; placebo, n = 22) completed this double blind and placebo controlled study which assessed the efficacy and safety of a 1200-mg dose of IMGX003 in patients with celiac disease (CD) exposed to 2 g of gluten per day for 6 weeks study

Key findings:

  • In IMGX003-treated patients, there was less damage to mucosa. The mean change in the ratio of villus height to crypt depth (primary endpoint) for IMGX003 vs placebo was –0.04 vs –0.35 (P = .057). The mean change in the density of intraepithelial lymphocytes (secondary endpoint) for IMGX003 vs placebo was 9.8 vs 24.8 cells/mm epithelium (P = .018). 
  • Measurements of gluten-immunogenic peptides (GIP) in urine indicated 95% gluten degradation in the stomach by latiglutenase.

The 2 g dose per meal of gluten allowed used in the study, “would likely substantially exceed that accidently occurring while on a GFD, 4 supporting such an approach for management for gluten-triggered symptoms in treated patients.”

Graphical abstract:

In both the placebo and IMGX003 groups, there was an increases in symptoms, but this was blunted in the treated group–Figure 2:

My take: This study shows the potential for latiglutenase to act as a ‘safety net’ to protect from CD from accidental gluten exposure. The findings reinforce the idea that this agent is not likely to be effective in the absence of gluten restriction. As an aside, I would be interested in finding out whether patients with presumed non-celiac gluten sensitivity would improve on this therapy.

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2023 ACG Celiac Guidelines for Adult and Children

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A Rubio-Tapia et al. Am J Gastroenterol 2023;118:59–76. Open Access! American College of Gastroenterology Guidelines Update: Diagnosis and Management of Celiac Disease Thanks to Ben Gold for this reference.

Here are some of the recommendations from updated ACG Celiac Guidelines:

Comments: The authors favor a non-biopsy approach for Celiac diagnosis in children with very elevated serology but not in adults. In adults, they cite a paucity of literature. “One multicenter international study of adults found that a 10-fold elevation of TTG IgA had a positive predictive value of 95% for CD (50). Given the life-long treatment implications of a GFD, this may be unacceptably low.”

The authors suggest assessing for mucosal healing after 2 years of treatment in all patients though they indicate a low quality of evidence for this recommendation. In those undergoing endoscopy, biopsies of the duodenal bulb along with at least 4 post-bulbar biopsies are recommended.

Figure 3 provides an algorithm for non-responsive celiac disease.

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Favorite Posts 2022

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Thank you to those who have helped me this past year with this blog –colleagues, friends and family. Wishing all of you a good 2023. Here are some of my favorite posts from this past year:

GI:

Nutrition:

Liver:

Endoscopy:

Health Policy:

Humor:

Treatment of Refractory Celiac Symptoms with a Low FODMAP Diet

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F van Megen et al. Clin Gastroenterol Hepatol 2022; 20: 2258-2266. Open Access! A Low FODMAP Diet Reduces Symptoms in Treated Celiac Patients With Ongoing Symptoms–A Randomized Controlled Trial

Methods: A randomized controlled trial was performed from 2018 to 2019 in 70 adults with biopsy-proven celiac disease. Inclusion criteria were as follows: persistent gastrointestinal symptoms defined by a Gastrointestinal Symptom Rating Scale (GSRS)–IBS version score of 30 or higher, gluten-free diet adherence for 12 months or longer, and serologic and mucosal remission. 

Key findings:

  • Compared to placebo-treated patients, there was significant improvement in pain, bloating, diarrhea and satiety, based on GSRS-IBS scores, in those assigned to a low FODMAPs diet (see below)

While this a low FODMAP diet can be helpful, the authors offer this cautionary advice:

  • “Following 2 complex diets increases the risk of inadequate nutritional intake, and patients should be followed up carefully. A low FODMAP diet should not be recommended to patients at nutritional risk or to patients at risk of developing an eating disorder.”
Figure 2 in Article

My take: Asking patients with celiac disease to further restrict their diet is akin to running the Peachtree Road Race in a fireman’s outfit. It can be done but doesn’t look like much fun.

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Selected Slides from NASPGHAN 2022 Postgraduate Course (Part 2)

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See previous post for lecturers

Oral small molecultes in IBD. Anne Griffiths, MD
Judith Kelsen, Very early onset IBD
VEO Evaluation
VEO Treatments
Jeremy Adler and Treat to Target for IBD
Jeremy Adler and Treat to Target for IBD
Jeremy Adler and Treat to Target for IBD
Jeremy Adler and Treat to Target for IBD
Jeremy Adler and Treat to Target for IBD
Timothy Sentongo and Growth and Nutrition Issues in the NICU
Maureen Leonard and Gluten-Related Disorders Update
Maureen Leonard and Gluten-Related Disorders Update
Maureen Leonard and Gluten-Related Disorders Update
Maureen Leonard and Gluten-Related Disorders Update
Rachel Rosen and Esophageal Motor Disorders
Katja Kovacic and Functional Nausea
This study was 20 yrs ago -we can do better today

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  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.

Predicting Risk of Celiac Disease in High-risk Families

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CR Meijer et al. Gastroenterol 2022; 163: 426-436. Open access: Prediction Models for Celiac Disease Development in Children From High-Risk Families: Data From the PreventCD Cohort

B Lebwohl, L Greco. Gastroenterol 2022; 163: 368-369 (editorial). Open access: Can We Predict the Onset of Celiac Disease?

Design: “In this study, the investigators analyze long-term follow-up data from the PreventCD trial, a randomized trial of infants [n=944] with a first-degree relative with CD that was designed to test the strategy of low-dose gluten introduction at age 4 months. The trial did not show that this strategy reduced the risk of CD development,7 but the abundant data collected during this trial have allowed these investigators to study risk factors for the development of CD among the trial participants.” The median f/u was 8.3 yrs.

Key points from study and editorial:

  • 135/944 (14%) children developed CD (mean age, 4.3 years)
  • CD developed significantly more often in girls (P = .005) and in Human Leukocyte Antigen (HLA)-DQ2 homozygous individuals (8-year cumulative incidence rate of 35.4%
  • Prediction application calculator with screening recommendations https://hputter.shinyapps.io/preventcd/. This screening calculator generally recommends screening every 6 months for those at greastest risk and every 12 months for those at lower risk.

HLA testing in this setting has historically been performed primarily due to its excellent negative predictive value. Because HLA DQ2 and DQ8 are present in nearly 100% of people with CD, the primary value of its use has been in ruling out CD when an individual is found to have neither haplotype. This study shows some usefulness in predicting the likelihood of CD.

My take: This study showed 14% of high-risk children developed celiac disease and the number is likely to escalate with more time. In first-degree relatives, checking HLA-DQ2/8–typing may help determine frequency of screening in asymptomatic individuals –though simply choosing to screen every 1-2 years would be a reasonable alternative.

It should be noted that current expert guidelines provide divergent advice; “NASPGHAN recommends that asymptomatic children in high-risk groups (including first-degree relatives) be screened, 4 but the United States Preventive Services Task Force concluded that the evidence is insufficient to warrant recommending for or against screening asymptomatic individuals.”

Related blog posts:

Westchester Lagoon, off Tony Knowles Coastal Trail. Anchorage, AK

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  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.

AAP Guidelines for Down Syndrome & Screening for Celiac Disease Plus One (How to Fix Diarrhea)

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The AAP has updated recommendations for Down syndrome: MJ Bull et al. Pediatrics (2022) 149 (5): e2022057010. Open Access: Health Supervision for Children and Adolescents With Down Syndrome

For gastroenterologists, one area of concern is screening for celiac disease in this population due to a mildly increased risk.

Here is what is recommended in children after 1 year of age:

“For children on a diet that contains gluten, review for symptoms potentially related to celiac disease at each health supervision visit because children with Down syndrome are at increased risk. These symptoms include diarrhea or protracted constipation, slow growth, unexplained failure to thrive, anemia, abdominal pain or bloating, or refractory developmental or behavioral problems.97–99  For those with symptoms, obtain a tissue transglutaminase immunoglobulin A (TTG IgA) concentration and simultaneous quantitative IgA. The quantitative IgA is important, because an IgA deficiency renders the TTG IgA unreliable. Refer patients with abnormal laboratory values for specialty assessment. Do not institute a gluten-free diet before confirmation of the diagnosis, because lack of gluten can make interpretation of endoscopic results difficult. There is no evidence that routine screening of asymptomatic individuals would be beneficial. There are neither data nor consensus that would indicate whether patients with persistent symptoms who had normal laboratory values on initial evaluation should have further laboratory tests.”

In addition to celiac disease, the AAP article has a ton of useful resources regarding Down syndrome for clinicians and families.

My take: Celiac disease is difficult to diagnose and is much more common in children with Down syndrome. It is worth noting that other Down syndrome groups, NICE and NASPGHAN have recommended screening for celiac in all children with Down syndrome. (Ref: M Pavlovic et al. World J Clin Cases. 2017 Jul 16; 5(7): 264–269. Open Access: Screening of celiac disease in Down syndrome – Old and new dilemmas)

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White Sands National Park, New Mexico

Also, a keen observation from Carlo Di Lorenzo’s twitter feed:

The corollary of this is how miraculous it is when a child who has not stooled for 3 weeks straight has no residual markers after swallowing a Sitz capsule.

Health Benefit from Disease State: Sucrase-Isomaltase Deficiency

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It is well-recognized that genetic mutations that persist often confer some advantages. For example, sickle cell trait (but not disease) provides protection against malaria.

A recent study shows potential health benefits in those with sucrase-isomaltase deficiency: MK Andersen, L Skotte, E Jorsboe et al. Gastroenterol 2022; 162: 1171-1182. Open Access: Loss of Sucrase-Isomaltase Function Increases Acetate Levels and Improves Metabolic Health in Greenlandic Cohorts

Methods: “The association between c.273_274delAG and phenotypes related to metabolic health was assessed in 2 cohorts of Greenlandic adults (n = 4922 and n = 1629). A sucrase-isomaltase knockout (Sis-KO) mouse model was used to further elucidate the findings”

Key findings:

  • Homozygous carriers of the variant had a markedly healthier metabolic profile than the remaining population, including lower body mass index ( –2.0 kg/m2; P = 3.1 × 10–5), body weight (–4.8 kg; P = 5.1 × 10–4), fat percentage (–3.3%; P = 3.7 × 10–4), fasting triglyceride (–0.27 mmol/L; P = 2.3 × 10–6), and remnant cholesterol (–0.11 mmol/L; P = 4.2 × 10–5).
  • The metabolic profile “was likely mediated partly by higher circulating levels of acetate observed in homozygous carriers” (0.056 mmol/L; P = 2.1 × 10–26), and partly by reduced sucrose uptake, but not lower caloric intake.
  • “These findings were verified in Sis-KO mice, which, compared with wild-type mice, were leaner on a sucrose-containing diet, despite similar caloric intake, had significantly higher plasma acetate levels in response to a sucrose gavage, and had lower plasma glucose level in response to a sucrose-tolerance test.” 

My take: It should not be surprising that a genetic condition that results in limited sucrose intake would have health benefits. Perhaps correcting this condition will result in unexpected health issues similar to health issues that can develop in those with celiac disease after institution of a gluten-free diet (Gastroenterol 2013; 144: 912-17).

Related blog posts:

Graphical Abstract:

Tricky Article Title: IBD and Celiac

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M Alkhayyat et al. Inflamm Bowel Dis 2022; 28: 385-392. Patients With Inflammatory Bowel Disease on Treatment Have Lower Rates of Celiac Disease

When I first saw this title, I mistakenly thought the title indicated that celiac disease (CD) occurred less often in those with inflammatory bowel disease (IBD). This would have been surprising given previous studies have found the opposite. In fact, this study confirms the bidirectional associated risk between patients with CD and in patients with IBD but with a twist. Most IBD treatments were associated with a lower risk of developing CD than those who were not treated.

Database study: Of the 72,965,940 individuals in the database (1999-2020), 133,400 had celiac disease (CD) (0.18%), 191,570 (0.26%) had ulcerative colitis (UC), and 230,670 (0.32%) had Crohn disease.

Key findings:

  • Patients with IBD were more likely to have a diagnosis of celiac disease (odds ratio [OR], 13.680), with a greater association with Crohn disease (OR 24.473).
  • Treated patients with IBD with UC and with Crohn disease, respectively, had a lower risk association with CD compared to those not undergoing IBD treatment, specifically corticosteroids (OR, 0.407 and 0.585), 5-aminosalicylates (OR, 0.124 and 0.127), immunomodulators (OR, 0.385 and 0.425), and anti-tumor necrosis factor drugs (OR, 0.215 and 0.242)
  • A new diagnosis of CD after 1 year of IBD diagnosis, was 1.59% for Crohn disease and 0.90% for UC compared to 0.16% in patients without IBD (P<0.0001)
  • A new diagnosis of IBD, Crohn disease and UC respectively, in patients with celiac disease was 2.75% and 1.11% compared to 0.29% and 0.25% in the non-celiac population (P<0.0001)
  • A new diagnosis of IBD and celiac disease among patients with microscopic colitis was 10.5% and 2.6% respectively; a new diagnosis of microscopic colitis among patients with celiac disease was 0.01%

My take: This study confirms the bidirectional associated risk between IBD and celiac disease. The risk of developing celiac disease in those with IBD may be lower in those receiving some treatments; however, this assertion is limited by the nature of a database study.

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Pelicans at Shem Creek, SC (near Charleston)

Celiac Disease, Hepatitis B and Paul Harvey

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Growing up, I heard a number of Paul Harvey broadcasts on the radio. Often there would be an important twist at the end and he would conclude with ‘and that’s the rest of the story.’

This came to mind after reading a recent article on celiac disease and hepatitis B infection:

N Habash et al. JPGN 2022; 74: 328-332. Celiac Disease: Risk of Hepatitis B Infection

Methods:

  • A cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) database (2009–2014) 
  • And a retrospective analysis of HBV infection in two cohorts: Mayo Clinic cohort (1998–2021) and the Rochester Epidemiology Project cohort (REP; 2010–2020)

Key findings:

  • Based on NHANES database, the rate of HBV infection in the United States was  0.33%
  • Of 93 patients with CD, 46 (49%) were vaccinated for HBV and of the remaining 19,422 without CD, 10,228 (53%) were vaccinated
  • Twenty-two (48%) vaccinated patients with CD had HBV immunity and 4405 (43.07%) vaccinated patients without CD had HBV immunity
  •  In NHANES data, there were no cases of HBV infection in patients with CD. Among the 3568 patients with CD seen at Mayo Clinic and 3918 patients with CD in the REP database, only four (0.11%) at Mayo Clinic and nine (0.23%) of the REP patients had HBV infection.

This finding is probably applicable to other conditions in which HBV immunity is ascertained.

My take: In contrast to other small studies, this study showed that the “rate of HBV vaccination and immunity was similar in individuals with and without CD.” In addition, there was no increased risk of HBV infection detected in CD patients. Thus, testing for HBV is not necessary in patients with CD.

And that’s the rest of the story.

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