Tag Archives: celiac disease

Acid Suppression and Antibiotics in Infancy Associated with Increased Risk of Celiac Disease

Posted on by

M Boechler et al. J Pediatr 2023; 254: 61-67. Acid Suppression and Antibiotics Administered during Infancy Are Associated with Celiac Disease

Methods: A retrospective cohort study was performed using the Military Healthcare System database. N=968,524 children with 1704 cases of celiac disease (CD) in this group (from 2001 to 2013) with prescription for PPIs, H2RAs or antibiotics in first 6 months of life.

Key findings:

  • PPIs (HR, 2.23; 95% CI, 1.76-2.83), H2RAs (HR, 1.94; 95% CI, 1.67-2.26), and antibiotics (HR, 1.14; 95% CI, 1.02-1.28) were all associated with an increased hazard of CD.
  • The risk is increased by use of multiple categories of these medications and/or if acid suppression medications are used for longer periods

There have been previous studies indicating an increased risk of CD in patients given acid suppression (Lebwohl et al. Dig Liver Dis 2014; 46: 36-40) and conflicting data regarding the use of antibiotics. With regard to acid suppression, recent studies have indicated that these medications in infancy may increase the risk of food allergies as well. The authors speculate in their discussion that the increased risk for CD could be related to changes in protein degradation, mucosal permeability, microbiome changes, and immune reactivity. The authors note that their dataset did NOT show an increased risk of CD associated with C-section delivery.

One of the limitations of this study is that early presentations of CD could lead to prescriptions of agents to to help reduce symptoms rather than the medications increasing the risk of developing CD. However, this is unlikely as gluten introduction is often later in infancy.

My take: Better stewardship of antibiotics and acid blockers is needed. Use of acid suppression medications is associated with an increased risk of celiac disease as well as food allergies.

Related blog posts:

Additional posts on Celiac Disease

Panoramic View of Tucson, AZ from Tumamoc Hill

Celiac Disease Identified After Family Index Case

Posted on by

MJ Gould et al. JPGN 2023; 76: 49-52. Characteristics of Pediatric Patients With Celiac Disease Identified Due to an Affected First-Degree Family Member

In this retrospective study, 49 patients were screened due to an affected first-degree relative with celiac disease. They were compared to 178 patients who were screened for other clinical indications. Key findings:

  • Although 51% of patients screened due to an affected first-degree relative were asymptomatic, their disease histology and TTG levels were as severe as those screened for symptoms suggestive of celiac disease (in the comparison group 16% were asymptomatic). 

Comments:

  1. “Previous studies have shown that asymptomatic adolescents and those diagnosed with CD by serologic screening are less likely to adhere strictly to a GFD when compared to younger children and adults diagnosed because of classical symptoms” (Dig Dis Sci. 2008 Jun; 53(6): 1573–1581).”
  2. Some individuals who are thought to be asymptomatic, clinically improve with a gluten free diet (GFD). In one study, “the GFD group also had reduced indigestion (P=.006), reflux (P=.05), and anxiety (P=.025), and better health, based on the visual analog scale (P=.017), than the gluten-containing diet group” (Gastroenterology  2014 Sep;147(3):610-617).

My take: In this study, being asymptomatic (identified due to affected first-degree relative) was NOT associated with milder celiac disease based on serology or histology.

Relate blog posts:

Garden Lights, Holiday Lights at Atlanta Botanical Gardens

Safety Net for Celiac Disease?

Posted on by

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.

Related blog posts:

2023 ACG Celiac Guidelines for Adult and Children

Posted on by

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.

Related blog posts:

Favorite Posts 2022

Posted on by

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

Posted on by

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.

Related blog posts:

Selected Slides from NASPGHAN 2022 Postgraduate Course (Part 2)

Posted on by

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

Posted on by

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)

Posted on by

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)

Related blog posts:

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

Posted on by

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: