Tag Archives: celiac disease

Outcomes in Pediatric “Potential” Celiac Disease Plus One

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B Laxer et al. J Pediatr Gastroenterol Nutr. 2026; 83: 717-722. Open Access! Heterogeneous outcomes in pediatric potential celiac disease: a multicenter longitudinal study.

Background: Potential celiac disease (PCD) is defined by positive celiac serology without villous atrophy.

Methods: This was a multicenter retrospective study with 88 children with mean follow-up of 3.3 years (with a range up to 6 years). Indications for repeat endoscopic evaluation while on a GCD included—a rise in tTG titers to >10× ULN, persistent tTG elevation >10× ULN for over 24 months and the emergence of clinical symptoms necessitating reassessment. During follow-up, only 23 patients (26.1%) underwent a repeat upper endoscopy, as per the clinician’s decision, after a median period of 29 (IQR 11.5–36.5) months from the initial PCD diagnosis.

Key findings:

  • 17/88 (19.3%) patients progressed to Celiac Disease (CeD).
  • 33/88 (37.5%) had normalization of anti-tissue transglutaminase antibodies (tTG), while continuing a diet containing gluten
  • 38/88 (43.2%) continue to have PCD
  • Among 16 patients with high tTG levels (>×10 upper limit of normal) at PCD diagnosis, the results were similar: three (18.8%) progressed to CeD and six (37.5%) normalized tTG
  • Asymptomatic patients were significantly more likely to achieve serological normalization compared to their symptomatic counterparts (61.9% vs. 35.8%, p = 0.011)

Discussion Points:

“A recent meta-analysis9 of 1010 patients reported a progression rate of approximately 33% to CeD, while another third achieved serological normalization.”

Limitations:

  • Follow-up period of up to 6 years may not capture late-onset progression.
  • Only a small subset had a follow-up endoscopy; if all patients had had a repeat endoscopy, there would have been a higher rate of CeD diagnosis

My take: This study found about one-fifth of patients progressed from potential celiac disease to celiac disease during a mean follow-up of 3.3 years. However, 70% of patients did not undergo repeat endoscopy.

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Also, in same issue:

MC Pacheco et al. J Pediatr Gastroenterol Nutr. 2026; 83: 723-727. Does diagnosis by biopsy versus serology-only affect follow-up in celiac disease? In this retrospective study wiht 54 children, there was no significant difference in frequency of clinical follow-up or decrease in TTG IgA levels between patients who were diagnosed with biopsy versus serology alone.

Bruarfoss (Iceland) is often called “Iceland’s Bluest Waterfall”

Micro-Computed Tomographic Imaging Shows the Blurry Line Between Potential Celiac Disease and Celiac Disease

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A Reunamo et al. Gastroenterology, 2026; 171, 553-555. Open Access! Three-Dimensional Micro-Computed Tomographic Imaging Reveals Early Mucosal Remodeling in Individuals With Potential Celiac Disease

Background: “A subset of individuals, characterized as having potential CeD (PCeD), present with positive transglutaminase 2 or endomysial antibodies, or both, but lack histologic findings that meet the diagnostic criteria.1 Importantly, only a subgroup of individuals with PCeD progress to CeD during follow-up.1“

Methods: The authors “recently developed a 3-dimensional (3D) x-ray micro-computed tomographic (micro-CT) imaging and analysis procedure for duodenal biopsy specimens.6,7 The method enables the precise histomorphometric quantification, including measurements of villus height–to–crypt depth ratio (VH:CrD) and mucosal surface area, with excellent reproducibility.7” This study used micro-CT imaging to investigate the early-stage mucosal changes in individuals initially diagnosed with PCeD. This study enrolled 20 patients with PCeD who progressed to CeD, 5 patients who continued with PCeD, and 16 control individuals.

Key findings:

  • Micro-CT imaging revealed a significantly reduced VH:CrD at both the PCeD and CeD stages compared with the controls, but the difference between PCeD and CeD did not reach significance
  • Only 7/20 with PCeD had normal biopsy VH:CrD values >2.0 across all sites
A) VH:CrD (left) and relative mucosal surface area (right) across PCeD (orange), CeD (blue), and nonCeD control (non-CeD) groups. Box and whisker plot: The boxes indicate the 25th percentile (bottom border), median (center line), and 75th percentile (top border), the whiskers show the maximum and minimum ranges, and the circles indicate outliers

Discussion:

“Most of the PCeD cases were already below the commonly used VH:CrD cutoff when assessed using micro-CT cross-sections, implying that histologic thresholds may lack sufficient sensitivity to capture signs of early CeD.”

My take (borrowed in part from the authors): This study strengthens the “concept that enteropathy in CeD represents a progressive continuum.5 In fact, pinpointing the exact moment when the condition becomes “CeD” is difficult, especially because what is considered normal can vary individually and depending on the biopsy site.” This study may help explain why many symptomatic patients with PCeD respond to a gluten-free diet.

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Adherence to a Gluten Free Diet in Pediatric Celiac Disease

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L Kallio et al. JPGN Reports. 2026; Epub 9/14/26. Open Access! Factors associated with adherence to gluten-free diet in patients with concomitant celiac disease and type 1 diabetes

Methods: In this study from Finland, the authors compared the baseline characteristics and follow-up data between adherent and nonadherent CeD children with a dual diagnosis (n = 69). 

Key findings:

  • Overall, 72% were found to be adherent to a gluten-free diet (based on self-report)
  • Adherent patients were detected significantly more often in annual CeD screening than by symptoms

Discussion:

“In Finland, GFD products are easily available, and children receive financial support to cover the additional costs.”

Though, not addressed by the authors, it is widely acknowledged that self-report of GFD adherence tends to overestimate true adherence compared with expert interviews, celiac serology and stool or urine for GIP (gluten immunogenic peptide). The reasons for this include the following:

  • Unintentional gluten ingestion. This can be due to food cross-contaminated during manufacturing, prepared with shared kitchen utensils, or laced with hidden gluten additives.
  • Knowledge gaps. A patient might regularly consume a specific product or sauce thinking it is perfectly safe, resulting in high self-reported compliance but low actual compliance
  • Social desirability and recall bias. The tendency to want to present oneself in a positive light or give the “correct” answer. Additionally, recall bias means people tend to forget minor dietary slips or intentional transgressions that occurred weeks prior.
  • Lack of symptoms. Many patients assume that if they do not experience immediate gastrointestinal pain, they have successfully avoided gluten.

My take: In this cohort, diagnosis through screening rather than due to symptoms was associated with higher adherence rates, contrary to expectations. Overall, regardless of how a diagnosis was established, there are a large number of individuals with celiac disease with ongoing gluten exposure. This occurs even in individuals who are making a lot of effort to follow this diet.

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Discordinate Recommendations for Celiac Screening with Down Syndrome

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VN Dargenio et al. J Pediatr Gastroenterol Nutr. 2026;83:304–313. A systematic review of celiac disease recommendations for children with Down syndrome

Background: “CD [celiac disease] prevalence in DS is higher than in the general population.10 The overlapping symptoms between CD and DS, such as growth failure, fatigue, GI disturbances, and, less frequently, neurological and behavioral problems, pose significant diagnostic challenges, as these are often attributed to underlying DS comorbidities, leading to delays in recognizing CD.4, 11 

Guidelines:

The authors note wide variation in the prevalence of CD in DS in various studies. “A meta-analysis of 31 studies including 4383 individuals found a pooled prevalence of biopsy-confirmed CD of 5.8% (95% CI 4.7%–7.2%), with slightly higher rates in children (6.6%) compared to mixed-age samples (5.1%)31…these findings align with the 5%–13% prevalence range documented in earlier European studies2“

The authors recommend the following strategy:

“Given the high prevalence of asymptomatic and atypical presentations, reliance on symptoms alone is insufficient. A pragmatic strategy should initiate with universal serological screening for all children with DS after gluten introduction (12–24 months of age), followed by periodic re-screening every 2–3 years, using tTG-IgA with total IgA assessment, supplemented by IgG-based assays in the context of the high rate of selective IgA deficiency in DS.”

My take: There are wide discrepancies in the recommendations for screening for celiac disease in asymptomatic individuals with Down syndrome.

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Should the Gluten Threshold Dose in Celiac Disease Change Based on Immune Activation?

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Background: Interleukin 2 (IL2) rises acutely after gluten ingestion, allowing the definition of threshold doses that trigger immune activation.

Methods: This was a randomized double-blind, placebo-controlled adaptive dose–response trial in adults with biopsy-proven celiac disease on a gluten-free diet for >2 years. Participants (n = 51; median age, 52 years; 69% were female) underwent 3 oral gluten (1–1000 mg) or placebo challenges at 4-week intervals. Eliciting dose (EDp, ie, the dose at which p% of people respond) was estimated by interval-censored survival analysis.

Key findings:

  • Gluten induced dose-dependent IL2 elevations, with ≥2-fold increases in 83% at 1000 mg, 83% at 610 mg, 36% at 90 mg, 17% at 13 mg, 27% at 8 mg, and 17% at 3 mg; none responded to 5 mg, 2 mg, 1 mg, or placebo.  
  • Estimated ED50 was 111 mg, ED10 was 2.4 mg, ED05 was 0.8 mg, and ED01 was 0.1 mg

From the editorial:

“To date, the few investigators who addressed this question defined tolerance in relation to quantifiable histologic damage (intestinal morphometry)…Bearing in mind that the typical Western diet contains 10–15 g of gluten per day, these studies found that the protracted, daily ingestion of 1000, 200, or 50 mg of gluten elicits significant damage at the mucosal level.2,3 A daily dose of 10 mg was also associated with minimal architectural changes in some patients…

In 2007, the Food and Agricultural Organization/World Health Organization Codex Alimentarius Commission4 applied these findings to establish that commercially available gluten-free food must not contain more than 20 mg/kg gluten (20 part per million [ppm]), as this would ensure that daily gluten intake does not exceed 10 mg…Not a single case of proven intolerance to 20 ppm gluten-free food has been described…in some 20-ppm countries, most labeled gluten-free products already contain much less than 20 ppm of gluten, usually <10 ppm5…

The authors concluded that the daily gluten threshold should be decreased because acute IL2 release occurred at 3 mg, which is less than is allowed by current food-labeling rules for gluten-free products…

Because symptoms did not correlate with the result of the IL2 test for gluten doses <1 g, further prolonged microchallenge studies remain the only reliable strategy to investigate the correlation between the IL2 test and the gold standard of CeD activity—histologic damage of the small intestinal mucosa.10,11“

My take: This study is intriguing that there is evidence of immune activation at lower gluten exposures; however, it does not prove that changing the gluten threshold is beneficial.

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Camp Weekaneatit 2026

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Last Sunday, along with my colleagues, Jeff Lewis, and Nirav Patel, I helped check in kids for Camp Weekaneeatit! (glutenfreecamp.org). This is a gluten-free camp for youth with ​Celiac Disease and ​Gluten Intolerance. This year’s staff shirt was “S’more Fun Without Gluten;” though, I elected to wear my T-shirt from 2018.

The camp was started more than 15 years ago by my partners, Dr. Jeff Lewis and Dr. Bill Meyers.

The camp is located just north of Atlanta at Ft Yargo (Winder, Georgia). The ~125 participants come from all over the U.S including Texas, Michigan, Ohio, Massachusetts, Colorado, Arizona, Florida, South Carolina, and Alabama. There was one kid, whose father is a marine, who flew in from Japan!

Most of the campers have come several times and have had a great experience. Here is an excerpt from a letter from a camper’s parent:

“My daughter was at camp with you this summer.  I can’t tell you how much fun she had.  She was diagnosed with celiac when she was just 2, so she has never known a world where she could just relax and be like everybody else.  Camp gave her so much freedom, and she grew so much in just one week.  Today is her birthday and her first day of school.  Her camp friends have already texted to wish her happy birthday!…This is the first time she has had friends with celiac disease — I can only imagine how much more supported that makes her feel…  I asked her what it was like to not have to ask a million questions before every bite she ate.  She said, “I felt like I didn’t even have celiac disease all week. I felt like a normal person.” 

Last year enrollment started in the middle of November for summer 2026. Space is limited!

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Low Risk of Solid Organ Transplantation with Celiac Disease

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JB Doyle et al. Clin Gastroenterol Hepatol 2026; Risk of solid organ transplantation in individuals with celiac disease: a nationwide cohort study

Background: “Celiac Disease (CeD) is associated with immune-mediated diseases of the liver, including autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis. Individuals with CeD are also at increased risk for non-autoimmune diseases of the liver, including metabolic dysfunction-associated fatty liver disease…CeD has also been associated with chronic kidney disease and cardiovascular disease. Multiple studies have demonstrated that individuals with CeD have increased rates of end-stage renal disease than the general population, with particularly strong associations between CeD and
autoimmune nephropathy, diabetic nephropathy, and systemic lupus erythematosus (19-22).
Population-level data also suggests that individuals with CeD have an increased risk of
cardiovascular disease and ischemic heart disease>”

Methods: Population-based matched cohort study in Sweden. We identified individuals with biopsy-proven CeD diagnosed between 2000-2023 using the nationwide histopathology cohort ESPRESSO. We calculated the incidence of solid organ transplantation (liver, heart, kidney, and lung) in CeD patients and estimated the risk relative to the general population. There were  41,277 individuals with CeD and 196,863 age- and sex-matched comparators with a mean follow-up of 12.1 years.

Key findings:

  • There were 85 solid organ transplantations in patients with CeD (17.0 per 100,000 person-years) and 111 in matched comparators (4.6 per 100,000 person-years). This corresponded to an adjusted hazard ratio (HR) of 2.76 
  • The highest relative risk was for liver transplantation: HR 7.26; for kidney HR 1.85. For heart, HR was 2.35 did not reach statistical significance (CI: CI 0.84-6.61)

Discussion:

“Shared genetic susceptibility may explain physiological links between CeD and autoimmune liver disease, especially since we also detected an increase in liver transplantation prior to CeD diagnosis…owever, CeD patients in our analysis had an increased risk of liver transplantation relative to their nonaffected siblings, suggesting that CeD itself may be a risk factor beyond genetic predisposition”

My take: While nearly triple the incidence compared to the general population, the absolute increased risk of needing a solid organ transplant was about 1 in 10,000. For comparison, the risk of dying in a bicycle accident in one’s lifetime is about 1 in 5,000. Nevertheless, it may be worthwhile to screen for CeD in those with end-organ disease. Additionally, checking liver tests periodically in patients with CeD would be reasonable.

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Should We Adopt Mass Screening for Celiac Disease?

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MG Stahl et al. Gastroenterol 2026; 170: 240-245. Open Access! Mass Screening of Celiac Disease: A Crossing Point Between Secondary and Primary Prevention?

The authors make several good arguments for mass screening for celiac disease.

Key Points:

  • “The worldwide prevalence is high, affecting an estimated 1% to 3% of the general population…One study showed that two-thirds of children remain undiagnosed.” (Dig Liver Dis. 2023; 55:608-613). Thus, screening would identify many cases that would otherwise go undiagnosed and untreated
  • ” As one of the most HLA-restricted diseases, nearly all patients carry HLA-DQ2.5, DQ2.2, or DQ8 (and very rarely DQ7.5), and their absence makes CeD extremely unlikely. Although 30% to 40% of the general population carry these alleles, only approximately 3% will go on to develop CeD”
  • “The Environmental Determinants of Diabetes in the Young (TEDDY) study showed that although there was some early anxiety reported, there was no long-term psychological harm in disclosing genetic risk to parents of children that were tested and most parents adapted over time”
  • “Children identified as highest risk at birth through HLA-DQ typing also represent an ideal cohort to test interventions such as dietary modifications or microbiome targeted therapies during the predisease phase, during the key “window of opportunity,” ideally before seroconversion (primary prevention).” There are no currently proven primary prevention interventions.
  • Some of the drawbacks to screening: 1. “Evidence on health benefits of treating asymptomatic CeD is limited.” 2. “The potential psychosocial effects of both newborn genetic testing and a strict gluten-free diet in individuals diagnosed through screening need to be considered.” 3. “HLA-DQ typing may be cost prohibitive in some regions of the world.” 4. “Most children identified to be at risk for CeD based on HLA-DQ will not develop CeD.”

My take: I am skeptical about the benefits of screening at birth and how it would work in our current health care system. We have plenty of examples in our field in which early screening is not followed up well (eg. Hepatitis C, Biliary Atresia). If more evidence emerges on the benefits of primary prevention, then more widespread screening at birth may be worthwhile. For example, there is “a clinical trial underway in Sweden, the GRAin study (NCT04593888) that aims to investigate whether eating a gluten reduced diet (<2 g of gluten per day) may reduce the risk of CeD in children with genetic risk.”

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Outcomes in Children with Celiac Disease Presenting with Constipation

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A Almallouhi et al. J Pediatr Gastroenterol Nutr. 2025 DOI: 10.1002/jpn3.70316. Clinical outcome of constipation as the presenting symptom in children with celiac disease

Background: “It is not clear if CeD prevalence is higher in children with refractory and chronic constipation or not.11–15 The current guidelines from the American Gastroenterological Association (AGA) and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) do not consider constipation an indication for CeD testing in the absence of suggestive family history, growth, or developmental delay.”

Methods: This was a retrospective study (1994-2024) of children (<18 years) who presented with constipation and then diagnosed with celiac disease (CeD). There were 248 children with CeD, 177 (71%) had biopsy-confirmed CeD, and 56 (23%) were diagnosed with serology-only criteria

Key findings:

My take:

  1. It is unclear if having constipation increases the risk of celiac disease
  2. Many children with celiac disease also have functional disorders like irritable bowel and constipation that often continue despite a gluten-free diet

Related blog posts:

Also, Dr. Balistreri gives a Bowel Sounds Podcast on Hep B. Here’s the link: https://t.co/BmEUoC9YQt

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Likelihood of Celiac Disease with Conflicting Serology Results

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R Mandile et al. J Pediatr Gastroenterol Nutr. 2025;81:1482–1487. Advantages of anti-endomysial evaluation in children with low titers of anti-transglutaminase antibodies: A retrospective study

This was a single center retrospective study examining children (n=202) undergoing EGD (2022-2024) to evaluate for celiac. Among those with low anti-TTG IgA titers, Group 1 (n=25) was EMA negative and Group 2 (n=100) was EMA positive.

Key findings:

  • The finding of discordant serology (anti-transglutaminase [anti-TG] positive and EMA negative) is infrequent (12% cases, 25 out of 202), and all patients with discordant serology had anti-TG positive at low titer (<4 times the upper limit of normality).
  • Group 1 (N = 25) had a mean anti-TG titer of 1.86× ULN and villous atrophy (VA) in only 8% (2/25). Group 2 (N = 100) had VA in 35% (35/100)
Percentage of patients with villous atrophy between EMA positive and EMA negative children.

Discussion Points:

  • The diagnosis of CD still requires performing an EGD in at least half of the cases
  • This “study suggests that patients with low levels of anti-TG but EMA positive antibodies should anyway receive an EGDS in the next 6 months, since in around one-third of the cases a duodenal atrophy will be detected”
  • In those with low anti-TG but EMA negative, ” it could be reasonable to initially follow-up patients over time with clinical and serological monitoring (in particular of anti-TG titer), postponing the EGDS to a later stage, when the disease is more advanced and the chance of finding a concomitant VA (and thus the need to start a GFD) is higher”

My take: In patients with minimal symptoms and low level anti-TG, my strategy has been to follow with serological monitoring and if repeatedly abnormal, proceed with endoscopy. This study suggests that obtaining EMA early may influence choice to proceed earlier with endoscopy.

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