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.

Related blog posts:

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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Icotrokinra for Patients with Ulcerative Colitis (ANTHEM-UC Phase 2 Trial)

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MT Abreu et al. N Engl J Med 2026;395:1495-1504. Phase 2 Trial of Icotrokinra for Patients with Ulcerative Colitis

Background: “Icotrokinra (JNJ-77242113) is a first-in-class targeted oral peptide that precisely blocks the interleukin-23 receptor. The development of oral peptide therapeutics has historically been limited by poor epithelial membrane permeability, susceptibility to enzymatic degradation in the gastrointestinal tract, and low intestinal absorption.7 The cyclic peptide technology used in icotrokinra enables high stability and epithelial permeability.7 These features, in combination with high selectivity and potent binding of the interleukin-23 receptor, result in an orally administered peptide that effectively inhibits the interleukin-23 pathway.8,9“

Methods: This was a “phase 2b, double-blind, randomized trial of oral icotrokinra, a peptide that blocks the interleukin-23 receptor, in adults with moderately to severely active ulcerative colitis. Participants were assigned to receive icotrokinra at a once-daily dose of 400 mg, 200 mg, or 100 mg or placebo. The primary end point was clinical response at week 12.” A total of 252 participants underwent randomization.

Key findings:

  • All the doses of icotrokinra were superior to placebo with respect to a clinical response at week 12, which occurred in 63% of the participants in the 400-mg group, 58% in the 200-mg group, and 55% in the 100-mg group, as compared with 27% in the placebo group (P<0.001)
  • The percentage of participants with clinical remission at week 12 was also significantly higher in the 400-mg group than in the placebo group (30% vs. 11%, P=0.006), as were…the percentage of participants with endoscopic improvement (37% vs. 14%, P=0.002)
Clinical response was defined as a decrease from baseline in the modified Mayo score by at least 30% and at least 2 points, with either a decrease of at least 1 point from baseline in the rectal bleeding
subscore or a rectal bleeding subscore of 0 or 1
Clinical remission was defined by a stool frequency subscore of 0 or 1,
a rectal bleeding subscore of 0, and an endoscopic subscore of 0 or 1.
Symptomatic remission was defined by a stool frequency subscore of 0 or 1
and a rectal bleeding subscore of 0
Endoscopic improvement was defined by an endoscopic subscore of 0 or 1.

Discussion:

  • “The benefits of treatment with once-daily icotrokinra appeared to be generally sustained or improved through week 28 for all outcomes and doses tested.”
  • “Although all the tested doses of icotrokinra appeared to attenuate systemic inflammation, the 400-mg and 200-mg doses appeared to result in greater reduction of the inflammatory burden than the 100-mg dose.”
  • “The incidence of adverse events with icotrokinra was similar to that with placebo, and no dose–response relationship for adverse events was observed. Among the 212 participants treated with icotrokinra in this trial, no deaths, serious infections, or adverse events of special interest were reported through 28 weeks of treatment.”

My take: This is an important study indicating that an oral IL-23 can be effective for ulcerative colitis which is not surprising based on its previous effectiveness with plaque psoriasis, another immune-mediated disease. It would be helpful to determine the efficacy of this oral agent compared to the IV/SC IL-23 biologic medications (eg. risankizumab, guselkumab, and mirikizumab).

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Enteral Rifaximin May Reduce Central Line Infections in Children with Short Bowel Syndrome

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Johnson E, Konicek C, Lamb N, Fishbein J, Jhaveri R, Cohran V. J Pediatr Gastroenterol Nutr. 2026; 83: 675-680. Effectiveness of rifaximin in reducing central line-associated bloodstream infections in pediatric intestinal failure

Methods: This was a retrospective cohort study of patients (n=33) with IF managed at a single pediatric center between January 2010 and December 2022. Patients in the cohort had at least 1 CLABSI prior to initiation of rifaximin. Rifaximin was prescribed one to two times a day for 2 weeks a month, every month; median dose was 22 mg/kg/day. Rifaximin was not administered concurrently with other antimicrobials.

Key findings:

  • The observed incidence of CLABSI for all patient, before and after rifaximin initiation, was 10.2 (8.2, 12.7) and 7.3 (5.8, 9.2) per 1000 central line days, respectively, p = 0.03. 
  • Subgroup analysis showed patients who received rifaximin without ethanol lock therapy had significant reduction in CLABSIs, 8.3 versus 3.0 (p < 0.001).
  • There were no statistically significant differences in the proportion of gram-positive or gram-negative bacteria or yeast isolated before and after rifaximin.

Discussion:

  • “Cole et al. showed a correlation between SIBO, intestinal permeability, bacterial translocation,and an increase in bloodstream infections. Patients with IF and SIBO had seven-fold higher odds of having a bloodstream infection than those with IF without SIBO.” However, this was a very small study with only 10 patients with SBS; 5 of the 10 were determined to have SIBO. In addition, there may have been a selection bias as there was a high rate of CLABSI in this study (80%). Ref: Cole CR, et al. The rate of bloodstream infection is high in infants with short bowel syndrome: relationship with small bowel bacterial overgrowth, enteral feeding, and inflammatory and immune responses. J Pediatr. 2010;156(6):941‐947.e1.
  • An important limitation of this retrospective study was the lack of correlation with the presence of SIBO. While studies have shown correlation of CLABSI with SIBO, presumably related to intestinal translocation, the exact mechanisms for how CLABSI occur in children with intestinal failure remain speculative. Intestinal translocation has been shown in animals but not proven to cause CLABSI in humans.

My take: The degree of CLABSI reduction seen in this rifaximin study indicates it is a reasonable option when central locks are unavailable. However, it may be difficult to get covered. In addition, a liquid preparation requires compounding of crushed pills. For most patients, meticulous line care is likely more important than SIBO treatment in preventing CLABSI.

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Faxafoss in Iceland

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.

Real-World Outcomes of Risankizumab in Children With Crohn’s Disease

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Briefly noted:

EA Spencer et al. Journal of Crohn’s and Colitis. 2026; 20: jjag134. https://doi.org/10.1093/ecco-jcc/jjag134 Real-world effectiveness and safety of risankizumab induction and maintenance therapy in pediatric patients with Crohn’s disease: a multicenter retrospective analysis.

Methods: This was a retrospective, global multicenter cohort of patients <18 years initiating risankizumab monotherapy (2022-2025). Among the 96 study participants, 38% had prior ustekinumab exposure.

Key findings:

  • Post-induction corticosteroid-free clinical remission (CFR) was achieved in 28/68 (41%), clinical response in 37/68 (54%), and combined CFR + CRP remission in 22/68 (32%).
  • Week 30 and 54 CFR were attained in 34/68 (50%) and 34/68 (50%), respectively.
  • No serious safety events occurred.

My take: This study bolsters previous studies showing that risankizumab is an effective treatment for Crohn’s disease in the pediatric age group.

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AFFIRM Study: Subcutaneous Induction-Maintenance Data for Risankizumab

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Charlie Lees is a Professor of Gastroenterology, University of Edinburgh.

From Charlie Lees on X (10/14/26):

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“Many Surgical Interventions Are Little Better Than Placebo”

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The Economist, 9/23/26. Many surgical interventions are little better than placebo (behind paywall). Thanks to my sons for sharing this article with me.

An excerpt:

“EACH YEAR, according to the World Health Organisation, over 300m operations are conducted worldwide. Patients in the rich world are more likely to go under the knife—about 60% of people in England are expected to undergo surgery at least once in their lifetime. Some of these procedures are clearly life-saving, such as organ transplants and emergency Caesareans…

Answers have long been hard to come by, in part because few randomised controlled trials (RCTs), the gold-standard type of research used to assess medications, were conducted on surgical procedures. That made it difficult to know if patients got better more often with surgery than they might have without. This is now changing. The number of surgical RCTs funded by Britain’s National Institute for Health and Care Research increased from 34 in 2011 to 188 in 2023…

Most striking, the data show that some widely used surgical procedures, such as spinal fusions and rotator-cuff repairs, have effects indistinguishable from placebo or non-surgical care such as physiotherapy…

Worse, some types of surgery may do more harm than good. A trial in Britain found that prostate-cancer surgery had no effect on patient mortality 15 years on, but worsened sexual and urological problems. A Finnish trial of a common knee procedure, meanwhile, concluded that patients who had real surgery had more problems in the affected knee ten years on than those who had had sham surgery (anaesthesia followed by a superficial incision)…

If so many operations are unnecessary, how to explain the fact that patients often leave the operating table feeling better? In a study published in 2022 in JAMA, a journal, researchers pooled data from 100 surgical trials covering 32 interventions. They found that two-thirds of the improvement patients felt after surgery was due, on average, either to the body healing on its own or else to the placebo effects of feeling cared for and prepped for surgery. Only one-third of the benefit, in other words, came from the procedure itself…

Natural healing is also powerful, if slow-acting. In the 2022 study in JAMA…the placebo effect could explain only a small part of the improvement in the sham-surgery group. Most of the benefit came instead from natural improvement…

Surgeons continue to perform some operations that have been shown to be no better than placebo surgery at the same rate as before. They find it hard to believe that something which they have been doing for years and seems to help their patients is, in fact, useless…

Surgeons who have been doing a procedure for years also tend to overestimate its benefits, says Stefan Lohmander from Lund University, in Sweden, because the patients who return for check-ups are mostly those who got better. Moreover, many of these returning patients do not want to disappoint their doctors…

The nature of a country’s health system also plays a role. Disfavoured operations decline faster in countries where surgeons are salaried, as in Britain and Scandinavia, than in countries such as America where they are paid per operation and act as small businesses. Shoulder surgeries to remove a bone spur fell from 28,000 in Britain in 2016-17 to 5,720 in 2019-20, after trials found that the procedure was no better in alleviating pain than sham surgery. In America the procedure remained popular…

But it is not just surgeons who need to trust the data: a growing number of patients insist on surgery on the basis of inconclusive tests. ..A growing number of studies, in fact, show that the abnormalities in knees, backs and shoulders that orthopaedic surgeons try to fix are very common in people who have no symptoms at all. But the promise of a quick fix is hard to resist.“

My take: This article reminds me of two expressions:

  • “Don’t just do something stand there”
  • “If you follow my advice, you will get better in 3 months. If not, it will take 90 days.”

The first expression I heard during my fellowship from Dr. Balistreri. With medications, diagnostic procedures, and surgery, many times natural healing is as effective as interventions and less costly.

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Wekiva Springs State Park. Apopka, FL. I did go swimming here despite the warning.

Rule of Two’s No Longer Valid For Diagnosis of Meckel’s Diverticulum

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Polachek A, Mehta MS, Shalaby A, Vadsariya A, Zong W, Troendle DM.J Pediatr Gastroenterol Nutr. 2026; 83: 658-664. Reevaluating the rule of two’s: age and epidemiological variations in Meckel’s diverticulum.

Background: “Meckel’s diverticulum (MD) is traditionally considered a disease of early childhood and is commonly summarized by the “Rule of Twos”; presenting before the age of 2 years, found 2 ft. from the ileocecal valve, approximately 2 in. in length, and present in roughly 2% of the population.” (I was taught an additional rule that it takes 2 physcians to diagnose)

Methods: A total of 1004 patients with a primary diagnosis of MD were identified from the Kids’ Inpatient Database (KID) for 2016 and 2019 in this retrospective review. In addition, 147 patients identified in the single-center cohort.

Key findings:

  • More than half were diagnosed after 5 years of age (n = 648, 64.8%) in the KID group and 63% in the single-center cohort
  • In the single-center cohort, patients ≤5 years more commonly presented with painless rectal bleeding (38.9%, p = 0.017) and underwent Meckel’s scintigraphy more frequently (48.1%, p < 0.005). In contrast, patients >5 years more often presented with abdominal pain (61.3%) or vomiting (54.8%) and were more likely to undergo abdominal computed tomography (68.9%, p < 0.0001).

My take: This study shows the “Rule of Two’s” for the diagnosis of Meckel’s is not helpful; nearly two-thirds of patients present after 5 years of age. The authors note that “overreliance on age-based assumptions and presenting symptoms associated with this paradigm may lead to missed or delayed diagnoses, especially in patients who present with atypical features.”

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Glymur Waterfall. This is the second tallest waterfall in Iceland
with a 198-meter (650-foot) drop into a narrow basalt canyon.

Diet Based on Confocal Laser Endomicroscopy Did Not Improve Irritable Bowel Syndrome Symptoms: A Randomized Controlled Crossover Trial

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L Balsiger et al. Gastroenterology, 2026. Individualized Targeted Exclusion Diet Based on Confocal Laser Endomicroscopy Does Not Improve Irritable Bowel Syndrome Symptoms: A Randomized Controlled Crossover Trial

While foods often trigger IBS symptoms, there has not been a simple way to identify these foods with objective testing. Previous small studies have indicated that confocal laser endomicroscopy has the potential to identify these triggers (See prior post: Is There a Way to Prove Which Dietary Factors Trigger Irritable Bowel Syndrome?).

“The advent of confocal laser endomicroscopy (CLE) has enabled in vivo real-time visualization of the gastrointestinal mucosa.9 Using this approach, researchers have demonstrated acute food-induced mucosal alterations in the duodenum of patients with IBS.10,11 …The reliable identification of foods responsible for symptoms in individual patients with IBS is of great interest. Not only would it streamline the current trial-and-error approach, but it could also potentially avoid overly restrictive dietary patterns, which potentially can lead to avoidant restrictive food intake disorder.”

Methods: “This was a double-blind, controlled, crossover study in patients with IBS. After CLE, patients excluded up to 2 foods that did (= real diet) and up to 2 foods that did not (= sham diet) cause alterations in a randomized order. Diets were followed for 4 weeks each. Clinical response was defined as improving ≥50 points on the IBS Symptom Severity Score. Healthy controls underwent the same CLE protocol as patients with IBS.” 31 patients (median age 33 years) completed both phases of dietary interventions.

Key findings:

  • Clinical response rates were not different between real and sham diet (42% vs 36%; odds ratio, 1.33; P = .6). Symptoms improved both on the real and the sham diet (−30 vs −20; P = .7). 
  • In 15 healthy volunteers, altered mucosa was visualized in 100% of the examinations either at baseline (13%) or after food administration.

My take: CLE-based tailored diet was not beneficial compared to a sham diet. In addition, CLE changes were present in all of the healthy volunteers indicating that altered mucosa is a nonspecific reaction rather than pathognomonic IBS reaction. Thus, there remains no proven way to identify trigger foods in IBS. Exclusion diets can improve symptoms but require careful monitoring.

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