Dupilumab Rarely Associated with Pediatric Neuroinflammatory and Neuropsychiatric Symptoms

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Yesterday’s post (Incredible Video of Lung Cell Cilia) now has an important addendum: a reader’s comment notes that the winning entry is “being re-evaluated following criticism from other scientists that it was made with AI.” Here is an article from the BBC on this investigation: Tiny image sparks big backlash in Nikon photo contest (https://www.bbc.com/news/articles/ck4gjn1yzprno)

L Mathiesen et al. J Pediatr 2026;297:115201. Pediatric Neuroinflammatory and Neuropsychiatric Syndromes Associated with Dupilumab Treatment for Atopic Dermatitis

This case series of children between the ages of 6 and 16 describes the development of serious neurologic sequelae associated with the use of dupilumab for atopic dermatitis. 3 of 4 children had pre-existing genetic or neurodevelopmental conditions, including ADHD, autism spectrum disorder, an ABCD1 mutation, and homozygous FECH mutations.

Case 1: An 11 year old, with a history of ADHD, “developed poor attention, increased hyperactivity, worsening school performance, and aggression after two months of treatment. Over the subsequent 8 months, symptoms gradually worsened and evolved to include irritability, oppositional behavior, vocal and motor tics, language regression, and ultimately suicidal ideation.” After resolution of his atopic dermatitis, he had ~80% improvement off dupilumab. “However, in the setting of atopic dermatitis exacerbation, dupilumab was restarted and was associated with a rapid decline in mental state within 4 weeks leading to dupilumab discontinuation. He continued to decline, developing severe akathisia, tics, language regression, and transient episodes of confusion. Repeat brain MRI showed bilateral symmetric frontotemporal T2 hyperintensity with hyperperfusion without gadolinium enhancement.” Extensive neuropsychiatric evaluation (genetics, autoimmune, CSF analysis) was otherwise unremarkable.

Three of the patients received intravenous methylprednisolone which was associated with improvement. However, the patient in Case#1 has not returned to baseline.

Imaging from Case 4:

Contrast-enhancing brain lesions were identified in case 4. (A) Axial T2/FLAIR sequences demonstrating multiple areas of signal prolongation at the gray-white junction in the frontal and parietal lobes. (B) Axial T1-post contrast imaging demonstrating heterogeneous contrast enhancement patterns in some lesions.

In their discussion, the authors discuss this “previously unreported association between dupilumab and neuroinflammatory syndromes in 4 pediatric patients with atopic dermatitis.” They discuss potential pathophysiology as well statig that dupilumab “may promote classical proinflammatory immune signaling…Although dupilumab is not expected to cross the intact blood-brain barrier, its potential neurological effects could be mediated through peripheral immune modulation. Systemic IL-4/IL-13 blockade could modulate immune cell trafficking to the central nervous system.”

My take: While neurologic adverse effects associated with dupilumab appear to be rare, there should be a low threshold for discontinuation when new neurological symptoms emerge. Only the first case had a rechallenge with dupilumab. This helped establish likely causality; however, this patient did not fully recover when dupilumab was stopped.

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Incredible Video of Lung Cell Cilia

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Stella Raine Chu, NY Times 9/17/26: Microscopic Videos That Show the Invisible Wonders Around Us

“The winners of this year’s Nikon Small World in Motion competition showcase the wiggly, feathery, undulating beauty of invisible life.” In total, there are seven short videos featured.

1st place: Abnormal beating of airway cilia from a child with a disease called primary ciliary dyskinesia. Cilia are about 1/100th the width of a human hair.

Addendum: **A reader’s comment notes that the winning entry is ” being re-evaluated following criticism from other scientists that it was made with AI.” Here is an article from the BBC on this: Link: Tiny image sparks big backlash in Nikon photo contest

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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Promising Pilot Study Using Substance P to Screen for Pediatric Aspiration

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DR Duncan et al. J Pediatr 2026; 297: 115212. Association Between Salivary Substance P and Aspiration on Videofluoroscopic Swallow Study in Infants and Toddlers

Background: Substance P (SP) is a neuropeptide signaling molecule that is secreted peripherally as a result of the activation of afferent neurons expressing TRPA1 and is involved in the pathogenesis of swallow dysfunction by (1) decreasing the activation
threshold of transient receptor potential channels, (2) enhancing the sensitivity of neurons in the pharynx, and (3) increasing cough reflex to improve airway protection. Pilot studies in adult populations have shown reduced SP levels in patients with neurologic causes of aspiration, including patients who are elderly and patients with stroke and Parkinson disease.

Methods: The authors recruited children younger than 2 years of age (n=50, mean age 8 months) who underwent VFSS within 3 months of study enrollment. Saliva samples were collected using absorbent saliva collection devices (salimetrics.com) and Substance P (SP) levels were measured by enzyme-linked immunosorbent immunoassays. Patients with laryngeal penetration but not aspiration were excluded.

Key findings:

  • SP concentrations were 344.7 ± 42.9 pg/mL for patients with aspiration compared with 105.7 ± 40.5 pg/mL for those without aspiration (P < .001). 
  • A cutoff of 65 pg/mL provided 97% sensitivity and 75% specificity for predicting aspiration on VFSS.
  • In a subgroup analysis with 29 subjects who had VFSS within 1 month of sample collection, a cutoff of 63.2 pg/mL provided 100% sensitivity and 83.3% specificity for predicting aspiration on VFSS. For this subgroup, the SP concentration was 250.9 ± 33 pg/mL for those with aspiration on VFSS compared with 57.1 ± 11.8 pg/mL for those without aspiration on VFSS (P < .001)
A, Boxplot comparing salivary SP concentration between children
with and without aspiration on VFSS in the full cohort.
B, Boxplot comparing SP concentrations in the subgroup of subjects
with saliva sample collection within 1 month of VFSS.

Discussion Points:

  • “SP levels were not affected by comorbidities or acid suppression medications” in this cohort.
  • “These data suggest that this test could be used to at least screen for who might need a VFSS or who might need thickening while the cause of aspiration is being evaluated.”
  • “Testing of salivary SP is experimental and only limited to research studies and therefore not widely available at the present time.”

Disclosures: “The funders had no role in the design and conduct of the study. D.D. and R.R. are named inventors on U.S. Provisional Patent Application Serial No. 63/804876, DEVICES AND METHODS FOR DETECTING AND TREATING ASPIRATION IN CHILDREN.”

My take: While this is a pilot study, if the findings are confirmed, this would be a huge advance. It would help triage infants and young children who need VFSS evaluation. A normal value could help many infants avoid a VFSS evaluation. In those with ongoing abnormal values, it could allow fewer followup VFSS evaluations.

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Impact of Night Shifts on Gut Disorders

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C Pennaneach et al. Clin Gastroenterol Hepatol 2026; 24: 2584-2594. High Prevalence of Disorders of Irritable Bowel Syndrome and Functional Dyspepsia in Night Shift Workers: A Cross-Sectional Study in Australia and the United Kingdom

Background: “Approximately 15% to 25% of the global workforce operates outside conventional daytime hours.1–3 These schedules typically occur between 6:00 pm and 6:00 am4 and typically take 2 forms: fixed night shifts (consistent night-time work) or rotating (alternating between day, afternoon and night). This distinction is physiologically significant; although fixed night workers may partially adapt to their schedule over time, rotating shift workers face continuous circadian disruption due to frequently changing schedules, preventing biological adaptation.5 This circadian misalignment creates a particularly vulnerable subset of workers and is associated with increased risk of chronic conditions, including cardiovascular disease,6 type 2 diabetes,7 and gastrointestinal (GI) disturbances.8 These adverse outcomes primarily stem from disruption of central and peripheral biological clocks.9“

Methods: This was a cross-sectional study of night shift workers (≥8 shifts/mo between 11 pm and 3 am) in Australia and the United Kingdom from March to July 2024. Participants (n=392) completed validated questionnaires including Rome IV criteria for IBS and FD. Fixed night shift workers constituted 54.1% of the sample, whereas 45.9% worked rotating shifts.

Key findings:

  • 21.3% met Rome IV criteria for IBS, 30.4% for FD, and 24.5% for both conditions.  The rates of IBS and FD in this cohort was substantially more than “general estimates of 4.1%” general population estimates (4.1% for IBS and 7.2% for FD),10“
  • Most participants (59.9%) reported night shifts negatively affected their GI symptoms, and 16.3% considered changing jobs due to symptoms.

The authors discuss the many ways that circadian disruption can adversely affect the GI tract. In addition, night shift workers are more likely to adopt irregular dietary habits which could be a contributing factor as well.

My take: This study shows that night shift work is associated with high rates of disorders of gut-brain interaction (DGBI) likely due to disturbance in circadian rhythms. It is in agreement with other studies showing that disturbed sleep worsens IBS symptoms (A Patel et al. Aliment Pharmacol Ther. 2016; 44(3):246–258).

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Fjadrargljufur. Iceland.  I would fail spelling in Iceland!  There is a powered hang glider in the distance.
This was a good hike with serpentine canyon walls and a long waterfall at the end

PODIUM Study: Jak Inhibitors and Ustekinumab Outperformed Vedolizumab as a 2nd Line Agent for Ulcerative Colitis

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G Privitera et al. Clin Gastroenterol Hepatl 2026; 24: 2539-2550. Open Access! Ustekinumab and Janus Kinase Inhibitors Outperform Vedolizumab as Second-Line Therapy in Anti-Tumor Necrosis Factor-Experienced Patients With Ulcerative Colitis

Before reading this article, I had to research why it was called “The Podium Study.” The research directly stacks three competing second-line classes of advanced therapies against each other: vedolizumab, ustekinumab, and JAK inhibitors; this is similar to a sports podium (1st, 2nd, and 3rd place), as the ultimate clinical goal of the study was to “rank” which medication performed best in terms of efficacy and safety after a patient fails anti-TNFα therapy. Of historical interest, there was an older, unrelated PODIUM trial, which stood for Pentasa Once Daily in Ulcerative Colitis for Maintenance of Remission.

Methods: In this retrospective, multicenter European study, there were 596 patients were included (301 vedolizumab, 149 ustekinumab, 146 JAKi) with a mean age of 43.9 ± 15.5 years.  JAKi included 114 with tofacitinib, 28 with upadacitinib, and 5 with filgotinib. Achievement of biochemical steroid-free clinical remission (SFCR) within 12 months was identified by having SFCR associated with biomarker normalization: FCP <250 μg/g or CRP <5 mg/L—if discordant, FCP was considered the reference biomarker.

Key findings:

  • Compared with vedolizumab, both ustekinumab and JAKi showed significantly higher probability of steroid-free clinical remission (SFCR) (aHR, 1.54 and aHR, 1.66, respectively) and biochemical SFCR (aHR, 2.26 and 3.37, respectively) at 12 months
  • The crude incidence rate of SFCR at 12 months was 65.3% for vedolizumab, 87.0% for ustekinumab, and 80.2% for JAKi.
  • From a safety standpoint, JAKi were associated with an approximately 4-fold increase in the incidence rate of treatment-related AEs—primarily infections—compared with both vedolizumab and ustekinumab.

Discussion Points:

“Optimal sequencing in UC after anti-TNF-α exposure remains an open issue, as direct comparisons are scarce. Overall, our findings are consistent with the network meta-analysis by Lasa et al, which reported superior efficacy of JAKi and ustekinumab compared with vedolizumab in inducing clinical remission and endoscopic improvement in anti-TNF-α-experienced patients.14 However, these conclusions derive from indirect comparisons across heterogeneous randomized trials.”

My take: Vedolizumab is a good choice as a 1st line agent for ulcerative colitis but has a lower success rate as a 2nd line agent. Also, this study likely underestimates the potential effectiveness of JAKi as most individuals received tofacitinib rather than upadacitinib.

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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.

ESPGHAN Position Paper: Management of Foreign Bodies (2026)

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O Ledder et al. J Pediatr Gastroenterol Nutr. 2026;83:539–554. Open Access! Foreign body ingestions in children and adolescents: A position paper of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) endoscopy special interest group

In 2015, NASPGHAN’s endoscopy committee published a report on the management of foreign bodies (see: Foreign Bodies in Children -Expert Guidance). This was quite helpful. This ESPGHAN position paper provides updated guidance though many of the recommendations are unchanged.

Overall Treatment Algorithm:

Button Batteries

Blunt Objects/Benign Foreign Bodies

  • Superabsorbent polymers (SAP) Since these items are translucent, imaging is useful only for identifying the sequelae of the ingestion, but not the SAP itself… In cases of witnessed or suspected ingestion of SAP, emergency endoscopy should be performed to attempt retrieval of the material. If this is unsuccessful, or not completely retrieved, the child should be admitted for close observation with surgical support.

Magnets:

  • On table fluoroscopy has been suggested to confirm removal of all magnets if there is doubt whether all have been retrieved. (My personal experience is that fluoroscopy is particularly helpful if a colonoscopy is needed.)

Sharp Objects

My take: These guidelines are similar the previous NASPGHAN endoscopy committee recommendations from 2015. They are still worth a read for more context and there are a lot of endoscopy pointers in this report.

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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.

“Being a Doctor Will Never Be the Same After A.I.”

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Rachael Bedard. NY Times 9/25/26: Being a Doctor Will Never Be the Same After A.I.

An excerpt:

“I have a confession: A.I. is making me a better doctor. And I worry that it’s making doctors-in-training worse…

I already use the technology in my practice all the time…This summer, I used an A.I. tool — a platform called OpenEvidence, accessible only to health care providers — to help me choose antibiotics for one patient and to interpret unusual bloodwork for another. A.I. reminded me to consider migraines when a woman presented with dizziness. ..

Almost every month, I’m confronted with a complaint or syndrome that I don’t recognize. I’m confident in my mastery over what doctors do — history-taking, reasoning, communicating. I’m less confident about my continued mastery of an ever-evolving universe of facts. Now, the chatbot in my pocket reassures me that I will always know enough, or have access to the cloud-based intelligence that generally does.

All of my students and residents also use OpenEvidence, however, and I worry about the consequences of introducing such a powerful decision aid so early in their careers. Not only have they memorized less than I’d like, but they can seem almost passive in their relationship to their machines…

OpenEvidence is trained exclusively on peer-reviewed evidence and guidelines, and includes citations for all its claims…To use the app well, you must stay skeptical as you scroll…

I’m surprised by how much I learn from, and enjoy, these interactions. More important, my patient care has improved as conversations with the agent push my thinking beyond its usual limits…

Adam Rodman, a physician and A.I. researcher at Harvard Medical School,… said he shared my concern that trainees aren’t benefiting from “productive struggles” as much as their predecessors. “In experienced hands, decision support might cause a little de-skilling, but a little de-skilling probably doesn’t matter much to you,” Dr. Rodman told me. “But if you do that to somebody who has much less skill, the cognitive offloading can cause never-skilling”…

Current doctors-to-be may be the most adversely affected generation when it comes to A.I. They’re training before we know enough about how to teach them well in this new paradigm.

My take: In all aspects of learning, not just medicine, using AI shortcuts may make learners increasingly dependent on their devices, undermine their judgment and hinder developing their own voice. How to best train individuals in this new era remains unclear.

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Svörtuloft Lighthouse is located at the westernmost tip of the Snæfellsnes Peninsula in West Iceland. It is perched atop a 2.5-mile stretch of pitch-black volcanic lava cliffs.

Outcomes of Biliary Atresia in Large Cohort

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G Boroni et al. J Pediatr Gastroenterol Nutr. 2026;83:491–499. The Italian biliary atresia registry: Insights and lessons from the retrospective analysis of a 10-year period cohort

This retrospective study (2012-2012) examined the outcomes of 309 children with biliary atresia (BA) from 13 centers. Clearance of jaundice (CoJ) was defined as total bilirubin <1.2 mg/dL within 6 months.

Key findings:

  • The calculated incidence of BA in Italy during the study period was 1/15,142 live births
  • Kasai portoenterostomy (KPE) was performed in 272 infants (88%) at a median age of 68.5 days.
  • CoJ was achieved in 39% of cases.
  • CoJ was significantly associated with younger age and lower total bilirubin at referral (p = 0.0446 and p = 0.0144, respectively), younger age at KPE (p = 0.0345), and postoperative corticosteroid use (p = 0.0036). 
  • Liver transplantation was performed in 212/309 patients, and overall 5-year actuarial patient survival was 97.4%.
  • Overall patient survival was excellent: 97% at 5 years and 95% at 10 years.
Steroids were used in 71% of KPE cases. Different centers had different steroid protocols
Steroids were associated with improved clearance of jaundice after Kasai.
In those with a failed Kasai, steroid use did not improve outcomes.

Discussion points:

  • “This analysis contributes further to the controversy surrounding the effect of steroids.”
  • “The success of KPE decreases progressively with age at operation, with each additional day reducing the odds of CoJ by approximately 1.3%.”
  • “Despite decades of calls for earlier diagnosis and earlier KPE, little progress has been made in achieving earlier access to surgery…The evidence suggests that fibrosis is already advanced when KPE is performed at around 60 days of life and is likely to persist for life even when CoJ is achieved. Cirrhosis and portal hypertension remain common in long‐term survivors, who may face severe comorbidities.”
  • “Standards should therefore aim for KPE closer to, or before, 30 days of age, rather than accepting the current usual timing of 50–70 days achieved worldwide.”

My take: In this cohort, ~70% needed a liver transplant. Even with optimal timing and management, more than 50% are likely to need a liver transplant for long-term survival.

Related blog posts:

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.