Category Archives: Pediatric Gastroenterology Intestinal Disorder

Interleukin-10 Autoantibodies and Development of IBD Plus One

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N Gharahdaghi et al. N Engl J Med 2026;394: 2212-2222. Interleukin-10 Autoantibodies and HLA-DRB1*01:03 in Inflammatory Bowel Disease

Background: “The allele HLA-DRB1*01:03 is the strongest genetic risk factor not only for susceptibility to ulcerative colitis but also for complicated phenotypes, including acute severe ulcerative colitis and an increased likelihood of surgical resection.2-5 However, the underlying pathogenic mechanism linking this HLA allele to disease remains unclear.”

“Neutralizing autoantibodies against interleukin-10 can result in a phenocopy of monogenic defects of interleukin-10 signaling in children and may be associated with inflammatory bowel disease (IBD)…In one child, anti–interleukin-10 titers and disease activity responded to B-cell–depleting anti-CD20 therapy.12“

Methods:

Key findings:

  • Interleukin-10–neutralizing autoantibodies were detected in 173 of 4909 patients with IBD (3.5%) and in none of 1006 controls (P<0.001)
  • High anti–interleukin-10 activity in serum was associated with a reduction in detectable interleukin-10 and with an exaggerated proinflammatory cytokine response
  • Anti–interleukin-10 seropositivity was strongly associated with HLA-DRB1*01:03 on the basis of imputed data from the Oxford cohort (odds ratio, 50.0), the U.K. IBD BioResource cohort (odds ratio, 24.7), and in a high-resolution sequencing analysis of data from the Oxford cohort (odds ratio, 29.5)

Discussion Points:

  • “The genetic association between HLA-DRB1*01:03 and anti–interleukin-10 autoreactivity provides mechanistic insight into one of the strongest known genetic susceptibility factors for IBD, with possible diagnostic, prognostic, and therapeutic implications.”
  • “Monogenic interleukin-10–signaling defects tend to manifest during infancy with colonic and penetrating disease, poor response to IBD therapies, high inflammatory activity with notably elevated C-reactive protein levels, and a high incidence of postoperative complications.27 It will be informative to establish the extent to which anti–interleukin-10 seropositivity associates with a similar disease pattern.”
  • “Our data highlight the need for research into therapeutic maneuvers to reduce anti–interleukin-10 titers — for example, by means of B-cell and plasma-cell depletion (e.g., anti-CD19, anti-CD20, anti-CD38, or CD19 chimeric antigen receptor [CAR] T-cell therapy),29-31 plasma exchange, or blockade of the neonatal Fc receptor.32“

My take: Historically, in younger patients (6 or younger) and those with more severe inflammatory bowel disease, it has been common to evaluate for monogenetic diseases which may require different treatment approaches. For similar reasons, assessing for neutralizing autoantibodies against interleukin-10 is likely to become part of routine care.

Related study: Q Zhang Q, Shakweh E, Sharip M et al. The Lancet Gastroenterology & Hepatology, 2026; 0. Open Access! HLA-DRB1*01:03 in patients with inflammatory bowel disease: a genotype–phenotype association study Key findings:

  • Among 43,762 patients with IBD (21 839 with Crohn’s disease and 21 923 with ulcerative colitis or IBD unclassified), HLA-DRB1*01:03 carriage was observed in 2009 (4·6%) patients with IBD and associated with multiple severe outcomes …including colonic resection in patients with Crohn’s disease (odds ratio 1·35), colectomy in patients with ulcerative colitis or IBD unclassified (1·99), and perianal disease in both patients with Crohn’s disease (1·65) and patients with ulcerative colitis or IBD unclassified (1·70)

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Dr. Valeria Cohran: Short Bowel Syndrome/Intestinal Failure in Pediatrics 2026

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Recently, Dr. Valeria Cohran gave our group a terrific update on Short Bowel Syndrome (SBS)/Intestinal Failure (IF). My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of her slides. Dr. Cohran has been a leader in intestinal rehabilitation. Among many accomplishments, she was the 2025 recipient of the 2025 Margaret Stallings NASPGHAN Distinguished Service Award.

Key points:

  • Most children with SBS/IF are able to taper off parenteral nutrition (PN). Even ~30% of those with extreme SBS (<10% of expected bowel length) are able to achieve enteral autonomy.
  • SBS/IF due to NEC has a generally more favorable outcome than other etiologies
  • Stoma takedown is associated with better outcomes (eg. more likely to taper off PN). (Raghu et al. JPEN. 2023;47:1047-55). Taking down stoma may be beneficial if unable to taper PN and in those developing liver disease
  • SBS/IF caretakers spend a median of 29 hrs/week managing PN, enteral nutrition, medications, and other tasks
  • In the nursery, one study reported that NICU patients with IF spent a median of 150 days and cost more than $500K
  • Overall, advances in SBS/IF management have been associated with lower death rates and lower intestinal transplant rates (~30 ITx last year), yet similar rates of achieving enteral autonomy
Overall, Group 1 SBS is least likely to achieve enteral autonomy
Intestinal length with maximal increase in first year of life
•N=362 children in over 26 centers world-wide, started 2018 (enrolled if PN >2 months)
Multi-organ effects of SBS
  • Fish oil based lipid emulsions do not always work; cirrhosis can still develop even with minimal biochemical marker alterations
  • IFALD mortality is associated with degree of conjugated hyperbilirubinemia, though we are not seeing this complication much with current management
  • GLP-2 can reduce PN requirements by more than 20% in the majority of those with SBS/IF and may help achieve enteral autonomy in about 20%. However, their use requires close monitoring for fluid overload and electrolyte disturbances
  • Lots of disparities noted along socioeconomic variables. For outpatient management, home nursing care is not available in some neighborhoods

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“Real-World” Impact of Vitamin D for Patients with Inflammatory Bowel Disease

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JA Sninsky et al. Clin Gastroenterol Hepatol 2026; 24: 1666-1674. Open Access! The Real-World Impact of Vitamin D Supplementation on Inflammatory Bowel Disease Clinical Outcomes

Methods: This was a retrospective cohort study of adult patients (n=5021) with IBD seen in the national Veterans Health Administration system from 2000 to 2023. The researchers used 3 different methods to try to determine causality of improved outcomes with supplementation of Vitamin D.

  1. “Difference-in-differences (DiD) approach to compare changes in clinical outcomes before and after vitamin D testing between patients who did and did not receive supplementation”
  2. “The regression discontinuity design leveraged the clinical threshold of 30 ng/mL serum 25-hydroxyvitamin D, comparing outcomes in patients just lower than and just higher than this cutoff, who are assumed to be otherwise similar”
  3. “The inverse probability weighting method adjusted for confounding by weighting patients based on their likelihood (propensity) of receiving vitamin D15“

Key findings:

  • The median 25-hydroxyvitamin D level was 23 ng/mL, and 41% received vitamin D supplementation
  • Vitamin D supplementation was associated with reduction in IBD-related emergency department visits by 2.17% (34.4% relative risk reduction; P = .007), hospitalizations by 2.64% (53.18% relative risk reduction; P = .003), and corticosteroid prescriptions by 1.29% (25.13% relative risk reduction; P = .066)

Discussion:

  • “Collectively, our data strongly suggest that vitamin D supplementation reduces the risk of IBD flare, underscoring its promise as an effective adjunctive therapy in clinical practice.”
  • “Vitamin D deficiency is prevalent among patients with IBD and is strongly linked to poor clinical outcomes, including higher rates of hospitalization and surgery. Patients with IBD are 64% more likely to be vitamin D deficient compared with healthy control subjects.29“
  • “Vitamin D deficiency is prevalent among patients with IBD and is strongly linked to poor clinical outcomes, including higher rates of hospitalization and surgery. Patients with IBD are 64% more likely to be vitamin D deficient compared with healthy control subjects.29“
  • “Although these findings support a strong association between vitamin D deficiency and worse clinical outcomes, they do not address whether supplementation itself mitigates the risk of adverse events, because disease severity confounds this relationship.33 Our study fills this knowledge gap and provides rigorous real-world data to support the effectiveness of vitamin D supplementation.”

My take: There have been large studies (eg. VITAL) study showing that Vitamin D supplementation does not help most people in the general population. In addition, many individuals with IBD who have low Vitamin D levels may see improvement in Vitamin D status by treating the IBD (without Vitamin D supplement). Yet, studies like this one by Sninsky indicate that Vitamin D supplementation is associated with improved outcomes in this retrospective cohort; the study methods likely indicate a causal effect of supplementation; however, a prospective randomized controlled study would be more definitive.

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Pediatric Experience with Subcutaneous Infliximab

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EH Boute et al. Inflamm Bowel Dis 2026; 32: 1086–1096. Open Access! Persistence and safety of subcutaneous infliximab up to 1 year after switching from intravenous infliximab in pediatric inflammatory bowel disease: a multicenter real-world cohort study

Methods: This was a retrospective multicenter study we identified pediatric IBD patients (n=66 including 41 with Crohn’s disease) who switched to SC-IFX. Median age 16.5 years. Pre-switch, the median IV-IFX maintenance dose was 10 mg/kg every 6 weeks. There were only 6 patients with a weight <40 kg.

Key findings:

  • The initial SC-IFX regimen was 120 mg every other week in 62/66 patients (94%).  4 patients (6%) were initiated on 120 mg every week
  • SC-IFX persistence was 78% at 12 months post-switch, with 89% of patients persisting on IFX, either intravenous (IV) or subcutaneous (SC), at the end of follow-up
  • 17% (n=11) of patients experienced relapses. 6 patients underwent dose intensification (3 regained response), 3 patients switched to a different advanced therapy, and 3 patients received concomitant therapy
  • 11 patients (17%) discontinued SC-IFX treatment after a median of 7.0 months
  • 6 patients underwent SC-IFX dose intensification, with 3 successfully regaining clinical response
  • Regarding anti-drug antibodies (ADA), 3 out of 4 patients who were ADA positive on IV-IFX resolved post-switch
  • Three patients (3/66, 5%) experienced serious AEs requiring hospitalization, namely IgA-mediated nephropathy, pyelonephritis requiring IV antibiotics, and perianal fistula requiring seton drainage

Discussion:

  • “Compared to IV-IFX, SC-IFX provides higher and more stable serum concentrations, avoiding peak-trough variability, potentially lowering immunogenicity and offering greater flexibility in TDM.”
  • “Careful monitoring by the IBD team remains essential to ensure treatment adherence during and after the switch. In our cohort, most discontinuations (64%) were related to difficulties with the SC route, highlighting the importance of identifying the most suitable candidates.”

My take: More pediatric studies are needed. This study suggests that the effectiveness of SC-IFX in children will be similar to the effectiveness in adults. As more patients receive SC therapy, it will be particularly important to work on adherence with scheduled dosing, lab monitoring, and careful followup visits; all of these can be more difficult with SC compared with IV infusions.

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Data Insufficient to Recommend Immobilized Lipase Cartridge Use in Children with Short Bowel Syndrome

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E Khenner et al. J Pediatr Gastroenterol Nutr. 2026;82:1488–1494. Open Access! Retrospective chart review of immobilized lipase cartridge use in children with short bowel syndrome

***Three of the authors of this study are/were employed or receive research support from Alcresta Therapeutics, Inc.

This small retrospective single-center study reports the use of in-line immobilized lipase cartridges (ILC) in 14 patients; 10 were PN-dependent, and four had enteral autonomy (Table 1). The mean age at the start of ILC use was 6 years (range 2–15 years). Mean estimated residual small bowel length was 66 cm (range 11–190 cm; n = 13). Eight patients received peptide-based EN and 6 elemental EN, typically delivered over 12–24 h.

Key findings:

  • In 9 PN-dependent patients (with Type II or III SBS), mean PN use at baseline was 45.3 kcal/kg/day (59% of supplemental nutrition). At final follow-up, mean PN use decreased by 10.6 kcal/kg/day (15.5%) and mean EN use increased by 6.0 kcal/kg/day (39.9%) after 3.8 to 23.9 months of ILC use.
  • In 4 patients with enteral autonomy (all Type III SBS), mean weight z-score improved by 0.60 and mean EN use decreased by 6.9% after 2.7 to 5.3 months of ILC use. The decrease from baseline in mean EN use at final follow-up was driven by data from one patient (#12) who had poor compliance with tube feeding.
  • None of these changes are statistically significant.

Discussion:

  • “There are limitations to ILC use in children with SBS: not all SBS patients receive EN, bolus feeding with ILC is limited to flow rates ≤400 mL/h, and ILC is not compatible with high fiber enteral formulas.6“
  • “Blenderized tube feeding is becoming the preferred method of enteral feeding in pediatrics.17 Although the use of blenderized tube feeds in children with SBS is associated with improved GI symptoms as well as a reduction in PN dependence, some patients experience intolerance or lack of weight gain.18, 19“
  • The authors conclusions: “ILC offers a low-risk option to potentially advance enteral autonomy or weight gain in some children with SBS.”

My take: I am not convinced that ILC is worthwhile for pediatric patients with SBS. I have received questions about this from our neonatal colleagues. When I have questioned leaders of several intestinal rehab centers, they have stated there is no solid data supporting its use. When I have asked the manufacturer to provide data in children with SBS less than two years of age, I have heard no response. The cost (without insurance) likely exceeds $9,000/month if using two ILCs per day. The use of this expensive product needs to be carefully evaluated in a prospective randomized trial.

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BAPS Shri Swaminarayan Mandir, Atlanta (Hindu Temple)

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

Oral Vancomycin For Pediatric Inflammatory Bowel Disease

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S Ancona et al. J Pediatr Gastroenterol Nutr. 2026;82:1416–1426. Effectiveness and safety of oral vancomycin in non-primary sclerosing cholangitis paediatric inflammatory bowel disease

Background: “Oral vancomycin (OV) has limited usage in paediatric inflammatory bowel disease (PIBD) with reported efficacy in primary sclerosing cholangitis (PSC-PIBD), acute severe colitis as part of quadruple-antibiotic regimen, and very early-onset IBD. This study evaluates OV effectiveness and safety as a single-agent in non-PSC PIBD.”

Methods: Retrospective, single center study with 31 children (median age 15.1); the presence of PSC and C diff were exclusion criteria. There were  23 ulcerative colitis (UC), 4 IBD-unclassified (IBDU) and 4 Crohn’s disease. OV was started at 250 mg for patients ≥30 kg or 125 mg for those <30 kg and administered four times daily (QDS) or three times daily (TDS). The majority were receiving concomitant medications: steroids in 16%, biologics in 32%, 5-ASA in 74%, and thiopurines in 42%.

Key findings:

  • Clinical and biochemical remission was achieved or maintained in 17/31 (55%), with 15/17 reducing/stopping other treatments and two remaining on OV monotherapy
  • At 1-month faecal calprotectin dropped from 686 to 60 μg/g in responders (p = 0.001) but remained high in nonresponders
  • Responders (Group 1) continued OV for a median of 7.0 months (IQR 2.5–23.5), maintaining consistently low PUCAI and FC levels throughout a median follow‐up of 19.0 months. After discontinuation, three relapsed and restarted OV,recapturing remission in 2/3.
  • Responders had lower baseline clinical disease activity
  • No serious adverse events occurred. No vancomycin-resistant enterococcus (VRE) colonization was seen

My take: This study’s vancomycin responders (55%) had significant improvement within four weeks. This is in agreement with other studies indicating that antimicrobial regimens may be helpful in a significant subset of children with inflammatory bowel disease. Larger prospective studies are warranted.

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Island Ford in Sandy Springs

Linaclotide Now FDA-Approved for 2-5 Year Olds with Functional Constipation

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Ironwood Pharmaceutical Press Releasse, 5/27/26: FDA Approves Use of LINZESS® (linaclotide) in Pediatric Patients Two Years of Age and Older with Functional Constipation (FC)

An excerpt:

Expanded indication extends availability to children ages 2-5 with FC; previously approved in pediatric patients 6 years of age and older –
– LINZESS remains the first-and-only FDA-approved prescription therapy for pediatric FC…

Parents can mix the contents of the LINZESS capsule with applesauce or water, providing flexibility for administration in young children...

The FDA approval for pediatric patients ages 2-5 was supported by data from a 12-week Phase 3 randomized, placebo-controlled clinical trial evaluating LINZESS in pediatric patients aged 2-5 years with FC. In the study, LINZESS 72 mcg demonstrated improvement in spontaneous bowel movement frequency compared with placebo. The safety profile of LINZESS observed in the trial was generally consistent with the established safety profile from trials in adults with chronic idiopathic constipation (CIC) and older pediatric patients with FC...

LINZESS 72mcg is available as a once-daily treatment of FC for pediatric patients 2 years of age and older

My take: In this age group, typical over-the-counter laxatives including polyethylene gylcol, magnesium products, and senna products along with diet and behavior modification will be effective for most children. Most children will not need a prescription medication to manage their constipation.

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Perito Moreno Glacier

Association Between Hypermobility Disorders, Orthostatic Intolerance and DGBIs

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N Santucci et al. J Pediatr Gastroenterol Nutr. 2026;82:1394–1399. Open Access! Children and adolescents with disorders of gut–braininteraction with comorbid hypermobility and orthostaticintolerance have worse outcom

Methods: This was a retrospecitive study from a multidisciplinary pediatric DGBI clinic which examined the relationship between hypermobility spectrum disorders (HSDs) and orthostatic intolerance (OI). HSD terms included Ehlers–Danlos syndrome, hypermobile Ehlers–Danlos syndrome, and generalized hypermobility; OI terms included postural orthostatic tachycardia syndrome, dysautonomia, and orthostatic hypotension. Of 175 patients, 46% had HSD and 43% had OI; 26% had both HSD and OI.

Key findings:

  • Patients with both HSD and OI had significantly worse nausea, depression, disability, and somatization scores than others (p < 0.01). 
  • HSD and OI groups individually also showed worse outcomes than non-HSD/non-OI groups. Moderate correlations were found between depression and anxiety in OI and nausea and disability in HSD.
  • Patients with both HSD and OI (n=45) had worse NSS (p < 0.0001), PHQ-9 (p = 0.007), FDI (p = 0.001), and CSI (p < 0.001) compared to patients with either OI or HSD and patients with neither.

Discussion:

  • “Autonomic dysfunction may explain the shared GI symptoms for OI and HSD patients. GI blood flow, motility, and secretion are regulated by an integral neural mechanism involving inputs from the central nervous system and the enteric nervous system. “
  • “Formal diagnosis of HSD and OI can be challenging and often requires involvement of multiple subspecialists…Studies comparing these groups run the risk of under-reporting diagnoses or including patients without the diagnosis. Strict clinical criteria are required using guidelines.”
  • There may be a selection bias for these patients in a specialized clinic for DGBIs; this was not discussed in this article. There is likely an increased rate of screening for HD and OI in patients with more severe DGBIs given previous reports of association with DGBIs.

My take: HSDs and OI are highly prevalent in DGBIs. In this study, both of these disorders were associated with worsened symptoms.

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Cyproheptadine: “Vitamin P”

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C Baker et al. J Pediatr Gastroenterol Nutr. 2026;82:1321–1324. Cyproheptadine: The secret sauce

Mechanism of action:

  • A first-generation antihistamine with anti-cholinergic, anti-serotonergic, and local anesthesia properties; its precise mechanism of action is poorly understood.

Formulation/pharmocokinetics:

  • Enteral tablet and syrup formulations appear to be well absorbed with peak serum levels 6–9 h after dosing in adults.2 However, anecdotally in pediatrics, the side effect of somnolence is often felt much more quickly.

Uses (off-label):

  • Promote weight gain: “There is ample literature to support success in varying populations, including mild to moderately undernourished toddler-aged children and children with cystic fibrosis.4–6“
  • Cyclic vomiting syndrome
  • Functional abdominal pain and dyspeptic symptoms
  • Post-operative Retching After Fundoplication

Dosing (by indication):

  • “For cyclic vomiting syndrome prophylaxis, the recommended dose is 0.25–0.5 mg/kg/day divided every 8–24 h with a maximum dose of 12 mg a day.”
  • “For appetite stimulation, the recommended dose is 0.25 mg/kg/day divided twice daily, with a maximum dose ranging from 12 to 32 mg depending on patient age.”
  • “An effective dosing range for use in disorders of the gut–brain interaction (DGBIs) in pediatric patients (median age 9 years) of 0.13–0.2 mg/kg/day has been reported when used on average for 9 months, with a mean initial dose of 4.85 mg/day and final dose of 5.34 mg/day.1“
  • “A large, systematic review from France identified the median dose for all pediatric clinical indications to be 0.25 mg/kg/day…Many clinicians use once-daily dosing to improve adherence.”

Contraindications, Drug Interactions, and Complications:

  • “Cyproheptadine is contraindicated in newborns and premature infants due to the potential for CNS depression and a lack of evidence in its safety and efficacy.”
  • “Cyproheptadine has potential for multiple drug-drug interactions, and dose adjustments may be required with concomitant therapies.”
  • “Recent publications suggest that up to 30% of patients will experience mild and self-limited side effects while taking cyproheptadine.8 The most common side effects are somnolence, increased appetite, weight gain, and behavior changes.1, 8 Caution should be exercised in the use of cyproheptadine in children who are already considerably overweight…A rare side effect of adrenal insufficiency…has been documented in pediatric patients.”

My take: Because cyproheptadine is so useful for pediatric GI disorders, some of my colleagues have referred to it as “Vitamin P” (periactin). This review provides a lot of helpful data and guidance.

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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

Familial Adenomatous Polyposis (FAP): Cancer Incidences and APC Mosaicism

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From Bouchiba et al:

From the editorial: “Bouchiba et al10 present a Dutch cohort study providing the most comprehensive evaluation of cancer incidence and temporal trends in FAP to date. Among 1230 patients with FAP followed over 5 decades, one-third developed cancer despite major preventive advances, underscoring the persistent lifetime risk in FAP…the 12-fold higher risk compared with the general population and the frequent late-stage detection of gastric cancer are concerning and underscore the need for improved endoscopic surveillance strategies.”

From Terlouw et al:

Background: A substantial proportion of patients with adenomatous polyposis have no germline pathogenic variant in APC. The aim of this study was to determine the prevalence of APC mosaicism in these patients with unexplained polyposis

Key findings:

  • The rate of APC mosaicism was 9.4%. This rate was 14.3% (46 of 322) in patients who met the scope of national hereditary polyposis testing guidelines (≥10 adenomas before the age of 60 or with ≥20 adenomas before the age of 70)
  • In patients who did not meet the scope of national guidelines, the detection rate was 2.3% (5 of 219)
  • None of the children tested in this cohort inherited the mosaic variant.

My take:

  1. Despite increasing knowledge of FAP, frequent cancers continue to occur
  2. In those with features of FAP without identified pathogenic mutations, testing for APC mosaicism should be considered. In addition, in those with APC gene mutation, regular colonoscopy is recommended along with at least one esophagogastroduodenoscopy.

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