Cyproheptadine: “Vitamin P”

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.46
  • 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.18 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.

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

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

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.

Related blog posts:

How to Take Care of Adolescents and Young Adults with Cannabnoid Hyperemesis Syndrome

A recent blog post summarized the recent Rome V recommendations which include useful tips for the diagnosis and management of Cannabinoid Hyperemesis Syndrome (Reference article: R Rosen et al. Gastroenterol 2026; 170: 1347-1366. Open Access! Rome V Pediatric Upper Gastrointestinal Disorders of Gut-Brain Interaction).

A practice management article by Nguyen et al (The Journal of Pediatrics, 2026; 291: 114966. Management of Cannabinoid Hyperemesis Syndrome in Adolescents and Young Adults) provides a lot of granular detail on how to improve outcomes.

Clinical manifestations:

  • “Recurrent vomiting that is not attributable to another disorder and in the context of cannabis use should raise concerns for cannabinoid hyperemesis syndrome (CHS). CHS typically presents with three phases. The prodromal phase is characterized by abdominal discomfort and early morning, episodic nausea on at least 1 day per week. This prodrome
    may precede acute vomiting by months or years. The emetogenic phase is characterized by sudden-onset, severe vomiting and abdominal pain episodes. Symptoms start within
    24 hours of last cannabis use, last typically for 24-48 hours, and may persist for up to 7-10 days. Abdominal pain is usually described as cramping in nature, radiating diffusely from
    the epigastrium or umbilicus. Patients often report symptom improvement with hot showers or baths. Acute nausea and vomiting gradually abate if patients abstain from cannabis, allowing transition from the acute emetogenic phase to the recovery phase and normalization of eating patterns. Symptoms typically recur with re-exposure to
    cannabis.”
  • “CHS is a separate disorder from CVS. It is critical that medical providers avoid providing CHS and CVS as interchangeable diagnoses to patients and families. Inconsistent
    diagnoses may erode families’ trust in the health care system by giving the impression that providers have not yet settled on an etiology. Furthermore, patients experiencing CHS
    who learn more about CVS outside the formal medical setting may gather that prophylactic medications are the mainstay of episode prevention, rather than cannabis cessation and abstinence.”

Evaluation:

  • “Bloodwork should include a comprehensive metabolic panel with liver function testing, complete blood count with differential, lipase, urinalysis, and a qualitative urine pregnancy test in a person capable of pregnancy.”
  • “An electrocardiogram is indicated if a patient has received multiple antiemetics, has an electrolyte abnormality, or is severely malnourished.”
  • “Abdominal imaging is most helpful to evaluate for suspected structural pathology.”
  • “A quantitative urine THC level may be helpful for longterm management of adolescents and young adults…A small study in adolescent patients suggests that urine THC levels >100 ng/mL are associated with cannabinoid hyperemesis syndrome….The test may be clinically useful to demonstrate significant marijuana exposure for patients who do not think their use is sufficient to cause their symptoms”

Management:

  • “Inpatient management can be conceptualized as having two phases. During the first 24 hours, patients require aggressive, proactive management. The goal isto break the vomiting
    cycle.”
  • “Our group’s practice is to select a single antiemetic with evidence in CHS treatment and to schedule this medication at the lowest therapeutic dose for vomiting relief at an interval that prevents recurrence of vomiting. An additional medication may be used as needed for breakthrough symptoms.”
  • “We typically use olanzapine or haloperidol as the initial agent. We recommend avoiding the use of multiple unscheduled antiemetics ordered “as needed” for nausea and vomiting. This approach risks drug interactions and QTc prolongation.” Typical antiemetics like ondansetron and prochloroperazine are usually ineffective for CHS.
  • “Regular application of capsaicin cream during the acute phase can decrease the need for oral medications by reducing or eliminating nausea and modestly reducing abdominal pain…We use capsaicin 0.1% cream in our clinical setting.”
  • “In the second phase of treatment, as the emetogenic phase abates and the patient can sustain oral nutrition, providers should focus on transitioning to a safe outpatient antiemetic
    plan.”
  • “Patients with pre-existing inherited or acquired long QTc should be treated with caution…When a prolonged QTc is identified, providers should consider using topical capsaicin and medications less likely to increase QTc, including lorazepam and aprepitant.”
**These medications, when used for CHS, would be considered “off label.”
**The use of lorazepam and aprepitant have only been report in case studies for CHS.
**Aprepitant can be administered intravenously as a one-time dose.
**Benzodiazepines should be limited to first 24-48 hours due to risk of addcition.

Malnutrition Often Associated with Chronic Cannabis Use:

  • Despite its perception as causing the ‘munchies,’ “chronic cannabis use is an underrecognized cause of weight loss and malnutrition. The insidious morning nausea and
    abdominal pain of the CHS prodrome can contribute to gradual weight loss, and a rapid weight drop may occur with vomiting episodes.”
  • “Potential medical complications of significant malnutrition include bradycardia, hypotension, hypothermia, orthostatic lightheadedness or presyncopal/syncopal episodes, cold intolerance, fatigue, worsening mood and anxiety, and change in menses…increases risks of superior mesenteric artery syndrome and the refeeding syndrome.”

Outpatient Management of CHS:

  • “Long-term management of CHS prioritizes cannabis abstinence, reestablishment of normal eating, and return to full daily function, including consistent participation in school
    and/or employment.”
  • “Indications for CHS prophylactic medication are extrapolated from existing literature in
    adults with CVS. Prophylaxis should be considered if exacerbations occur more frequently than once a month and last for over 2 days in an adolescent…Amitriptyline, a tricyclic antidepressant, is the first line agent for CHS prophylaxis…Nortriptyline, which is less sedating than amitriptyline, has also shown success in children and adults with CVS.” The authors discussed typical dosing of amitriptyline and nortriptyline (starting at 10-25 mg and titrating up to 1 to 1.5 mg/kg at bedtime [max 75 mg to 100 m])
  • “We continue the tricyclic antidepressant until hyperemesis exacerbations have been suppressed and the patient has maintained cannabis abstinence for 6-12 months, then slowly taper prophylaxis.”
  • “CHS is definitively treated with complete cessation and long-term abstinence from marijuana use for weeks to months. Focused treatment of concurrent cannabis use disorder is critical to recovery. We note that patients who intend to abstain from cannabis often struggle for 2-4 weeks after cessation due to withdrawal symptoms.”

My take: This article offers a lot of practical advice for CHS.

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.

The Spectrum of Esophageal Inflammatory Diseases

L Bertin et al. Clin Gastroenterol Hepatol 2026; 24: 1220-1231. Open Access! Beyond Eosinophils: Redefining the Spectrum of Esophageal Inflammatory Diseases Through an Immune-Centric Paradigm

This narrative article reviews the four distinct variants that exist beyond classical EoE: EoE-like esophagitis (histologic EoE features with <15 eosinophils/hpf), lymphocytic esophagitis (LyE) (≥30 lymphocytes/hpf), nonspecific esophagitis (NsE) (mixed inflammatory infiltrates), and mast cell esophagitis (elevated intraepithelial mast cells).

Key points:

  • Differential diagnosis: “Esophageal eosinophilia is not pathognomonic for EoE or EoE-like esophagitis. Alternative causes include GERD, achalasia and other esophageal motility disorders, infectious esophagitis, drug hypersensitivity reactions, connective tissue disorders (systemic sclerosis and dermatomyositis), hypereosinophilic syndrome, graft-versus-host disease, and Crohn’s disease with esophageal involvement.”
  • “EIDs [esophageal inflammatory diseases] manifest with overlapping yet distinct clinical and endoscopic features.49 Dysphagia remains the most consistent symptom across the spectrum, although its prevalence varies significantly”
  • “EoE-like esophagitis shows interleukin-13 pathway overlap with classical EoE and may progress to EoE (62.2% by 6 years)”
  • “LyE treatment remains largely empirical, with PPIs showing variable efficacy (24%–86% improvement),53 with a recent multicenter study showing it achieved even lower histological (13% vs 48%) and symptomatic improvement (6.7% vs 43%).59 As a second-line therapy, topical steroids should be considered.60
  • “NsE lacks consensus management strategies, with empiric approaches based on presenting symptoms typically employed.16
  • “McE treatment evidence derives primarily from case reports showing response to combinations targeting mast cell activity.”

My take: Esophageal inflammatory disorders besides EoE are uncommon in the pediatric age group. This article provides a useful review and guidance.

Normalizing Diet with Dupilumab Therapy

N Wolfest et al. Clin Gastroenterol Hepatol 2026; 24: 1271-1279. Open Access! Efficacy of Dupilumab on Facilitated Food Reintroduction in Eosinophilic Esophagitis

Methods: This open-label pilot study — patients who demonstrated disease control in the dupilumab run-in stage were able to continue into the food reintroduction stage for a total of 52 weeks. Reintroduction of trigger foods occurred at months 3, 6, and 9, while continuing on dupilumab treatment. Symptoms, histology, endoscopy, and esophageal diameter were compared prior to and following every phase of food reintroduction to month 12. All patients had previously failed trigger food reintroduction on their current EoE medication.

Key findings:

Dupilumab effectiveness: At month 3 of the dupilumab run-in stage, 17 of 19 evaluable patients (89%) per protocol had a PEC (peak eosinophil count) of <6 eos/hpf. One patient had a PEC of 6 eos/hpf but was permitted to proceed to the food reintroduction stage.

Food reintroduction:

  • Reintroduction of an EoE trigger food was successful in 86% of instances (54/63), as defined by a PEC <6 eos/hpf and no symptoms
  • At month 6, 75% of patients (12/16) successfully reintroduced an EoE trigger food, and, as portion size was increased or additional trigger foods were added, 93% (13/14) and 79% (11/14) successfully introduced EoE trigger foods at months 9 and 12, respectively
  • By the end of the study, 5 patients successfully achieved unrestricted serving sizes of an EoE trigger food without worsening esophageal biopsies
  • The mean PEC did not significantly change following food reintroduction at month 6 (5.3 [SD, 8.9]), month 9 (1.3 [SD, 2.8]), or month 12 (2.6 [SD, 4.5]) (see Figures below)

My take (borrowed in part from authors): For most newly-diagnosed patients, the majority prefer medical therapy over dietary restricitons. In those currently managed with dietary restrictions, “dupilumab treatment may provide a safe method for patients with EoE to gradually taper elimination diets for some trigger foods.”

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

Real-life Study of Ustekinumab for Pediatric Crohn’s Disease (REALITI Study)

SJ Steiner et al. J Pediatr Gastroenterol Nutr. 2026;82:1242–1250. Open Access! Effectiveness and safety of ustekinumab in pediatric Crohn’s disease: Results of the REALITI study

This retrospective study used prospectively-collected data from the ImproveCareNow (ICN) registry for pediatric patients. Overall, 479 patients with CD were treated with ustekinumab, 348 pediatric patients and 131 young adults; most were biologic-exposed (pediatric, 98.9%; young adult, 95.4%).

Key findings:

  • At week 52, clinical remission was achieved by 47.3% (125/264) of pediatric patients and 44.8% (39/87) of young adults, and CF (corticosteroid-free) clinical remission by 41.3% (109/264) and 39.1% (34/87), respectively
  • At Week 52 (observed case), among patients with moderately-to-severely active CD, clinical remission was achieved by 36.9% (41/111) of pediatric patients and 34.3% (12/35) of young adults, and CF clinical remission by 31.5% (35/111) and 28.6% (10/35), respectively.
  • Ustekinumab was well tolerated, with no new safety signals identified; however, a majority (89.4%) of the pediatric patients were 12–17 years old and most (76.5%) weighed ≥40 kg. Thus, further evaluations of ustekinumab in younger pediatric patients with CD and in those weighing <40 kg are still needed.
Observed case analysis of clinical effectiveness endpoints at Week 52 in (A) all patients with CD treated with ustekinumab, and (B) patients with moderately-to-severely active CD treated with ustekinumab.

My take: Studies indicate that newer selective IL-23 agents like risanizumab outperform ustekinumab. However, ustekinumab has FDA approval* for patients 2 years and older. In addition, there are several generic versions of ustekinumab which are less expensive than the newer agents. As such, I anticipate it will continue to be used.

Related blog posts:

*There has been recent approval recent of Stelara (ustekinumab) for the treatment of pediatric patients 2 years and older with moderately to severely active Crohn’s disease. Here’s a link: Johnson & Johnson (JNJ) Gains FDA Approval for Pediatric Crohn’s Disease Treatment

Rome V: Lower GI Tract and Biliary Disorders of Gut-Brain Interaction in Pediatrics (Part 2)

C DiLorenzo, M Saps et al. Gastroenterol 2026; 170: 1367-1387. Open Access! Lower and Biliary Disorders of Gut–Brain Interaction: Child and Adolescent

Yesterday’s post reviewed DGBIs related to the lower GI tract causing either abdominal pain or discomfort disorders. Today’s post focuses on DGBIS related to Defecation and Anorectal Disorders.

Functional Constipation

  • “The committee debated whether it was beneficial to remove the term “functional” from this entity to maintain uniformity with other DGBI. It was concluded that there was no better alternative to describe this condition.” (JH: ??dysfunctional)
  • “There is evidence that abdominal radiographs are neither sensitive nor specific to diagnose FC so they should only be used when clinically indicated. However, a moderate to large amount of stool found in the rectum has a high sensitivity and positive predictive value (>80%) for fecal retention as assessed by abdominal radiograph.132
  • Treatment should include adequate fiber and fluid intake. “Regarding maintenance [medication] therapy, the ESPGHAN-NASPGHAN guidelines recommend polyethylene glycol as the first-line therapy for children older than 6 months with constipation.139 In children not improving with stool softeners, adding a stimulant laxative, such as senna or bisacodyl, to the treatment may be beneficial.140 … [also] linaclotide… is now approved in the United States at the dosage of 72 μg/day in patients aged 6–17 years.141,142
  • “NASPGHAN defined refractory constipation as ongoing constipation in children who meet Rome IV Criteria for FC, who failed to improve after a minimum of 3 months of appropriate conventional therapies.”
  • Related blog posts: Position Paper: Pediatric Refractory Constipation Management & Willie Sutton and Refractory Constipation

Nonretentive Fecal Incontinence

  • “The word “functional” was removed to maintain consistency with the other DGBI. The Committee understands that the current definition does not capture the subset of children who have never been toilet-trained and have purposeful incontinence because of emotional or psychological issues…these children do not have a classic DGBI, and … exclude them from this definition by adding a statement that the incontinence should not be purposeful.”
  • Psychology: “The pressure from peers and from family members due to the unpleasant odor is usually substantial. Thus, it is unsurprising that most children with this symptom have psychological problems, irrespective of what causes the incontinence.155,156 They also face significant risks of child maltreatment.154,155
  • Treatment: “Patients should be instructed to sit on the toilet for approximately 5–10 minutes with appropriate seating methods at least 3 times per day, especially when they return from school…One case report showed the efficacy of loperamide in treating children with NRFI.157 There is no benefit to treating children with NRFI with laxatives, which may worsen the symptoms.158 The use of fiber may be beneficial in certain cases.”

Infant Dyschezia

  • Prevalence is estimated at 4-5% of all infants
  • Treatment: “Caregivers are frequently reassured by a methodical physical examination. They usually accept the explanation that the child needs to learn to relax the pelvic floor at the same time as bearing down. The caregivers are advised to avoid rectal stimulation, which produces sensory experiences that may be noxious or that may condition the child to wait for stimulation before defecating. Laxatives are usually unnecessary.”
  • Related blog post: Are There Any Babies with a Normal GI Tract?

Proctalgia Fugax

  • “The pain in PF is characterized by a sudden onset of severe cramping or stabbing pain in the rectum that lasts from seconds to several minutes and disappears completely.”
  • “Most children are managed with a simple explanation of the transient and benign nature of the disorder. Treatment is indicated in severe cases only. In adults, persistent symptoms can be treated with local application of 0.2% glyceryl trinitrate or 2% diltiazem at the onset of symptoms.169

Functional Diarrhea

  • “FDr is characterized by diarrhea without significant pain, whereas IBS-D presents with pain as the predominant symptom.”
  • Evaluation: “Attention should be given to ruling out conditions such as celiac disease, inflammatory bowel disease, malabsorption syndromes (eg, sucrase–isomaltase deficiency), and infectious causes. The physical examination should specifically assess hydration, nutritional status, and alarm signs (Table 3).186,187 In most cases, the likelihood of an underlying organic disease can be reasonably excluded through basic bloodwork and stool tests.”
  • Treatment: “Most toddlers and preschoolers do not require medical therapy. In older children, treatment depends on symptom severity and impact on quality of life…Dietary evaluation is recommended—especially reduction of juice and fructose intake in young children.188,189 A low-FODMAP diet may be trialed in older children. Other treatments include loperamide,79 bile acid sequestrants (eg, cholestyramine),78 and 5hydroxytryptamine type 3 antagonists when symptoms are persistent.”
  • Related blog post: AGA Guidelines for Evaluation of Functional Diarrhea and IBS-D

My take: Overall, the Rome V guidelines make a lot of incremental improvements.

Rome V: Lower GI Tract and Biliary Disorders of Gut-Brain Interaction in Pediatrics (Part 1)

C DiLorenzo, M Saps et al. Gastroenterol 2026; 170: 1367-1387. Open Access! Lower and Biliary Disorders of Gut–Brain Interaction: Child and Adolescent

Before reviewing this article, I wanted to point out that Dr. DiLorenzo, who was the 2025 ANMS Lifetime Achievement Award recipient, overcame great hardship to become a leader in neurogastroenterology. Elsewhere in this same issue, Wong et al (Gastroenterol 2026; 170: 1190-1204) point out that in Italy (& Spain) there is not even a word for bloating!

Key points:

  • For the Rome V recommendations, the Pediatric Committees decided to depart from the age-based divisions used in Rome IV

Irritable Bowel Syndrome:

  • “In Rome IV, for those children with constipation, there was an attempt to differentiate functional constipation (FC) from IBS by first attempting to treat constipation.7 …the Rome V Committee proposes a shift akin to that described in the adult IBS criteria, with a focus on the predominant symptom of abdominal pain as the differentiating factor between IBS-C and FC.”
  • Pathophysiology of IBS includes early life events, heightened nerve sensitivity, and increased gut permeability. Also, “more than 90% of children and adolescents with IBS identify at least 1 food that exacerbates their GI symptoms.34,35
  • Evaluation: “testing for celiac disease is recommended in those with IBS-D” and possibly testing for parasites and fecal calprotectin
  • Psycholological features: “studies have reported the association between abdominal pain–related DGBI and clinically evident as well as subclinical anxiety and depression.43–47 Anxiety and depression are as likely to follow as to precede pain48 and are not the main factors influencing pain outcomes.49–51…hildren with IBS may have increased school absenteeism, sleep disturbances, multisite pain, and functional disability.54,55
  • Treatments: Hyponotherapy, cognitive behavioral therapy, percutaneous nerve field stimulation, dietary interventions, probiotics, peppermint oil, psyllium, and pharmacologic interventions (lack of RCT evidence with most medications). Dietary intevertions: “The majority of lactose challenge RCTs in children with abdominal pain–predominant DGBI do not support the role of lactose as the trigger of the child’s symptoms.60…Given concerns for abnormal eating behaviors and the potential occurrence of avoidant and restrictive food intake disorders, it is strongly recommended that a dietitian be involved in any restriction diet and that liberalization of the restriction be instrumented when possible.65Related blog post: Treatment Guidelines for Pediatric Irritable Bowel Syndrome

Abdominal Pain Syndrome–Not Otherwise Specified

  • “The committee revised the criteria to differentiate intermittent pain (APS-NOS) from constant pain (CAPS) and specified that pain in APS-NOS should not be exclusively associated with meals, menses, or bowel movements.”

Biliary Pain Sydrome

  • “A key difference is the requirement for pain to be in the right upper quadrant with or without epigastric pain, helping distinguish it from functional dyspepsia.99
  • “Biliary dyskinesia may resolve spontaneously, with conservative treatment often showing equivalent or better outcomes than cholecystectomy in long-term follow-up.104 Therefore, cholecystectomy should be considered only when other nonsurgical treatments have been appropriately trialed and have failed to improve symptoms…surgery may not alleviate symptoms or may exacerbate symptoms or result in complications.”

Abdominal migraine

  • “In cases of overlapping symptoms with cyclic vomiting syndrome, the predominant and most bothersome symptom will guide the primary diagnosis.”
  • “There are no US Food and Drug Administration–approved medications or evidence-based guidelines for treating AM in children…Treatment should be individualized…Children with frequent and debilitating episodes may benefit from prophylactic therapy, as some evidence suggests that antimigraine medications.”

Centrally Mediated Abdominal Pain Syndrome

  • “Continuous pain as in the case of CAPS is much less frequent. There is no specific epidemiologic data for this diagnosis, as CAPS was not part of previous pediatric Rome Criteria.”
  • “Some of the treatment strategies listed in the ESPGHAN-NAPGHAN guidelines related to IBS and FAP-NOS may apply to this condition as well.68 Brain–gut therapies are strongly recommended,122,123 given the central sensitization that is likely present in these patients.”

Functional Abdominal Bloating

  • “Functional abdominal bloating is a recent addition to the pediatric Rome Criteria.”
  • “Potential organic causes of both bloating and distention include small bowel bacterial overgrowth, celiac disease,199 congenital sucrase-isomaltase deficiency, and other malabsorption disorders.195

Infant Distress Syndrome

  • “IDS is a new name proposed by the Rome V Committee in lieu of the term “infant colic.” The Rome V Committee agrees that this syndrome of excessive crying in infancy belongs to the DGBI group because there is evidence for a role of both brain and gut in its pathophysiology. However, the term “colic” suggests that the pain arises in the colon, which has not been proven to date. “
  • “The Rome V committee, however, agreed that this criterion of 3 hours was arbitrary and that many infants present to the pediatrician with excessive crying of a duration of less than 3 hours per day but with severe impact on at least 1 of the caregivers.”
  • Pathophysiology: “The pathophysiological mechanisms underlying IDS are still poorly understood, but IDS is likely to be a multifactorial disorder with GI, neurologic, and psychosocial disturbances.207 The pathogenesis of excessive crying may be closely related to the development of the GI microbiome.”
  • Maternal Psychology: “Maternal anxiety has been consistently found to be both a preceding and concurrent condition of excessive crying…However, depression seems to be a result of IDS, with excessive crying and maternal depression exacerbating simultaneously in a vicious cycle.214
  • Treatment: “The cornerstone of helping infants with IDS is to validate the infant’s symptoms and the emotional burden of the parents, reassure the parents that their child is healthy, and educate them about the self-limited nature of IDS and the need for support by family members…Probiotics may reduce crying time in infants with IDS…Evidence for the effectiveness of dietary modifications to treat IDS is scarce and presents a significant risk of bias.222 However, removing cow’s milk from the infant’s diet or from the maternal diet in those who are breastfed may be beneficial..Tthe evidence for using …proton pump inhibitors is very weak.224

My take: This is a very useful article and worth reading. I like the change in terminology from colic to infant distress syndrome and labeling IBS-C instead of FC when patient has predominantly abdominal pain.

Rome V Pediatric Upper Gastrointestinal Disorders of Gut-Brain Interaction (Part 3)

R Rosen et al. Gastroenterol 2026; 170: 1347-1366. Open Access! Rome V Pediatric Upper Gastrointestinal Disorders of Gut-Brain Interaction

This article has a lot of useful information and I recommend reading the article in full. The two previous days, the blog posts reviewed Esophageal Disorders and Functional Pediatric Feeding disorders. Today’s covers gastrduodenal disorders, including the following:

Gastroduodenal Disorders

  • Rumination Syndrome
  • Cyclic Vomiting Syndrome
  • Cannabinoid hyperemesis subgroup
  • Chronic Nausea
  • Functional Dyspepsia
  • Postprandial Distress Syndrome
  • Epigastric Pain syndrome

The key points:

Rumination syndrome: “The revised criteria require lack of response to GERD treatment—or, in infants, troubling regurgitation—before diagnosing RS…Delayed gastric emptying is seen in up to 45% of pediatric RS cases.106…Clinical observation during or after meals is often sufficient for diagnosis.111 Confirmatory tests, such as HRIM (R-wave), 24-hour pH-impedance monitoring, or upper endoscopy and contrast studies may be needed for atypical presentations or when there is diagnostic uncertainty.109,112,113…In older children, up to 70% of children have at least 1 psychiatric comorbidity.109,110 Anxiety, depression, and eating disorders are most common, although attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and adjustment disorder have been reported.111

Treatment of rumination syndrome:  “23% of children diagnosed with RS showed self-resolution of symptomatology without treatment after only the initial counseling.115 … The treatment in older children and adolescents focuses on implementing behavioral strategies, modulating food and liquid intake, managing mental health–related issues, and implementing diaphragmatic breathing around mealtimes.107,116…Baclofen may be an adjunctive therapy, although data in children are limited. A recent retrospective study in children found that baclofen is safe and is effective in almost 50% of children.119

Cyclic Vomiting Syndrome: “CVS leads to significant disability, including an average of 24 missed school days per year and more quality of life impairment than other DGBI.123…The committee supports the treatment approach outlined in the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition CVS guidelines.120

Cannabinoid Hyperemesis Subgroup: “CHS treatment mirrors CVS and includes abortive and preventive therapies.120,132,133 Long-term management centers on cannabis cessation and TCAs like amitriptyline. As sudden cessation may cause withdrawal and relapse, gradual reduction and lower-THC products may improve success.”

Chronic Nausea Syndrome: “Since its inclusion in Rome IV, studies have confirmed the prevalence of functional nausea and its link to comorbidities like POTS and other autonomic disorders, suggesting it may be part of a broader syndrome. Rome V now uses the term “chronic nausea syndrome” to better reflect this. The diagnostic criteria remain similar to Rome IV. Vomiting is excluded from the definition, as children typically present with nausea alone.” Testing: “routine laboratory tests may be done, but extensive testing rarely provides alternative diagnoses.138 Diagnostic endoscopy is not recommended unless “red flags” are present.138 Gastric-emptying studies are also not routinely needed unless vomiting is severe, the diagnosis is unclear, or the nausea is intractable.”

Function dyspepsia (FD) describes upper GI discomfort that may include a variable combination of features, including epigastric pain, postprandial upper abdominal fullness, early satiety, bloating, nausea, belching, and vomiting. Two main subtypes have been identified: postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS).152–154

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Rome V Pediatric Upper Gastrointestinal Disorders of Gut-Brain Interaction (Part 2)

R Rosen et al. Gastroenterol 2026; 170: 1347-1366. Open Access! Rome V Pediatric Upper Gastrointestinal Disorders of Gut-Brain Interaction

This article has a lot of useful information and I recommend reading the article in full. Yesterday’s post focused on Esophageal Disorders. Today’s reviews functional pediatric feeding disorders.

Functional Pediatric Feeding Disorders

  • Hypersensitvie dysphagia
  • Anticipatory Restrictive Feeding
  • Hunger dysregulation feeding disorder
  • Medically-triggered functional feeding disorder

The key points:

  • “Pediatric feeding disorders affect 5%–20% of children and are associated with significant morbidity, decreased quality of life, and increased resource utilization.63,64
  • “By merging examples of different feeding disorders under a single term, ARFID, the definition lacks needed granularity to refer patients for appropriate therapies. Therefore, we propose that the term ARFID should be eliminated and replaced by more precise terms.”
  • “As these are new diagnoses, the relative proportions of subgroups are not known. In 1 study of children with ARFID, 43%–82% had a lack of interest in eating (the new “hunger dysregulation” diagnosis), 21%–68% had sensory-driven food refusal, and 11%–21% had swallowing difficulties (the new “hypersensitive dysphagia” [HD] diagnosis).67
  • “Children with HD [hypersensitive dysphagia] present with sensations of food feeling stuck despite normal esophageal anatomy, motor function, and bolus clearance.” This is similar to “functional dysphagia” in adults. However, HD includes both oropharyngeal and esophageal sensations because children cannot often differentiate locations or they will not put food in the mouth or will chew and spit food or drinks. Second, normal bolus transit (as measured by HRIM or esophagram if the former is not available) was added to the definition.”
  • Anticipatory restrictive feeding (ARF) is characterized by the fear of an aversive experience with eating (eg, nausea, pain, bloating, gagging, choking, or vomiting). Clinically, these patients may present with significant diet restrictions resulting in elimination of entire food groups, specific food textures, or food temperatures. Children may express experiences of anxiety, disgust, or fear when consuming new, symptom-triggering, or nonpreferred foods…ARF is common in children with concurrent DGBI and the majority (>80%) of these patients have underlying GI symptoms.68,69
  • Testing: “Unlike many other DGBI, significant testing may be required before an FPFD diagnosis can be made because of the medical masqueraders (Figure 2) that may mimic an FPFD.73 Testing by feeding diagnosis is shown in Supplementary Table 2. Upper GI endoscopy is almost always recommended for pediatric feeding disorders because EoE can present with symptoms mimicking an FPFD; 25%–50% of patients with EoE have dysphagia and feeding issues and 15% of children with feeding issues have EoE.82–84 Laboratory testing for celiac disease, thyroid disease, a complete blood count, and electrolytes are indicated and, potentially expanded laboratory testing for iron, vitamin A, C, D, B12, carnitine, folate, liver function tests, thiamin, and zinc, depending on the history.83,85” The authors note that endoscopy is sometimes helpful for HD but is recommended in the other FPFD.

Treatments:

  • “Restrictive diets such as the low fermentable oligo-saccharides, di-saccharides, mono-saccharides, and polyols diet, gluten-free diets, and dairy-free diets are not usually recommended for symptom control as they may increase meal-related anxiety, thus worsening or triggering an FPFD.86
  • “The majority of patients do not need enteral tube support. In the ARFID literature, 20%–46% of patients were reliant on some form of enteral support, although the approach to ARFID has recently moved away from enteral tube use toward multidisciplinary behavioral therapies.67
  • “Intravenous parenteral nutrition is not recommended for FPFD.”
  • “For patients lacking a hunger drive, cyproheptadine has been found to increase appetite and improve gastric accommodation.87,88
  • “A retrospective review of intrapyloric botulinum toxin injections (IPBIs) in 85 young children with feeding disorders found some improvement with IPBIs.89

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