The Spectrum of Esophageal Inflammatory Diseases

Posted on June 10, 2026 by gutsandgrowth

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

Posted on June 9, 2026 by gutsandgrowth

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)

Posted on June 8, 2026 by gutsandgrowth

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

Cheaper Generic Ozempic (semaglutide) Is Coming Soon — But Not for Americans

Posted on June 7, 2026 by gutsandgrowth

NBC News 5/13/26: Cheaper Generic Ozempic (semaglutide) Is Coming Soon — But Not for Americans

An excerpt:

Outside the U.S., approved generic versions of semaglutide are beginning to hit the market. India and Canada recently approved their first generic versions of Ozempic, and countries including China, Brazil and South Africa are expected to soon follow…The U.S., however, remains on a very different timeline.

Evergreening

The standard length of a drug patent in the U.S. is 20 years from the filing date. Novo Nordisk first applied for a U.S. patent on semaglutide in 2006. Due to patent extensions, approved generic versions of semaglutide aren’t expected in the U.S. until at least the end of 2031…

Drugmakers often file additional, secondary patents — a tactic known as evergreening — to extend their monopoly on their product and delay generics. The additional patents can include new doses, formulations or delivery devices…

Novo Nordisk has filed at least 49 semaglutide patents…

Drugmakers’ use of the patent system has delayed cheaper competition and kept prices high for patients.

My take: This is a bad deal for U.S. There is no good reason why patients in the U.S. need to be paying 5-10 times as much for semaglutide as patients in Europe.

Related blog post: “Gaming” U.S. Patent System by Big Pharma

This Day in Gastroenterology History

Posted on June 6, 2026 by gutsandgrowth

From a previous blog post (538: Gut Science Week):

One of the major leaps forward in gut science began with an accidental shooting at a trading post on June 6, 1822. A fur trader named Alexis St. Martin took a bullet in the abdomen, leaving him with a hole ripped through his muscle, bone and internal organs…

His doctor, William Beaumont, could literally tie a bit of food on a string, shove it into St. Martin’s stomach through the hole, and pull it back out again. Using this one weird trick, Beaumont extracted samples of the man’s gastric juices. Over eight years and more than 200 awkwardly invasive experiments, St. Martin and Beaumont gave humanity its first real understanding of how digestion works.

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

Posted on June 5, 2026 by gutsandgrowth

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 5–hydroxytryptamine 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)

Posted on June 4, 2026 by gutsandgrowth

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.⁶⁵” Related 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)

Posted on June 3, 2026 by gutsandgrowth

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“

Related blog posts:

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

Posted on June 2, 2026 by gutsandgrowth

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“

Related blog posts:

Rome V Pediatric Upper Gastrointestinal Disorders of Gut-Brain Interaction (Part 1)

Posted on June 1, 2026 by gutsandgrowth

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 disorders covered include the following:

Esophageal Disorders:

Reflux hypersensitivity
Reflux-negative esophageal pain disorder (similar to functional heartburn in adults)
Aerophagia syndrome
Supragastric belching syndrome

Functional Pediatric Feeding Disorders

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

Gastroduodenal Disorders

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

The authors note that the Rome V criteria have expanded to include several more disorders. “This expansion provides a diagnostic framework for patients presenting with chest and throat pain, feeding difficulties, belching, pain with eating, nausea, and vomiting. Given the advances in impedance technology and high-resolution manometry, testing plays a greater role in many of these diagnostic criteria than they have in past Rome iterations. This harmony between symptoms and testing results in more precision in therapeutic approaches that are critically multidisciplinary. The ability to assign new, positive diagnoses across the upper gastrointestinal tract offers new opportunities for pediatric-focused therapeutic trials.”

With regard to esophageal disorders, the key points:

“In the past, nonerosive reflux disease was the all-encompassing diagnosis for children without pathologic amounts of gastroesophageal reflux. The use of pH-impedance testing has allowed for additional phenotyping of patients with significant symptoms that are typically associated with gastroesophageal reflux disease”
“PPI response does not reliably predict reflux phenotype…Empiric acid suppression trials should be time-limited up to 8 weeks and further diagnostic testing (ie, endoscopy, pH-impedance, and CYP2C19 gene testing if possible) should be pursued if there is no symptom improvement.²⁰ Histamine-2 receptor antagonists can also treat esophageal hypersensitivity and are a first-line therapy for patients awaiting endoscopy.”
“Patients with reflux-negative esophageal pain disorder (RNEPD) have a visually normal upper endoscopy and no evidence of pathologic acid reflux with negative reflux-symptom correlation by pH-impedance (or pH-metry or wireless testing). This is equivalent to functional heartburn (FH) in adults. However, unlike adult FH, symptoms of RNEPD may include intermittent retrosternal pain, heartburn, throat pain, or burning sensation in the throat, at least 3 times per week for 2 months.³¹ Younger children may present with crying or repeatedly pointing to areas of discomfort. Two studies found that 38%–44% of pediatric patients with normal endoscopy undergoing pH-impedance testing met criteria for FH per the adult Rome IV definition.³^,⁴…Because RNEPD falls on the spectrum of visceral hypersensitivity, neuromodulators should be the mainstay of therapy”
“Aerophagia, a normal physiologic phenomenon, should only be considered a syndrome if it impacts quality of life and causes symptoms. Previously, increased flatus was considered a major criterion but because flatus may go unnoticed, it is no longer a major criterion…Treatment No therapeutic trials exist. However, in patients with severe distention, a nasogastric tube or an existing gastrostomy tube can be used to vent air from the stomach.⁵⁵ If colonic distention is present, rectal decompression may be appropriate. In patients with chronic stable symptoms, a conservative approach is sufficient. Speech therapy or CBT aimed at reducing the air swallowing may be tried. Benzodiazepines can be considered in severe cases. Circumstantial evidence suggests that infants swallow less air using different bottle or nipple systems.⁵⁶“
Supragastric Belching Syndrome “SGB is a voluntary yet subconscious behavior…Most patients present with excessive belching as the primary symptom. However, the symptoms may sound like hiccups to patients or parents. Often no tests are needed, as the story of multiple repeated belches is nearly pathognomonic for SGB. SGB typically occurs outside of meal periods and does not occur during sleep. pH-impedance or HRIM can be performed to confirm the diagnosis. However, absence of belching during testing does not exclude the diagnosis, as events can be sporadic. Treatment In a single randomized trial of behavioral interventions in adults, which included education about the disorder, warning signs for oncoming events, and breathing exercises, patients who received the behavioral interventions had higher rates of symptom improvement lasting up to 6 months”

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