Esophagus/Reflux, in full.

ACG 2025 makes 19 GRADE-rated statements plus non-graded key concepts. DIAGNOSIS: EoE is diagnosed by symptoms of esophageal dysfunction plus at least 15 eos/hpf in at least 1 hpf on esophageal biopsy, after evaluating for non-EoE disorders that cause or potentially contribute to esophageal eosinophilia (strong recommendation, low-quality evidence). A PPI trial is NOT a diagnostic criterion and the term PPI-REE is abandoned; PPIs are positioned purely as a treatment. Obtain at least 6 esophageal biopsies from at least 2 esophageal levels (e.g., proximal/mid and distal), targeting endoscopic findings if possible (strong, low). Use a systematic endoscopic scoring system such as the EoE Endoscopic Reference Score (EREFS) at every endoscopy (strong, low). Quantify eosinophil counts, not merely report them as above threshold, on biopsies from every endoscopy performed for EoE (strong, low), since serial counts gauge anti-inflammatory effect; the guideline notes eosinophil density (~60 eos/mm2) may be preferable for cross-setting comparison but that this has not yet been adopted in practice. Key concept: perform the diagnostic endoscopy off treatment (no dietary restriction and no PPI) to maximize diagnostic sensitivity. TREATMENT, the three anti-inflammatory options do NOT carry equal recommendation strength: swallowed topical steroids are recommended (STRONG, moderate evidence); PPIs are suggested (CONDITIONAL, low); empiric food elimination diet is suggested (CONDITIONAL, low). Because the field lacks comparative efficacy trials, the guideline states the choice among them is individualized to disease characteristics and patient preference within a shared decision-making framework, and advises that a single anti-inflammatory therapy be selected initially. Either fluticasone propionate or budesonide is a reasonable initial topical steroid (conditional, low); options include the FDA-approved budesonide oral suspension, the EMA-approved budesonide orodispersible tablet, and off-label asthma preparations adapted for esophageal delivery. Administer topical steroids after meals or at bedtime with nothing to eat or drink for 30-60 minutes to maximize esophageal dwell time; in young children prefer a slurry/suspension over an inhaler device. Dosing (Table 6): high-dose PPI, adults, double the approved reflux dose per day (e.g., omeprazole 20 mg twice daily or 40 mg daily or PPI equivalent); children, 2 mg/kg/day (or 1 mg/kg twice daily). Budesonide, adults 2-4 mg/day, divisible twice daily (approved budesonide oral suspension dosing is 2 mg twice daily); children 1-2 mg/day by age/height/weight. Fluticasone, adults 1,760 mcg/day in divided doses; children 110-880 mcg/day in divided doses. Currently available allergy testing (skin prick, patch, or serum Ig panels) is NOT suggested to direct elimination diets (conditional, very low). Providers MAY consider starting with a less-restrictive empiric elimination (1FED or 2FED) as the initial diet choice, incorporating patient preference through shared decision-making, and should collaborate with a dietician or nutritionist; after an initial dietary response a structured food reintroduction process is advised, with endoscopy and biopsy after each food reintroduced, because symptoms alone must not be used to determine food triggers. BIOLOGICS: dupilumab is suggested for EoE in individuals 12 years of age or older who are nonresponsive to PPI therapy (conditional, moderate) and, as a separate statement, for pediatric patients aged 1-11 years weighing at least 15 kg who are nonresponsive to PPI therapy (conditional, low). Dosing: 15 to <30 kg, 200 mg subcutaneously every other week; 30 to <40 kg, 300 mg subcutaneously every other week; >=40 kg, 300 mg subcutaneously weekly. Key concept: use dupilumab as step-up therapy in difficult-to-treat patients, and consider it in patients with multiple atopic conditions that would independently meet requirements for its use; the guideline explicitly states its position in the treatment algorithm is still being determined. No recommendation can be made for or against cendakimab, benralizumab, lirentelimab, mepolizumab, or reslizumab. Omalizumab is suggested AGAINST (conditional, low), as are cromolyn and montelukast (conditional, very low). DILATION: endoscopic dilation is suggested as an ADJUNCT to medical therapy for esophageal strictures causing dysphagia (conditional, low). Dilation alone does not affect underlying inflammatory disease activity, so in fibrostenotic EoE it should occur in conjunction with effective medical or dietary anti-inflammatory therapy. Use a start-low-and-go-slow approach: begin with a dilator size that may underestimate esophageal caliber, relook after dilation, and work to larger sizes until a mucosal disruption ('dilation effect') or the target diameter is reached. In adults and adolescents, a goal luminal diameter that relieves dysphagia and food impaction, typically at least 16 mm, should be achieved over one or more sessions, depending on initial luminal caliber and the effect observed during dilation. Dilation technique may be chosen by stricture characteristics and endoscopist preference. MAINTENANCE: continuation of EFFECTIVE dietary or pharmacologic therapy is advised to prevent recurrence of symptoms, histologic inflammation, and endoscopic abnormalities, notably graded STRONG despite low-quality evidence, because disease activity almost universally recurs when treatment is stopped. For patients on pharmacologic treatment, providers should consider identifying the lowest effective dose for long-term use, with any dose-reduction decision individualized. MONITORING AND RESPONSE: evaluate treatment response with symptomatic AND endoscopic AND histologic outcomes (strong, low); providers are advised NOT to monitor symptoms alone, since symptoms do not strongly correlate with endoscopic or histologic disease activity. Perform endoscopy to assess response 8-12 weeks after starting a new therapy such as PPI, topical steroid, or food elimination diet; for dupilumab the assessment interval may range from 12 to 24 weeks based on clinical trial findings. Providers MAY consider using a histologic response threshold of <15 eos/hpf, with the improvement in eosinophil count interpreted in the context of other histologic features, endoscopic findings, and symptoms, the guideline frames this as a 'may consider' key concept rather than a fixed target. Follow-up should be individualized and at shorter intervals for patients with complications (food impaction, perforation, strictures requiring dilation, malnutrition); repeat endoscopy after any treatment change such as dose reduction; care gaps of 2 years or more are associated with progression to fibrostenosis. PEDIATRIC-SPECIFIC: in children with EoE and dysphagia, an esophagram is suggested to evaluate fibrostenotic disease (conditional, very low); evaluation by a feeding therapist and/or dietician is suggested as an adjunctive intervention in children with feeding dysfunction (conditional, very low); growth, development including eating skills, and nutrition are treatment goals in children in addition to symptomatic, endoscopic, and histologic goals.

In patients with classic GERD symptoms (heartburn, regurgitation) and no alarm symptoms, give an 8-week trial of empiric PPI ONCE DAILY before a meal (strong, moderate evidence); administer PPI 30-60 minutes before a meal rather than at bedtime (strong, moderate). Endoscopy is the FIRST test in patients presenting with dysphagia or other alarm symptoms, the guideline names weight loss and GI bleeding, and also in patients with multiple risk factors for Barrett's esophagus (strong, low). If classic symptoms respond to the 8-week trial, attempt to discontinue the PPI (conditional, low); for patients without erosive esophagitis or Barrett's whose symptoms resolved, an attempt at discontinuation should be made; patients requiring maintenance should take the lowest effective dose. If symptoms do not respond adequately to the 8-week trial, or return on discontinuation, perform diagnostic endoscopy, ideally after PPIs are stopped for 2-4 weeks (strong, low). Where GERD is suspected but unclear and endoscopy shows no objective evidence, perform reflux monitoring OFF therapy to establish the diagnosis (strong, low); conversely, do NOT perform off-therapy reflux monitoring solely as a diagnostic test in patients already known to have LA grade C or D esophagitis or long-segment Barrett's, because the diagnosis is already established (strong, low). In refractory GERD, optimize PPI therapy first (strong, moderate); then pH monitoring OFF PPIs if GERD was not previously established by pH study, long-segment Barrett's, or LA grade C/D esophagitis, versus impedance-pH ON PPIs where GERD is already established but symptoms persist on twice-daily PPI (both conditional, low). Before antireflux surgery or endoscopic therapy, HRM is recommended to rule out achalasia and absent contractility, with provocative testing (e.g., multiple rapid swallows) to identify contractile reserve in ineffective esophageal motility; on-therapy reflux monitoring is suggested before intervention in patients with prior objective GERD findings who remain symptomatic. Antireflux surgery by an experienced surgeon is an option for patients with OBJECTIVE evidence of GERD, with severe esophagitis (LA C/D), large hiatal hernia, or persistent troublesome symptoms benefiting most; TIF is suggested only for troublesome regurgitation or heartburn in patients who do not wish to undergo antireflux surgery and who are WITHOUT severe esophagitis (LA C/D) or hiatal hernia >2 cm. For extraesophageal symptoms WITHOUT typical GERD symptoms, perform reflux testing BEFORE starting PPI therapy (strong, moderate); with concomitant typical symptoms, consider twice-daily PPI for 8-12 weeks before further testing (conditional, low). Lifestyle: weight loss in overweight/obese patients (strong, moderate); avoid meals within 2-3 hours of bedtime, avoid tobacco, avoid trigger foods, and elevate the head of the bed for nighttime symptoms (all conditional, low).

In patients with classic GERD symptoms (heartburn, regurgitation) and no alarm symptoms, give an 8-week trial of empiric PPI ONCE DAILY before a meal (strong, moderate evidence); administer PPI 30-60 minutes before a meal rather than at bedtime (strong, moderate). Endoscopy is the FIRST test in patients presenting with dysphagia or other alarm symptoms, the guideline names weight loss and GI bleeding, and also in patients with multiple risk factors for Barrett's esophagus (strong, low). If classic symptoms respond to the 8-week trial, attempt to discontinue the PPI (conditional, low); for patients without erosive esophagitis or Barrett's whose symptoms resolved, an attempt at discontinuation should be made; patients requiring maintenance should take the lowest effective dose. If symptoms do not respond adequately to the 8-week trial, or return on discontinuation, perform diagnostic endoscopy, ideally after PPIs are stopped for 2-4 weeks (strong, low). Where GERD is suspected but unclear and endoscopy shows no objective evidence, perform reflux monitoring OFF therapy to establish the diagnosis (strong, low); conversely, do NOT perform off-therapy reflux monitoring solely as a diagnostic test in patients already known to have LA grade C or D esophagitis or long-segment Barrett's, because the diagnosis is already established (strong, low). In refractory GERD, optimize PPI therapy first (strong, moderate); then pH monitoring OFF PPIs if GERD was not previously established by pH study, long-segment Barrett's, or LA grade C/D esophagitis, versus impedance-pH ON PPIs where GERD is already established but symptoms persist on twice-daily PPI (both conditional, low). Before antireflux surgery or endoscopic therapy, HRM is recommended to rule out achalasia and absent contractility, with provocative testing (e.g., multiple rapid swallows) to identify contractile reserve in ineffective esophageal motility; on-therapy reflux monitoring is suggested before intervention in patients with prior objective GERD findings who remain symptomatic. Antireflux surgery by an experienced surgeon is an option for patients with OBJECTIVE evidence of GERD, with severe esophagitis (LA C/D), large hiatal hernia, or persistent troublesome symptoms benefiting most; TIF is suggested only for troublesome regurgitation or heartburn in patients who do not wish to undergo antireflux surgery and who are WITHOUT severe esophagitis (LA C/D) or hiatal hernia >2 cm. For extraesophageal symptoms WITHOUT typical GERD symptoms, perform reflux testing BEFORE starting PPI therapy (strong, moderate); with concomitant typical symptoms, consider twice-daily PPI for 8-12 weeks before further testing (conditional, low). Lifestyle: weight loss in overweight/obese patients (strong, moderate); avoid meals within 2-3 hours of bedtime, avoid tobacco, avoid trigger foods, and elevate the head of the bed for nighttime symptoms (all conditional, low).

For heartburn or regurgitation persisting despite PPI therapy, current practice (ACG 2022 GERD guideline, still the operative ACG guideline, plus the AGA 2022 personalized-GERD CPU) is to first optimize the PPI: confirm adherence, dose 30-60 minutes before meals, escalate to twice-daily dosing or switch agents for an 8-week trial. Empiric escalation to vonoprazan/P-CAB is NOT a routine pre-testing step: the AGA 2024 P-CAB clinical practice update advises against P-CABs as first-line therapy and reserves them for PPI failure with confirmatory GERD evidence (LA grade B or worse erosive esophagitis, biopsy-proven Barrett's, peptic stricture, or acid exposure time >6%). If symptoms persist after optimization, perform EGD (ideally 2-4 weeks off PPI when GERD is unproven) with esophageal biopsies to exclude EoE (>=15 eos/hpf; the ACG 2025 EoE guideline has removed the PPI trial from the diagnostic pathway) and then physiologic testing per Lyon Consensus 2.0: in unproven GERD, ambulatory reflux monitoring OFF therapy, applying Lyon 2.0's modality-specific thresholds -- on catheter-based single-day (24-hour) pH or pH-impedance, AET >6% is conclusive for GERD, 4-6% is inconclusive, and <4% argues against GERD; on prolonged wireless (Bravo, up to 96-hour) monitoring, AET >6% on >=2 days is conclusive for GERD while AET <4% on all days excludes it, and a study meeting neither threshold is inconclusive (the number of days with AET <4% carries prognostic weight for PPI discontinuation) -- and, in either modality, a normal-AET (<4%) study with positive symptom association indicates reflux hypersensitivity or, without it, functional heartburn; in previously proven GERD, pH-impedance ON optimized therapy, where AET >4% plus >80 reflux episodes defines actionable refractory GERD (MNBI <1500 ohms supportive, >2300 ohms against). High-resolution manometry per Chicago Classification 4.0 (still current) excludes achalasia and major motility disorders and is required before anti-reflux surgery. Therapy is phenotype-directed: surgical or endoscopic anti-reflux intervention for confirmed refractory pathologic reflux, and neuromodulators with or without brain-gut behavioral therapy for reflux hypersensitivity and functional heartburn.

ACG 2025 makes 19 GRADE-rated statements plus non-graded key concepts. DIAGNOSIS: EoE is diagnosed by symptoms of esophageal dysfunction plus at least 15 eos/hpf in at least 1 hpf on esophageal biopsy, after evaluating for non-EoE disorders that cause or potentially contribute to esophageal eosinophilia (strong recommendation, low-quality evidence). A PPI trial is NOT a diagnostic criterion and the term PPI-REE is abandoned; PPIs are positioned purely as a treatment. Obtain at least 6 esophageal biopsies from at least 2 esophageal levels (e.g., proximal/mid and distal), targeting endoscopic findings if possible (strong, low). Use a systematic endoscopic scoring system such as the EoE Endoscopic Reference Score (EREFS) at every endoscopy (strong, low). Quantify eosinophil counts, not merely report them as above threshold, on biopsies from every endoscopy performed for EoE (strong, low), since serial counts gauge anti-inflammatory effect; the guideline notes eosinophil density (~60 eos/mm2) may be preferable for cross-setting comparison but that this has not yet been adopted in practice. Key concept: perform the diagnostic endoscopy off treatment (no dietary restriction and no PPI) to maximize diagnostic sensitivity. TREATMENT, the three anti-inflammatory options do NOT carry equal recommendation strength: swallowed topical steroids are recommended (STRONG, moderate evidence); PPIs are suggested (CONDITIONAL, low); empiric food elimination diet is suggested (CONDITIONAL, low). Because the field lacks comparative efficacy trials, the guideline states the choice among them is individualized to disease characteristics and patient preference within a shared decision-making framework, and advises that a single anti-inflammatory therapy be selected initially. Either fluticasone propionate or budesonide is a reasonable initial topical steroid (conditional, low); options include the FDA-approved budesonide oral suspension, the EMA-approved budesonide orodispersible tablet, and off-label asthma preparations adapted for esophageal delivery. Administer topical steroids after meals or at bedtime with nothing to eat or drink for 30-60 minutes to maximize esophageal dwell time; in young children prefer a slurry/suspension over an inhaler device. Dosing (Table 6): high-dose PPI, adults, double the approved reflux dose per day (e.g., omeprazole 20 mg twice daily or 40 mg daily or PPI equivalent); children, 2 mg/kg/day (or 1 mg/kg twice daily). Budesonide, adults 2-4 mg/day, divisible twice daily (approved budesonide oral suspension dosing is 2 mg twice daily); children 1-2 mg/day by age/height/weight. Fluticasone, adults 1,760 mcg/day in divided doses; children 110-880 mcg/day in divided doses. Currently available allergy testing (skin prick, patch, or serum Ig panels) is NOT suggested to direct elimination diets (conditional, very low). Providers MAY consider starting with a less-restrictive empiric elimination (1FED or 2FED) as the initial diet choice, incorporating patient preference through shared decision-making, and should collaborate with a dietician or nutritionist; after an initial dietary response a structured food reintroduction process is advised, with endoscopy and biopsy after each food reintroduced, because symptoms alone must not be used to determine food triggers. BIOLOGICS: dupilumab is suggested for EoE in individuals 12 years of age or older who are nonresponsive to PPI therapy (conditional, moderate) and, as a separate statement, for pediatric patients aged 1-11 years weighing at least 15 kg who are nonresponsive to PPI therapy (conditional, low). Dosing: 15 to <30 kg, 200 mg subcutaneously every other week; 30 to <40 kg, 300 mg subcutaneously every other week; >=40 kg, 300 mg subcutaneously weekly. Key concept: use dupilumab as step-up therapy in difficult-to-treat patients, and consider it in patients with multiple atopic conditions that would independently meet requirements for its use; the guideline explicitly states its position in the treatment algorithm is still being determined. No recommendation can be made for or against cendakimab, benralizumab, lirentelimab, mepolizumab, or reslizumab. Omalizumab is suggested AGAINST (conditional, low), as are cromolyn and montelukast (conditional, very low). DILATION: endoscopic dilation is suggested as an ADJUNCT to medical therapy for esophageal strictures causing dysphagia (conditional, low). Dilation alone does not affect underlying inflammatory disease activity, so in fibrostenotic EoE it should occur in conjunction with effective medical or dietary anti-inflammatory therapy. Use a start-low-and-go-slow approach: begin with a dilator size that may underestimate esophageal caliber, relook after dilation, and work to larger sizes until a mucosal disruption ('dilation effect') or the target diameter is reached. In adults and adolescents, a goal luminal diameter that relieves dysphagia and food impaction, typically at least 16 mm, should be achieved over one or more sessions, depending on initial luminal caliber and the effect observed during dilation. Dilation technique may be chosen by stricture characteristics and endoscopist preference. MAINTENANCE: continuation of EFFECTIVE dietary or pharmacologic therapy is advised to prevent recurrence of symptoms, histologic inflammation, and endoscopic abnormalities, notably graded STRONG despite low-quality evidence, because disease activity almost universally recurs when treatment is stopped. For patients on pharmacologic treatment, providers should consider identifying the lowest effective dose for long-term use, with any dose-reduction decision individualized. MONITORING AND RESPONSE: evaluate treatment response with symptomatic AND endoscopic AND histologic outcomes (strong, low); providers are advised NOT to monitor symptoms alone, since symptoms do not strongly correlate with endoscopic or histologic disease activity. Perform endoscopy to assess response 8-12 weeks after starting a new therapy such as PPI, topical steroid, or food elimination diet; for dupilumab the assessment interval may range from 12 to 24 weeks based on clinical trial findings. Providers MAY consider using a histologic response threshold of <15 eos/hpf, with the improvement in eosinophil count interpreted in the context of other histologic features, endoscopic findings, and symptoms, the guideline frames this as a 'may consider' key concept rather than a fixed target. Follow-up should be individualized and at shorter intervals for patients with complications (food impaction, perforation, strictures requiring dilation, malnutrition); repeat endoscopy after any treatment change such as dose reduction; care gaps of 2 years or more are associated with progression to fibrostenosis. PEDIATRIC-SPECIFIC: in children with EoE and dysphagia, an esophagram is suggested to evaluate fibrostenotic disease (conditional, very low); evaluation by a feeding therapist and/or dietician is suggested as an adjunctive intervention in children with feeding dysfunction (conditional, very low); growth, development including eating skills, and nutrition are treatment goals in children in addition to symptomatic, endoscopic, and histologic goals.