High recurrence of reflux symptoms following proton pump inhibitor therapy discontinuation in patients with Los Angeles grade A/B erosive esophagitis: What is the next step?

Abstract

Gastroesophageal reflux disease (GERD) exhibits a global prevalence ranging from 8% to 33%.¹ Esophagogastroduodenoscopy serves as a crucial diagnostic tool for providing objective evidence of GERD, such as erosive esophagitis and Barrett's esophagus, and for excluding other potential causes. It is the preferred initial modality for GERD surveillance as mandated by the national health insurance policy in Taiwan.² GERD diagnosis is typically established through a synthesis of clinical, endoscopic, and physiological criteria, as recently outlined in the Lyon Consensus 2.0. GERD is conclusively diagnosed based on the endoscopic evidence of esophagitis (Los Angeles grades B, C, and D), Barrett's esophagus, or peptic stricture. Additionally, a diagnosis of GERD can be confirmed by acid exposure time (AET) exceeding 6% during pH impedance testing, or over 2 days with AET exceeding 6% as determined by wireless pH monitoring.²

Symptomatic relapse frequently occurs swiftly among patients with GERD symptoms following the discontinuation of treatment. Previous prospective studies have indicated that up to 30.4% of GERD patients experience symptom recurrence within the first year of follow-up, with symptom recurrence associated with the initial symptom burden.³ A severe GERD phenotype, characterized by advanced-grade esophagitis (Los Angeles grade C or D), and/or AET exceeding 12.0%, or a DeMeester score greater than 50, has been identified. Management of this phenotype often necessitates continuous long-term proton pump inhibitor (PPI) therapy or invasive anti-reflux procedures, alongside lifestyle optimization.⁴ According to the AGA clinical practice update on a personalized approach to GERD evaluation and management, clinicians should assess the appropriateness and dosing of PPI therapy within 12 months of initiation for patients with unproven GERD, and should consider offering endoscopy along with prolonged wireless reflux monitoring off PPI therapy to validate the long-term use of PPIs.⁴ In this context, it is recommended that endoscopy coupled with prolonged reflux monitoring be ideally conducted after withholding PPI therapy for 2 to 4 weeks, whenever feasible.⁵ This approach is vital for shared decision-making, as it helps patients understand the necessity for potential chronic lifelong maintenance therapy.⁴

Shih et al. have demonstrated that within a 12-week period following the initial administration of PPIs, the cumulative incidence of symptom relapse among patients diagnosed with Los Angeles grade A and B erosive esophagitis can reach up to 50.2%. Additionally, advanced age and smoking have been identified as independent predictors of symptom relapse. This study underscores the significant reliance on PPIs even among patients with mild erosive esophagitis.⁶ It emphasizes the necessity for clinicians to consider a comprehensive care plan that includes the investigation of symptoms indicative of GERD, the selection of therapy with a detailed discussion of its potential risks and benefits, and the long-term management of the condition. This approach should involve a shared decision-making model with the patient, potentially including strategies for de-escalation of therapy.⁴

Notably, within the cohort studied by Shih et al., 69.9% of patients were identified with Los Angeles grade A erosive esophagitis. According to the updated criteria of the Lyon Consensus 2.0, this classification does not conclusively diagnose GERD.^{2, 6} This observation highlights the need for further research into the pathophysiological mechanisms that contribute to symptom relapse in patients with Los Angeles grade A erosive esophagitis. Determining whether these symptom relapses are predominantly due to reflux that requires pharmacological therapy, or whether they are influenced by psychological factors such as stress or esophageal hypervigilance, is crucial for guiding appropriate therapeutic strategies.⁴ Recently, esophageal hypervigilance and anxiety scale (EHAS) has been introduced as a validated cognitive-affective tool to assess centrally mediated esophageal symptom perception.⁷ Studies have linked EHAS scores with symptom severity and psychological stress in GERD patients, albeit without correlations to acid reflux burden or mucosal integrity.^{8, 9} Collectively, it is advisable for clinicians to furnish patients exhibiting reflux symptoms with standardized health education. These should encompass explanations of GERD mechanisms, strategies for weight management, and guidance on lifestyle and dietary modifications. Additionally, they should also include diaphragmatic breathing and raise awareness about the brain–gut axis relationship, thereby equipping patients with comprehensive knowledge to manage their condition effectively.⁴

Concurrently, as anti-reflux mucosal intervention becomes a promising endoscopic GERD treatment alternative to medical treatment with PPIs, it is important to note its potential adverse effects, such as increased AET or exacerbated erosive esophagitis.^{10, 11} Therefore, in future scenarios where there is no conclusive evidence of GERD, the application of ambulatory reflux monitoring combined with EHAS evaluations may provide comprehensive and personalized management strategies for symptomatic relapse following PPI cessation. This approach could guide clinicians in optimizing anti-reflux treatments or providing alternative therapeutic options, such as neuromodulation, beyond the long-term use of PPIs.

The author declares no conflicts of interest.