Gastroesophageal reflux disease (GERD) resistant to proton pump inhibitors: Causes of ineffective treatment (Part 1)

Posted by Master, Doctor Mai Vien Phuong - Department of Examination & Internal Medicine - Vinmec Central Park International General Hospital

There are many potential causes of refractory gastroesophageal reflux disease (GERD), which vary in incidence, clinical importance, and symptom severity and frequency. Compliance and poor compliance should first be assessed before continuing with the assessment.

Gastroesophageal reflux disease (GERD) is the most common upper gastrointestinal (GI) disorder in the United States, defined as symptoms or lesions caused by the reflux of gastric contents into the esophagus. manage. Proton pump inhibitors (PPIs), after acid activation to sulfonamides, covalently bind to the cysteine ​​residues on the luminous surface of the proton pump H + / K + ATPase in parietal cells, blocking transport ion transfer and acid secretion.
Chemically, all PPIs consist of a benzimidazole ring and a pyridine ring but differ in side ring substitutions. Although PPIs are currently the most effective treatment for GERD and its complications, up to 40% of patients with non-erosive reflux disease (NERD) remain symptomatic under standard treatment, and Approximately 10-15% of patients with erosive esophagitis (EE) do not have complete remission after 8 weeks of treatment.
Patients who continue to have symptoms despite PPI therapy are considered to have refractory GERD, usually defined as the persistence of typical symptoms unresponsive to stable, 2-fold PPIs. every day for at least 12 weeks of treatment. Up to 30% of GERD patients have treatment-resistant GERD.

There are many potential causes of refractory GERD, which vary in incidence, clinical importance, and symptom severity and frequency. Compliance and poor compliance should first be assessed before continuing with the assessment. The most common mechanisms of resistant GERD include bowel dysfunction, weak acid reflux, and excess acid. Factors related to metabolism and bioavailability play a limited role in PPI treatment failure. GERD-like symptoms can also result from a variety of other disorders, such as eosinophilic esophagitis (EoE), drug-induced esophagitis, infectious esophagitis, and achalasia, which should be considered. when differential diagnosis with patients whose symptoms do not improve.
Causes of resistant GERD:
Adherence to treatment and adherence to PPI Esophageal dysfunction Functional heartburn, oesophagitis hypersensitive, IBS Weakly acidic or acid-free reflux Weak acid reflux, Gastroduodenal reflux Residual Acidity Nocturnal acidosis (NAB), acid sacs Slow gastric emptying Rapid PPI metabolism Eosinophilic esophagitis Causes unrelated to GERD

3.1 Adherence and adherence to PPI use An important initial consideration for all patients who do not respond adequately to PPI therapy is the assessment of medication adherence, as regular dosing is important. to achieve maximum efficiency. Several studies indicate that PPI users have poor adherence, with 2 reports showing that only 53.8% and 67.7% of patients filled their monthly PPI prescriptions with more than 80%. Furthermore, many patients discontinue PPIs when their symptoms have resolved, as evidenced by a large population-based survey in which only 55% of patients took PPIs once daily for 4 weeks at follow-up. regulations, with 37% taking it on 12 or fewer days of the month.
Medication adherence is also important to investigate, as several studies show that patients are not taking PPIs at the appropriate time. A study of 100 patients with persistent GERD symptoms found that only 8% of patients reported taking their medication at the optimal time 30-60 minutes before a meal. Common reasons for non-compliance and non-compliance include absence of symptoms, personal preference, side effects, and lack of knowledge or misinformation about medications, as demonstrated by a survey. national survey that 36% of physicians do not give their patients instructions or incorrect instructions about taking medication at mealtime, 26% do not give instructions or say time is not important, and 10% incorrectly advised their patients to take their medication with or after food.
3.2 PPI drug selection Limited data are available for direct comparison of the effectiveness of different PPIs. Although some studies suggest that certain PPIs may be more effective for GERD, this is not supported by a meta-analysis of pooled data. Thus, the choice of PPI is an unlikely cause of refractory GERD.

Functional gastrointestinal disorders have traditionally been defined as symptomatic disorders with unknown structural, metabolic, or infectious etiology. Dysfunction may result from a diverse set of underlying mechanisms, which may include increased sensitivity of the mucosa to mechanical and chemical stimuli or worsening central perception of pain. .
4.1 Functional heartburn The Rome IV Standard defines functional heartburn as 3 months of burning pain in the retrosternal region with no evidence of ongoing reflux or an underlying movement disorder not relieved by therapy optimal secretion resistance. Up to 58% of patients with treatment-resistant GERD fall into this category.
4.2 Esophageal Hypersensitivity Esophageal hypersensitivity, defined as an excessive response to various stimuli, including acid, temperature, mechanical distension, and electrical stimulation, may contribute to persistent GERD symptoms despite PPI therapy. The mechanism of esophageal hypersensitivity is unclear but is likely related to both peripheral and central sensitization through dilated intracellular spaces (DISs) and exposure of subepithelial nerves to acid. Esophageal hypersensitivity can also be affected by stress, which can alter brain sensory processing, autonomic neuronal activity, cortisol release, and pathways involved in sensory signaling. reach the spinal cord.
Although the role of esophageal hypersensitivity in treatment failure with PPIs has not been clearly studied, most patients with refractory reflux have a lower pain threshold with esophageal distension or electrical stimulation. . Studies of GERD patients exposed to anxiety induction or acute auditory stress show an increased perceptual response to acid exposure and worsening of symptoms. Further supporting the contribution of esophageal hypersensitivity to refractory GERD, intracellular spaces have been shown to resolve in patients who respond to PPI therapy, but persist in those who do not. symptoms are still present.

Most people with GERD will have no serious complications, especially if treated. However, potentially serious complications can sometimes occur in people with severe GERD. Vinmec International General Hospital is a prestigious address trusted by many patients in performing diagnostic and treatment techniques for reflux esophagitis, refractory reflux esophagitis, gastritis .. Along with that, at Vinmec Hospital, the diagnosis through colonoscopy with the Olympus CV 190 endoscope, with the function (Narrow Banding Imaging - endoscopy with narrow light frequency band) gives imaging results. The analysis of mucosal pathology is clearer than that of conventional endoscopy, detecting ulcerative lesions, reflux in the esophagus, stomach, Barrett's modified lesions, and early cancerous lesions. .... Vinmec Hospital with modern facilities and equipment and a team of experienced experts who are always dedicated in medical examination and treatment, customers can rest assured with the online endoscopy service. colon at Vinmec International General Hospital.

References
Mermelstein J, Mermelstein AC, Chait MM. Proton pump inhibitors for the treatment of patients with erosive esophagitis and gastroesophageal reflux disease: current evidence and safety of dexlansoprazole. Clin Exp Gastroenterol. 2016;9:163–172. [PMC free article] [PubMed] [Google Scholar] Scarpellini E, Ang D, Pauwels A, De Santis A, Vanuytsel T, Tack J. Management of refractory typical GERD symptoms. Nat Rev Gastroenterol Hepatol. 2016;13(5):281–294. [PubMed] [Google Scholar] Horn J. The proton-pump inhibitors: similarities and differences. Clin Ther. 2000;22(3):266–280. discussion 265. [PubMed] [Google Scholar] Chiba N, De Gara CJ, Wilkinson JM, Hunt RH. Speed ​​of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology. 1997;112(6):1798-1810. [PubMed] [Google Scholar] Joseph Mermelstein, Alanna Chait Mermelstein, and Maxwell M Chait. Gastroesophageal reflux disease resistant to proton pump inhibitors: challenges and solutions. Clin Exp Gastroenterol. 2018; 11: 119–13 4.