22 Gastroesophageal Reflux Disease and Infectious Esophagitis


22 Gastroesophageal Reflux Disease and Infectious Esophagitis

Hye Yeon Jhun and Prateek Sharma

Gastroesophageal reflux disease (GERD) is one of the most common reason for a patient to visit to a gastroenterologist. This is characterized as a condition when reflux of the stomach contents into the esophagus cause troublesome symptoms and complications. 1 It remains a highly prevalent disease worldwide with an estimate of 18 to 28% in North America with only East Asia showing prevalence less than 10%. 2 GERD includes a constellation of symptoms including heartburn, regurgitation, dysphagia, chest pain, and extraesophageal syndromes including chronic cough, asthma, and laryngitis that can easily affect the quality of life. 3 In addition, the spectrum of injury and long-term complications include erosive esophagitis, esophageal stricture formation, and Barrett’s esophagus which can progress to esophageal adenocarcinoma. 4 Therefore, accurate diagnosis and appropriate management are imperative.

22.1 Diagnostic Approaches

A presumptive diagnosis of GERD can be made in the setting of typical symptoms including heartburn and regurgitation. 5 An empiric trial with proton pump inhibitor (PPI) can be a simple method for diagnosing GERD and assessing symptoms. GERD can be established if symptoms respond to 1 to 2 weeks of therapy and recur when medication is discontinued. Although practical, this approach has shown to have a sensitivity of 78% and a low specificity of 54% with using 24-hour pH monitoring as a reference standard, suggesting that a negative trial with PPI does not rule out GERD. 6

Upper gastrointestinal (GI) endoscopy is the standard diagnostic method used to evaluate the esophageal mucosa in patients with GERD. This should be especially considered in patients with alarm symptoms such as dysphagia, odynophagia, involuntary weight loss, evidence of GI bleeding, anemia, abnormal imaging studies, persistent vomiting for 7 to 10 days 7 or inadequate response to appropriate medical therapy. Endoscopic findings suggestive of reflux esophagitis include the presence of definitive mucosal breaks (erosions), ulceration, peptic stricture, and Barrett’s esophagus. However, more than 50% of patients with heartburn and regurgitation have normal endoscopic findings. Thus, the sensitivity of diagnosing GERD by endoscopy is low, but the specificity has been reported as high as 90 to 95%. 8

Erosive esophagitis has been reported in up to 30 to 40% in patients with GERD symptoms. 9 However, the correlation between severity of GERD symptoms and degree of underline esophageal mucosal damage is poor. Early signs of acid reflux could potentially include subtle findings of erythema and edematous changes of the mucosa. With progressive acid injury, erosions can develop near the gastroesophageal junction (GEJ) that are characterized by a mucosal break with whitish or yellowish exudates.

There are multiple classification systems that have been developed to characterize the degree and severity of erosive esophagitis. The most commonly used classification systems are the Los Angeles (LA) classification and Savary-Miller system that have been used in multiple clinical studies and practices to document the severity of the disease. The LA classification (▶Table 22.1, ▶Fig. 22.1) has excellent intraobserver and interobserver reliability regardless of the experience of the endoscopist 10 and is commonly used in clinical practice to document disease severity.

Table 22.1 Los Angeles classification of erosive esophagitis




Los Angeles


One (or more) mucosal break not longer than 5 mm that does not extend between the tops of two mucosal folds



One (or more) mucosal break longer than 5 mm that does not extend between the tops of two mucosal folds



One (or more) mucosal break that is continuous between the tops of more than two mucosal folds but involves < 75% of the circumference



One (or more) mucosal break that involves at least 75% of the circumference

Fig. 22.1 Los Angeles classification of erosive esophagitis.

Endoscopy also provides utility as biopsy for histology can be obtained during the procedure. It is currently recommended to take biopsies for esophagitis for immune-compromised patients, to rule out eosinophilic esophagitis in those with dysphagia, presence of irregular or deep ulcers, proximal location of esophagitis, columnar lined esophagus, presence of esophageal mass, nodularity, and irregular esophageal strictures to rule out other diagnosis including infection and malignancy. 7 Furthermore, endoscopic evaluation is recommended by several guidelines in patients with chronic GERD with multiple risk factors including male gender, age above 50 years, Caucasian race, and central obesity to screen for Barrett’s esophagus. 11

Ambulatory pH monitoring is another diagnostic test for GERD that allows correlation between symptoms and reflux episodes and determines reflux frequency and abnormal esophageal acid exposure. This can be performed by either insertion of a transnasal catheter (impedance–pH monitoring for 24 hours) or by placing a telemetry capsule (pH monitoring for 48 hours) endoscopically. Reflux monitoring is recommended while off PPI in both modalities, however, testing on PPI can be performed with impedance–pH monitoring to measure nonacid reflux. 5

22.2 Therapeutic Approaches

Treatment for GERD should be targeted based on specific goals. For patients without erosive esophagitis, the goals are to provide complete or sufficient control of symptoms and to prevent symptomatic relapse. For patients with esophagitis, the goals are to heal the underline mucosa, maintain endoscopic remission, and to treat and prevent possible complications. 12

Lifestyle modifications should be recommended in all patients with GERD. Several randomized control studies have demonstrated improvement in GERD symptoms and esophageal acid exposure as measured by 24-hour pH testing when the head of the bed is elevated by wedges or blocks specially in patients that have nocturnal GERD. 13 , 14 , 15 , 16 Multiple case–control studies 15 , 16 have shown significant association between weight loss and improvement in GERD symptoms and esophageal acid exposure. Increase in body mass index (BMI), even in patients with normal BMI of more than 3.5 was associated with increased reflux symptoms. Therefore, it is recommended to encourage weight reduction in patients with BMI greater than 25 or patients with recent weight gain. 7 Smoking cessation in normal-weight individuals on antireflux therapy have also shown to reduce reflux symptoms in a large prospective cohort study. 17 Currently, there is insufficient evidence to show clinical improvement with cessation of caffeine, chocolate, or carbonated beverages, and this is not routinely recommended unless patients notice correlation of symptoms and symptom improvement with elimination. 3

Medical options for GERD include antacids, histamine-receptor antagonists (H2RA), or PPI therapy. PPI therapy has shown to have a significantly faster healing rate and relief of symptoms compared to H2RA in all grades of erosive esophagitis. 18 A meta-analysis of 7,635 patients with erosive esophagitis reported overall improvement with PPI therapy in 84% of the patients compared to 52% with H2RA therapy and 28% with placebo. 18 Currently, an 8-week course of PPI is the standard treatment for patients with erosive esophagitis. No clinically significant difference in efficacy between different PPIs have been demonstrated. 19 Maintenance therapy with PPI should be considered to those who have recurrent symptoms once PPI is discontinued and in patients with erosive esophagitis and Barrett’s esophagus. 5 A double-blinded comparison study with lansoprazole and ranitidine for long-term maintenance therapy of healed erosive esophagitis after acute treatment in 1 year showed 67% treated with lansoprazole remained healed, compared to 13% treated with ranitidine. 20

22.3 Surgical Therapy

Surgical therapy (Nissen’s fundoplication) is another long-term therapy option for patients with chronic GERD. This can be considered in patients who wish to discontinue medical therapy, who have refractory esophagitis, or persistent symptoms specifically regurgitation in those with documented GERD. The best response to surgical therapy is seen in those GERD patients with typical symptoms and those with a good response to PPI therapy. In a randomized, open study by Galmiche et al, 21 a total of 372 patients were randomized to receive either PPI or undergo laparoscopic antireflux surgery (LARS) for chronic GERD and were followed up for 5 years. Symptom remission was reported in 92% of the patients on PPI and in 85% who received surgical fundoplication at 5 years. Complication rates were similar in both groups: 24% in PPI group and 29% in LARS group. Overall, this study demonstrated that most patients remained in remission with either antireflux therapy for GERD in 5 years.

A recent advance in minimally invasive surgical approaches to GERD has been the use of the “Linx” procedure, which gives augmentation of the esophageal sphincter with a magnetic device. This can be considered in patients who have incomplete response with PPI or who are reluctant to undergo surgical fundoplication. A recent study by Ganz et al 22 prospectively assessed 100 patients with GERD before and after sphincter augmentation. This showed a decrease of acid exposure in 64% of the patients and decreased use of PPI in 93% of the patients. Most frequent adverse effects were dysphagia seen in 68% of patients postoperatively, which was 11% at 1 year and 4% at 3 years.

22.4 Endoscopic Therapy for GERD

Endoscopic therapies for GERD include radiofrequency energy, suturing, and transoral incisionless fundoplication (TIF). The “Stretta” procedure is a technique that uses radiofrequency energy to the lower esophageal sphincter. In theory, this is to induce muscle proliferation and fibrosis in the submucosa and muscle layer to create a less compliant esophagus. However, there are no human histopathologic data to indicate increase in smooth muscle density after the Stretta procedure at this time. The two main physiologic effects of the Stretta procedure are to create an increase in lower esophageal sphincter pressure and a decrease in transient lower esophageal relaxations.

An open-label trial in 118 patients observed objective improvement in esophageal acid exposure and GERD symptom scores with repeat measured analysis in 12 months. 23 Subsequent studies have demonstrated Stretta to eliminate PPI usage in 43 to 72% of the patients and achieving effective and satisfactory long-term symptom control for 5 to 10 years with infrequent adverse effects. 24 , 25 Corley et al 26 studied 64 patients who were randomized to receive either Stretta (n = 35) or sham (n =29) therapy. This study showed that radiofrequency energy delivery improved reflux symptoms and quality of life, but did not decrease the acid exposure time or medication use in 6 months compared to the sham group. A recent meta-analysis 27 including four randomized control trials overall demonstrated no difference with Stretta versus sham in acid exposure time, PPI withdrawal, or quality of life. Overall studies have not shown consistent efficacy with Stretta therapy and therefore, is not recommended as an alternative over medical therapy or surgery for treatment of GERD. 5

TIF procedure has gone through a number of technical revisions since its initial approval in 2007 to closely replicate surgical fundoplication. The device is placed in the stomach to construct a full-thickness plication with polypropylene stiches 3 to 5 cm above the GEJ to create a gastroesophageal flap valve. 28 Most studies involving TIF have been based on short-term follow-up. In a recent randomized, blinded, sham-control trial with 129 patients which excluded patients with hiatal hernia greater than 2 cm in length showed TIF to eliminate troublesome regurgitation in 67% of the patients compared to 45% in patients who received sham treatment and PPI in 6 months. 29 TIF was also associated with decrease in number of reflux episodes and showed modest improvement of intraesophageal pH. However, it failed to provide improvement in heartburn symptoms suggesting this procedure may not be useful for PPI refractory heartburn patients.

Limited studies with long-term follow-up have reported that TIF may provide reduction or cession of PPI use up to 2 to 6 years. 30 , 31 , 32 Periprocedural complication rates have been described to be low. Among 492 patients who underwent TIF procedure, both esophageal perforation and pneumothorax were reported as 0.4%. 33 Although there is no evidence to propose, TIF is more effective than surgical fundoplication. TIF can be considered most effective in a subgroup of patients with chronic GERD with hiatal hernia less than 2 cm. 31 , 32 Therefore, careful patient selection and experience of the endoscopist should be considered prior to receiving therapy. Further prospective studies evaluating long-term treatment efficacy and complications are needed in this field.

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May 22, 2020 | Posted by in GASTROENTEROLOGY | Comments Off on 22 Gastroesophageal Reflux Disease and Infectious Esophagitis
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