Roy K. H. Wong

Prevalence of Eosinophilic Esophagitis in an Adult Population Undergoing Upper Endoscopy: A Prospective Study

BACKGROUND & AIMS Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration of the esophagus. The purpose of this prospective study was to determine the prevalence and clinical predictors of EoE in patients undergoing elective upper endoscopy. METHODS We enrolled 400 consecutive adults (median age, 50 years; range, 19-92 years) who underwent routine upper endoscopy from March to September 2007 at a tertiary care military hospital. All patients completed a symptom questionnaire. All endoscopic findings were noted. Eight biopsies were obtained from proximal and distal esophagus and were reviewed by a blinded gastrointestinal pathologist. Patients had EoE if > or =20 eosinophils/high-power field were present. RESULTS The prevalence of EoE in this cohort was 6.5% (25/385; 95% confidence interval, 4.3%-9.4%). Compared with EoE negative patients, EoE positive patients were more likely to be male (80.0% vs 48.1%, P = .003), younger than 50 years (72.0% vs 48.9%, P = .037), and have asthma (32.0% vs 10.8%, P = .006), a food impaction (32.0% vs 8.9%, P = .002), dysphagia (64.0% vs 38.1%, P = .018), and classic endoscopic findings (rings, furrows, plaques, or strictures) of EoE (all P < .01). Logistic regression identified asthma (odds ratio [OR], 4.48), male gender (OR, 4.23), and esophageal rings (OR, 13.1) as independent predictors of EoE. The presence of classic endoscopic findings of EoE had a sensitivity of 72% (54%-88%), specificity of 89% (87%-90%), and negative predictive value of 98% (95.6%-99.1%). CONCLUSIONS The prevalence of EoE in an outpatient population undergoing upper endoscopy was 6.5%. The characteristic findings of EoE patients included male gender, history of asthma, and the presence of classic findings of EoE on endoscopy, which is the strongest predictor of this disease process.

Correlation between eosinophilic oesophagitis and aeroallergens.

Aliment Pharmacol Ther 31, 509–515

ENT manifestations of gastroesophageal reflux.

Reflux laryngitis is a common disease and is probably only one of several laryngeal manifestations associated with GERD. The hypothesis that GER causes laryngeal symptoms and conditions remains to be definitively proved. In many patients, the cause of laryngeal symptoms may well be multifactorial, and to identify definitively those patients in which GER may be playing a role remains a challenge. Documentation of GER using 24-h pH monitoring may assist in identifying such patients. Pharyngeal pH probe monitoring, although not without limitations, may be the optimal method to evaluate such patients in terms of documenting the presence of EPR. A suggested algorithm based on the available data in evaluating and treating patients with suspected reflux laryngitis is shown in Figure 5. First, rule out other causes of hoarseness and laryngitis. An ENT consultation is appropriate for hoarseness present >4 wk. Second, empirically treat with PPIs b.i.d. for 2-3 months, as esophageal and pharyngeal pH monitoring is costly, not readily available, time consuming, and not sensitive in making the diagnosis of GERD related laryngitis. If the patient improves after 2-3 months, therapy should be stopped and the patient observed. If symptoms recur, reinstitution of the PPI at the lowest possible dose or with use of an H2RA to maintain remission should be initiated. Third, if no improvement is noted, the patient should undergo 24-h pH monitoring with an esophageal and, if possible, a pharyngeal probe if the diagnoses of GERD and EPR are still in question. In patients in whom there is a high suspicion for GERD, pH monitoring should be performed on PPI therapy to determine whether acid suppression is adequate. A pH probe should be placed in the stomach if the question to be answered is whether 1) the PPI regimen is maintaining a pH of >4, or 2) if the addition of a bedtime H2RA maintains nocturnal intragastric pH of >4 (52-56). Patients with a completely normal pH study who are on no medications should be referred back to the ENT physician for further evaluation, as other risk factors for chronic laryngitis such as voice overuse may benefit from concomitant voice therapy. If upright reflux is the predominant reflux pattern, increasing the b.i.d. PPI dose is reasonable; but if nighttime supine reflux is predominant, recent literature suggests that the addition of a bedtime H2RA will suppress nocturnal acid breakthrough. There are, however, no long-term studies with the PPI plus H2RA regimen that document persistent nocturnal acid suppression and that show clinically significant differences in patients with nocturnal acid breakthrough. Surgery should be cautiously considered for patients who are unresponsive to PPI therapy and who have documented or undocumented evidence of GERD or EPR. The body of experience concerning GERD and the extraesophageal manifestations of GERD suggests that patients who do not respond to adequate PPI acid suppression will do poorly after antireflux surgery.

Esophageal manometry and ambulatory 24-hour pH monitoring in patients with short and long segment Barrett's esophagus

Objective:Short segment Barretts esophagus (SSBE) is defined as the presence of specialized intestinal metaplasia (SIM) in the distal 2–3 cm of the esophagus. Although gastroesophageal reflux and heartburn is very common in these patients, the pathophysiology of the development of a short segment of SIM versus a longer segment of Barretts epithelium is not clear. The aim of this study was to assess the extent of gastroesophageal reflux in short versus long segments of SIM.Methods:Of 203 consecutive patients undergoing endoscopy with two biopsies performed just distal to the squamocolumnar junction, 28 patients were identified as having SSBE as evidenced by SIM on biopsy. Twenty-two SSBE patients underwent esophageal manometry and 24-h dual pH monitoring, and the results were compared with 18 long segment Barretts esophagus (LSBE) patients and 15 patients with normal 24-h pH studies.Results:SSBE and LSBE patients were significantly older than normal subjects (p < 0.0001). Also, lower esophageal sphincter pressure was significantly greater in SSBE patients compared with LSBE patients (12.3 ± 1.6 vs 5.2 ± 1.0 mm Hg, p < 0.0008). LSBE patients had a significantly lower distal esophageal peristaltic amplitude as compared with normals (p < 0.012). At 5 cm proximal to the LES, SSBE patients had significantly lower total 24-h pH scores, percent upright and percent supine reflux as compared with LSBE patients. Similarly, when measured at the proximal LES (0 cm), SSBE patients had significantly lower 24-h pH scores when compared with LSBE patients (p < 0.03), whereas percent upright and percent supine reflux were not significantly different. Both LSBE and SSBE patients had a greater degree of GER measured at 5 cm above and just proximal to the LES when compared with normals.Conclusion:As a group, SSBE patients have more competent LES sphincters and less gastroesophageal reflux at 0 and 5 cm above the LES as compared with patients with LSBE. These data indicate that the degree and length of acid exposure in the esophagus are important factors in the pathogenesis of SIM involvement of the esophagus.

Evaluation of gastroesophageal reflux as a cause of idiopathic hoarseness

Eleven patients presenting to an ear, nose, and throat specialist were diagnosed as having idiopathic hoarseness and prospectively evaluated for evidence of gastroesophageal reflux (GER) to determine if an association existed. Testing for GER included voice analysis, EGD, esophageal manometry, Bernstein test, and ambulatory 24-hr pH monitoring. Six of the 11 (55%) hoarse patients studied had GER by pH monitoring (mean score 105±23), and most reflux episodes were supine and prolonged (20.9±8.2% supine pH<4.0, longest 129 min). All patients with abnormal pH monitoring had endoscopic esophagitis (Barretts esophagus in two, peptic stricture in one, and erosive esophagitis in three), while none of the patients with normal scores had esophagitis. Symptoms of throat pain or nocturnal heartburn were more common in the GER-positive patients (6 of 6 vs 1 of 5), and clinically helpful in discriminating which hoarse patients had pathologic GER. Treatment with ranitidine 150 mgper os twice a day for 12 weeks improved esophagitis in all patients, but the voice improved in only one of the two patients with completely healed esophagitis. This study suggests that (1) GER is frequently seen in patients with idiopathic hoarseness (55%), (2) hoarse patients with throat pain or nocturnal heartburn are likely to have severe esophagitis and should be evaluated by EGD, and (3) additional antireflux and voice therapy may be necessary to heal esophagitis and improve the voice.

Significant DQw1 association in achalasia.

Achalasia is a neuromuscular disorder of the esophagus with unknown etiology. There have been suggestions that this disorder is immunologically mediated. To examine this possibility, HLA phenotyping was prospectively performed on 40 patients with documented achalasia (24 Caucasian, 16 blacks). Results showed a positive association for the class II HLA antigen, DQwl, with 83% of Caucasians (P <0.02) and 86% of blacks having the antigen (NS). The relative risk for developing achalasia with the presence of DQw1 was 4.2 in Caucasians and 3.6 in blacks. A negative correlation for the DRw53 antigen was noted in Caucasian patients with a relative risk of 0.23. These results indicate an immunogenetic association for achalasia and provide insight into the pathogenesis of this disorder.Achalasia is a neuromuscular disorder of the esophagus with unknown etiology. There have been suggestions that this disorder is immunologically mediated. To examine this possibility, HLA phenotyping was prospectively performed on 40 patients with documented achalasia (24 Caucasian, 16 blacks). Results showed a positive association for the class II HLA antigen, DQwl, with 83% of Caucasians (P <0.02) and 86% of blacks having the antigen (NS). The relative risk for developing achalasia with the presence of DQw1 was 4.2 in Caucasians and 3.6 in blacks. A negative correlation for the DRw53 antigen was noted in Caucasian patients with a relative risk of 0.23. These results indicate an immunogenetic association for achalasia and provide insight into the pathogenesis of this disorder.

Eosinophilic oesophagitis and proton pump inhibitor-responsive oesophageal eosinophilia have similar clinical, endoscopic and histological findings.

Some patients with a phenotypic appearance of eosinophilic oesophagitis (EoE) respond histologically to PPI, and are described as having PPI‐responsive oesophageal eosinophilia (PPI‐REE). It is unclear if PPI‐REE is a GERD‐related phenomenon, a subtype of EoE, or a completely unique entity.

Nocturnal reflux episodes following the administration of a standardized meal. Does timing matter

OBJECTIVES:Prospective evidence supporting lifestyle modifications, including avoidance of late evening meals, for gastroesophageal reflux disease (GERD) sufferers is lacking. The aim of this study was to determine the difference of supine esophageal acid exposure in patients consuming an early or late standard meal relative to bedtime.METHODS:This is a prospective, randomized unblinded crossover trial. Thirty-two patients with typical reflux symptoms were enrolled and randomized to consume a standard meal either at 6 h or 2 h prior to going to bed for 2 consecutive nights. Acid exposure was measured for 48-h using a Bravo wireless pH system. Reflux symptom frequency and severity were recorded.RESULTS:Thirty patients successfully completed the study (63% male, 70% white, mean age 46 [24–74], mean body mass index [BMI] 28 kg/m2 [18–40]). EGD revealed esophagitis in 37% and hiatal hernia (HH) in 47% of patients. Following the late evening meal, there was significantly more supine reflux (P = 0.002) when compared to the early meal. Significantly more supine reflux was also noted following the late evening meal in patients with HH, in overweight individuals (25 ≤ BMI ≤ 29.9), and those reporting heartburn as their chief complaint. Patients with esophagitis had more supine reflux following both the late and early evening meals. There was no significant difference in total symptom score between the 2 days.CONCLUSIONS:GERD patients consuming a late-evening meal had significantly greater supine acid reflux compared to when they consumed an early meal, especially in overweight patients, and in patients with esophagitis or HH. These findings support the recommendations to our GERD patients to eat dinner early and to lose weight.

Reflux laryngitis: pathophysiology, diagnosis, and management

Gastroesophageal reflux disease is felt to be associated with a variety of laryngeal conditions and symptoms of which “reflux laryngitis” is perhaps the most common. The most likely mechanism for laryngeal injury and symptoms is secondary to direct acid and pepsin contact, although studies concerning the cause and effect between gastroesophageal reflux disease and laryngeal disorders are conflicting. Likewise, the most effective method to diagnose such patients is unclear. Empiric treatment of patients with reflux laryngitis has been shown to be effective though none of the studies are controlled.

Extraesophageal manifestations of GERD

&NA; The association between gastroesophageal reflux disease (GERD) and extraesophageal disease is often referred to as extraesophageal reflux (EER). This article reviews EER, discussing epidemiology, pathogenesis, diagnosis, and treatment with a focus on the most studied and convincing EER disorders—asthma, cough, and laryngitis. Although EER comprises a heterogeneous group of disorders, some general characterizations can be made, as follows. First, although GERDs association with extraesophageal diseases is well‐established, definitive evidence of causation has been more elusive, rendering epidemiological data scarce. Secondly, regarding the pathogenesis of EER, 2 basic models have been proposed: direct injury to extraesophageal tissue by acid and pepsin exposure or injury mediated through an esophageal reflex mechanism. Third, because heartburn and regurgitation are often absent in patients with EER, GERD may not be suspected. Even when GERD is suspected, the diagnosis may be difficult to confirm. Although endoscopy and barium esophagram remain important tools for detecting esophageal complications, they may fail to establish the presence of GERD. Even when GERD is diagnosed by endoscopy or barium esophagram, causation between GERD and extraesophageal symptoms cannot be determined. Esophageal pH is the most sensitive tool for detecting GERD, and it plays an important role in EER. However, even pH testing cannot establish GERDs causative relationship to extraesophageal symptoms. In this regard, effective treatment of GERD resulting in significant improvement or remission of the extraesophageal symptoms provides the best evidence for GERDs pathogenic role. Finally, EER generally requires more prolonged and aggressive antisecretory therapy than typical GERD requires.