Prevalence of asymptomatic erosive esophagitis and factors associated with symptom presentation of erosive esophagitis

Abstract

Objective. Asymptomatic erosive esophagitis (EE) is incidentally found during endoscopy for health screening. The authors have aimed to investigate the prevalence of asymptomatic EE in subjects undergoing health checkups and factors associated with symptom presentation of EE. Methods. Among the consecutive 13,342 adults who underwent esophagogastroduodenoscopy in health checkup programs of Ajou University Hospital from May 2010 to April 2011, 8840 subjects (5683 men and 3157 women; median age, 45 years) who met the enrollment criteria were included in the analysis. They completed a questionnaire that evaluated smoking, medication history, anxiety, depression, esophagopharyngeal symptoms, and dyspeptic symptoms. The mucosal damage of the esophagus was assessed using the Los Angeles classification system. Individuals who had EE but no esophagopharyngeal symptoms were classified into the asymptomatic EE group. Results. A total of 768 subjects were diagnosed with gastroesophageal reflux disease based on the occurrence of heartburn and/or acid regurgitation at least once a week. The prevalence of symptomatic and asymptomatic EE in 8840 subjects was 4.3% and 3.3%, respectively. About 43% of individuals with EE did not exhibit any esophagopharyngeal symptoms. Male gender and postprandial distress syndrome were independently associated with asymptomatic EE. Male gender, current smoking, anxiety, epigastric pain syndrome (EPS), and postprandial distress syndrome were independently associated with symptomatic EE. Compared with the asymptomatic EE group, anxiety and EPS were independent factors associated with symptomatic EE. Conclusions. Asymptomatic EE is common in subjects undergoing a health checkup. The coexistence of anxiety or EPS appears to be the predictors for the symptom presentation of EE.     

Efficacy of famotidine 20 mg twice a day versus 40 mg twice a day in the treatment of erosive or ulcerative reflux esophagitis

Two different doses of famotidine (20 mg twice a day versus 40 mg twice a day) were evaluated in a double-blind, randomized multicenter study in 474 symptomatic patients with erosive ulcerative reflux esophagitis. A total of 238 patients were treated with famotidine 20 mg and 236 patients with 40 mg at breakfast and dinnertime. Relief of symptoms was significant in all patients after six and 12 weeks and not different in both treatment groups. Overall endoscopic healing was significantly better in the famotidine 40 mg twice a day group compared with 20 mg twice a day at week 6 (58% versus 43%;P<0.05) and at week 12 (76% versus 67%;P<0.05). Extending treatment to 24 weeks with 40 mg of famotidine twice a day in those patients not healed after 12 weeks did not result in further symptom relief or in significantly better overall healing. The differences in efficacy of these two doses were more pronounced with increasing severity of esophagitis. Analyzed by grade of esophagitis at entrance, healing was significantly better with famotidine 40 mg twice a day at week 6 for grade II, at week 12 for grades III and IV, and at week 24 for grade IV esophagitis. The results show that in the treatment of erosive/ ulcerative reflux patients famotidine 40 mg twice a day is more effective and achieves faster healing than famotidine 20 mg twice a day.for the Dutch Esophagitis Study Group.Participating physicians: P. Batenburg, J. Beker, J. Bellaar Spruijt, L. van Bergeijk, J. Bergmann, W. Bode, J. de Boer, H. Boot, G. Dorrepaal, J. Douma, J. Drapers, J. Ferwerda, H. Festen, A. Geraedts, J. Götz, E. van der Hoek, R. van Hogezand, J. Juttmann, M. Kloppenburg, F. Lalisang, W. Lesterhuis, D. van der Linde, G. van der Linden, J. van Maanen, J. Minkema, C. Mulder, I. van Munster, J. Nadorp, G. Nelis, J. Nicolai, R. Ouwendijk, D. Overbosch, A. van der Putten, J. Raats, F. Schuitemaker, J. Sindram, G. Slagboom, P. Snel, P. Stijnen, J. Thies, J. Thijs, H. Tuynman, B. Uyterlinde, J. ten Veen, K. te Velde, M. Vidakovic-Vukic, F. Vismans, A. Vogten, G. Vosmaer, P. de Vries, H. Walinga, S. van der Werf, I. Wesdorp, B. Westerveld, A. Wolff, R. Ypma.This study was supported by a grant from Merck Sharp & Dohme, The Netherlands.This study was presented in part at the annual meeting of the American Gastroenterology Association, May 1991 (Gastroenterology 100:63A, 1991).     

Efficacy of leukotriene receptor antagonist for erosive esophagitis: a preliminary retrospective comparative study

While diagnostic overlap exists between gastroesophageal reflux disease and eosinophilic esophagitis especially on histological findings, therapeutic approaches for the two disease entities are very different. Recently, anti-inflammatory treatment, in addition to acid suppressants, has been investigated for gastroesophageal reflux disease. This study investigated whether the incidence of endoscopic erosive esophagitis was lower in recipients of long-term leukotriene receptor antagonist (LTRA) treatment. This retrospective comparative study included 207 recipients of an LTRA and an equal number of controls who underwent screening upper endoscopic examination. Twenty-two (10.6%) and 51 (24.6%) cases of erosive esophagitis were detected in the LTRA and control groups, respectively (P < 0.001). A significantly higher incidence of minimal change esophagitis was also found in the controls compared with the LTRA group (14.5% vs. 2.4%, P < 0.001). On multivariate analysis, LTRA treatment was significantly and inversely associated with erosive esophagitis (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.13 to 0.46). Within the LTRA treatment group, an increased risk of erosive esophagitis was strongly associated with the presence of hiatal hernia (OR, 5.89; 95% CI, 2.20-15.73, P < 0.001) and short duration of LTRA treatment (OR, 0.64; 95% CI, 0.37-0.89, P= 0.022). In conclusion, this preliminary retrospective analysis demonstrated that patients who underwent long-term treatment with a LTRA had low incidence of endoscopic minimal change esophagitis.     

Randomized comparative study of omeprazole and famotidine in reflux esophagitis

BACKGROUND: Although proton pump inhibitors (PPI) and H2-receptor antagonists (H2-RA) are routinely used in the treatment of reflux esophagitis (RE), no consensus has been reached yet as to whether the first-choice drug should be PPI or H2-RA. In this study, the effects of omeprazole (OMP) and famotidine (FAM) on RE have been examined in a randomized comparative study. METHODS: Protocols of OMP 20 mg once daily or FAM 20 mg twice daily for 8 weeks were allocated to 56 cases with RE at random, using an envelope randomization method. Their efficacy in achieving healing was examined endoscopically and a relief from subjective symptoms was compared. RESULTS: Patient's background such as sex, age, recurrence, hiatal hernia, smoking and drinking habits, and complications, and the severity of esophagitis at the time of enrolment were not significantly different between the two groups. Healing in the OMP group and the FAM group was observed in 72 and 32% (P = 0.025) of patients at week 4 and 95 and 53% (P = 0.003) of patients at week 8, respectively. Subjective symptoms were relieved more frequently in the OMP group (at week 2, 67% compared with 29%, P = 0.005; at week 4, 95% compared with 55%, P = 0.009), but this superiority was not significant at week 8 (94% compared with 65%, P = 0.085). No serious adverse events occurred. CONCLUSIONS: Omeprazole provided quicker healing and a greater relief from subjective symptoms than did FAM in the treatment of RE, and was considered more suitable as a first-choice drug.     

Male sex, hiatus hernia, and Helicobacter pylori infection associated with asymptomatic erosive esophagitis

Background and Aims: Asymptomatic erosive esophagitis (AEE) is an easily forgotten subgroup of gastroesophageal reflux disease due to its lack of warning symptoms, despite having the risk of developing complications, such as bleeding, stricture, or even esophageal adenocarcinoma. Methods: A total of 2843 potentially eligible patients were screened at the health management center of Buddhist Tzu Chi General Hospital. A total of 1001 patients responded to the survey and gave informed consent; 998 patients who completed the reflux disease diagnostic questionnaire were enrolled. Of them, 594 patients who had no reflux symptoms were included for final analysis. The presence and severity of erosive esophagitis was graded according to the Los Angeles classification. Active infection of Helicobacter pylori (H. pylori) was determined by the Campylo‐like organism (CLO) test during endoscopies. Results: A total of 14.5% (86/594) of asymptomatic patients had endoscopic findings of erosive esophagitis. In the univariate analysis, male sex and hiatus hernia were significantly associated with AEE. Positive CLO tests had a trend association. Based on the multivariate analysis, male sex (odds ratio [OR]: 2.32, 95% confidence interval [CI]: 1.35–3.98), hiatus hernia (OR: 4.48, 95% CI: 2.35–89.17), and positive CLO test (OR: 0.57, 95% CI: 0.34–0.95) were associated with AEE, as compared to the healthy controls. Conclusions: AEE is not a rare condition, and constitutes 14.5% of the asymptomatic population. Male sex, hiatus hernia, and H. pylori infection are factors associated with AEE. These findings are not only helpful in identifying such asymptomatic patients, but also provide information to improve understanding of the relationship between H. pylori infection, reflux symptoms, and erosive esophagitis.     

幽门螺杆菌感染与反流性食管炎相关关系分析

[目的]探讨幽门螺杆菌感染与反流性食管炎的相关关系。[方法]将经电子胃镜检查确诊为反流性食管炎患者90例(反流性食管炎组)及慢性胃炎患者100例(慢性胃炎组),同时经13 C尿素呼气试验法进行幽门螺杆菌检测,对比2组幽门螺杆菌感染情况。将反流性食管炎组患者根据内镜分级标准分为4级,比较各级间的幽门螺杆菌感染情况;根据临床症状程度分为轻、中、重度,比较各程度间的幽门螺杆菌感染情况。[结果]反流性食管炎组幽门螺杆菌感染率(36.7%)明显低于慢性胃炎组(65.0%),差异有统计学意义(P0.01)。反流性食管炎组不同内镜分级及不同临床症状程度者间的幽门螺杆菌感染率比较,差异均无统计学意义(P0.05)。[结论]幽门螺杆菌感染可能在反流性食管炎的发生过程中起保护作用,幽门螺杆菌与反流性食管炎及患者症状程度无相关性。     

Clinical characteristics of asymptomatic esophagitis

Background. Asymptomatic esophagitis is not rare in gastroesophageal reflux disease. However, little attention has been given to this disease so far. We evaluated the clinical characteristics of patients with asymptomatic esophagitis and determined the factors associated with this disease. Methods. A cross-sectional survey was performed of 87 patients with esophagitis, aged 23 to 90 years, diagnosed by endoscopy. We assessed 12 clinical variables at the time of the endoscopy: symptoms, age, sex, severity of esophagitis (Los Angeles classification), grade of gastric mucosal atrophy, presence or absence of Barrett’s epithelium and sliding hernia, alcohol, smoking, body-mass index (BMI), comorbid diseases such as hypertension, diabetes and asthma, and medications such as calcium blocker and theophylline. Results. Most patients had grade A or B esophagitis; 64 patients were symptomatic, and the remaining 23 were asymptomatic. In a univariate analysis, the assessed variables sex, BMI, drinking, and smoking (habit and amount of consumption) were associated with asymptomatic esophagitis (P < 0.05). Then, multivariate logistic analysis performed using these four variables demonstrated that sex, BMI, and smoking (habit and number of cigarettes smoked daily) were significantly and in dependently associated with this disease (P < 0.05). Conclusions. Smoking, male sex, and lower BMI are independent factors associated with asymptomatic esophagitis. Since no information is available on the natural history of this disease, we should pay attention to patients with these characteristics.     

Differences in the risk factors of reflux esophagitis according to age in Korea

The prevalence of gastroesophageal reflux disease in Korea has been believed to be low, but the incidence of gastroesophageal reflux disease in Korea is expected to increase because of the longer life expectancy and more ingestion of westernized food. The aim of this study was to report differences in the risk factors of reflux esophagitis (RE) according to age in Korea. We prospectively recruited the subjects who had RE among those who visited a health promotion center for upper gastrointestinal cancer surveillance at Hallym Medical Center (five institutions) between January 2008 and February 2009. The enrolled study participants comprised 742 subjects with RE and 1484 healthy controls. The independent risk factors of RE in young and adult group were male sex, smoking, coffee, body mass index ≥ 25, hiatal hernia, and Helicobacter pylori negativity. The risk factors of RE in elderly group were smoking, coffee, and hiatal hernia. The risk factors for RE according to age group were found to differ. In elderly group, Helicobacter pylori infection was not a significant protective factor contrary to young and adult groups.     

Helicobacter pylori eradication may induce de novo, but transient and mild, reflux esophagitis: Prospective endoscopic evaluation

Backgrounds and Aim:  The effect on reflux esophagitis of eradicating Helicobacter pylori is variable and not fully defined. We previously reported that in patients who have reflux esophagitis associated with duodenal ulcer, a significant improvement in the pre-existing reflux esophagitis occurred after H. pylori was eradicated. In the present study, we asked whether H. pylori eradication leads to de novo development of reflux esophagitis in peptic ulcer patients.
Methods:  Prospective post-eradication evaluations were conducted in 1195 H. pylori -positive patients with peptic ulcer diseases who were confirmed not to have reflux esophagitis by endoscopic examination before eradication therapy. After eradication therapy, endoscopy and a urea breath test were performed yearly.
Results:  A total of 1187 patients were followed for up to 10.0 years (a mean of 3.6 years). Reflux esophagitis developed in 279 of 1000 patients cured of infection and in 26 of 187 patients who had persistent infection ( P  < 0.0001, Fisher's exact test). The esophagitis was mild (Los Angeles grade A) in most patients, transient in approximately one-half, and rarely necessitated long-term medication for the condition. Cure of infection, alcohol consumption, younger age, and high body mass index were identified as significant factors for the risk of developing non-transient reflux esophagitis.
Conclusions:  Cure of H. pylori infection may increase the risk of developing reflux esophagitis in patients with peptic ulcer, but the esophagitis is mostly mild and transient, and long-term medication is rarely required. Thus, H. pylori eradication therapy need not be withheld for fear of provoking reflux esophagitis.     

Macroscopic healing of esophagitis does not improve esophageal motility

The purpose of the present study was to prospectively determine if healing of esophagitis as assessed by endoscopy results in improved esophageal motility. Thirty-one patients with erosive esophagitis who were randomized to receive either omeprazole 20 mg once daily or placebo completed the double-blind study. All patients underwent endoscopy and esophageal motility before treatment and at four weeks after treatment. Twenty-two healthy volunteers underwent esophageal manometry and served as normal controls. Manometric tracings were coded, randomized, and analyzed blindly. Compared to normal controls, patients with esophagitis had significantly lower LESP, decreased amplitude of peristaltic contractions, and increased occurrence of abnormal contractions. Omeprazole was superior to placebo in healing of esophagitis. However, healing of esophagitis was not associated with any improvement in esophageal motility. The manometric data suggest that the motility disturbance seen in esophagitis is not secondary to the esophagitis but rather a primary phenomenon. The lack of improvement of esophageal motility with healing may explain the high recurrence of esophagitis in clinical trials following discontinuation of omeprazole.This work was supported by a grant from Astra Canada, Mississauga, Ontario, Canada.     

Endoscopic reflux esophagitis in patients with upper abdominal pain-predominant dyspepsia

BACKGROUND: Reflux symptom assessment had reliable accuracy in the diagnosis of gastroesophageal reflux disease (GERD). However, patients may recognize heartburn or regurgitation as dyspepsia because of inaccurate understanding or atypical presentation. The aim of the present study was to estimate endoscopic reflux esophagitis in patients with upper abdominal pain as a predominant symptom in the absence of heartburn or regurgitation. METHODS: Two hundred and sixty-three consecutive patients presenting dyspepsia without heartburn or regurgitation were enrolled. Patients with heartburn or regurgitation were excluded using the symptom interviewer method. Dyspepsia was categorized into pain-predominant or dysmotility-predominant groups according to the Rome II proposal. Endoscopic reflux esophagitis was graded using the Los Angeles classification. RESULTS: One hundred and five patients were included in the pain-predominant group and 119 in the dysmotility-predominant group. Reflux esophagitis was found in 18.8% (42/224) of all dyspeptic patients. Grade A esophagitis was noted in 27.6% (29/105) of the pain-predominant group and in 7.6% (9/119) of the dysmotility-predominant group. Grade B was noted in two patients in each group. A total of 29.5% (31/105) and 9.3% (11/119) had reflux esophagitis, respectively (P < 0.001). Comparing patients with or without reflux esophagitis, there was no difference in body mass index, smoking habit, alcohol consumption, or Helicobacter pylori infection status. CONCLUSIONS: A significant proportion of patients presenting dyspepsia, especially pain-predominant dyspepsia, have endoscopic reflux esophagitis. In view of GERD, pain-predominant dyspepsia should be investigated and managed differently from dysmotility-predominant dyspepsia.     

Healing of severe reflux esophagitis with PPI does not improve esophageal dysmotility

Esophageal dysmotility is frequently associated with gastroesophageal reflux disease (GERD). The aim of this study was to investigate the relationship between the severity of reflux esophagitis and esophageal dysmotility and evaluate the effect of prolonged treatment with proton pump inhibitor (lansoprazole 30 mg/day) on esophageal motility in patients with severe reflux esophagitis associated with esophageal motility disorder. Twelve healthy subjects (HS) and 100 patients with reflux disease were involved in the study consisting of two parts: (i) comparison of esophageal motility in HS and patients with non-eroseive reflux disease (NERD), mild esophagitis and severe esophagitis; (ii) effect of 3-6 months lansoprazole therapy on esophageal motility in 23 patients with severe esophagitis, pathologic acid reflux and esophageal peristaltic dysfunction. Results included the following. (i) Esophageal dysmotility was noted in both patients with NERD and erosive GERD. (ii) Severe esophagitis was associated with severe esophageal dysmotility. (iii) Healing of severe esophagitis did not improve esophageal dysmotility. The resting lower esophageal sphincter pressure was 3.9 mmHg (range 1.7-20) before treatment and 4.8 mmHg (range 1.2-18.3) after esophagitis healing (P = 0.23, vs. before treatment), the amplitude of distal esophageal contraction was 28.8 mmHg (range 10.9-80.6) before treatment and 33.3 mmHg (range 10.0-72.5) after esophagitis healing (P = 0.59, vs. before treatment) and the frequency of failed peristalsis was 70% (range 0-100%) before treatment and 70% (range 0-100%) after esophagitis healing (P = 0.78, vs. before treatment). Both esophageal motility disorders and acid reflux play important roles in the mechanism of GERD, especially in severe esophagitis. Esophageal dysmotility is not secondary to acid reflux and esophagitis; it should be a primary motility disorder.     

Erosive esophagitis in the Philippines: a comparison between two time periods

BACKGROUND: In Asia, the incidence of gastroesophageal reflux disease diagnosed through endoscopy has increased from 3-9% to 14-16% in the last decade. The aim of this study was to determine the prevalence of erosive esophagitis (EE) over a span of 10 years in a tertiary care facility in the Philippines. METHODS: All patients diagnosed with EE from 1994 to 1997 (period A) and from 2000 to 2003 (period B) were included in the study. The modified Savary-Miller and Los Angeles classifications were used to grade EE for periods A and B, respectively. RESULTS: A total of 15 981 upper endoscopies were evaluated for this study. There was no significant difference in the male: female ratio (period A 1.43:1 vs period B 1.25:1, P = 0.459) and in the mean age of patients with EE (period A 46.4 vs period B 47.5, P = 0.395). The prevalence of EE was significantly higher (P < 0.0001) in period B (6.3%) as compared to period A (2.9%). However, despite a higher prevalence, more patients had mild esophagitis in period B as compared to period A. Conversely, there were more patients with esophageal ulcers (18.6%vs 5.9%, P < 0.001), esophageal strictures (2.3%vs 0%, P = 0.003), and hiatal hernia (15.8%vs 7.5%, P = 0.001) in period A. The presence of concomitant Barrett's esophagus was not significantly different between the two time periods (period A 3.2%vs period B 5%, P = 0.367). CONCLUSIONS: The prevalence of EE was higher in 2000-2003 than in 1994-1997, although the complications associated with the disease diminished. The prevalence of concomitant Barrett's esophagus remained stable.     

老年人反流性食管炎393例分析

目的为了解老年人反流性食管炎的特点，对反流性食管炎患者的内镜表现与特点进行分析。方法将本院１０年来６８１例反流性食管炎患者分为老年组和非老年组，对两组的患病率、病变程度、病理结果、并存疾病进行了比较。结果老年组患病率２３８％，非老年组０８３％（Ｐ＜０００１）；老年组病变程度较非老年组严重（Ｐ＜００５）；病理活检，非老年组中仅发现２例轻度不典型增生，而老年组中共发现９例不同程度的不典型增生及１例癌变；老年患者并存疾病以食管裂孔疝多见。结论反流性食管炎是老年人的常见病，内镜检查对该病的诊治具有重要价值。     

Non‐erosive reflux disease,functional heartburn and gastroesophageal reflux disease; insights into pathophysiology and clinical presentation

Non‐erosive reflux disease (NERD) has emerged as a real entity in the spectrum of gastroesophageal reflux disease (GERD) and may, indeed, represent the most common manifestation of reflux disease. Recent information indicates NERD can be further subclassified based on the results of pH studies and suggests that functional heartburn needs to be differentiated as that subgroup of patients in which there appears to be no relationship between symptoms, however ‘typical’ of GERD, and acid exposure. Other aspects of NERD need to be appreciated, including overlap with functional dyspepsia and the potential variations in response to such therapeutic interventions as acid‐suppressive therapy and fundoplication. It seems quite possible that our failure to separate functional heartburn from NERD, in general, has contributed, in large measure, to diagnostic difficulties and therapeutic disappointment in GERD. An appreciation of the range of entities, of different etiology and pathology, within NERD will foster the development of effective approaches to the assessment and therapy of this challenging disorder.     

Diagnosis of eosinophilic esophagitis after fundoplication for ‘refractory reflux’: implications for preoperative evaluation

A small percentage of patients who carry the diagnosis of refractory gastroesophageal reflux disease (GERD) actually have eosinophilic esophagitis (EoE). The purpose of this study was to describe a series of patients who underwent fundoplication for presumed refractory GERD, but subsequently were found to have EoE. We performed a retrospective analysis of our EoE database. Patients diagnosed with EoE after Nissen were identified. Cases were defined according to recent consensus guidelines. Five patients underwent anti‐reflux surgery for refractory GERD, but were subsequently diagnosed with EoE. None had esophageal biopsies prior to surgery, and in all subjects, symptoms persisted afterward, with no evidence of wrap failure. The diagnosis of EoE was typically delayed (range: 3–14 years), and when made, there were high levels of esophageal eosinophilia (range: 30–170 eos/hpf). A proportion of patients undergoing fundoplication for incomplete resolution of GERD symptoms will be undiagnosed cases of EoE. Given the rising prevalence of EoE, we recommend obtaining proximal and distal esophageal biopsies in such patients prior to performing anti‐reflux surgery.     

Double-blind comparison of cisapride and cimetidine in treatment of reflux esophagitis

In a double-blind, randomized, comparative trial of the prokinetic drug cisapride and the H₂-blocker cimetidine, mucosal healing and changes in symptoms of gastroesophageal reflux were evaluated in patients with erosive reflux esophagitis. The patients were treated with either cisapride, 10 mg four times a day (N=36) or cimetidine, 400 mg four times a day (N=37) for six weeks, or for 12 weeks if mucosal healing was not obtained by week 6. Upon entry, two thirds of the patients in each group had grade I (Savary-Miller) esophagitis, and the remainder grade II or III. At the end of treatment, endoscopy showed mucosal healing in 56% (38–72%; 95% confidence interval) of cisapride and 57% (39–73%; 95% confidence interval) of cimetidine patients. After six weeks, both drugs significantly (P<0.01) decreased the intensity and frequency of heartburn, regurgitation, and the postural syndrome. No significant inter group differences were found regarding endoscopic parameters or the improvement of heartburn and regurgitation. Concomitant antacid use was also comparable. Adverse effects were reported by four cisapride and nine cimetidine patients. These results indicate that the effects of cisapride compare well with those of cimetidine in terms of both esophageal mucosal healing and symptom relief.