Eosinophilic esophagitis (EoE) are characterized by a significant infiltration of eosinophils in the esophageal mucosa, as observed in biopsies. While the exact threshold of eosinophils per HPF for diagnosing EoE remains debated, many researchers agree on a criterion of 20 or more cells. Initially recognized primarily in children, this condition has more recently been acknowledged in adults as well [11]. The increased prevalence of EoE in recent years can be attributed to heightened awareness of the disease and possible changes in its underlying mechanisms [12, 13]. Prevalence rates vary widely across different study populations. Recent prospective studies indicate a low prevalence (0.05–0.4%) in the general population, yet it can be as high as 15% among patients with dysphagia and up to 48% in those experiencing food bolus impaction [14].
Our cross-sectional study involved 300 patients diagnosed with refractory GERD who visited the Internal Medicine Department at Menoufia University Hospital between November 2022 and February 2024. The study revealed that 195 (65%) patients were male and 105 (35%) were female, with a mean age of 44.88±8.2 years and a mean BMI of 30.2±2.2 kg/m². Our findings are consistent with those of Tarigan and Pratomo [15], who reported a higher incidence of GERD in males, particularly those over 40 years old (63.16%). Similar observations were noted by Syam et al. [16], who also found GERD to be more prevalent in males and individuals aged over 50 years.
In contrast to our findings, Anis et al. [17] reported a higher prevalence of GERD among females (5:3 ratio), with a median age of 58 years (range: 41-63 years). Kaurrany et al. [18] noted no significant gender disparity in the risk of developing refractory GERD, highlighting that individuals aged 25-36 years faced the highest risk, with a majority (56.3%) falling within the normal BMI range (18.5-22.9 kg/m²). Additionally, Sá et al. [19] observed a predominance of females, with 79 out of 103 patients (76.7%) being female, and reported a mean age of 45.5 years and a median age of 47 years.
In our study, 96 (32%) of the cases were smokers, 120 (40%) had diabetes mellitus (DM), and 96 (32%) had hypertension (HTN). These findings are consistent with the research by Chen et al. [20], which highlighted that GERD patients exhibit a higher prevalence of comorbidities compared to non-GERD patients. They identified associations between GERD and conditions such as hypertension, diabetes, hyperlipidemia, alcohol-related disorders, and obesity
Patel and Yadlapati [21] found that smoking tobacco increases reflux symptoms in a manner dependent on the amount smoked. Moreover, a meta-analysis by Eusebi et al. [22] indicated a significantly elevated risk of GERD and its associated symptoms in smokers compared to non-smokers. Research from Norway by Ness-Jensen et al. [23] suggested that quitting smoking may improve severe reflux symptoms in individuals with a normal BMI, although this benefit was not observed in overweight individuals.
Similarly, Sun et al. [24] discovered a notable association between GERD and diabetes mellitus (DM). Additionally, Lee et al. [25] noted that patients with DM, particularly type 2 DM and obesity, may have an increased risk of GERD. They proposed that autonomic neuropathy, particularly vagal nerve damage, likely plays a role, as many diabetic patients with esophageal dysfunction exhibit signs of peripheral motor or autonomic neuropathy.
This study found that all cases experienced heartburn and regurgitation, with 36 (12%) also reporting dysphagia, 264 (88%) experiencing abdominal pain, and 120 (40%) showing pallor. Kaurrany et al. [26] similarly noted that 62.5% of subjects cited heartburn as their primary complaint. Tarigan and Pratomo [27] identified epigastric pain as the most common complaint (33.3%). Additional studies by Clarrett and Hachem [28] and Richter and Rubenstein [29] reported heartburn and acid regurgitation as frequent symptoms.
Anis et al. [17] observed that dysphagia, food impaction, and heartburn were prevalent symptoms. Garcia et al. [30] found that all patients with esophagitis experienced dysphagia, while 50% reported heartburn. Other studies by Mulder et al. [31] in Canada and Anis et al. [17] in Pakistan also highlighted dysphagia as a primary complaint (74%). Fujiwara et al. [32] in Japan identified 7 cases of eosinophilic esophagitis (9.9%) out of 13,634 subjects undergoing upper GI tract endoscopy, with dysphagia and heartburn being predominant, particularly in men.
Regarding liver function tests, this study found that ALT (IU/L) ranged from 31 to 49 IU/L (mean 40.96 IU/L) and AST (IU/L) ranged from 30 to 49 IU/L (mean 38.64 IU/L). Consistent with these findings, Ghiga et al. [33] reported no abnormalities in liver function tests.
The pathological findings from our study revealed that 4.0% of cases had eosinophilic infiltration, 27.0% showed neutrophilic infiltration, 15.0% presented with Barrett’s esophagus, 28.0% exhibited edema and basal hyperplasia, 16.0% had lymphocytic infiltration, 8.0% showed dysplasia, and 2.0% had carcinoma. According to Maev et al. [34], the key features of reflux esophagitis include basal cell hyperplasia, inflammatory cells in the squamous epithelium, and elongation of lamina propria papillae. These signs serve as semi-quantitative diagnostic criteria for reflux esophagitis.
In our study, the prevalence of eosinophilic esophagitis was 4%, consistent with findings by García-Compeán et al. [30] who also reported a prevalence of 4% among their patients. This prevalence is higher than that in the general population [35, 36] but lower than in patients with dysphagia and food impaction [35, 37, 38], and comparable to that seen in patients undergoing endoscopy for various indications [39]. Kaurrany et al. [26] found a prevalence of 6.3% for eosinophilic esophagitis, while Fujiwara et al. [32] reported a prevalence of 0.04% in Japan. However, Foroutan et al. [40] in Iran reported a prevalence of 8.8% for eosinophilic esophagitis in patients with refractory GERD.
Our study also indicated that 56.0% of cases tested negative for H. Pylori, while 44.0% were positive. Hirata et al. [41] found that eradication of H. Pylori has a beneficial effect on GERD. Conversely, Hojo et al. [42] argued that H. Pylori eradication can lead to GERD. Contrarily, some researchers, such as Bor et al. [43], have suggested no correlation between H. Pylori and GERD. Zullo et al. [44] reported that in some patients, H. Pylori preferentially colonize the antrum, leading to antrum-dominant gastritis characterized by worsened GERD symptoms, increased gastrin, and acid secretion. Eradication of H. Pylori reduced acid secretion
One mechanism attributed to H. pylori infection is its potential to increase acid reflux by neutralizing bacterial ammonia [45]. Conversely, the protective mechanism hypothesis suggests that H. pylori induces gastric mucosal atrophy, impairing acid production [41]. Some researchers propose that H. Pylori's protective effect involves its impact on ghrelin and gastric acid production. Ghrelin suppression by H. pylori may mitigate GERD risk by reducing appetite and potentially decreasing obesity, a known GERD risk factor [46].
In our study, according to endoscopy alarm signs, 47.0% of cases presented with melena, 20.0% with dyspepsia, and 20.0% lacked alarm signs. Claret and Hachem [47] emphasized the importance of screening GERD patients for alarm symptoms, which warrant endoscopic evaluation due to possible underlying malignancy. They noted that typical GERD symptoms alone do not necessitate upper endoscopy. Katz et al. [48] outlined alarm symptoms such as dysphagia and odynophagia, indicating potential complications like strictures, ulcers, or malignancy. Other alarm signs include anemia, bleeding, and weight loss.
Our study also found that 20.0% of cases reported no NSAID use, while 80.0% did use NSAIDs. Kim et al. [49] associated NSAID use with increased risk of reflux esophagitis and esophageal strictures, noting cases of dysphagia linked to NSAID intake. In contrast, Koutlas et al. [50] observed a trend toward improved histologic response in EoE patients using NSAIDs, attributing this effect to NSAIDs' inhibition of COX-2 enzyme production and subsequent reduction in esophageal inflammation. Hill et al. [51] suggested that chronic NSAID use may desensitize patients to allergic conditions, akin to aspirin-exacerbated respiratory disease.
In our study, within the EoE group, 25.0% were smokers, 75.0% experienced dysphagia, 100.0% reported heartburn, none had persistent vomiting, 100.0% presented with melena, none reported dyspepsia, 100.0% had abdominal pain, 100.0% were NSAID users, 100.0% had occult blood in stool, and 100.0% tested positive for H. Pylori antigen.
Our findings are consistent with García-Compeán et al. [52], who found that the most common symptoms were heartburn in 114 (76%) patients and regurgitation in 84 (56%) patients, with only 30 (20%) reporting dysphagia.
Regression analysis in our study identified dysphagia, H. Pylori antigen positivity, and occult blood in stool as significant predictors of EoE among our patients (P<0.05). Other parameters did not show a significant association with EoE (P>0.05). Common symptoms of EoE in adults include dysphagia, food impaction, and heartburn [53].
Similarly, Fouad et al. [54] reported dysphagia as the most prevalent symptom in EoE, present in 75% of their patients (p<0.001), with no cases of weight loss reported. Other studies have also identified dysphagia in 64.0% [55] and up to 89% [56] of EoE patients. Kapel et al. [57] noted that dysphagia was the most common reason for endoscopy in adults with EoE (70.1%), followed by GERD/heartburn (27.1%).