Erosive esophageal reflux vs. non erosive esophageal reflux: oral findings in 71 patients

One of the most important clinical conditions for retrograde movement of gastric acid into the oesophagus is the gastroesophageal reflux disease (GERD) affecting approximately 10–20 % of the population in the western world [1]. Clinically, typical esophageal symptoms of GERD can occur such as heartburn and acid regurgitation, while on the other hand atypical symptoms such as a burning feeling on the tongue and oral mucosa can be found [2].

However, GERD patients are not a homogenous group. According to the endoscopic diagnosis, an erosive esophagitis (ERD) and a non erosive reflux disease (NERD) may be differentiated. These two main phenotypes of GERD appear to have different pathophysiological and clinical characteristics [3]. The standard therapeutic medical therapy of both phenotypes of GERD includes the administration of acid-suppressive agents, proton pump inhibitors (PPI) [4]. However, erosive esophagitis and NERD clearly diverge when it comes to response to antireflux treatment. NERD patients have a significantly lower response rate to proton pump inhibitor (PPI) therapy, and consequently they constitute the majority of the refractory heartburn group [3].

Recent literature has pointed out that other extraesophageal symptoms of GERD are acidic lesions of the oral mucosa. It has been demonstrated histologically in rats [5] that gastric acid reflux can cause acidic lesions of the palatal mucosa. These findings suggested that these pathological changes may reflect the relationship between laryngopharyngeal reflux and airway obstruction also in humans. Moreover, GERD was reported to be associated with microscopic alterations in the palatal mucosa, such as epithelial atrophy and increased fibroblast numbers [6]. In addition, objective oral mucosal changes were found to be significantly associated with GERD [7]. Also Järvinen et al. pointed out the presence of burning mouth, aphthoid lesions and hoarseness in patients with disorders of the upper digestive tract. Erythema of the soft palate and uvula, glossitis, epithelial atrophy, xerostomia could be common in GERD patients [8]. However, it was objected that the mucosal changes described are quite common and not pathognomonic and specific of GERD patients [9, 10]. Similarly, in a clinical study on 117 patients with reflux disease, no mucosal changes could be observed to be linked with the reflux disease [11].

Accordingly, it may be assumed that these controversial findings are attributable to different proportions of ERD and NERD patients in the respective studies. Nevertheless, in most studies on oral findings, GERD patients were not subdivided in the two subgroups. Similarly, most recent literature has stated that GERD was independently associated with an increased incidence of chronic periodontitis; however, the two phenotypes of GERD were not evaluated separately [12]. Therefore, the purpose of this study was to determine if ERD patients show different oral soft tissue findings and periodontal conditions as compared to NERD patients, both with ongoing PPI therapy.

Recent literature has pointed out that, with respect to GERD patients, only controversial epidemiological data on the prevalence of acidic oral mucosa lesions are available [9]. Moreover, most recent literature demonstrated that GERD is independently associated with an increased incidence of chronic periodontits. However, GERD and periodontitis are frequent chronic diseases and PPI medication generates costs for the public health care system. Therefore, clinical studies are urgently necessary to find out if there is an association between the main two subgroups of GERD and acidic oral mucosal lesions (erythema or ulcer) and periodontal conditions with respect to PPI medication.

Several studies on oral findings in GERD patients provide only limited information if or how GERD was diagnosed (endoscopy solely [19], esophageal pH monitoring in combination with impedance measurement [20]) or treated before the study was carried out [19, 21‐23], which hampers reliable comparison with the present results. In this study, all patients had shown evidence for GERD on functional testing (pH monitoring combined with impedance measurement) and/or the histological confirmation of an erosive GERD (esophagogastroduodenoscopy). Moreover, in this study, both groups of GERD patients were treated with PPI for at least 1 year which allows conclusions on the clinical impact on oral conditions of PPI in this sample of patients.

With respect to the dental status, patients with removable dentures were not excluded in all studies, which, again, hampers comparison of the present results with the literature. In a recent study [13], three patients with GERD were completely edentulous; however, one participant, a 72-year old woman in the GERD group, was found to have a mucosal lesion, a small ulcer-like lesion associated with redness on the dorsal tongue. Accordingly, it remains unclear if ulcer was attributable to the prosthodontic construction or to GERD. In this study, none of the subjects had removable dentures to eliminate bias if mucosal alterations were caused by the prosthodontic construction.

Although GERD affects all age groups [21], the incidence of this disease increases considerably after 40 years of age [19]. Similarly, in this study, the mean age of patients was 48.0 ± 16.03 years in the ERD group vs. 50.9 ± 14.5 years in the NERD patients, which is in the order published in the literature [20]. Moreover, with respect to age, there was no statistically significant difference between the ERD and the NERD group in this study. In accordance with the literature, among all 71 GERD patients, a total of 41 (55.7 %) were females. Also in previously published studies, a higher incidence of GERD in women has been reported [23]. With respect to ethnicity, number of teeth and smoking habits, no differences were found. Due to the fact that the smokers among the study participants did not consume other forms of tobacco such as spit tobacco, cigars or pipes, the study focussed on “cigarette smoking”. Therefore, due to the fact that the aforementioned characteristics were very similar in both groups, the results of this study seem not to be compromised by these general factors.

Due to the fact that all study participants had confirmed to attend regularely medical and dental care, it seems unlikely that periodontal findings in this study may be attributed to lack of accessing routine dental care including dental prophylaxis. All 71 patients (100 %) were prescribed periodically PPI over the long term. However, three patients of the NERD group were classified as non responders. Clinical efficacy of PPI medication has been documented by Wang and coworkers who collected gastric fluid during routine endoscopy in patients on PPIs, on H2-receptor blockers and on no acid suppression therapy [24]. The mean pH values were 5.11, 4.12 and 2.91, respectively. However, a recent study has PPI even proved to be ineffective in a number of patients [2]. Data from a meta analysis have shown that a high-dose proton pump inhibitor is no more effective than placebo in producing symptomatic improvement or resolution of laryngo-pharyngeal symptoms [25]. Accordingly, the three non responders found in this study are in accordance with the literature.

Many investigators have proposed an association between GERD and laryngo-pharyngeal symptoms such as hoarseness, globus pharyngeus, vocal fatigue, frequent sore throat, frequent throat clearing, chronic cough [26‐30]. Moreover, oral mucosal lesions may result from GERD by direct acid or acidic vapor contact in the oral cavity [9].

It has been demonstrated histopathologically in the rat model that reflux affects the soft palate, which suggests that these pathological changes may reflect the relationship between laryngopharyngeal reflux and airway obstruction [5]. One clinical large case-controlled study observed a significant association of GERD with erythema of the palatal mucosa and uvula [7]. In another study, histologic examination of palatal mucosa found a greater prevalence of epithelial atrophy, deepening of epithelial crests in connective tissue and a higher prevalence of fibroblasts in 31 GERD patients compared with 14 control subjects [6]. But, these changes were not visible to the naked eye, unlike the mucosal changes that may be more readily observed in esophagitis and laryngitis where the pH of the gastric reflux at these sites is lower than in the mouth [31, 32]. Other studies have not found any abnormal appearances of the oral mucosa or associated oral symptoms in patients with confirmed GERD [8, 11].

Also in this study, there was no statistical significant difference with regard to the total number of oral mucosal lesions and their localization when the ERD and the NERD group were compared. However, there is a paucity of information on the effect of GERD and PPI on oral mucosal changes in the literature. Acid regurgitation may exacerbate oral mucosal changes associated with co-existing hyposalivation, which can arise from systemic conditions, local salivary gland conditions and intake of drugs including PPIs [9]. PPIs inhibit the H⁺/K⁺-ATPase pump in the stomach and other tissue [33]. Altman and coworkers have demonstrated the presence of this pump in laryngeal seromucinous glands [34]. In addition, there is evidence that systemic medication may enter saliva through diffusion [35]. Thus, it is possible for the pH of the seromucinous secretions to be affected by PPI use, and this could alter the oral mucosa, and, in addition, the bacteria growth environment in the oropharynx [33]. Especially, patients with diabetes and a history of recent PPI use are more likely to have abnormal oral flora [33]. However, due to the fact that lesions of the oral mucosa did not differ significantly between the ERD and the NERD group in the current study it may be assumed that PPI medication had no adverse impact on oral mucosal health in both groups.

Periodontal evaluation consisted of clinical three dimensional evaluation by probing due to the fact that two dimensional radiographs are not highly reflective of the real periodontal situation [36]. With respect to the oral plaque index, bleeding index and clinical attachment loss, similar levels were found in both groups (Table 3). Differences between these two groups were not statistically significant on the 5 % level. However, significantly more ERD patients suffered from severe periodontitis (CAL ≥ 5 mm) as compared to NERD patients. This is, in part, in accordance with the most recent literature. Also Song and coworkers [12] have shown that GERD was independently associated with an increased incidence of chronic periodontitis. The most reasonable explanation for GERD as a predisposing factor for chronic periodontitis would be poor salivary function [12], which has been demonstrated in GERD patients in several papers [7, 37, 38]. Nevertheless, hyposalivation can explain the present findings only in part, because incidence of severe periodontitis was different in ERD and NERD patients. Accordingly, it may be assumed in concordance with the mucosal findings in this study that PPI medication had no adverse effect on periodontal health in ERD and NERD patients. Other parameters such as more aggressive acidic reflux must contribute to the more severe periodontal destruction in ERD patients. Unfortunately, to our knowledge, there is no similar study in the literature available on periodontitis in ERD and NERD patients. Therefore, further studies are available in GERD subgroup patients.

This study has some limitations. First, patients were recruited from an outpatient setting of a university hospital. Therefore, it cannot be excluded that patients are not representative for the whole population. Second, salivary gland function has not been evaluated. It can not be excluded completely that ERD and NERD patients show different degrees of hyposalivation. Third, frequency and chronicity of use of tobacco were not recorded. Accordingly, it can not be excluded that frequency and chronicity of use of tobacco differed significantly between the two groups (ERD, NERD). Four, erythema and ulceration of the oral mucosa is a very common finding with multiple confounding etiologies. It can not be excluded that some lesions in this group of GERD patients are caused by other origin and not by reflux acid.

Within the limitations of this study, the authors failed to demonstrate significant differences between ERD and NERD patients with respect to the prevalence of acidic lesions of the oral mucosa and their localization. Therefore, the association of GERD and oral erythema could not be demonstrated in the present patients. In contrast, the results indicated that ERD patients may suffer from more severe periodontitis as compared to NERD patients. However, the study failed to show a clinical impact of long term PPI medication on the prevalence of acidic oral mucosal lesions and periodontal destruction. Further studies are necessary to elucidate the role of reflux in the periodontal destruction of especially ERD individuals.