Systematic review: gastro-oesophageal reflux disease and dental lesions

Transcription

1 Alimentary Pharmacology & Therapeutics Systematic review: gastro-oesophageal reflux disease and dental lesions F. PACE*, S. PALLOTTA*, M. TONINI, N.VAKILà &G.BIANCHIPORRO* *Division of Gastroenterology, Department of Clinical Sciences L. Sacco, University of Milan, Milan; Department of Physiological and Pharmacological Sciences, University of Pavia, Pavia, Italy; àuniversity of Wisconsin School of Medicine and Public Health, Madison, WI and Marquette University College of Health Sciences, Milwaukee, WI, USA Correspondence to: Dr F. Pace, Division of Gastroenterology, L. Sacco University Hospital, Via G.B. Grassi, 74, Milan, Italy. Publication data Submitted 13 February 2008 First decision 11 March 2008 Resubmitted 20 March 2008 Accepted 20 March 2008 Epub OnlineAccepted 27 March 2008 SUMMARY Background Dental erosion (DE), which is the irreversible loss of tooth substance that does not involve bacteria ranging from a minimal loss of surface enamel to the partial or complete exposure of dentine by a chemical process, is acknowledged as an established extra-oesophageal manifestation of gastro-oesophageal reflux disease (GERD). However, the real impact of GERD in the genesis of this lesion remains unclear. Aim To review the existing literature to assess the relationship between DE and GERD. Methods Studies that assessed the prevalence of DE in individuals with GERD or vice versa were identified in Medline and the Cochrane Controlled Trials Register via a systematic research strategy. Results Seventeen studies met the selection criteria. Studies, however, differed greatly as far as design, population methods of diagnosing GERD, duration of follow-up and, consequently, findings. The median prevalence of DE in GERD patients was 24%, with a large range (5 47.5%), and the median prevalence of GERD in DE adults patients was 32.5% (range: 21 83%) and in paediatric population 17% (range: 14 87%). Children with GERD are found by a majority of studies at increased risk of developing DEs in comparison with healthy subjects, as are intellectually disabled people. Conclusions This systematic review shows that there is a strong association between GERD and DE. The severity of DEs seems to be correlated with the presence of GERD symptoms, and also, at least in adults, with the severity of proximal oesophageal or oral exposure to an acidic ph. The inspection of the oral cavity in search for DEs should become a routine manoeuvre in patients with GERD. Aliment Pharmacol Ther 27, ª 2008 The Authors 1179 doi: /j x

2 1180 F. PACE et al. INTRODUCTION Dental erosion (DE) is presently recognized as an important cause of tooth damage both in children and in adults, occurring in a percentage varying from 2% of the general population described in the US 1 to 5% reported in Finland. 2 It can be defined as the loss of tooth substance by a chemical process that does not involve bacteria, in contrast to carious tooth damage. 1, 3 In DEs, the extent of damage may range from a barely noticeable loss of surface lustre evident on a clean, dry enamel to the partial or complete exposure of dentine with its characteristic yellow colour through the thinned overlying enamel. 1, 3 Dental erosion is caused by the presence of intrinsic or extrinsic acid of non-bacterial origin in the mouth, or by a combination of them. 4 Intrinsic sources of acid include vomiting, regurgitation, gastro-oesophageal reflux or rumination. Extrinsic sources of acid are most commonly dietary acids. Medications, in particular, some asthma drugs, chewable vitamin C tablets or iron tonics, patient s lifestyle choices such as unusual eating and drinking habits, or socio-economic aspects and environment, can also increase the risk of DE, particularly in children. 5, 6 The first modern description of DEs associated with gastro-oesophageal reflux disease (GERD) is due to Howden, 7 in a case report published more than 35 years ago. In recent years, GERD has been described as an important aggravating factor of DEs and DE is now considered a comorbid syndrome with an established epidemiological association with GERD. As an example, the recently published Montreal Criteria, dealing with a global classification of GERD, state: The prevalence of DEs, especially on the lingual and palatal tooth surfaces, is increased in patients with GERD. 8 This statement (statement no. 48) has been approved with 98% of agreement among the Montreal Group panelists and, reportedly, is based on a high level of evidence, possibly the highest level of evidence linking GERD with any extra-oesophageal clinical manifestation. 8 Thus, it is not surprising that some authors have advocated that the examination of the oral cavity, in search for atypical DEs, should be an integral part of the physical examination of the patient with suspected GERD. 9 On the other hand, other authors have denied, at least in children, that DEs may represent a relevant problem in GERD patients. 10 The aim of this systematic review was to: (i) analyse all the published reports dealing with the association between DEs and GERD to define the size of the problem; (ii) verify the presumed pathophysiology and (iii) highlight whether particular subgroups of population can have an increased risk of DEs as a consequence of GERD. MATERIALS AND METHODS The Medline database (from January 1966 to September 2007) and the Cochrane Controlled Trials Register were searched. The search terms used were: dental erosion AND gastro esophageal reflux OR esophagitis. The only limits employed in this search were English and Human studies. Review articles using the same search terms were also sought to help identify additional original studies. A careful review of references was conducted of all retrieved articles. Only studies published in extenso were included. A data extraction form was developed to standardize the methodological and quantitative information that was extracted from each study (available from authors on request). This consisted of: inclusion criteria of patients in the study, patient setting (gastrointestinal (GI) vs. dentistry clinics, adult vs. children study), diagnosis of GERD (based on symptoms alone, on upper endoscopy and or ph profile as well), study design, sample size, number of dropouts, main outcome measures used to assess efficacy and study conclusion. Each study was reviewed at least by two authors. RESULTS The search (final date September 2007) resulted in 19 citations, eight of which were reviews. The Cochrane search and the additional search through cross references resulted in six more citations. This left a total of 17 eligible studies Of these, five concerned the children population 10, and the remaining the adult one; 9, furthermore, one study 24 was conducted on a special population, i.e. institutionalized intellectually disabled individuals. Because of the marked variation in outcome measures (see Table 1), it was not possible to perform a formal meta-analysis, that is a statistical pooling of results. Instead, the results were analysed in a qualitative fashion. In the following paragraphs, we will first consider the results of studies conducted on adult populations and subsequently those studies conducted on paediatric patients and finally those conducted on special populations (i.e. intellectually disabled).

3 SYSTEMATIC REVIEW: DENTAL EROSIONS AND GERD 1181 Table 1. Characteristics of studies included in the review Author (reference) Type of study No. of subjects, type of population Outcome variable Munoz et al. 11 Case control 181 GERD patients, 72 HC DE: presence, severity, location. Periodontal lesions. Moazzez et al. 13 Case control 31 patients with extra-oesophageal GERD, 7 HC Proximal GER extension Gregory-Head et al. 14 Cross-sectional 20 patients with DE % of patients with GERD Schroeder et al. 9 Cross-sectional 12 patients with DE, 30 with GERD referred for 24-h ph % DE in GERD, % GERD in DE Loffeld 15 Retrospective inventory Patients with reflux oesophagitis No dental prosthesis, % damage of incisors Jarvinen et al. 16 Observational 44 patients with GERD DU, 48 postcholecystectomy, 17 with GU Meurman et al. 17 Observational 117 patients with GERD % DE Bartlett et al. 12 Observational 36 patients with DE, 10 HC Oesophageal ph profile Myklebust et al. 18 Questionnaire study General population DEs Dahshan et al. 20 Observational 37 children with possible GERD % DE O Sullivan et al. 10 Observational 53 children with GERD % DEs Linnett et al. 21 Case control 52 children with GERD history, 52 healthy sibling % DEs Aine et al. 22 Observational 15 children with GERD % DEs Ersin et al. 23 Case control 38 children with GERD, 42 HC % DEs Bohmer et al. 24 Case control Intellectually disabled % DEs, ph profile Oginni et al. 19 Case control 125 GERD patients, 100 HC % DEs Gudmundsson et al. 25 Observational 14 patients with DE referred for dual 24-h ph Oesophageal and oral ph profile %DE GERD, gastro-oesophageal reflux disease; DE, dental erosion; DU, duodenal ulcer; GU, gastric ulcer; HC, healthy controls; 24-h ph, 24-hour oesophageal ph-monitoring.

4 1182 F. PACE et al. Studies conducted on adults 9, 11 19, 25 Overall, 11 original studies were found; of these, seven were conducted on GERD patients (see Table 2). Vice versa, studies by Bartlett et al., 12 Gregory-Head et al. 14 and Gudmundsson et al. 25 were conducted on patients with DEs, to investigate the presence of GERD (Table 3). The study by Myklebust et al. 18 is a questionnaire survey conducted in Norway, but information on the dental status were provided by the personal dentists only for a minority of respondents, and therefore were not included in the further analysis. Finally, the study by Schroeder et al. 9 had both a dental group, which was screened for GERD, and a gastroenterological group, referred for dental evaluation. Dental erosions were found ranging between 5% and 47.5%, with a median value of 32.5%, of the GERD patient samples; the greatest prevalence was found in studies defining GERD patients on the basis of symptoms alone, 11 whereas the lowest was found in a study using endoscopic criteria. 16 In those studies where a control group was used, such as, for example, the studies by Munoz et al., 11 Bartlett et al., 12 or Jarvinen et al. 16 the prevalence of DEs (or the DE score) was statistically greater in GERD subjects than in controls. No data regarding the prevalence of DEs were provided by two studies, namely Moazzez et al. 13 and Gregory-Head et al. 14 In the former, a score was assessed of teeth with palatal tooth wear, where 0 represents no damage and four represents pulpal exposure: it was found that the proportion of patients with a score 2 was 70.8% vs. 0% in controls, the proportion of those with score 3 was 8.3% vs. 0%, and none had a score 4 in either group, whereas the ph-monitoring found a higher percentage of time spent in distal oesophagus with ph < 4 in GERD groups only for the supine period. Interestingly, in this study, a significant correlation was found between the proportion of the total time with pharyngeal ph below 5.5 and the proportion of teeth with palatal score 2 (r = 0.44) or 3 (r = 0.44), P < In the study by Gregory-Head et al., 14 the Tooth Wear Index (TWI) score was assessed in GERD patients and in controls; it was Study (reference) No. of patients with GERD GERD diagnostic method Prevalence (%) Munoz et al Symptoms h ph-metry 78 Endoscopy Moazzez et al h dual ph-metry Not stated* Schroeder et al h ph-metry 40 (GI group) 9 Loffeld Endoscopy 32.5 Jarvinen et al Endoscopyà 5 Meurman et al Symptoms 24 Oginni et al Symptoms 16 Table 2. Prevalence of dental erosions in adults with GERD (for abbreviations, see Table 1) * A dental erosion score was used: GERD patients higher score then non-gerd. Only the incisor teeth status was assessed. à Endoscopic oesophagitis and duodenal ulcer were grouped together. Study (reference) No. of patients with dental erosions GERD diagnostic method Bartlett et al h oesophageal ph-metry 64 Gregory-Head et al h dual oesophageal ph-metry 50 Gudmundsson et al h oesophageal ph-metry 21 Schroeder et al. (dental group) h oesophageal ph-metry 83 Prevalence (%) Table 3. Prevalence of GERD in adults patients with dental erosions (for abbreviations, see Table 1)

5 SYSTEMATIC REVIEW: DENTAL EROSIONS AND GERD 1183 found that both the overall score and the maxillary and mandibular surfaces of GERD subjects were significantly higher than those observed in controls: vs , vs and vs , respectively (P < 0.005), suggesting that a relationship exists between loss of teeth structure, as measured by the TWI score and the occurrence of GERD. Studies conducted on children (Table 4) A total of five studies were found. 10, In the study by Dahshan et al., children undergoing elective upper endoscopy for possible GERD were evaluated for the presence, severity and pattern of erosion and stage of dentition of teeth. It was found that 24 of them had GERD, 20 of whom had DEs as well, 10 with mild erosion (tooth score 1), six with moderate erosion (at least one tooth scored 2), and four with severe erosion (at least one tooth scored 3) according to the fourpoint score proposed by Aine et al. 22 In the study by O Sullivan et al., children with moderate to severe GERD as defined by ph monitoring, were examined for DEs. No control group was investigated. Results showed that the prevalence of DE was low when compared with the UK National Survey, with only nine (17%) of children showing any sign of erosion, and of these only one had erosion involving dentine. In the study by Linnett et al., children with a definitive history of GERD underwent a dental examination and were compared on an individual basis with a healthy control sibling without GERD symptoms; the prevalence of teeth erosion was found to be statistically higher in GERD subjects (14%) than in controls (10%), P < Furthermore, GERD subjects had erosion in more permanent teeth compared with controls (4% vs. 0.8%, P < 0.05), and more severe erosions. In the study by Aine et al., children who attended a university hospital paediatric outpatient clinic for GERD and who were found to have a pathological reflux at 24-h oesophageal ph monitoring were submitted to dental examination, with teeth erosion scored according to the previously quoted Aine Index (from 0 to three); no control group was investigated. Overall, two patients had score 0, two patients score 1, six patients score 2 and seven patients score 3, suggesting that only a minority of GERD patients had intact teeth. Finally, in the study by Ersin et al., 23 the effects were investigated of GERD on DE vs. caries formation, on salivary function and on salivary microbiological counts. Thirty-eight GERD patients with a mean age of years and 42 healthy children of the same age and gender and social background comprised the study group. All subjects answered a detailed frequency questionnaire related to acidic drinks, foods, and sugar consumption and underwent a clinical dental examination. The caries experience of the children was recorded according to World Health Organization criteria, and erosions were scored according to the Eccles and Jenkins grading scale. 26 The children were also investigated for stimulated salivary flow rate, buffer capacity, and salivary mutans streptococci (MS), lactobacilli, and yeast colonization. The results of this rather complicated study are the following: the prevalence of DE and the salivary yeast and MS colonization was found to be significantly higher in GERD children than in healthy subjects (P <.05); the caries experience, salivary flow rate, buffering capacities of the children, and frequency of acidic drinks, foods, and sugar consumption were found to be similar in both groups. The authors concluded that GERD children were at an increased risk of developing erosion and caries compared with healthy subjects. 23 Table 4. Prevalence of dental erosions in children with GERD (for abbreviations, see Table 1) Study (reference) No. patients with GERD Age (range) GERD diagnostic method Prevalence (%) Dahshan et al years Endoscopy 83 O Sullivan et al years 24-h ph-metry 17 Linnett et al months 12 years Symptoms + histology 14 Aine et al months 16 years Symptoms 87 Ersin et al years Symptoms NA NA, not applicable.

6 1184 F. PACE et al. Studies conducted on special groups Only one such study was found, dealing with intellectually disabled. 24 In this study, authors argued that not only GERD but also vomiting, rumination and regurgitation are conditions more frequently encountered in the intellectually disabled population. Therefore, they investigated the presence of DEs in combination with GERD among intellectually disabled inhabitants, arbitrarily defined as having an IQ < 50, taken from three Dutch institutes. In their study, 63 individuals randomly selected underwent an oesophageal ph test and dental screening, and possible predisposing and attributable factors were determined. They defined an abnormal ph level as a ph < 4, >4.5% of the measured time. Subjects with DEs were compared with those without DEs. The results of this study showed that in 29 of 63 (46.0%) cases, evidence of DEs was found. In 19 of these 29 subjects with erosions (65.5%), GERD was diagnosed, compared with nine (26.5%) of 34 subjects without erosions (P = 0.04). In the subjects with erosions, mean duration of ph <4 was 15.6% (range: ) compared with 6.3% (range ) in subjects without erosions (P = 0.02). An IQ <35 was found to be predisposing (P < 0.001). Authors concluded that, in this population of 63 institutionalized intellectually disabled persons, DEs were diagnosed in 46% and that 65% of them had GERD. Individuals with longer duration of ph < 4 than 6.3% of the measured time and with an IQ < 35 were at higher risk to develop DEs. 24 This study shows that DEs in the intellectually disabled population might be an oral manifestation of GERD. DISCUSSION The variety of extra-oesophageal manifestations of GERD is incompletely appreciated. This may be because of many factors, including the uncertainty in classification of GERD patients, and in particular, of patients with typical GERD symptoms but absence of oesophagitis. Consequently, the published estimates of extraoesophageal disorders vary widely and symptoms other than heartburn and regurgitation are reported in up to 50% of patients with endoscopically proven reflux oesophagitis. 32 Nevertheless, for some of the proposed associated manifestations, the evidence linking them with GERD is robust, whereas that for the other is less impressive. As an example, the recent novel definition and classification of GERD, referred to as the Montreal global classification, strongly suggested causality between reflux and cough, laryngitis, asthma, and DEs, although recognizing the rarity of extraoesophageal syndromes occurring in isolation without a concomitant manifestations of the typical oesophageal syndrome. Furthermore, it emphasizes the fact that these syndromes are usually multifactorial, with GERD acting as one potential aggravating cofactor. 8 For other syndromes, such as sinusitis, pulmonary fibrosis, pharyngitis, or recurrent otitis media, the Montreal Working team concluded that adequate evidence of causal linkage is lacking. 8 Among the sufficiently proven positive associations with GERD, DE was found to be a clear-cut one. Studies since the early 1970s 7 have highlighted the injurious role of gastro-duodenal contents in oral soft-tissue pathology as well as DEs. The studies we have reviewed are based on a heterogeneous definition of GERD, which is, in some cases, obtained by the demonstration of endoscopic oesophagitis, 11, 15, 16 in others by a pathological ph 9, 11 14, 25 metry or by the presence of GERD symptoms. 11, 17, 19 They confirm an prevalence of DEs in adult GERD patients, which is, on average, higher (median value 50%) than that observed in the general population (Table 2), where it is estimated to be as high as 5%. 2 As far as the paediatric population is concerned, we found the prevalence extremely variable, with a range between 13 and 87%, according to the method used to diagnose GERD. Finally, we explored the other way round, i.e. the prevalence of GERD in patients with DEs, and found an observed prevalence ranging from 21 to 83%, depending on the method used to diagnose GERD (Table 3). Finally, we found a study indicating that intellectually disabled people are at particularly high risk for developing DEs. 24 As far as the third aim of our systematic review is concerned, i.e. the pathophysiology of DEs in patients with GERD, a majority of studies here reviewed confirm that DEs may be because of acid reflux damage, while on the contrary, dental caries appear to be unrelated or conversely related to GERD; 11 in one study, it is even suggested that acid reflux may play a role in preventing the formation of dental caries by inhibiting bacterial growth in the mouth. 9 In general, DE appears to be a multi-factorial phenomenon in which the protective buffering capacity of the oral cavity is overcome by either reduced salivary secretion or increased volume of injurious gastric refluxate. Although GERD may have a noxious effect on other oral structures, it

7 SYSTEMATIC REVIEW: DENTAL EROSIONS AND GERD 1185 appears to be the most prevalent injury. 4 The site of teeth involvement may be universal, but the most commonly seen damage occurs on the facial, occlusal, and lingual surfaces. The severity of DEs according to the Eccles and Jenkins 26 classification appears to be correlated with the duration and severity of reflux symptoms. 17, 19 While a majority of patients ( 60%) with DE and GERD report typical GERD symptoms, no association has been found between severity of reflux symptoms and subjective symptoms in the mouth. 17 A relationship has also been found between the severity of DEs and the severity of oesophageal acid exposure as measured by ph-metry; in the study by Schroeder et al. 9 conducted in adults, the cumulative erosion score correlated with proximal upright reflux (r = 0.55, P < 0.01), but this association was not found in the study by Munoz et al. 11 or not specifically sought in the study by Moazzez et al., 13 Gregory-Head et al., 14 Gudmundsson et al. 25 among the studies conducted in adults and by O Sullivan et al. 10 among the ones conducted in children. In the study by Bartlett et al., 12 the relationship was found between percentage of time with distal oesophagus ph <4 and oral acid exposure time <6 as measured by oral ph-metry, and between the latter and the severity of DE. The injurious effect of acidic juice of extrinsic (citric fruits and acidic beverages) or intrinsic origin (gastro-oesophageal reflux (GER)) on the teeth and 2, 12, 17 oral tissues has been extensively studied. The direct contact of acid is considered to be the main mechanism of injury; GER can result in dental injury by the dissolving of the inorganic material of the teeth (hydroxyapatite crystals in enamel), which occurs below the critical ph level of This leads to DE, an irreversible loss of tooth substance without bacterial involvement, 9 which may be encountered at different stages, from the very early stages, where the only sign may be a barely noticeable loss of surface lustre evident on a clean, dry enamel to the typical yellowish areas on the surface of the tooth, because of the exposition of the underlying dentine through the thinned overlying enamel. 1 DE predisposes the teeth to attrition (flattening of occlusal surface) and abrasion (wearing away of teeth substance), which can lead to tooth loss, cosmetic disfigurement and altered facial appearance. 33 In conclusion, from a practical point of view, as DE is the predominant oral manifestation of GERD and is highly prevalent in the general population, dental examination plays an important role in the evaluation of patients with typical and atypical symptoms of GERD and in the above categories of patients. DE might be easily diagnosed by primary care physicians and gastroenterologists who are familiar with its physical characteristics. Early diagnosis and suppression of refluxed acid through lifestyle changes and medications have been reported to prevent further damage and tooth loss potentially. 33 For patients with signs of erosion, a dental referral is appropriate for evaluation and restoration of lost tooth structure and institution of preventive dental measures. Thus, not only is it important for the dentist to be familiar with and inquire about typical and atypical reflux symptoms, but also the primary care physician and the gastroenterologist need to pay more attention to the often neglected oral examination. ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCES 1 Pindborg JJ. Chemical and physical injuries. In: Pindborg JJ, ed. Pathology of the Dental Hard Tissues. Philadelphia: WB Saunders, 1970: Jarvinen VK, Rytomaa II, Heinonen OP. Risk factors in dental erosion. J Dent Res 1991; 70: Shafer WG, Hine MK, Levy BM. A Textbook of Oral Pathology, 3rd edn. Philadelphia: WB Saunders, Lazarchik DA, Filler SJ. Effects of gastroesophageal reflux on the oral cavity. Am J Med 1997; 103: 107S 13S. 5 Mahoney EK, Kilpatrick NM. Dental erosion: part 1. Aetiology and prevalence of dental erosion. N Z Dent J 2003; 99: Lussi A, Jaeggi T. Dental erosions in children. Monogr Oral Sci 2006; 20: Howden GF. Erosion as the presenting symptom in hiatus hernia. Br Dent J 1971; 131: Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R, The Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol 2006; 101: Schroeder PL, Filler SJ, Ramirez B, Lazarchik DA, Vaezi MF, Richter JE. Dental erosion and acid reflux disease. Ann Intern Med 1995; 122:

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