The Presentation of Reflux Esophagitis, Hiatal Hernia, Barrett's

ORIGINAL ARTICLE

The presentation of reflux esophagitis, hiatal hernia, Barrett's esophagus and 'reflux-like' dyspepsia: a prospective clinical and endoscopic study Downloaded from https://academic.oup.com/dote/article/9/4/285/4210318 by guest on 28 September 2021 B. F. M. Werdmuller, A. B. M. M. van der Putten, R. J. L. F. Loffeld Department of Internal Medicine, Ziekenhuis De Heel, Zaandam, The Netherlands

SUMMARY. The prevalence, number, and severity of symptoms in patients with esophagitis, hiatal hernia, Barrett's esophagus and 'reflux-like' dyspepsia was assessed in a prospective consecutive endoscopic and clinical study. Consecutive patients received a questionnaire consisting of 82 questions, 12 of which referred to upper abdominal complaints. A symptom score was calculated. A total of 115 patients with esophagitis, 29 patients with Barrett's esophagus, 108 patients with hiatal hernia and 439 patients with dyspepsia without endoscopic abnormalities ('reflux-like dyspepsia') were included. Only 5.5% of the patients had no reflux complaints. The symptom score and the number of complaints in patients with Grades I or II reflux esophagitis were significantly higher than in patients of the other groups. Presence of dysphagia was significantly higher in patients with Grades III or IV esophagitis. Patients with Grades III or IV esophagitis had a significantly shorter history. The presence of the majority of reflux symptoms with a high symptom score has a high predictive value for Grades I or II esophagitis, while the presence of dysphagia has a high predictive value for Grades III and IV esophagitis. In case of a lower number of symptoms or a lower symptom score, it is not possible to discriminate between hiatal hernia, esophagitis, Barrett's esophagus or 'reflux-like' dyspepsia.

INTRODUCTION PATIENTS AND METHODS

Gastroesophageal reflux disease (GERD) is believed A prospective study was done amongst 1432 consecu to be the most common clinical condition arising in the tive patients referred for upper gastrointestinal endo gastrointestinal tract. ''2 The development of esophagi scopy. tis is a multifactorial process depending on compo Prior to endoscopy, all patients received a ques nents such as: frequency and duration of reflux, effi tionnaire consisting of 82 different questions. Of cacy of esophageal clearance, resistance of the these, 12 questions were related to the upper abdomen esophageal mucosa and the contents of the refluxate. (Table 1). Hiatal hernia is a major contributor to esophagitis.3 For the assessment of a symptom score, eight ques The pathogenesis of the reflux-related symptoms is tions were scored on a linear scale ranging from 1 to 5 still not understood. A significant number of patients (absent = 1, mild = 2, moderate = 3, severe = 4, and very with more severe esophagitis appear to be free of severe = 5). The symptom score was calculated by sum symptoms.4 In addition, the overall prevalence of ming up the scores of 2 and higher. This makes a mini reflux-related symptoms decreases with increasing mum score of complaints of 2 and a maximum score of severity of esophagitis.3 40. The reason for the endoscopy was noted. A prospective study was done in order to assess both Endoscopy was done using the Olympus EVIS 100 the prevalence of reflux-related symptoms, the number video-endoscopy system. of symptoms and a symptom score in patients pre Patients with reflux esophagitis and/or hiatal hernia senting with reflux esophagitis, hiatal hernia, and and/or BE were included in the study. Patients with con Barrett's esophagus (BE). comitant abnormalities in stomach and/or duodenum were excluded. As a control group, patients in whom endoscopy revealed no macroscopic abnormalities were scored for the same symptoms and, for the sake of the Correspondence to: R.J.L.F. Loffeld MD PhD Department of Internal Medicine, Ziekenhuis De Heel, PO Box 210, 1500 EE study, these patients were designated as having 'reflux Zaandam, The Netherlands like' dyspepsia.

285 286 DISEASES OF THE ESOPHAGUS

Table 1 Clinical characteristics of the different patient groups

Reflux eisophagiti s grade Barrett's Hiatal 'Reflux-like' I II III IV esophagus hernia dyspepsia n = 64 « = 24 «=14 n=13 « = 29 n=108 « = 439

Incomplete questionnaire 2 3 1 2 0 11 46 Concomitant hiatal hernia 42 (66) 13 (54) 7(50) 8(62) 17 (59) - - Indications Upper abdominal complaints 58% 42% 37% 18% 41% 46% 58% Dysphagia 5% 11% 16% 29% 3% 4% 4% Reflux symptoms 21% 33% 26% 24% 18% 18% 7% Miscellaneous 16% 14% 21% 29% 38% 32% 31% Downloaded from https://academic.oup.com/dote/article/9/4/285/4210318 by guest on 28 September 2021 Complaints Epigastric pain 43 (68) 14(65) 3(23) 4(40) 11 (39) 56 (50) 233(58) Retrosternal pain 43 (70) 15(75) 6(46) 4(36) 16 (57) 51 (54) 208 (54) Nocturnal pain 36 (40) 12 (60) 2(17) 2(20) 5(29) 44(47) 224 (56) Odynophagia 12(12) 8(40) 2(15) 3(30) 4(15) 15(16) 78 (20) Belching 51(84) 12 (57) 2(15) 7(64) 20(71) 66(71) 252 (65) Dysphagia 17 (28) 5(25) 6(46) 8(80) 5(18) 30 (33) 80(21) Heartburn 54 (88) 19 (90) 7(54) 10(91) 9(70) 60 (64) 212(56) Retrosternal heartburn 50 (82) 15 (75) 5(42) 7(64) 14 (52) 54 (60) 163 (43) Halitosis 15 (25) 4(19) 0 1(10) 4(14) 16(17) 117(32)

Influence of position Bending 33 (55) 12(57) 7(58) 4(40) 14 (50) 40 (44) 145 (39) Supine 28 (48) 7(37) 3(25) 4(36) 16(59) 28 (32) 105(28) Supine heartburn 37 (72) 10(53) 6(60) 5(55) 16(73) 35(51) 124(45)

Numbers denote patients presenting with a complaint. Numbers within parentheses are percentages.

Hiatal hernia was defined as a distance of more than III or IV esophagitis (P<0.001). Patients with 'reflux 2 cm between the esophageal epithelium and the like' dyspepsia were significantly younger than all other diaphragm. patients (P< 0.0001). Grade of esophagitis was scored according to the However, considerable overlap in age was present. well-known grading system of Savary Miller.5 Grade In Table 1 the clinical characteristics of the different 1: one or more, non-confluent mucosal lesions accom patient groups are shown. A concomitant hiatal hernia panied by erythema or superficial erosion; Grade 2: was present in a substantial number of patients with confluent erosive and exudative mucosal lesions that esophagitis or BE. do not cover over the entire circumference of the Mean symptom score in Grade I esophagitis was 15.3 esophagus; Grade 3: erosive and exudative lesions (SD 5.8); in Grade II 15 (SD 6.5); in Grade III 8.9 (SD covering the entire circumference without stricture; 7); and in Grade IV 11.4 (SD 5.1). Symptom score in and Grade 4: appearance of chronic mucosal lesions patients with BE was 10.3 (SD 6), in hiatal hernia 12.2 like ulcers, stricture and fibrosis. Presence of BE was (SD 6.8), and in 'reflux-like' dyspepsia 11.5 (SD 6.7). noted separately. Symptom score in patients with grades III or IV Statistical analysis was carried out using %2 test and esophagitis was significantly lower than in patients with Mest. Grades I or II esophagitis, mean 15.2 (SD 6) versus 10 (SD 6.2) (P< 0.001). Patients with BE and/or hiatal her nia without inflammation and/or 'reflux-like' dyspepsia RESULTS had significantly lower symptom scores than patients with Grades I or II esophagitis, 10.3 (SD 6) versus 15.2 A total of 691 consecutive patients fulfilled the inclu (SD 6) (P< 0.001) and 12.2 (SD 6.8) versus 15.2 (SD 6) sion criteria. The questionnaire was completed in (P = 0.01), and 11.5 (SD 6.7) versus 15.2 (SD 6) 93% of the cases. The different patient groups are (P< 0.0001) respectively. No difference in symptom shown in Table 2. The number of men was signifi score was present when grades III or IV esophagitis, cantly higher in cases of esophagitis and BE hiatal hernia, BE and patients with 'reflux-like' dyspep (P< 0.0001), while the number of women was signif sia were compared. icantly higher in cases of hiatal hernia and 'reflux Patients with Grades I or II esophagitis had signifi like' dyspepsia (P<0.0001). cantly more reflux complaints, mean 5.1 (SD 1.5), than Patients with Grades I or II reflux esophagitis were patients with Grades III or IV esophagitis, mean 3.5 (SD significantly younger compared to patients with Grades 1.8), patients with BE, mean 3.7 (SD 1.9), patients with REFLUX ESOPHAGITIS, HIATAL HERNIA, BE AND 'REFLUX-LIKE' DYSPEPSIA 287

Table 2 Demographic data of different groups of patients

Esophagitis n Men Women Mean age SD Range

Grade I 64 39 25 52 18.6 12-86 Grade II 24 15 9 58 17 26-84 Grade III 14 6 8 57 16.9 23-82 Grade IV 13 8 5 61 15.7 37-86 Barrett's eso]phagu s 29 17 12 60.5 13.8 33-83 Hiatal hernia 108 43 65 56.9 16 12-87 'Reflux-like' dyspepsia 439 182 257 47 17.6 12-91

Table 3 Comparison of different groups of patients. Only Grades I & II Barrett's esophagus Downloaded from https://academic.oup.com/dote/article/9/4/285/4210318 by guest on 28 September 2021 significant differences are shown Epigastric pain 57 (67) 11(39) P< 0.0001 Grades I & II Grades III & IV Nocturnal pain 48 (60) 5 (29) P = 0.04 Heartburn 73 (89) 9(70) P< 0.001 Epigastric pain 57 (67) 7(33) P< 0.001 Retrosternal heartburn 65 (80) 14(52) P< 0.001 Retrosternal pain 58 (72) 10 (42) P< 0.001 Nocturnal pain 48 (60) 4(18) P< 0.001 Barrett's Belching 63 (77) 9(38) P< 0.001 esophagus 'Reflux-like' dyspepsia Dysphagia 22 (28) 14 (58) P = 0.02 Heartburn 73 (89) 17(71) P = 0.02 Epigastric pain 11 (39) 233(61) P = 0.03 Retrosternal heartburn 65 (80) 12 (52) P< 0.001 Nocturnal pain 5 (29) Halitosis 19 (23) 1(4) P = 0.04 Duration of complaints 222 (56) P = 0.03 Duration of complaints >lyear 17(62) <3 months 18(22) 10 (48) P = 0.03 Indication for endoscopy 125(33.5) P< 0.0001 Indication for endoscopy Reflux symptoms 7(18) Upper abdominal 63 (53) 10 (28) P< 0.001 Influence of position 35 (7) P = 0.03 complaints Supine 16(5) Dysphagia 8(7) 8(22) P< 0.001 Supine heartburn 16(73) 105(28) P< 0.001 124(45) P = 0.02 Hiatal hernia 'Reflux-like' dyspepsia Grades III &IV 'Reflux-like' dyspepsia Epigastric pain 56 (50) 233 (61) P = 0.03 Nocturnal pain 44 (46) 224 (56) P = 0.03 Epigastric pain 7(33) 233(61) P = 0.02 Retrosternal heartburn 54 (60) 163 (43) P< 0.001 Nocturnal pain 4(18) 224(56) P< 0.0001 Halitosis 16(17) 117(32) P< 0.001 Dysphagia 14(58) 80(21) P< 0.0001 Halitosis 1(4) 117(32) P = Q.Q\ Indication for endoscopy Reflux symptoms 26(19) 35(7) P< 0.001 Indication for endoscopy Upper abdominal 10(28) 291 (58) P< 0.0001 Grades I & II Hiatal hernia complaints Dysphagia 8(22) 22(4) P< 0.0001 Epigastric pain 57 (67) 46 (50) P = 0.02 Reflux symptoms 9(25) 35(7) P< 0.001 Retrosternal pain 58 (72) 51 (54) P = 0.02 Heartburn 73 (89) 60 (64) P < 0.001 Grades III Retrosternal heartburn 65 (80) 54 (60) P< 0.001 &IV Barrett's esophagus

Indication for endoscopy Dysphagia 14(58) 5(18) P< 0.001 Miscellaneous 18(15) 36 (27) P = 0.03 Indication for endoscopy Grades I & II 'Reflux-like' dyspepsia Upper abdominal 10(28) 20(51) P = 0.06 complaints Retrosternal pain 58 (72) 208 (54) P< 0.001 Dysphagia 8(22) 1(3) P< 0.001 Belching 63 (77) 252 (65) P< 0.001 Heartburn 73 (89) 212(55) P< 0.001 Grades III Hiatal hernia Retrosternal heartburn 65 (80) 163 (53) P< 0.001 &IV Influence of position Nocturnal pain 4(18) 44(46) P = 0.02 Bending 45 (56) 145(39) P< 0.001 Belching 9(38) 66(71) P = 0.04 Duration of complaints Indication for endoscopy <3 months 18(22) 127 (34.5)i P = 0.04 Upper abdominal 10(28) 69(50) P = Q.Q2 complaints Indication for endoscopy Dysphagia 8(22) 6(4) P< 0.001 Reflux symptoms 30 (25) 35(7) P < 0.001 Miscellaneous 18(15) 151(31) P< 0.001 Numbers within parentheses are percentages. 288 DISEASES OF THE ESOPHAGUS hiatal hernia, mean 4.1 (SD 1.9) and 'reflux-like' dys Previous reports have shown increased impairment peptics, mean 4.0 (SD 1.9) (P = 0.03). of esophageal motility in patients with more severe In Table 3, the prevalence and duration of com esophagitis.12 Patients with grades III or IV esophagitis plaints, and the reason for the endoscopy are noted. have shorter duration and lower amplitude of pressures Only the significant differences (P < 0.05) between the in the esophagus than patients with Grades I or II different patient groups are shown. esophagitis .13 Another explanation could be less sensi tivity of acid sensitive nerve fibers. In analogy with patients with asymptomatic duodenal ulcer disease, DISCUSSION older people could have higher beta-endorphin levels which render them insensitive to pain.14 Patients with The majority of patients with esophagitis, BE or hiatal BE appear to have a lower symptom score. It can be hernia have one or more complaints related to gastro assumed that the metaplastic epithelium protects the Downloaded from https://academic.oup.com/dote/article/9/4/285/4210318 by guest on 28 September 2021 esophageal reflux. Only 5.5% of the patients are free esophagus against acid. A more striking phenomenon is of symptoms. The reason for performing an endoscopy the fact that almost half of the patients presenting with in these cases was mostly anemia of unknown origin. Grades III or IV esophagitis have a duration of com This is in disagreement with earlier studies, in which a plaints of less than 3 months. It can be expected that significant number of these patients were reported as esophagitis Grades III or IV once started as Grade I. asymptomatic.3'6 The obvious explanation for this is Two explanations for this short history can be postu the use of the detailed questionnaire that explicitly lated. First, the esophageal inflammation progresses assessed presence or absence of symptoms. Although very rapidly to fibrosis and narrowing leading to dys the sensitivity of reflux symptoms generally is consid phagia as the presenting symptom. Second, since the ered to be low,7 this is certainly not the case in patients perception of pH can vary substantially,' ^ these patients presenting with Grades I or II esophagitis. The major could represent a subset with a very high threshold for ity of these patients suffered from reflux-related symp esophageal symptoms and/or ineffective esophageal toms. However, the opposite is true for patients with peristalsis.13 Psychological factors in older people Grades III or IV esophagitis. A substantial number of could also influence the perception of pain or other these patients only had dysphagia. It is not possible to reflux complaints.16 calculate sensitivity and specificity, positive and nega The clinical reason for doing the endoscopy was the tive predictive value of complaints because it is not presence of typical reflux symptoms in only 25% of the certain that the control group of 'reflux-like' dyspep cases. Mostly endoscopy was done because of upper tics do not have pathological reflux during 24-h pH abdominal complaints and/or dysphagia. Because the monitoring. majority of patients had one or more symptoms indica In disagreement with the literature,8 only a small tive of reflux disease, this discrepancy can be explained number of patients presenting with reflux symptoms by the fact that the patient is offered time to think during actually suffer from esophagitis. A drawback, of answering the questionnaire. This indicates that the use course, is the absence of 24-h pH monitoring in the of a standardized questionnaire can be useful in clinical 'reflux-like' dyspeptics. However, it is known that gastroenterology. patients with esophagitis have a higher number of It is concluded that the presence of a majority of reflux episodes and a longer duration of mucosal acid typical reflux symptoms has a high predictive value for exposure compared with reflux patients without the presence of Grades I or II esophagitis, and that dys esophagitis.9 phagia is indicative for Grades III or IV esophagitis. In Patients with Grades I or II esophagitis have a sig cases of less symptomatology or lower symptom score, nificantly higher symptom score compared with it is not possible to distinguish between BE hiatal hernia patients of the other groups. It could be postulated that or 'reflux-like' dyspepsia. the longer duration of acid exposure in the esophagus of these patients results in more stimulation of acid- REFERENCES sensitive receptor nerve fibres in the esophageal 10 mucosa. Primary esophageal peristalsis is the domi 1. Dodd W J, Hogan W J, Miller W N. Reflux esophagitis: a nant type of motor activity that occurs during acid progress report. Am J Dig 1976; 21: 49-67. reflux.'' Primary peristaltic activity after an episode of 2. Castell D O, Holtz A. Gastro-esophageal reflux. Don't forget to ask about heartburn. Postgrad Med J 1989; 86: 141-144. reflux is greater in patients with mild esophagitis than 3. Loffeld R J L F, van der Putten A B M M. Hiatal hernia, reflux- 11 in patients without esophagitis. Because of the oesophagitis, and Barrett's oesophagus. A retrospective higher symptom score in patients with Grades I or II endoscopic and clinical study. Dis Esoph 1993; 6: 57-61. 4. Johnson D A, Winters C, Spurling T J, Chobanion S J, Cattau E esophagitis, it is conceivable to assume that both pri L. Esophageal acid sensitivity in Barrett's esophagus. J Clin mary peristalsis and mucosal inflammation are respon Gastroenterol 1987; 9: 23-27. sible for generation of complaints. Patients with 5. Savary Miller. The Oesophagus. Solothurn, Switzerland: Verlag Gassman, 1978: 135-142. Grades III or IV esophagitis have lower symptom 6. Raiha, I, Hutanen E, Soande L. Symptoms of gastro-oesophageal score and fewer symptoms. reflux disease in elderly people. Age Ageing 1991; 20/5: 365-370. REFLUX ESOPHAGITIS, HIATAL HERNIA, BE AND 'REFLUX-LIKE' DYSPEPSIA 289

7. Klauser A G, Schindlbeck N E, Muller-Lissner S A. Symptoms 12. Kahrilas P, Dodds W J, Hogan W J et al. Esophageal peristaltic in gastro-esophageal reflux disease. Lancet 1990; 335: 20508. dysfunction in peptide esophagitis. Gastroenterology 1986; 91: 8. Johansson K E, Ask P, Boerijd B, Fransson S-G, Tibbling L. 897-907. Oesophagitis, signs of reflux and acid secretion in patients with 13. Timmer R, Breumelhof R, Nadorp JHSM, Smout A J P M. symptoms of gastro-esophageal reflux disease. Scand J Oesophageal motility and gastro-esophageal reflux before and after Gastroenterology 1986; 21: 837-847. healing of reflux oesophagitis. A study using 24 hour ambulatory 9. Rokkas T, Sladen G E. Ambulatory esophageal pH recording in pH and pressure monitoring. Gut 1994; 35: 1519-1522. gastroesophageal reflux: relevance to the development of 14. Tannarini G F, Delia Fave G F, Chianelli M, Mariani P. Negri esophagitis. Am J Gastroenterology 1988; 83: 629-632. M. Beta-endorphin in silent duodenal ulcer. Eur J Gastroenterol 10. Bontempo I, Piretta L, Corazziari E et al. Effects of intraluminal Hepatol 1995; 7: 357-360. acidification on oesophageal motor activity. Gut 1994; 35: 15. Smith J L, Opekun A R, Larkai E, Graham D Y. Sensitivity of 884-890. the esophageal mucosa to pH in gastro-esophageal reflux 1 I. Anggiansah A, Taylor G, Bright N et al. Primary peristalsis is the disease. Gastroenterology 1989; 96: 683-689. major acid clearance mechanism in reflux patients. Gut 1994; 35: 16. Johnston B T, Lewis S A, Love A H G. Psychological factors in 1536-1542. gastro-oesophageal reflux disease. Gut 1995; 36: 481^182. Downloaded from https://academic.oup.com/dote/article/9/4/285/4210318 by guest on 28 September 2021