Reflux complaints , symptom score and the use of medication in patients with reflux esophagitis : Results of a long term follow-up study

Department of Internal Medicine, De Heel Zaans Medisch Centrum, Zaandam, the Netherlands Correspondence: Dr Ruud JLF Loffeld, Department of Internal Medicine, De Heel Zaans Medisch Centrum PO Box 21

G astroesophageal reflux disease is a chronic disorder, especially if reflux esophagitis is diagnosed endoscopically.Reflux esophagitis can be treated effectively with acid suppressive therapy with good clinical and endoscopic results (1).However, without maintenance therapy, complaints and inflammation are likely to recur.Data on the long term use of acid suppressive therapy in these patients are available from patients participating in clinical trials, who have a fair compliance with prescribed therapy (2).Data on normal daily practice are lacking.
For this reason, a cross-sectional, retrospective, descriptive study was done in a group of consecutive patients diagnosed with reflux esophagitis at least 4.5 to 5.5 years earlier to assess current complaints and use of acid suppressive therapy.

PATIENTS AND METHODS
All consecutive patients sent for upper gastrointestinal endoscopy in the year 1995, in whom the diagnosis of active reflux esophagitis was confirmed endoscopically, were included in the study.All patients underwent upper gastrointestinal endoscopy using Olympus EVIS 100 videoendoscopes (Olympus Optical Company, Japan).Esophagitis was scored according to the well known Savary-Miller system (3).Additional endoscopic diagnoses were noted.A hiatal hernia was defined as a distance of more than 2 cm between the Z-line and the diaphragm.
All patients received a questionnaire (4) in the summer of 2000.Apart from reflux and upper abdominal complaints, use of medication (daily or intermittently) and dose of drugs used (proton pump inhibitors [PPIs], H 2 receptor antagonists, prokinetic drugs or antacids) were assessed.Ten questions (Table 1) were scored on a five-point Likert scale for assessment of severity of complaints (0 = absence of the specific complaint, 1 = complaint mildly present, 2 = complaint moderately present, 3 = complaint severely present, and 4 = complaint severely present and interfering with daily life).A score of symptom severity was calculated by adding up the scores of each complaint.Hence, the minimum score was 0 and the maximum score 50.In addition, frequency of occurrence of complaints was scored on a sixpoint scale (1 = complaint present once a month, 2 = complaint present two to three times a month, 3 = complaint present once a week, 4 = complaint present a few times a week, 5 = complaint present daily, 6 = complaint present on several occasions per day).The minimum score was 9, and the maximum score was 54.
Statistical analysis was done with χ 2 test for contingency tables, if appropriate, and t test.
The Medical Ethics Committee of De Heel Zaans Medisch Centrum, the Netherlands, approved the study protocol.

RESULTS
In 1995, reflux esophagitis was diagnosed in 173 patients at the De Heel Zaans Medisch Centrum.Thirty (17%) of these patients died, and the current address was not known for 13 (8%).The questionnaire was sent to 130 patients, of whom 95 (74%) responded.Table 2 shows the details of these three groups of patients.The patients who died belonged to the oldest age group.There were no differences in sex or endoscopic diagnosis.
Four groups of responders were identified: patients in clinical remission (free of symptoms) with (group 1, n=18) or without (group 2, n=20) maintenance therapy, and patients suffering from reflux complaints with (group 3, n=48) or without (group 4, n=9) medication.Table 3 shows the details and the initial endoscopic diagnoses of these patients.There was no statistically significant difference among the four groups of patients with respect to initial endoscopic diagnosis and severity of esophagitis.Seventeen (94%) patients from group 1 used medication on a daily basis, and only one patient used the medication intermittently.In group 3, these figures were 32 (67%) and 16 (33%), respectively (P=0.04).There was no statistically significant difference between the two groups with respect to the dose of acid suppressive therapy actually used.
Ninety four per cent of patients in group 1 and 79% of patients in group 3 used the initially prescribed dose.Only 6% of patients in group 1 and 14% in group 3 used a higher dose than initially prescribed, and 7% in group 3 a lower dose.
Sixteen patients (88%) in group 1 used PPIs; one patient used an H 2 blocker, and one patient used a combination of PPI and a prokinetic drug.In group 3, PPIs were used by 35 patients (75%); five used a PPI in combination with prokinetic agents, two used a PPI in combination with sucralfate, two used antacids, three used H 2 receptor antagonists, and one used a combination of PPI and H 2 receptor antagonist (Table 4).
No statistically significant difference in symptom score was seen between the two symptomatic subgroups.The mean symptom score ± SD was 7.8±5.3 in group 3 patients and 8.6±8.6 in group 4 patients.The frequency score of complaints also showed no significant difference between these two groups of patients: 14.3±10 and 11±7, respectively.Table 1 shows the specific complaints in groups 3 and 4.
Of the deceased patients, data were retrieved from seven.Three used acid suppressive therapy before their death.Only one patient died due to disease in the upper gastrointestinal tract (distal stomach cancer).

DISCUSSION
After healing of reflux esophagitis, it appears that most patients participating in clinical trials cannot sustain remission without some form of maintenance therapy (5,6).The population under study was a nonselected group of patients diagnosed with reflux esophagitis who were not included in a clinical trial and hence reflect normal daily practice and long term compliance to prescribed therapy.There was no difference in the sex or endoscopic diagnosis of patients who responded and those who died or did not respond.This is of importance in reviewing the results.The response to the questionnaire in the present study is in keeping with results from other studies in the field (7).In an earlier study, 58% of patients with esophagitis were no longer taking medication five years after diagnosis, and a number as low as 10% were taking antisecretory drugs (8).Conversely, it is also reported that 90% of patients were still on treatment and, in addition, 31% still presented with symptoms at a follow-up of a median of four years (8).The present data are in accordance with results from the latter study.
The majority of patients still use acid suppressive therapy, mostly in adequate daily dose.Despite this, only 27% are in complete clinical remission.A group of 20 (21%) patients are in clinical remission without current use of any medication.
Nine patients stopped taking acid suppressive therapy despite that they suffered from reflux complaints.However, there is no significant difference in the severity score and frequency score between patients taking medication and those who stopped taking medication.It is striking that the symptom score in these groups of patients was rather low, 7 to 8, while the maximum possible score was 50.In a previous study using the same five-point Likert scale, the symptom score at the time of diagnosis of esophagitis was markedly higher (4).One can only speculate as to why   Complaints present with maintenance therapy some patients stopped using medication and others still suffered from reflux complaints despite medication.Patients with a low symptom score while on medication possibly are satisfied with the result, and patients without medication possibly are satisfied because, in their opinion, they only have minor complaints not necessitating maintenance therapy.Individual symptom tolerance and reporting behaviour are the best explanations for the differences.Psychological well-being will influence the results of every questionnaire.Higher grades of esophagitis are linked to maintenance treatment (8).The present data contradict this study.The initial grade of esophagitis was not a determinant of use of maintenance therapy.Need for acid suppression at followup is predicted by any grade of esophageal inflammation at initial endoscopy (7).
It is easy to accept that, if all patients were compliant with the initial prescribed therapy, the number of persons in clinical remission would be higher.Complaints occur because gastric acid secretion is not adequately suppressed, or they are the result of reflux of duodenal contents.The number of patients in complete clinical remission taking their medication daily was significantly higher than the number who did not take medication daily.The reason why patients of group 4 stopped using the acid suppressive therapy can only be speculated, but may be explained by the fact that their complaints are only of minor severity and that most patients do not like to take medication chronically.
A possible confounding factor is that the study was not controlled.The symptom score of the patients was rather low.It would be interesting to know the prevalence of reflux complaints in the general population without diagnosed reflux esophagitis.It is tempting to assume that the prevalence of these complaints in our patients is no higher than that in the general population.
A low dose of PPI is not sufficient to maintain remission of esophagitis after initial healing (6,9).Even continuous therapy with an adequate dose of PPI did not maintain remission (6,10).
In the present study, patients who took PPIs even in higher doses still experienced complaints.It is possible that reflux of duodenal contents, which cannot be treated with acid suppression, was responsible for the complaints in these patients.
It is disappointing to see that only a minority of patients were in complete clinical remission with or without the use of acid suppressive drugs.The results of antireflux surgery in patients fit for operation and refractory to medical treatment are very promising.A majority of patients are in clinical remission more than 10 years after successful surgery without the need for any maintenance therapy (11).
This study clearly shows that there is a trend toward chronicity of complaints, despite continuous use of acid suppressive therapy.Chronic low symptom scores are relatively common.
Reflux complaints and use of medicationCan J Gastroenterol Vol 15 No 8 August 2001 507

TABLE 2 Demographics and endoscopic diagnoses of patients who did not respond to the study questionnaire Patients Patients with no who died known address Nonresponders
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