What data do the prospective epidemiologic studies of esophagitis provide?
F. Klotz, JM. Debonne, J.C. Grimaud (Marseilles)
The epidemiology of reflux esophagitis (RE) is known retrospectively with its major and minor clinical features being manifested in different ways in each individual. Only a prospective study of a cohort of patients presenting gastroesophageal reflux (GER) and followed up clinically, endoscopically and histologically until esophagitis occurs, then throughout its progression, would allow a greater knowledge of the determinant epidemiological factors in this condition. Although it would seem that there are some trials of this sort in progress, none has so far appeared in the literature. For a knowledge of the epidemiology of RE, the secrets of its natural history need to be understood. There have been many retrospective studies on the epidemiological features of patients presenting RE and a few partially isolated prospective studies which already provide some answers to these questions.
If only RE is looked at, without taking into account the studies of the prevalence of GER and its features, the first prospective study began in 1946 and was published in 1968 by Palmer , and involved the follow-up of patients presenting RE. It was, however, really a progressive follow-up study using old classification criteria without specifically looking at epidemiological factors. In Nantes in 1981, Dedieu published an epidemiological study of a series of 123 cases of esophagitis . Apart from that, in the 1980s, many retrospective studies including personal studies and literature reviews were published, the most important being those by Savary  and Zeitoun . Also, the results of Micaleffs study of the epidemiological factors seen by private gastroenterologists in 679 cases of RE, published in 1986, appear to be of interest .
Frequency of RE
The incidence of RE in the general population is difficult to quantify, in the USA it has been estimated at 2% . However, in a study of 1,000 autopsies, it was found to be present in 27% of cases, although this high incidence is, of course, not applicable to the general population . In studies of patients who have had an endoscopy, the incidence of RE varies from 10 to 20% depending on the region and on the author [4,8-10]. Amongst the patients consulting for symptoms of GER, the incidence of RE varies from 50 to 65% [11,12]. In Micaleff's multicentric study , it was 86%.
Age and sex
More men than women are affected by RE, the sex ratio being more than two [9,13]. This moderate male predominance becomes much more pronounced in severe RE (71% men and 29% women) . The incidence of esophagitis increases markedly with age, the mean age of patients who present RE being around 55 years old [3,14]. Fifty percent of Pantin's patients were over 70 years old, the women being affected at a significantly older age than the men . This correlates well with the GER annual incidence curve  (Fig. 1). Tibbling  found RE to affect 5% of the population over 55 years old.
What are the determinant factors of RE?
Alcohol. Alcoholism is certainly an important factor. Many studies have found that the higher the alcohol consumption, the more severe is the esophagitis, with an overall rate of confirmed alcoholism in 55% of cases [2,5]. In Lausanne , the incidence was found to be the same, with a large majority of cases being in men. Alcohol may act in potentiating the toxic action of the reflux fluids by stimulation of the gastric acid secretion and by modification of esophageal clearance and saliva secretion .
Tobacco. Tobacco consumption is also found to be increasing with frequency, which is proportional to the severity of the RE and greater than the incidence in the general population [2,5]. The role of tobacco in the functioning of the lower esophageal sphincter (LES), on the resistance of the esophageal mucosa and on acid secretion has already been clearly demonstrated. Other general or dietetic factors have not proved to be important in the etiology of RE, nevertheless they are significant determinant factors in reflux.
The role of nonsteroidal anti-inflammatory drugs (NSAIDS). In Savary's study, it was found that severe or complicated RE occurred more frequently in patients taking NSAIDS, with 24% of them presenting Barrett's esophagus (BE), 27% with peptic
Figure 1. .Annual occurrence of the disease related to GER .
Associated gastrointestinal pathology. Hiatus hernia has been viewed for a long time as an important factor in RE. In the studies reviewed by Stadelmann , hiatus hernia was found in 46-96% of patients presenting RE. Amongst the more recent important studies, Savary found hiatus hernias in 37% of cases , Zeitoun in 42.1% , whereas in the general population, it is only 10%. Hiatus hernia would therefore appear to have a definite role in promoting the occurrence of RE. The link with gastroduodenal ulcers is more controversial. Zeitoun noted 11.7% of patients with RE to have a duodenal ulcer, compared with 6.2% in a total of 20,598 patients studied . Gastric ulcers were found in 5.9 and 4.4% of cases, respectively. In Savary's study of complicated RE, no clear link was found with ulcer disease .
Is there a link between the severity of the symptoms and the grade of the RE?
Dedieu found that there were symptoms of GER overall in 61% of cases of RE, without any noticeable difference between the different stages of RE . In his study of 679 cases of RE, Micaleff observed symptomatology suggestive of GER in 88% of cases, with atypical ENT, respiratory and pseudocoronary symptoms occurring in 23% of cases , There would not seem to be any link between the severity of the symptoms and the grade of RE except in cases where stenosis is present, in which dysphagia predominates the picture.
Frequency of the various grades of RE
This is difficult to assess from the studies in the literature, because the classifications used are not the same. With reference to the studies using Savary and Miller's classification:
- Schindlbeck  studied a group of 160 patients with characteristic GER and found 32% to have RE of which 11 % was grade I, 9% grade II, 7% grade III and 5% grade IV.
- Savary's study of 2,673 cases of RE  found a predominance of grades I and IV with 50.7% being grade I, 13.6% grade II, 5.1% grade III and 30.6% grade IV.
According to Spechler , the incidence of RE with associated complications lies between 10 and 15% for BE, is 2-7% in esophageal ulcers, less than 0.2% in perforation and from 4-20% for peptic stenosis. Among 1,047 cases of esophagitis with complications studied by the Lausanne team, in 64% there was BE, in 34% stenosis, in 20% ulcer, and in 27% brachy-esophagus. The incidence of BE in the literature varies from 9-12.4% in those who are endoscoped . In their study of 2,448 cases of RE, the Reims team  found fewer complicated cases including only 2.4% with peptic stenosis. This would seem to be closer to what is currently seen in most gastroenterological endoscopic centers.
Evaluation of the risk of progression of RE
No prospective study has so far been published on the progression of RE, although a retrospective study by the Lausanne team showed that 32.5% of their cases of RE progressed to stenosis, an ulcer or to BE in the end . In patients with BE, there is a genuine risk of malignant transformation, they being 300-1,200 times more likely than the general population to develop an adenocarcinoma . In a group of 360 cases of BE, the Lausanne team discovered that in 12% there was an adenocarcinoma . This justifies an annual endoscopic surveillance of all patients with Barrett's esophagus. The occurrence of peptic stenosis appears to be encouraged directly by NS AID consumption in 31 and 49% of cases, respectively [20,26] compared with 14 and 12%, respectively, in the controls.
These drugs are therefore an aggravating factor for RE, by reducing the tissue concentration of prostaglandins, whose protective role on the esophageal mucosa is well known.
Can it be a complication of surgery?
About 15 to 20% of cases of peptic stenoses are thought to occur as a result of surgery with nasogastric intubation , this occurs within 6 months of the operation in 50% of cases. Included amongst the determinant factors are prolonged peri- or postoperative GER and the use of a nasogastric tube. All these epidemiological data about RE highlight the complexity of the etiological factors and the lack of
knowledge of the long-term effects of the condition, there being notable differences between the various groups of patients studied. The numerous retrospective studies and the few incomplete prospective studies suggest that a large multicenter prospective trial of GER with a long-term follow-up is necessary.
5. Micaleff A, Richard-Berthe C, Huyghe J-L. Oesophagite de reflux. Résultats d'une enquête épidémiologique et endo-scopique chez 679 patients, réalisée par 146 gastroentérologues de ville. Med Chir Dig 1986;15:8-14.
11. Behar J. Gastroesophageal reflux disease and its complications with a critical analysis of treatment. In: Cohen S and Soloway RD (eds) Diseases of the Esophagus. New York: Churchill Livingstone, 1982;195-213.
12. Johansson KE, Ask P, Boeryd B, Fransson SO, Tibbling L. Esophagitis, signs of reflux and gastric acid secretion in patients with symptoms of gastroesophageal reflux disease. Scand J Gastroenterol 1986:21:837-847.
24. Brossard E, Monnier P, Ollyo J-B, Fontolliet C, Levi F, Krayenbuhl M, Savary M. Serious complications stenosis, ulcer and Barrett's epithelium develop in 21.6% of adults with erosive reflux esophagitis. Gastroenterology 1991;100(5,part 2): A36.
27. Savary M, Ollyo J-B, Monnier P. L'oesophagite sténosante par reflux. In: Galmiche J-P, Colin R (eds) Troubles de la motricité de I'oesophage, Reflux Gastro-oesophagien. Paris: Doin Edit 1987:193-229.