Peptic ulcer disease has changed profoundly in the last decades in Western countries in both children and adults (1,2). Indeed, the prevalence of Helicobacter pylori–positive ulcers has declined, and a “new” disease has emerged: H pylori–negative gastric or duodenal ulcers (3). In adults, most cases of the latter are due to nonsteroidal anti-inflammatory drugs (NSAIDs) and/or alcohol, and tobacco use can be associated, whereas in children they are not, and their etiology is mostly unknown as are their prevalence and long-term history.
This issue of JPGN contains an interesting study about idiopathic peptic ulcer in Chinese children in which the authors report prevalence, symptoms at presentation, and long-term follow-up data (4). The authors enrolled children in whom an ulcer was found during esophago-gastro-duodenoscopy (EGDS), and cases of peptic ulcer secondary to drug use or associated with chronic or acute diseases were excluded. The study, although retrospective, gives important clues about the disease in childhood, the most interesting of which being not only the existence of H pylori–negative ulcers but also their high prevalence. In this series, 6.9% of children undergoing EGDS had an ulcer and in almost half of them (46.5%) no H pylori infection was found. The second most important information we have from this study is the high prevalence of acute gastrointestinal bleeding at presentation. These data are different from other studies, in which only 20% or 27% of childhood peptic ulcers were not associated with either NSAIDs or H pylori (5,6) and in which the most common symptoms at presentation were dyspepsia and/or abdominal pain (7,8).
PREVALENCE OF PEPTIC ULCERS IN CHILDHOOD
Data on the prevalence of gastric or duodenal ulcers (ie, peptic ulcers) in children are scant. Recently, new information on the prevalence of peptic ulcer in H pylori–infected European children was collected by a register established on the Web site of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition to collect information on the treatment of children with H pylori infection diagnosed during endoscopy by European pediatricians (9). From January 2001 to December 2002, information on 518 children was collected (262 males, median age 9 years, range 1–14 years). At endoscopy, 454 children had gastritis and 64 had an ulcer (12.3%). However, this series included 102 children from Russia and they had a significantly higher prevalence of peptic ulcer (35% vs 6.7% in the remainder of European children, P < 0.0001, odds ratio [OR] 7.5, 95% confidence interval [CI] 4–13). Although bias in the data collected by the register could not be excluded because of the nonrandomized approach to data collection, the prevalence of H pylori–positive ulcers in children differs among countries, and this is not completely explained by the prevalence of the infection in the population studied.
The prevalence reported in Chinese children by Tam et al (4) seems higher than in European children. We, therefore, tried to compare it with the prevalence in Italian children (Table 1) by analyzing our database containing data of children undergoing EGDS in the last 20 years. Indeed, the prevalence of peptic ulcer in Chinese children is higher (6.9% vs 3.4% in Italian children, P < 0.0001, OR 2.3, 95% CI 1.5–3.4). Some clinical characteristics were similar in the 2 populations, such as a higher number of males in the group with H pylori–positive ulcers, and their older age as compared with H pylori–negative ulcers, and a lower prevalence of gastric than duodenal ulcer (14% in Chinese and 33% in Italian children). However, there are several important differences between the 2 populations, namely, symptoms at presentation where bleeding is more frequent in Chinese than in Italian children, and the recurrence rate is higher in Chinese children, particularly in H pylori–negative children (Table 1). Moreover, both Italian and Chinese children with H pylori–negative ulcers are younger, and the prevalence of males and females is similar. From these and other data, mainly obtained in adults, it is evident that H pylori–positive and H pylori–negative peptic ulcers are 2 different diseases, and the prevalence of the latter is increasing in both Italian children and adults (10); but the prevalence of H pylori–positive ulcer is not decreasing in children, as it is decreasing in adults. H pylori–positive ulcers in children share some features with those in adults: they occur more frequently in older children and in males, and recurrence rate is low if the infection is eradicated. H pylori–negative ulcers, due to unknown causes, are more frequent in younger children, do not have a gender preference, and tend to have a higher recurrence rate, particularly in Chinese children (4).
In the pre-endoscopic era, recurrence rate was reported to be variable: from 13% found 16 years after radiologically diagnosed peptic ulcer (11), to 70% when the recurrence of symptoms was judged as ulcer relapse (12). When endoscopy became more widely available for use in children, the recurrence rate—endoscopically proven—was 43% in children monitored for 1 year or more (13), and 47% in children monitored until adulthood (14). The natural history of peptic ulcers changed again after the discovery of H pylori, when even in children, eradication of the infection was associated with a cure of the ulcer without long-term recurrence (15). So, the finding of a recurrent ulcer in 1 Chinese child after successful H pylori eradication is surprising, but it is reassuring that all children with recurrent ulcers were asymptomatic and ulcer-free both after a second 4-week course of proton pump inhibitor and at long-term after therapy with proton pump inhibitor, which suggests that all were responders and none had to undergo surgery. In our series of Italian children, no recurrence was seen after successful H pylori eradication and the 2 children with recurrent H pylori–negative ulcers were successfully treated with a second course of ranitidine (unpublished, personal data). So, it seems that even H pylori–negative bleeding ulcers can have a favourable long-term outcome in children.
The main question that remains open is the etiology of H pylori–negative and NSAID-negative peptic ulcers in children whose prevalence seems to be increasing. According to Davenport (16), ulcer disease originates from an imbalance between defense mechanisms, such as the mucus gel layer, the confluence between epithelial cells, secretion of bicarbonates, gastric motility and prostaglandins, and aggressive factors such as hydrochloric acid secretion, pepsin, bile, H pylori, and NSAIDs. Thus far, studies on the pathogenesis of gastric and duodenal ulcers have mainly focused on changes in prostaglandins and the mucus gel layer (17), or pepsin production (18) in H pylori–infected children. Similar studies in H pylori–negative children are lacking and are warranted if prevention measures and long-term cure are to be implemented.
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