Chemical gastropathy is a pattern of gastric antral mucosal injury with characteristic mucosal changes and minimal or no inflammatory cell infiltrates. It is a well-described histopathologic entity in adults (1–5). Dixon et al. described the histopathologic features of chemical gastropathy and also proposed a diagnostic scoring system based on the antral foveolar hyperplasia, vascular congestion, edema and smooth muscle fibers in the lamina propria, and a paucity of inflammatory cells (2).
There are many reports of chemical gastropathy in adults (2–6), and different investigators have used other terms such as chemical gastritis, reactive gastritis, reflux gastritis, “type C” gastritis, and reactive gastropathy to describe this histopathologic entity (2–6). The term “chemical gastropathy” seems preferable because it indicates lack of inflammation and conveys an image of chemical injury (1). We report here the clinical course, endoscopic findings, and histologic features in children with chemical gastropathy.
All children (up to the age of 19 years) showing histologic features of chemical gastropathy were identified from our pathology database over 4 years, from 1997 to 2000. Included were patients with any of the following histologic findings: foveolar hyperplasia, lamina propria edema, smooth muscle fibers in the lamina propria, and vascular congestion. All of the gastric biopsy specimens were reviewed by a single pathologist (FAM) using Dixon's diagnostic scoring system of five criteria (2) as follows: foveolar hyperplasia, lamina propria edema and smooth muscle fibers, and vascular congestion were each scored on a scale of 0 to 3 (0 = none, 1 = mild, 2 = moderate, 3 = severe). Acute and chronic inflammation were scored separately (0 = severe inflammation to 3 = none). The total score possible was 15. The antral biopsy specimens with a score of more than 10 were said to have chemical gastropathy. These biopsy specimens were also reviewed for the presence of Helicobacter pylori infection. Concurrent esophageal biopsy specimens were reviewed for evidence of reflux esophagitis such as eosinophils, basal hyperplasia, and papillary elongation. Repeat gastric biopsy specimens were studied for the features of chemical gastropathy in patients who had another endoscopy after initial diagnosis.
Hospital records of the patients with chemical gastropathy (based on a score of > 10) were reviewed for demographic data, clinical features, and clinical course. Endoscopy reports were reviewed for abnormal macroscopic findings, including the presence of thick bile in the stomach. Telephone contacts were made with patients to clarify further clinical course, if necessary.
We also reviewed our pathology database to estimate the total number of children younger than 19 years who had any other form of gastritis or gastropathy during the 4-year period from 1997 to 2000.
During 4 years, 35 children had a gastric biopsy specimen showing one or more features of chemical gastropathy. Review of biopsy specimens using the Dixon scoring system showed that 28 children had a score of more than 8, and 21 children had a score of more than 10 of a possible 15. The clinical data of these 21 patients with chemical gastropathy are shown in Table 1. All but three children were older than 10 years. The common clinical symptoms were vomiting, epigastric pain, and nausea. The majority of patients (57%) had a combination of symptoms. Significant associated conditions were depression and behavior disorders in five, seizure disorders in two, and cancer (brain tumor and acute leukemia) in two patients. History of concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) was present in four patients (19%). Seven patients (33%) were on either psychiatric medications (selective serotonin reuptake inhibitors and antidepressants) or anticonvulsants, and two patients (10%) were receiving cancer chemotherapy.
Table 2 shows the histologic features of antral biopsy specimens in 21 patients with chemical gastropathy. Lack of inflammation was a prominent feature in 19 patients. There was no evidence of Helicobacter infection in any of the patients. Figure 1 depicts the histologic appearance of chemical gastropathy. Figures 2 and 3 show architectural changes caused by medication exposure and bile reflux, respectively. Six patients (29%) had histologic evidence of reflux esophagitis. Table 3 shows the causes of gastritis in 165 children during 4-year period in our institution.
All 21 patients were treated with acid-suppressing medications, and the use of NSAIDs was discontinued in all 4 patients. The medications used were proton pump inhibitors in 15, H2 receptor antagonists in 5, and sucralfate in 1 patient. Three patients were also given a prokinetic agent. Four patients were lost to follow-up. In 17 patients, including 4 who were contacted by telephone, the mean follow-up duration was 11.5 months (range, 3–24 months). Eleven patients reported complete resolution of symptoms, and seven of them had stopped taking acid-suppressing medications. Six patients reported partial improvement. Two patients died because of underlying malignancy, and four patients were still taking acid-suppressing medication at the time of follow-up. Four patients had a repeat endoscopy 1 to 14 months after diagnosis. In two there was resolution of histologic features of chemical gastropathy, whereas two patients continued to show milder changes.
The first comprehensive histopathologic description of chemical gastropathy was made by Dixon et al. (2). In their initial report, they associated this histologic finding with duodenogastric bile reflux after partial gastrectomy. They proposed a scoring system based on five characteristic histologic features and reported significant association of the findings with hypochlorhydria and increased gastric bile acid concentration (2). Their scoring system has been widely used in studies on chemical gastropathy in adults (3–7). According to this scoring system, higher scores indicate greater severity of chemical gastropathy. Scores greater than 8 (4,6) and 10 (2,3,5,7) have been used to define chemical gastropathy in various studies. In our study, we used scores of greater than 10 for diagnosis, because this score indicates histologic changes that are strikingly different from both normal histology and other types of gastritis.
Partial gastrectomy is not the only cause of chemical gastropathy. Similar changes have been reported in the intact stomach (3,5). Sobala et al. reported an association between an elevated fasting bile acid concentration in gastric juice and chemical gastropathy rated greater than 10 by the Dixon scoring system (5). They concluded that enterogastric bile reflux was a cause of chemical gastropathy in patients with intact stomachs (5). Recently, Haber and Lopez studied gastric histology in patients with gastroesophageal reflux disease, using the Dixon criteria (6). They noted chemical gastropathy (reflux gastritis) in 15% and 90% of patients with erosive reflux disease, using a score of greater than 10 and greater than 8, respectively, as the diagnostic criterion (6).
Another risk factor for chemical gastropathy is the use of NSAIDs. Sobala et al. reported an association between the use of NSAIDs and histologic findings of chemical gastropathy (3). In two other studies, chemical gastropathy (based on the Dixon scoring system) was diagnosed in 26% and 45% of adult patients taking NSAIDs, as opposed to 7% and 13% of patients in a control group (4,8). However, in a study by El-Zimaity et al., the features of chemical gastropathy were present only in a subset of patients taking NSAIDs (7). In these studies, a variable number of patients had H. pylori infection (4,7,8). The common denominator in all of these associations seems to be exposure to chemical substances, either exogenous (e.g., NSAIDs) or endogenous (e.g., bile), that irritate the gastric mucosa without causing inflammation (9).
We looked for similar risk factors in children with chemical gastropathy in our study. The majority of our patients were taking multiple medications, including NSAIDs, cancer chemotherapy, and medicines for behavior or seizure disorders. NSAIDs are well known to cause gastric injury in children (10), but there are no studies describing the gastric histologic features caused by NSAIDs in children. Nausea and vomiting are common side effects of cancer chemotherapy, and of medications used for therapy of behavior and seizure disorders, but no specific gastric histologic abnormalities have been reported. It is possible that chemical irritation caused by these medications may have played a role in pathogenesis of chemical gastropathy in some patients in our study. There was some evidence of gastroesophageal reflux disease in 12 of 21 patients in our study, similar to the association reported in adults (6). There were no specific gross endoscopic features of chemical gastropathy except for antral erythema. The significance of thick bile in the stomach noted in some patients is not clear. It could be an indicator of bile reflux, as suggested by Appleman (1), or it could simply be a normal phenomenon during endoscopy (11). Thus, similar to studies in adults, bile reflux, gastroesophageal reflux disease, and use of medications such as NSAIDs may have a role to play in the pathogenesis of chemical gastropathy in children, although we have not proved any causal association in this study.
The most common symptoms in our patients were vomiting, epigastric pain, and nausea. Some of our patients also had gastroesophageal reflux disease, and it is possible that the symptoms in those patients were caused by reflux disease. However, as other patients without reflux disease had similar symptoms, we feel that the symptoms in our patients were partly caused by chemical gastropathy. In a recent large study of children with dyspepsia, endoscopic and histologic assessments were performed to look for mucosal inflammation in the gastrointestinal tract (12). The majority of children did not have any inflammation and were given the diagnosis of functional dyspepsia (12). Our study demonstrates that children with symptoms of dyspepsia may have changes of chemical gastropathy without inflammatory infiltrate. There was symptomatic improvement with acid-suppression treatment in our patients with chemical gastropathy. Because a similar therapeutic response is also seen in children with functional dyspepsia (12), we wonder whether chemical gastropathy may be present in some children with dyspepsia.
As reported in adults, we were able to identify all the classic histopathologic features of chemical gastropathy in children. In our opinion, features of chemical gastropathy are distinctive and very different from normal or any other gastritis or gastropathy described in children. Thus, in our study, we did not have the confounding variable of H. pylori infection that is commonly present in studies in adults.
To the best of our knowledge, this is the first report systematically describing chemical gastropathy in children. Bile reflux has been suggested as a cause of gastropathy in pediatric gastroenterology textbooks and in comprehensive reviews of gastritis in children (13–15). In a review of 360 pediatric patients with gastritis, Dimmick et al. (15) reported that the most common diagnoses were chronic nonspecific gastritis (56%), H. pylori infection (19%), and Crohn disease (18%). As in their report, these three conditions were seen in our series, but chemical gastropathy was seen slightly more frequently than H. pylori infection (Table 3).
In conclusion, the distinctive histopathologic changes of chemical gastropathy are seen in children. The factors associated with chemical gastropathy appear to be gastroesophageal reflux disease, bile reflux, and use of multiple medications, including NSAIDs. We recommend looking for changes of chemical gastropathy in children presenting with dyspepsia.
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