Diagnostic Yield of UGT Endoscopy
Noncaseating epithelioid granulomas in the UGT were present in 21 (30%) children with CD. Granulomas were found in the esophagus in 3 patients, in the stomach in 19 children (antral, 10 patients; corpus, 5 patients; both, 4 patients), and in the duodenum in 2 children. In all 3 patients with granulomas in the esophagus, granulomas were also found in the colon and the stomach. Nonorganized aggregates of histiocytes and Langerhans giant cells in the UGT were seen in 10 (14%) children with CD.
In 8 children (11%), the diagnosis based on histopathological assessment of the ileocolonic biopsies alone (2 UC, 4 IC, 2 non-IBD) was changed to CD after assessing the biopsies from the UGT (Fig. 1). In these children, a granulomatous inflammation was found in UGT consisting of granulomas (n = 5) and nonorganized aggregates of histiocytes and Langerhans giant cells (n = 3), whereas the biopsies from the lower GI tract showed no specific features of CD. These 8 children would have been diagnosed incorrectly if endoscopy of the UGT had not been performed and the diagnosis was based on biopsies from the lower gastrointestinal tract alone. In 11 patients, the diagnosis after histological reassessment of biopsies from the upper and lower gastrointestinal tract differed from the final diagnosis (Fig. 1, Table 3). Seven patients were diagnosed as having IC after histological reassessment of all of the biopsies, but turned out to have CD as the final diagnosis, and 2 patients diagnosed as having UC after histological reassessment of all of the biopsies turned out to have CD. Two patients diagnosed as having IC after histological reassessment of biopsies turned out to have UC as the final diagnosis.
Histopathological Findings in the UGT
The presence of esophageal inflammation was significantly higher in patients with CD compared with children with UC (P = 0.008), but was not significantly different compared with children with non-IBD (P = 0.28). Diffuse inflammation, consistent with gastroesopagheal reflux, was similarly found in all 3 groups. The presence of focal inflammation was significantly higher in patients with CD compared with the children with non-IBD (11% vs 0%; P = 0.006) (Table 4).
The presence of microscopic gastric inflammation was significantly higher (P < 0.0001) in patients with CD compared with children with non-IBD, but it was not significantly different compared with children with UC (P = 0.19). Several patients had >1 type of inflammation in their biopsies from the antral and corpus mucosa. Focally enhanced gastritis was significantly more frequently seen in patients with CD (69%) compared with patients with UC (24%, P < 0.001) and patients with non-IBD (7%, P < 0.0001). The lesions were located in the antral mucosa in 22, in the corpus mucosa in 12, and in both in 27 patients. Specificity and positive predictive value of focally enhanced gastritis in CD were 87.1% and 78.6%, respectively. The lesions in all 3 groups consisted of a focal accumulation of chronic inflammatory cells (mononuclear cells; lymphocytes and plasma cells), active inflammatory cells (granulocytes; neutrophils and eosinophils), or both types of inflammatory cells. There was no significant difference in the composition of inflammatory infiltrates between the groups. Focal and diffuse inflammation occurred more frequently in patients with CD compared with non-IBD patients (P = 0.002 and P < 0.0001, respectively) but was found with equal frequency in patients with UC (both not significant). The composition of these inflammatory infiltrates was not significantly different between the groups. Reactive antrum gastritis, which may point to a bile-associated chemical gastritis, was frequently seen in non-IBD children (43%). H pylori infection was found in the biopsies of 10 patients with no significant difference between the groups (3 CD, 3 UC, 4 non-IBD) (Table 4).
The presence of duodenal inflammation was significantly higher in patients with CD compared with children with UC and non-IBD children. Focal cryptitis was seen significantly more frequently in patients with CD (19%) compared with children with UC and non-IBD children (0% and 1%; P = 0.008 and P = 0.001, respectively). Specificity and positive predictive value of focal cryptitis in CD were 99% and 93%, respectively (Table 4).
In our study, the diagnosis of CD was based solely on granulomatous inflammation of the UGT in 11% of the children. These children would not have been diagnosed correctly without UGT endoscopy. Furthermore, focal cryptitis of the duodenum and focally enhanced gastritis were found significantly more frequently in children with CD compared with children with UC and non-IBD children. Of these inflammatory changes, focal cryptitis of the duodenum showed a good specificity and positive predictive value of 99% and 93%, respectively, whereas the specificity and positive predictive value of focally enhanced gastritis in CD, 87.1% and 78.6%, respectively, were less convincing.
The value of UGT endoscopy is still a topic of debate. Performing endoscopy of the UGT increases the duration of the procedure, the risk of anesthesia, and procedural complications. Moreover, the increased number of biopsies also increases the costs. The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition IBD Working Group has recommended routine UGT endoscopy at initial presentation in every child suspected of IBD (17). In contrast, a report from the working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn's and Colitis Foundation of America refrained from recommending routine diagnostic use of endoscopy of the UGT in the diagnostic assessment of children with suspected IBD (18). In the published, so far sparse, literature, the frequency of pediatric patients with CD whose diagnosis relies on detection of granulomas in the UGT ranges between 7% and 20% (7,11,19). Based on the latter data, we advise the routine use of endoscopy of the UGT, to start in an early phase as being the most appropriate treatment.
The number of children with the diagnosis of CD based on inflammation isolated to the UGT would increase if besides granulomas, other histological markers for CD could be identified. To date, few studies have evaluated UGT histology in children with suspected IBD at initial diagnostic assessment and compared the histopathological findings in the UGT of patients with CD and UC and patients without IBD (6,7,9–11). Approximately two-thirds of all patients with CD and half of those with UC have microscopic mucosal lesions in the UGT (6,10,11); however, it remains controversial whether the frequently found nonspecific microscopic UGT lesions are of clinical relevance for the patient with IBD. To our knowledge, this is the first study showing that focal duodenal cryptitis differentiates between CD and UC or non-IBD. In 2 other pediatric studies, cryptitis of the duodenum was reported in, respectively, 26% (10) and 8% (20) of children with CD but was not seen in patients with UC or non-IBD patients; but because of the small number of patients in both studies, the difference between groups did not reach statistical significance.
Furthermore, our study shows that focally enhanced gastritis supports the diagnosis of CD but does not differentiate reliably between CD and UC or non-IBD. This finding corresponds with the study of Sharif et al (13). Oberhuber et al (21) found that focally enhanced gastritis was present in 76% of adult patients with CD compared with 0.8% of healthy controls.
Our data should be interpreted in the context of the following limitations. First, data were collected retrospectively; however, IBD is a disease without well-defined diagnostic criteria and no diagnostic criterion standard. Because of the retrospective design, we were able to integrate clinical, endoscopic, histological, and radiological features and use the final diagnosis as our reference standard. We used stringent criteria to classify our patients and were able to follow all of the patients for a long period. Furthermore, the non-IBD group is not an average of the general population; therefore, the prevalence of inflammation in the UGT may be higher in the non-IBD group compared with the general healthy population. None of these patients developed IBD or other gastrointestinal disease during the follow-up period.
In conclusion, in 11% of the children with CD, the diagnosis was based solely on finding granulomatous inflammation in the UGT. These children would have been misdiagnosed if endoscopy of the UGT had not been performed and the diagnosis would have been based on biopsies from the lower GI tract alone. Focal duodenal cryptitis is a significant finding, pointing toward a diagnosis of CD. The presence of focally enhanced gastritis suggests underlying CD but is not exclusive to this condition. It does not reliably differentiate among patients with CD or UC and patients without IBD. All of the other histological findings in the UGT do not differentiate between CD and UC or non-IBD. Therefore, the present study underlines that endoscopy of the UGT is essential in the diagnostic assessment of childhood IBD.
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Keywords:Copyright 2012 by ESPGHAN and NASPGHAN
Crohn disease; gastroscopy; histopathology; inflammatory bowel disease; ulcerative colitis