In children, granulomas may also be seen in chronic granulomatous disease with pigmented macrophages in the lamina propria; common variable immune deficiency with its lack of plasma cells; and tuberculous infection with disproportionate submucosal inflammation and epithelioid histiocytes.48-50 The frequency of granulomas is higher in children with Crohn's colitis even when the difference in the number of colonoscopic biopsies is taken into account.51-53 Granulomas were identified in 61% of fully investigated pediatric patients at diagnosis, and 42% of these granulomas were found only in the terminal ileum and upper gastrointestinal tract, a finding that emphasizes the need to biopsy these sites.51
In a pediatric study, a significant proportion of children with new onset UC had patchy microscopic features of chronicity, with rectal sparing and little or no architectural distortion. This now-recognized rectal sparing phenomenon, in otherwise typical cases of UC, may cause confusion with CD.21 In another study, the rectal biopsies in children did not differ with those from an adult control group.19 Focal crypt atrophy is also less common in children.20 In colonic resections, microscopic inflammatory foci are common in grossly normal-appearing mucosa at surgical margins, raising the possibility of an increased recurrence rate. However, studies have concluded that the rate of recurrence is not increased by the presence of microscopic disease at the margins.52-54 In general, it is recommended that only the grossly involved bowel should be resected.55 Granulomas in the absence of associated inflammation at the margin are not considered clinically significant.
In children and adults, the histologic changes of early UC and CD differ from that of established disease, and the degree of clinical activity of disease correlates with the histologic degree of inflammation in UC and CD to a lesser extent.56,57 In both groups, drugs used for treatment can induce mucosal healing, and the rectal mucosa may appear to revert to normal following therapy.44,58,59 Mucosal involvement may become patchy or discontinuous, an appearance that closely resembles that seen in CD.60 Post-treatment biopsies may also resemble those obtained in the early phases of IBD when crypt distortion may not be present.61
CD is particularly associated with inflammation of the upper part of the gastrointestinal tract. The performance of upper endoscopy in children with IBD has provided an additional diagnostic yield and guided the differentiation of disease type in many patients. In one study of children with IBD, some of the children with unaffected colons were diagnosed with CD solely on the basis of information from upper endoscopy.62 Investigators suggested that, in the absence of Helicobacter pylori infection, focal chronic gastritis and active gastritis were evidence of CD in those patients with colitis (Figure 5).63,64 In the stomach, characteristic focal mucosal collections of lymphocytes, sometimes accompanied by neutrophils with associated inflammatory damage to the epithelium, have been referred to as focally enhanced gastritis.65 In a review of upper gastrointestinal tract biopsies in children with CD, there was an increased incidence of gastric erosions with ulceration and histologic abnormalities. In addition, abnormal histology was noted in biopsy areas that appeared normal endoscopically.66 These microscopic findings have defined the role of upper gastrointestinal endoscopy with biopsy in the investigation of IBD, particularly in the distinction of CD. Granulomas confirming the diagnosis of CD were found in the upper gastrointestinal tracts of 28% of children with CD. In some cases, granulomas were found solely in the upper gastrointestinal tracts.67
Figure 5
Figure 5
Focal antral inflammation in Crohn's disease.
However, reports have described inflammatory changes in the stomach and proximal gastrointestinal tract of patients with UC as well; hence, pathology in the upper gastrointestinal tract should no longer exclude its diagnosis.68 Ruuska and coworkers first drew attention to inflammatory changes in the upper gastrointestinal tract in 1994.69 In the endoscopic and biopsy examinations of children with IBD, UC patients had esophagitis, nonspecific gastritis, gastric ulcers, and duodenal ulcers. Kaufman and associates reported chronic active gastritis in children initially diagnosed with CD, which was called UC after colectomy.70 Chronic nonspecific inflammation is seen most frequently, whereas focal antritis in UC is uncommonly reported. Focal antritis, particularly if there are features of activity, is more suggestive of CD, but not diagnostic on its own.68,71,72 In an adult population, focal periglandular inflammation was more frequent in CD (43% of 94 patients), but this pattern of inflammation was also seen in 12% of patients with UC and 19% of controls.73
Pascasio and colleagues reviewed 438 biopsies in children with gastritis looking for specific histopathologic parameters, including markers for CD such as focal neutrophilic glandulitis.64 Of these cases, 58 were diagnosed as having CD by colonic biopsy and other standard criteria, 77% of which were predicted to have CD by gastric biopsy alone. In this study, none of the focal glandulitis biopsies had a history of UC. The prevalence of endoscopic esophageal CD in children was 7.6%, though histologic evidence is greater in children with colonic CD. Not all esophageal disease is associated with gastric lesions.27
