Criteria for histological diagnosis

In establishing the diagnosis of indeterminate colitis, it is essential to exclude other causes of colitis such as infections (Clostridium difficile,

Yersinia, Mycobacterium tuberculosis, Entamoeba histolytica, Escherichia coli 0157:H7 or other vero-cytotoxin-producing strains), drugs (non-steroidal anti-inflammatory drugs (NSAIDs)), Behget's disease, malignancy, vasculitis and other identifiable causes of colitis.

Riddell stated that to differentiate indeterminate colitis lesions from Crohn's disease lesions such as submucosal and subserosal lymphoid aggregates away from areas of ulceration, non-necrotizing granulomas and skip areas should be absent.16 This is particularly true where there is nonspecific ileal involvement or gastritis and special stains for Helibacter pylori are negative. The most frequently used diagnostic study for distinguishing indeterminate colitis from Crohn's disease (in addition to ileocolonoscopy with biopsy) is the small-bowel X-ray.

The endoscopic and histological findings differ from classic ulcerative colitis in that there may be relative rectal sparing, focal inflammation or deep fissuring ulceration. The latter is most common in patients with fulminant colitis. It is also important to recognize that some medications, such as corti-costeroids or aminosalicylic acid preparations, may change the diffuse histological appearance in ulcerative colitis to a more focal appearance.6,16 Thus, slides from the original or pretreatment colonoscopy should be reviewed when considering a diagnosis of indeterminate colitis.

Although the above criteria would appear to allow differentiation between Crohn's disease and ulcerative colitis on the basis of pathology, Farmer et al documented disparity among pathologists reviewing cases of colonic IBD.17 The diagnoses of gastrointestinal pathologists differed from that of the referring institution in 45% of surgical specimens and 54% of biopsy specimens. Of 70 cases initially diagnosed with ulcerative colitis, 30 (43%) were changed to Crohn's disease or indeterminate colitis; in contrast, 17% of cases initially diagnosed with Crohn's disease were changed to ulcerative colitis or indeterminate colitis.

The performance of upper gastrointestinal endoscopy and biopsy (EGD) identifies some patients with Crohn's disease whose colonoscopy biopsies were indeterminate.12,18 Kundhal et al reported that, while diffuse non-specific gastritis occurred with similar frequency in children with

Serologic markers and defining IBD categories 381

either Crohn's disease or ulcerative colitis (92% vs. 75%), focal antral gastritis was significantly more common in Crohn's disease than ulcerative colitis (52% vs. 8%).12 The authors defined focal inflammation as 'localized inflammation of the gastric pits, glands, or foveolae by mononuclear and polymorphonuclear leukocytes bordering directly on uninflamed mucosa'. This is similar to the statements previously published by Riddell.16 Granulomas in the stomach or duodenum provided evidence confirming the diagnosis of Crohn's disease even in endoscopically normal-appearing mucosa.12 Hence, performing an EGD should be strongly considered during the initial evaluation of patients for IBD. In order to further categorize our patients with indeterminate colitis further, an X-ray study of the upper gastrointestinal tract with small-bowel follow-through was performed in all patients to exclude the possibility of Crohn's disease. EGD with biopsy may be particularly useful in those children whose symptoms (such as nausea, vomiting, early satiety) suggest gastroduodenal Crohn's disease.18

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