Is it justified to order an upfront cytomegalovirus immunohistochemical stain in patients with severe inflammatory bowel disease and ulceration?
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Is it justified to order an upfront cytomegalovirus immunohistochemical stain in patients with severe inflammatory bowel disease and ulceration?

Abstract

BACKGROUND: Cytomegalovirus (CMV) infection is common amongst both immunocompetent and immunocompromised patients. Patients with inflammatory bowel disease (IBD) are more prone to suffer from CMV complications. In this study, we investigated the utility of immunohistochemistry to diagnose CMV infection in patients with severe IBD. METHODS: We searched our pathology data system to identify patients with IBD from January 1, 2017 to December 31, 2021. We identified 5782 IBD cases, out of which 784 cases had severe activity with ulceration. CMV immunohistochemical stain (IHC) was performed on all 784 cases. Hematoxylin and eosin (H&E) staining slides were reviewed to evaluate the presence of characteristic nuclear or cytoplasmic CMV inclusions. H&E and IHC results were categorized as "single" if 1 cell stained positive or had characteristic inclusions, "rare" if 2-5 cells stained positive or had characteristic inclusions and "many" if more than 5 cells stained or had characteristic inclusions. Clinical outcomes, treatment and serum CMV viral loads were examined. RESULTS: A total of 29 cases out of 784 cases (3.7%) were positive for CMV by IHC. Seven cases (0.9%) showed many positive cells, 14 (1.8%) had rare positive cells and 8 cases (1%) showed single positive cells on IHC. The most frequently involved specimen type was the left colon. Twelve out of 29 cases (41%) didn't show characteristic cytoplasmic or nuclear inclusions on H&E stains prior to IHC. Out of these 12 cases, CMV IHC showed rare cells in 7 cases (58%) and single cells in 5 cases (42%). None of these cases show many positive cells on IHC. CMV viral load PCR was tested in 10 out of 29 cases (34%) and was positive in 80% of tested patients (8 out of 10). The majority of positive cases by PCR had many CMV inclusions on IHC (5 out of 8, 63%). Only 3 out of 12 patients with no H&E inclusions were tested with CMV PCR with 2 cases being positive (2 out of 12, 17%). These 2 cases were treated with antiviral treatment. Overall, CMV IHC helped to detect CMV positivity in only 12 out of 784 cases (1.5%) that were otherwise not apparent on H&E. CONCLUSIONS: These results suggest that CMV infection is rare in IBD patients with severe activity and ulceration and H&E should be used as a first line to detect viral inclusions in such patients. CMV IHC could only help to identify the CMV infection in a minority of cases with no characteristic inclusions on H&E stain.

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