Background: Medical therapy of Crohn's disease (CD)with immunomodulator drugs (azathioprine, 6 MP, methotrexate, infliximab) is associated with prolonged remissions as well as decreased intra-abdominal septic complications following surgery. We hypothesized that immunomodulator management would be associated with altered histologic findings. We also evaluated prior histologic scoring systems in an effort to refine them to improve management of CD.
Methods: A retrospective analysis of consecutive resected small intestinal CD histology at a tertiary IBD center between 2000 and 2005 was performed. Patients with strictureplasties with no tissue resection could not be included. Demographic data and concomitant medical therapy were recorded. Histological specimens were graded and confirmed by pathologists blinded to treatment and demographic data. Pathology was characterized by stricture formation, ulcerations, fistula, perforation, and abscess. Inflammation was scored as acute, mixed or chronic in nature. The presence of granulomas, fibrosis and dysplasia was identified. Patients were scored on a scale of 1 - 16 for epithelial damage, architectural changes, monocytosis, PMNs/low powered field, PMNs, erosions granulomas and depth of invasion in the method described by Gebos et al. Multivariate analysis was performed and results confirmed by Mann-Whitney testing.
Results: Specimens from 151 small intestinal CD patients were available for review. Demographic data revealed no significant correlation with gender, smoking status, disease location and age of onset, duration of disease, steroid use and pathologic or histopathology characteristics. The histologic score was 12.19 + 3.81 and did not correlate with immunomodulator therapy. Treatment was correlated with a decrease in mixed inflammation as well as acute inflammation independently in univariate analysis. When corrected for age and smoking, mixed inflammation remained negatively correlated with treatment with immunomodulators (p=0.077).
Discussion and Conclusions: Acute inflammatory infiltrates consist primarily of lymphocytes while chronic inflammatory processes are characterized by varying degrees of fibrosis. Mixed inflammatory infiltrate is composed of lymphocytes, plasma cells, neutrophils. We conclude that histology and the immune cell population is altered by immunomodulator therapy for CD. Histologic grading of mixed inflammatory response and potentially acute inflammatory response may represent a novel way to evaluate efficacy of treatment and estimate risk of post surgical complications in patients with CD.