Jacob R. Sweeney, Carl V. Crawford, Rhonda K. Yantiss

Patients with inflammatory bowel disease (IBD) are at increased risk for Clostridioides difficile infection, although clinically important infections can be difficult to recognize. C. difficile infection does not produce pseudomembranes when it occurs in IBD patients. These individuals may also be colonized by the organism, in which case diarrheal symptoms are not necessarily attributed to C. difficile. We performed this study to determine whether any features distinguished C. difficile-associated colitis from an IBD flare. We reviewed the clinical, endoscopic, and biopsy findings from 50 patients with established IBD and worsening diarrhea, including 22 with concurrent positive C. difficile stool toxin PCR assays and 28 with negative C. difficile assay results. We found that C. difficile infected patients had symptoms and endoscopic findings that were indistinguishable from active IBD. Although most biopsy samples from patients with C. difficile infection showed chronic active colitis indistinguishable from IBD, some displayed neutrophilic infiltrates unaccompanied by plasma cell-rich inflammation involving superficial (41%) and crypt (18%) epithelium as well as neutrophilic infiltrates within lamina propria distant from foci of cryptitis (32%). All three of these features were significantly more common among infected than uninfected patients (4%, 0%, and 4%; p=0.002, p=0.03, and p=0.02, respectively). Although colonic biopsies from IBD patients with C. difficile infection usually lack features that aid distinction from colitic flares, some cases show an acute colitis pattern not seen in IBD alone. When identified in biopsies from symptomatic IBD patients, these changes should alert pathologists to the possibility of this clinically important infection.