S5067 Evolving Diagnosis in Persistent Diarrhea: The Critical Role of Ongoing Re-Evaluation in Identifying Infectious Colitis

Introduction: In patients presenting with subacute diarrhea, infectious and inflammatory causes are commonly considered. When clinical features are unclear, infectious workup is typically prioritized - particularly testing for Clostridioides difficile in hospitalized patients or those with recent antibiotic exposure. This distinction is crucial, as initiating immunosuppressive therapy for presumed inflammatory diarrhea may exacerbate undiagnosed infections and worsen outcomes. Case Description/Methods: We present an 80-year-old woman with a history of diverticulitis and suspected segmental colitis associated with diverticulosis (SCAD) who presented with 1 day of acute non-bloody diarrhea, reporting 20 episodes with abdominal pain, fever and chills. She endorsed 6 months of chronic, mild diarrhea previously attributed to SCAD based on endoscopic findings and unresponsive to antibiotics 2 weeks prior. Initial labs showed marked leukocytosis (white blood cell 27.9K) and elevated C-reactive protein (10.6 mg/dL). Abdominal computed tomography (CT) revealed new pancolitis. Empiric intravenous vancomycin and cefepime were started. An enteric pathogen panel, including polymerase chain reaction (PCR) for C. difficile toxin genes, was negative and enzyme immunoassay (EIA) testing was not reflexed. Given these findings, SCAD versus new-onset inflammatory bowel disease was considered and mesalamine was initiated. Colonoscopy revealed rectosigmoid nodular plaques and punctate mucosal nodules. Biopsies demonstrated active colitis with ulcerative exudates. Intravenous steroids were started for presumed inflammatory colitis. However, her symptoms persisted and leukocytosis worsened, peaking at 46.8K. Surgery was consulted to evaluate for possible laparoscopic sigmoidectomy versus total colectomy. Given ongoing clinical decline and endoscopic findings, repeat stool studies were sent, which resulted positive for C. difficile toxin B by polymerase chain reaction with a positive reflex EIA. Steroids and mesalamine were promptly discontinued and oral vancomycin was initiated. The patient demonstrated marked clinical improvement and normalization of white blood cell. Discussion: This case highlights the diagnostic challenge of distinguishing inflammatory from infectious colitis, particularly in patients with chronic symptoms and known colonic pathology. Early, accurate identification of C. difficile is critical, as misdiagnosis can lead to inappropriate immunosuppression and clinical deterioration. This case underscores the importance of considering C. difficile retesting if clinical suspicion remains high and the patient is not improving.