Ixekizumab-associated severe Crohn’s in a patient without definitive immune-mediated inflammatory disease: case report and evidence-informed guidance for non-IBD clinicians

Interleukin-17 inhibitors (IL-17i) are used for dermatologic and rheumatologic immune-mediated inflammatory diseases (IMIDs), yet paradoxical inflammatory bowel disease (IBD) can occur. Although trials report low incidence, recognition and management remain difficult outside tertiary care centers. A 54-year-old woman treated with ixekizumab (IXE) for presumptive psoriatic arthritis (PsA) without definitive confirmation developed anorexia, weight loss, abdominal pain, rectal urgency, and hematochezia 16 weeks after IXE initiation. Limited access to gastroenterology contributed to the delayed workup. Catastrophic complications, including bowel perforation, postoperative abscesses, and severe malnutrition, resulted from the cumulative effects of longstanding, inadequately treated disease; excessive immunosuppression with high-dose corticosteroids and infliximab; and concurrent use of opioids and antidiarrheals, among other factors. On transfer to a center skilled in IBD, care included withdrawal of excessive immunosuppression, targeted antimicrobials, and nutrition rehabilitation. Histopathology of the surgical specimen was most consistent with features of Crohn’s disease (CD). After recovery, she achieved clinical, endoscopic, and histologic remission. On rheumatologic reassessment at an independent practice, she did not meet classification criteria for PsA. With continued specialty follow-up, the patient has remained in sustained clinical, laboratory, and endoscopic remission for 16 months, underscoring that timely recognition and disciplined, evidence-based care grounded in the principles used for severe IBD and drug-induced colitis can deliver favorable long-term outcomes. This case highlights the need for structured, accessible clinical guidance, not only to support non-IBD specialists in managing IL-17i-associated complications but also to guide clinicians during the pre-therapy phase in selecting appropriate candidates for treatment and assessing potential gastrointestinal risks before initiating therapy. We present an evidence-informed framework for resource-limited settings that addresses screening, early recognition, diagnostic workup, and therapeutic decision-making to guide safer IL-17i use and improve outcomes.