A53-51 Multisystem Immune-related Adverse Events (irAEs) Presenting as Undifferentiated Shock Secondary to Colitis

Abstract Background Immune checkpoint inhibitors (ICIs), including CTLA-4 and PD-1 inhibitors such as ipilimumab and nivolumab, have transformed the management of advanced malignancies like metastatic melanoma. While these therapies significantly improve survival, they are increasingly associated with immune-related adverse events (irAEs) that may even involve multiple organ systems. Severe or overlapping irAE can mimic septic or distributive shock, presenting a diagnostic and therapeutic challenge in the intensive care setting. Case Description We present the case of a 67-year-old female with metastatic melanoma on combination ipilimumab and nivolumab who presented with profuse watery diarrhea, dehydration, and undifferentiated shock. Imaging demonstrated colitis and incidental thromboembolic disease in the lungs and infrarenal aorta. She was admitted to the intensive care unit for pressor support and broad spectrum antibiotics. Infectious etiologies were ruled out with cultures and stool studies. Hypotension and diarrhea persisted, leading to suspicion for immune-mediated colitis. She was started on high dose steroids, but symptoms were refractory over the next few days leading to the initiation of infliximab. Though there were improvements in gastrointestinal symptoms her clinical course was complicated by severe cutaneous eruptions concerning for Steven Johnson syndrome/toxic epidermal necrolysis and progressive hypoxemic respiratory failure, likely immune-mediated pneumonitis. Despite multidisciplinary management, she ultimately succumbed to multisystem irAEs. Discussion This case highlights the emergence of multisystem irAES and the need for increased awareness among clinicians. Multiple reviews have shown the prevalence of multisystem irAEs to be between 5 and 40%, however simultaneous and overlapping irAEs are rarer still. Current practice generally mandates withholding ICIs and initiating corticosteroids and other immunosuppressants, yet ongoing evidence suggests patients experiencing irAEs often exhibit stronger antitumor responses and improved survival outcomes. As the use of ICIs expands, the balance between maintaining therapeutic efficiency and managing toxicity becomes increasingly critical. Developing standardized evidence-based guidelines for severe irAEs is essential to prevent premature discontinuation of these life-prolonging treatments. As immunotherapy use broadens across oncology, intensivists will encounter more patients with life threatening irAEs. Expanded education on recognition and managing critical irAEs is urgently needed with critical care disciplines. Further research should focus on refining treatment protocols that control immune toxicity without compromising antitumor efficacy, ensuring that one of the most effective cancer therapies of our era is not limited by fear of its complications. This abstract is funded by: None