Fatal ulcerative enteritis of the small intestine in a patient with ulcerative colitis treated with vedolizumab

Abstract

Vedolizumab (VDZ) inhibits α4β7 integrins and is used to target intestinal immune responses in patients with inflammatory bowel disease, which is considered to be relatively safe. Here we report on a fatal complication following VDZ administration. A 64-year-old female patient with ulcerative colitis (UC) refractory to tumor necrosis factor inhibitors was treated with VDZ. One week after the second VDZ infusion, she was admitted to hospital with severe diarrhea and systemic inflammatory response syndrome (SIRS). Blood stream infections were ruled out, and endoscopy revealed extensive ulcerations of the small intestine covered with pseudomembranes, reminiscent of invasive candidiasis or mesenteric ischemia. Histology confirmed subtotal destruction of small intestinal epithelia and colonization with Candida. Moreover, small mesenteric vessels were occluded by hyaline thrombi, likely as a result of SIRS, while perfusion of large mesenteric vessels was not compromised. Beta-D-glucan concentrations were highly elevated, and antimycotic therapy was initiated for suspected invasive candidiasis but did not result in any clinical benefit. Given the non-responsiveness to anti-infective therapies, an autoimmune phenomenon was suspected and immunosuppressive therapy was escalated. However, the patient eventually died from multi-organ failure. This case should raise the awareness for rare but severe complications related to immunosuppressive therapy, particularly in high risk patients.

Expression of Th17/Treg Cells in Peripheral Blood and Related Cytokines of Patients with Ulcerative Colitis of Different Syndrome Types and Correlation with the Disease

“…Moreover, when chronic inflammation is repeatedly irritated, it also quickly progresses to malignant lesions of the colorectal, which poses a threat to the quality of life and life safety of patients [3]. Regarding the pathogenesis of UC, clinical considerations are mainly about colonic mucosal epithelial cells secreting abnormal mucus glycoproteins, changes in the permeability of intestinal mucosal, and antigens entering the intestinal mucosa, leading to a series of inflammatory changes and immune responses, and further production of inflammatory mediators and antibodies, cytokines, and oxygen free radicals, but its ultimate pathogenesis and reasons still need to be further studied [4][5][6]. At present, many scholars tend to believe that it may be related to the autoimmune system, among which, T helper cell 17 ( 17), regulatory T cells (Treg), and cytokines are closely related to their occurrence and recurrence [7].…”

Anti-Inflammatory Biologics and Anti-Tumoral Immune Therapies-Associated Colitis: A Focused Review of Literature

“…Preoperative use of vedolizumab did not affect the risk of 30-day postoperative complications in UC and CD [ 43 ]. One case of fatal ulcerative enteritis of the small bowel in a patient with UC treated with vedolizumab was reported [ 44 ]. This 64-year-old female patient had UC refractory to TNF inhibitors.…”