Immune checkpoint inhibitors-induced systemic capillary leak syndrome: A report of two cases

Abstract

Introduction: The occurrence of systemic capillary leak syndrome under immune checkpoint inhibitors has seldom been reported in the literature.

Observation: We report two cases of systemic capillary leak syndrome that occurred with nivolumab (anti-PD-1 antibody) for one, and with an anti-PD-1/CTLA-4 bi-specific antibody for the other. Patients presented with anasarca, hypoalbuminemia, acute kidney injury and, in one case, circulatory collapse. Immune checkpoint inhibitor causality was retained in the lack of evidence for other causes of secondary capillary leak syndrome or for an idiopathic form. The symptoms resolved after a few days of supportive measures (associated with glucocorticoids in one case).

Discussion: A high index of suspicion is required for the diagnosis of immune checkpoint inhibitors-induced systemic capillary leak syndrome because its presentation may differ from that of the idiopathic form. Activated CD8⁺ T-cells play a prominent role in the occurrence of immune checkpoint inhibitors-induced capillary leakage via their cytolytic action on the vascular endothelium. Treatment relies on supportive measures and discontinuation of the immune checkpoint inhibitor while the place of immunomodulatory drugs remains to be defined.

Keywords: Antigène CTLA-4; CTLA-4 antigen; Capillary leak syndrome; Cas clinique; Case report; Immune checkpoint inhibitors; Inhibiteurs de checkpoint; Programmed cell death 1 receptor; Récepteur programmed cell death 1; Syndrome de fuite capillaire.