Systemic capillary leak syndrome triggered by anti‐programmed death 1 checkpoint inhibitor in psoriasis

• Published in: Journal of dermatology Vol. 47; no. 11; pp. 1322 - 1325
• Main Authors: Umeda, Yoshiyasu, Hayashi, Hiroaki, Sugiyama, Seiko, Aoyama, Yumi
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.11.2020
• Subjects: anti‐programmed death 1 antibody; Capillary Leak Syndrome - chemically induced; Capillary Leak Syndrome - diagnosis; Cytokines; Humans; Immune checkpoint; immune checkpoint inhibitor; Inflammation; Interferon; Leukocytes (neutrophilic); Lymphocytes; Patients; PD-1 protein; Psoriasis; Psoriasis - chemically induced; Psoriasis - drug therapy; psoriasis vulgaris; Retrospective Studies; systemic capillary leak syndrome; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A; anti-programmed death 1 antibody; immune checkpoint inhibitor; systemic capillary leak syndrome; psoriasis vulgaris; vascular endothelial growth factor
• ISSN: 0385-2407; 1346-8138
• DOI: 10.1111/1346-8138.15541

Programmed death 1 (PD‐1) inhibitors are increasingly used for the treatment of malignancies. Despite the clinical benefits, unpredictable and potentially fatal side‐effects may occur. We report a psoriatic patient who developed systemic capillary leak syndrome (SCLS) after starting a PD‐1 checkpoint inhibitor. In order to determine which factors could trigger the development of SCLS in a patient with stable psoriasis after starting anti‐PD‐1 therapy, serum cytokines were serially measured before and after the development of SCLS in this patient. We also retrospectively reviewed 28 previously reported patients presenting clinical exacerbations of pre‐existing psoriasis or the de novo induction of psoriasis after anti‐PD‐1 therapy. In 16 of the 28 patients (57.1%), the interval between last anti‐PD‐1 therapy and exacerbations of pre‐existing psoriasis or the de novo induction of psoriasis was less than 28 days. The timing of the onset of SCLS in this patient was coincident with the increase in lymphocyte counts and at 22 days after last anti‐PD‐1 therapy. In 75%, however, anti‐PD‐1 therapy was able to be restarted and was tolerated well. Increased levels of interleukin (IL)‐2, IL‐6, interferon‐γ and tumor necrosis factor‐α, in addition to a persistent increase in vascular endothelial growth factor (VEGF), were detected at onset of SCLS. An increase in pro‐inflammatory cytokines and VEGF, when combined with a rapid and sequential recovery of neutrophils and lymphocytes after anti‐PD‐1 therapy, would predict the development of SCLS. Clinicians need to be aware that patients with psoriasis are at risk of a potentially fatal disease, SCLS, when anti‐PD‐1 therapy is started.