Risks of Ruxolitinib in STAT1 Gain-of-Function-Associated Severe Fungal Disease

Ofer Zimmerman; Berenice Rösler; Christa S Zerbe; Lindsey B Rosen; Amy P Hsu; Gulbu Uzel; Alexandra F Freeman; Elizabeth P Sampaio; Sergio D Rosenzweig; Hye Sun Kuehn; Tiffany Kim; Kristina M Brooks; Parag Kumar; Xiaowen Wang; Mihai G Netea; Frank L van de Veerdonk; Steven M Holland

doi:10.1093/ofid/ofx202

Risks of Ruxolitinib in STAT1 Gain-of-Function-Associated Severe Fungal Disease

Open Forum Infect Dis. 2017 Sep 22;4(4):ofx202. doi: 10.1093/ofid/ofx202. eCollection 2017 Fall.

Authors

Ofer Zimmerman¹, Berenice Rösler², Christa S Zerbe¹, Lindsey B Rosen¹, Amy P Hsu¹, Gulbu Uzel¹, Alexandra F Freeman¹, Elizabeth P Sampaio¹, Sergio D Rosenzweig³, Hye Sun Kuehn³, Tiffany Kim⁴, Kristina M Brooks⁴, Parag Kumar⁴, Xiaowen Wang^{2

5}, Mihai G Netea², Frank L van de Veerdonk², Steven M Holland¹

Affiliations

¹ Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Immunology, National Institutes of Health, Bethesda, Maryland.
² Department of Internal Medicine and Radboud Center for Infectious diseases (RCI), Radboud University Medical Centre, Nijmegen, the Netherlands.
³ Immunology Service, Department of Laboratory Medicine, National Institutes Clinical Center, National Institutes of Health, Bethesda, Maryland.
⁴ Department of Pharmacy, Clinical Center, National Institutes of Health, Bethesda, Maryland.
⁵ Department of Dermatology, Peking University First Hospital, Beijing, China.

Abstract

Heterozygous STAT1 gain-of-function (GOF) mutations are associated with chronic mucocutaneous candidiasis and a broad spectrum of infectious, inflammatory, and vascular manifestations. We describe therapeutic failures with the Janus Kinase (JAK) inhibitor ruxolitinib in 2 STAT1 GOF patients with severe invasive or cutaneous fungal infections.

Keywords: STAT1; coccidiomycosis; dermatophytosis; gain of function; ruxolitinib.

Grants and funding

310372/ERC_/European Research Council/International