From Aortitis to Sweet's: The Immune Spectrum of G-CSF Adverse Events

Area of Science:

• Immunology
• Hematology
• Rheumatology

Background:

• Granulocyte colony-stimulating factor (G-CSF) and pegfilgrastim are crucial for neutropenia prevention and stem cell mobilization.
• Beyond hematopoiesis, G-CSF can modulate immunity, potentially triggering immune-mediated events in susceptible individuals.
• Clinical observations suggest G-CSF may be linked to large-vessel vasculitis/aortitis and neutrophil-dominant inflammatory conditions.

Purpose of the Study:

• To review and synthesize clinical reports on autoimmune/rheumatic diseases triggered or worsened by exogenous G-CSF.
• To describe the phenotypes, onset latency, management strategies, and outcomes of these G-CSF-associated immune events.
• To provide insights for clinical practice regarding G-CSF's potential immunomodulatory adverse effects.

Main Methods:

• Conducted a narrative review of primary clinical studies, including observational cohorts and case reports.
• Searched major databases (PubMed/MEDLINE, Scopus, Embase) and reviewed investigator-curated references.
• Included studies reporting autoimmune, inflammatory, or rheumatic manifestations post-G-CSF exposure, focusing on predefined phenotypes.

Main Results:

• Twenty-four studies (2 cohorts, 22 case reports/series) met inclusion criteria.
• Pegfilgrastim-associated aortitis occurred with a latency of 7-15 days, affecting the aortic arch.
• Non-vascular events (Sweet's syndrome, vasculitis, CPPD flares) appeared earlier (2-7 days); withdrawal and short glucocorticoid courses were often effective.
• Re-exposure data indicated phenotype-specific risks, with formulation switching beneficial for CPPD.

Conclusions:

• Exogenous G-CSF can precipitate a spectrum of immune-mediated toxicities with distinct timing windows.
• Vascular events peak 7-15 days post-pegfilgrastim, while cutaneous, articular, and pulmonary issues arise within 2-7 days.
• Management requires phenotype awareness, drug withdrawal, ± glucocorticoids, or targeted therapies like IL-6 blockade for refractory cases, balancing hematologic support with immune safety.