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

Granulocyte colony-stimulating factor (G-CSF) and its PEGylated formulation (pegfilgrastim) are indispensable for preventing chemotherapy-induced neutropenia and for stem-cell mobilization. Beyond hematopoiesis, G-CSF modulates innate/adaptive immunity and may precipitate immune-mediated events in s...

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Publicado en:Seminars in Arthritis & Rheumatism Vol. 77
Autores principales: de Carvalho, Jozélio Freire, Caldas, Cezar Augusto Muniz
Formato: review Journal Article
Publicado: W B Saunders Apr2026
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Apr2026
      vid: 77
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      pub: W B Saunders
      place: Philadelphia, Pennsylvania
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        10.1016/j.semarthrit.2026.152939
        192259449
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        atl: From Aortitis to Sweet's: The Immune Spectrum of G-CSF Adverse Events.
      aug:
        au:
          de Carvalho, Jozélio Freire
          Caldas, Cezar Augusto Muniz
        affil: Núcleo de Pesquisa em Doenças Crônicas não Transmissíveis (NUPEN), School of Nutrition from the Federal University of Bahia, Salvador, Bahia, Brazil
      sug:
        subj:
          Colony-Stimulating Factors Adverse Effects
          Autoimmune Diseases Chemically Induced
          Rheumatic Diseases Chemically Induced
          Vasculitis Chemically Induced
          Sweet's Syndrome Chemically Induced
          Drug Hypersensitivity
          Inflammation Chemically Induced
          Glucocorticoids Therapeutic Use
          Interleukins Antagonists and Inhibitors
          Recurrence
          Phenotype
          Arthritis
          Dermatitis
          Pyoderma Gangrenosum
      ab: Granulocyte colony-stimulating factor (G-CSF) and its PEGylated formulation (pegfilgrastim) are indispensable for preventing chemotherapy-induced neutropenia and for stem-cell mobilization. Beyond hematopoiesis, G-CSF modulates innate/adaptive immunity and may precipitate immune-mediated events in susceptible hosts. Clinical signals span large-vessel vasculitis/aortitis and non-vascular neutrophil-dominant phenotypes, yet timing, spectrum, and management remain variably characterized. To identify and synthesize primary clinical reports of autoimmune/rheumatic disease triggered or exacerbated by exogenous G-CSF (filgrastim or pegfilgrastim), describing phenotypes, latency, management, outcomes, and implications for practice. We performed a narrative review of primary clinical studies, including observational cohorts and case reports or short case series, identified through targeted searches of PubMed/MEDLINE, Scopus, and Embase, complemented by investigator-curated references. Eligible reports described autoimmune, inflammatory, or rheumatic manifestations occurring after exposure to exogenous G-CSF. Predefined phenotypes included large-vessel vasculitis/aortitis; neutrophilic dermatoses (e.g., Sweet's syndrome, neutrophilic dermatosis of the dorsal hands); cutaneous small-vessel vasculitis; inflammatory or crystal arthritis (e.g., calcium pyrophosphate deposition disease); pulmonary inflammatory injury (e.g., diffuse alveolar hemorrhage); and clear flares of established autoimmune disease. Narrative or mechanistic reviews and trials of GM-CSF pathway blockade were excluded from qualitative synthesis. Twenty-four studies met inclusion criteria: two observational cohorts and twenty-two single-patient reports/short series. Cohorts quantified a low but reproducible burden of pegfilgrastim-associated aortitis, with stereotyped involvement of the aortic arch/proximal branches and typical latency of 7–15 days. Case-level data confirmed marked elevation of acute phase reactants, usually negative autoantibodies, favorable outcomes after G-CSF withdrawal with or without short glucocorticoid courses, and recurrence/migration on re-exposure. Non-vascular events clustered earlier (2–7 days) and included biopsy-proven Sweet's/NDDH, leukocytoclastic vasculitis, CPPD flares, and rare diffuse alveolar hemorrhage; granulomatous dermatitis and perioperative pyoderma gangrenosum were also observed. Re -exposure information suggested phenotype-specific risk: recurrent CPPD with pegfilgrastim was mitigated by switching to short-acting filgrastim; selected limited aortitis resolved without steroids; refractory aortitis responded to IL-6 blockade, enabling uninterrupted chemotherapy. Exogenous G-CSF can precipitate a coherent spectrum of immune-mediated toxicity with distinct, clinically actionable timing windows: vascular events peak 7–15 days after pegfilgrastim, whereas cutaneous, articular, and pulmonary manifestations arise within 2–7 days. Recognition hinges on temporal linkage, imaging/histology, and exclusion of mimics. Management is phenotype-aware—drug withdrawal ± short glucocorticoids, formulation switching for CPPD, and targeted IL-6 blockade in selected refractory aortitis—allowing preservation of hematologic benefits while minimizing immune toxicity. Prospective surveillance and structured re-exposure studies (including formulation tailoring) are priorities to move from signal detection to prevention. [Display omitted]
      pubtype: Academic Journal
      doctype:
        review
        Journal Article
      ougenre: Article
    language: English
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