Granulocyte colony-stimulating factor- and chemotherapy-induced large-vessel vasculitis: six patient cases and a systematic literature review

Abstract

Objective Patients receiving chemotherapy are prone to neutropoenic infections, presenting with non-specific symptoms such as a high fever and elevated inflammatory parameters. Large-vessel vasculitis (LVV) may have a similar clinical presentation and should be included in differential diagnostics. A few published case reports and adverse event reports suggest a causal association between LVV and the use of granulocyte colony-stimulating factor (G-CSF) and chemotherapy. Our objective was to evaluate the relationship between LVV, G-CSF and chemotherapy. Methods Between 2016 and 2018, we identified six patients in Finland with probable drug-induced LVV associated with G-CSF and chemotherapy. All six patients had breast cancer. A systematic literature review was performed according to PRISMA guidelines using comprehensive search terms for cancer, chemotherapy, G-CSF and LVV. Results The literature search identified 18 similar published case reports, of which most were published after 2014. In all patients combined (n = 24), the time delay from the last drug administration to the LVV symptoms was on average 5 days with G-CSF (range = 1–8 days) and 9 days with chemotherapy (range = 1–21 days). Common symptoms were fever (88%), neck pain (50%) and chest pain (42%). Based on imaging, 17/24 (71%) had vascular inflammation in the thoracic aorta and supra-aortic vessels, but 5/24 (21%) reportedly had inflammation limited to the carotid area. Conclusion This review suggests that LVV may be a possible serious adverse event associated with G-CSF and chemotherapy. Successful management of drug-induced LVV requires early identification, through diagnostic imaging, and discontinuation of the drug.

The incidence and clinical features of PEGylated filgrastim-induced acute aortitis in patients with breast cancer

“…Few case reports showed the aortitis caused by gemcitabine or bevacizumab 30 – 32 . Similary with the preivous data 8 , 11 – 13 , 17 – 19 , docetaxel was concorrently used in our aortitis patients. However, aortitis did not recur during the remainder of docetaxel chemotherapy without G-CSF after aortitis.…”

“…Because mild fever and general ache are frequently observed in cancer patients after chemotherapy regardless of G-CSF administration, we defined aortitis-indicating symptoms as extremely high fever and localizing chest/back pain without other infection-related signs. Therefore, the symptom onset time was longer than the previous data 17 . Immediate chest CT or CT aortography is indicated considering the risk of disease spread to proximal aorta, such as aortic arch or ascending thoracic aorta.…”

“…Therefore, considering the fact that most of the breast cancer patients undergoes chemotherapy with PEGylated filgrastim, aortitis could occur more easily in breast cancer patients. However, for breast cancer, few data pertained to G-CSF-related aortitis including several case reports 6 , 8 – 15 , 17 – 19 and two study from Adverse Drug Reporting (ADR) systems 16 , 20 . Data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) reported that the frequency of G-CSF-related aortitis was 0.0014% 20 .…”

“…Therefore, we thought docetaxel was not the primary cause of aortitis. Some data have suggested there might be a potential interaction between taxanes and G-CSF, and their synergistic effect might promote vasculitis 17 , 33 .…”

ROS-producing immature neutrophils in giant cell arteritis are linked to vascular pathologies

“…The sudden increase of G-CSF in the circulation of the treated donors mimics emergency granulopoiesis that prematurely releases immature neutrophils into the circulation. Of relevance, cancer patients on chemotherapy and G-CSF treatment can develop large-vessel vasculitis as a possible serious adverse event ( 46 ).…”