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.

Keywords: adverse drug reaction; aortitis; chemotherapy; febrile neutropoenia; granulocyte colony-stimulating factor; large vessel vasculitis; vasculitis.

Fig. 1

Timelines of the presented cases 1–6 Abbreviations: DG: diagnosis; DOC: docetaxel; FEC: 5-fluorouracil, epirubicin and CYC; FIL: filgrastim; LIP: lipegfilgrastim; MTH: a month mark; PEG: pegfilgrastim; PER: pertuzumab; SYM: symptoms; TRA: trastuzumab.

Fig. 2

Different imaging techniques showing vascular inflammation in the carotid area in Patient 1 (A) US images of both common carotid arteries (CCA) showing normal right CCA and abnormal left CCA with a hypoechoic and thickened wall. (B) CT on the same day shows a perivascular mass around the left CCA. (C, D) Next day, with MRI: T2-weighted Dixon image (C) shows perivascular increased signal intensity around the left CCA, and the same areas are enhanced on a T1-weighted, fat-saturated, post-contrast image (D). (E, F) Five weeks afterwards, with a control US, the wall of the left CCA was normal.

Fig. 3

Aortitis in Patient 2 (A, B) CT shows diffuse wall thickening in the thoracic aorta and in the arteries ascending from the aortic arch. (C, D) Six days later, MRI shows that there is increased signal intensity around the thoracic aorta on the short tau inversion recovery image (C) and contrast enhancement in the same areas on T1 weighted, post-contrast Dixon images (D). (E) Three months afterwards, with a control CT showing that the wall of the thoracic aorta has recovered.