Granulocyte-colony stimulating factor-associated aortitis in a woman with advanced breast cancer: a case report and review of the literature

Abstract

BackgroundGranulocyte-colony stimulating factor (G-CSF) is increasingly been used to prevent febrile neutropenia (FN) associated with the administration of chemotherapy for various cancers. The most common adverse effects of G-CSF are bone pain and injection-site reactions and aortitis has rarely been reported. We report herein a rare case of G-CSF associated with aortitis in a woman with advanced breast cancer.Case presentationA 72-year-old woman with estrogen receptor-negative human epidermal growth factor 2-positive breast cancer with distant metastases in the lung was admitted. Her treatment was initiated with docetaxel in combination with trastuzumab and pertuzumab followed by the supportive use of a long-acting G-CSF, pegfilgrastim. After administration of pegfilgrastim on day 5, the patient had an intermittent fever (body temperature up to 39.6 °C) on day 9 which continued irrespective of taking levofloxacin. She visited our outpatient clinic on day 13 with no objective symptoms other than fever. Laboratory tests revealed a high neutrophil count (15,000/μl) and a high C-reactive protein (CRP) level (46.35 mg/dl) without any other abnormalities. There was no response upon administration of antimicrobial agents. An 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) revealed thickening of the wall of the descending thoracic aorta and left pleural effusion. Therefore, thoracic aortitis induced by pegfilgrastim was suspected. On day 19, the fever resolved spontaneously followed by a gradual reduction in the neutrophil count and CRP level. In the follow-up CT, the aortic wall thickness and pleural effusion had disappeared.ConclusionsG-CSF may cause aortitis due to stimulation of the production of inflammatory cytokines. In case of high continuous fever after administration of pegfilgrastim, aortitis should be suspected unless there are other infectious findings.

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.…”

“…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 .…”

A Rare Case of Large-Vessel Vasculitis following Checkpoint Inhibitor Therapy and Pegfilgrastim

“…G-CSF aids the differentiation and maturation of neutrophils as well as stimulates inflammatory cytokine production. For these reasons, G-CSF may trigger vasculitis [ 11 ]. Interestingly, one case report suggests a higher incidence of G-CSF-related vasculitis in advanced cancer compared to earlier stage disease [ 11 ].…”

Granulocyte Colony-Stimulating Factor (G-CSF) Induced Aortitis: A Case Report with Literature Review

“…In a large vessel vasculitis, there are many reported complications such as aneurysm, stenosis, dissection, and even rupture (8). Some reported G-CSF-induced vasculitis cases revealed aortic dissection ( 9), iliac artery aneurysms (4), and left pleural effusion (10). It is recommended for suspected G-CSF-induced aortitis patients to undergo follow-up contrast-enhanced CT to evaluate the subacute or late complications.…”