Case Report: Carotidynia Correlated to Cancer Treatment?

Carotidynia refers to an idiopathic, self-limiting, benign condition of head and neck pain emanating from a tender carotid artery. We report a case where a patient presenting with carotidynia combined with fever elevated white blood count and C-reactive protein (CRP), nine days after treatment with chemotherapy (paclitaxel-carboplatin) and granulocyte-colony stimulating factor (G-CSF). The condition resolved after treatment with glucocorticoids in combination with antibiotics. The radiological ﬁ ndings were congruent with caritodynia and the conclusion from the case was that the anti-cancer treatment was causative, supported by the literature reviewed, although paclitaxel has previously not been implicated.


Introduction
Carotidynia was irst described by Temple Fay in 1927 [1] though the condition didn't gain status as a distinct disease entity until 1988 by the International Headache Society (IHS) [2].The criteria proposed are listed in Table 1.With improved imaging technology in the 1990s, some of the cases previously de ined as carotidynia turned out to be vascular diseases such as carotid dissection and arteritis [3,4].Hence, when the IHS updated the classi ication in 2003, carotidynia was degraded to the appendix.
Despite the lack of internationally accepted criteria, many authors today agree that carotidynia exists as a syndrome of pain in the head and neck, with distinct palpable tenderness over the carotid bifurcation (Fay's sign).The pain is typically unilateral and is often aggravated by turning of head, swallowing, coughing, etc.As it is self-limiting within weeks in most reported cases, the proposed treatment varies from expectance to anti-in lammatory drugs such as NSAID or corticosteroids.The nomenclature has been debated, and carotiditis or carotid periarteritis has been suggested as a more accurate designation [5,6].The possibility of designating

Abstract
Carotidynia refers to an idiopathic, self-limiting, benign condition of head and neck pain emanating from a tender carotid artery.We report a case where a patient presenting with carotidynia combined with fever elevated white blood count and C-reactive protein (CRP), nine days after treatment with chemotherapy (paclitaxel-carboplatin) and granulocyte-colony stimulating factor (G-CSF).The condition resolved after treatment with glucocorticoids in combination with antibiotics.The radiological fi ndings were congruent with caritodynia and the conclusion from the case was that the anti-cancer treatment was causative, supported by the literature reviewed, although paclitaxel has previously not been implicated.
the condition as a subset of vasculitis has also been advocated [7].Speci ic structural radiographic indings associated with the symptoms of caritodynia have been described in the literature [8].
MRI indings include swelling of the soft tissue surrounding the carotid bifurcation, thickening of the vessel wall, and possibly a marginally decreased lumen though an affected circulation can be detected on neither MRI, CT nor ultrasound [9,10].The outer layers of the artery are involved, but not the intima [11].There are also histological case reports that verify a low-grade in lammation of the artery [12,13].

Case
A 64-year-old woman suffering from generalized ovarian cancer was referred to the infectious disease department with a history of four days with intermittent fever and increasing pain in the left side of her face and neck.Nine days before the onset she had received her last treatment with chemotherapy (Paclitaxel-Carboplatin), and one day later she was treated with the Granulocyte-Colony Stimulating Factor (G-CSF) peg ilgrastim.On examination, she was extremely tender under her left mandibular angle and was found to have a poor dental status.CRP was 277 mg/L and body temperature 37,9 °C.Her blood count was de-arranged due to the G-CSF treatment with leukocytes 40000 whereof neutrophils 34000.A dental infection was suspected and she was referred to the ENT clinic.Further examination revealed a pronounced soreness over her left carotid artery.The patient received antibiotic i.v.(Piperacillin/Tazobactam 4g x 3) and underwent an acute CT scan, that con irmed a diffuse swelling of the soft tissue surrounding the common carotid artery and more cranial the internal and external carotid artery.No signs of abscess were seen, and the radiology report suggested metastasis as a possible explanation (Figure 1).Due to the clinical presentation, caritodynia was immediately suspected, and supported by a PUBMED search where taxanes and G-CSF been implicated as causative in carotidynia.Treatment with antibiotics continued since the blood tests were elevated in combination with fever.Differential diagnoses such as metastasis or other forms of vasculitis were discussed and discarded.On the 2 nd day corticosteroid treatment was initiated (40 mg Prednisolone daily) and continued until recovery.During the following days, the patient underwent two additional CT scans that indicated regression of the swelling around the artery (Figure 2).After seven days the neck pain was gone, CRP was reduced to 50 mg/L and the patient subjectively recovered.She was discharged with Prednisolone in tapering dosage together with Clindamycin.No culture was positive (blood, naso-and oropharynx).On the day of discharge, an MRI still showed a thickened carotid wall involving the tunica adventitia and media, with the intima and lumen intact (Figure 3).The patients' oncologist considered the cancer treatment as the most possible cause of the carotidynia, and future treatment excluded both Paclitaxel and G-CSF.CRP was normalized 20 days after the onset of symptoms, and during a follow-up period of six months, the pain did not recur.

Discussion
The patient in the reported case presented with symptoms and radiological indings congruent with carotidynia.The onset of pain was nine days after treatment with paclitaxel and eight days after G-CSF administration, which induced us to suspect either of those as a triggering factor.This theory is to some extent supported by other case reports.To our knowledge carotidynia after paclitaxel treatment never has been reported before, but the use of another taxane (docetaxel) as well as G-CSF has previously been implicated as causative agents of carotidynia [14][15][16][17].Similar to our case the onset was usually delayed after treatment and also combined with fever and increased in lammatory parameters in blood tests.These parameters are not typically enhanced in carotidynia but rather suggest a more severe form of the condition when occurring simultaneously with anti-cancer treatment.The clinical challenge is thus to recognize the condition, refrain from surgery (on the suspicion of abscess), and instead start potent anti-in lammatory treatment.
G-CSF has a range of pro-in lammatory effects and is known to be a causative agent of cutaneous vasculitis [18] as well as exacerbating other forms of vasculitis [19].Two cases of aortitis after G-CSF treatment have also been reported, of which one also had received docetaxel [20,21].

Conclusion
The reported case indicates that anti-cancer treatment  may be capable of triggering carotidynia.The authors have no conclusion as to whether the chemotherapy or the G-CSF is more likely to be the causative agent, nor what mechanisms may be involved.There is also a chance that the relationship between treatment and illness is only temporally and that further treatment might not induce the condition again.Future studies and reports hopefully will address these issues.The case also highlights the use of imaging in distinguishing acrodynia from other causes of neck pain and signs of in lammation.

Table 1 :
Criteria stated by the International Headache Society (IHS)) 1988.A. At least one of the following overlying the carotid artery 1. Tenderness 2. Swelling 3. Increased pulsations B. Appropriate investigations not revealing structural abnormality C. Pain over the aff ected side of the neck; may project to the ipsilateral side of the head D. A self-limiting syndrome of less than 2 weeks' duration https://doi.org/10.29328/journal.acr.1001078

Figure 1 :Figure 2 :
Figure 1: CT scan day 1 shows accumulation of contrast in the tissue surrounding the carotid sheet.

Figure 3 :
Figure 3: The MRI on day 8 present a thickened carotid wall involving the tunica adventitia and media, with the intima and lumen intact.