Discussion
We report a case of TIPIC syndrome induced by G-CSF injection. TIPIC syndrome is a rare and newly clinically-radiologic entity characterized by neck pain near the carotid area.
To our knowledge, this is the first report of a TIPIC syndrome related to G-CSF. G-CSF was prescribed in the setting of a grade IV neutropenia related to MDS treatment.
Recognition of this syndrome is important for physicians who must avoid the exposure of the causative medication.
Physicians should delay the use of corticosteroids given the spontaneous improvement of the carotid inflammation in most cases after discontinuation of the causative treatment (1) .
Four diagnostic criteria are necessary for the diagnostic of TIPIC (4): occurrence of pain in the area of the carotid bifurcation, of acute onset (1), visualization of perivascular infiltrative tissue on imaging (2) and exclusion of different vascular or non vascular entities based on imaging findings (3) and improvement of clinical and imaging findings within two weeks spontaneous or with the use of anti-inflammatory medication (4). Our patient met the four criterias.
The physiopathology of TIPIC syndrome remains unknown. The main hypothesis is vascular proliferation with fibroblasts and chronic active inflammation.
Neutrophils are known to have a role in regulation of inflammatory pathways, notably by the production of PGE2. G-CSF is a myeloid growth and differentiation factor, promoting neutrophils. It has been described in rheumatoid arthritis that G-CSF plays a role in precipitating and exacerbating, as will in other inflammatory disorders (3). We hypothesized that the injections G-CSF promoted neutrophils, with massive flow and infiltration of neutrophils, with recruitment of inflammatory cells leading to perivascular infiltration and inflammation. CRP levels are usually normal in TIPIC syndrome, contrarily in our case where CRP levels were highly elevated. This can be explained by the inflammatory state induced by G-CSF injections.
Differential diagnoses such as Horton’s disease, Takayasu’s or myelodysplastic aortitis were eliminated due to the acute onset a few days after the G-CSF injection, atypical halo isoechoic at the ultrasound and the clinical and imaging improvement spontaneously.
Our patient had perivascular infiltration of the carotid, extending to the aortic arch and the anterior wall of the aorta. The extension to the aorta wasn’t described in the series of Leclerc and al. neither in the series of Micieli et al . We can extrapolate that due to the massive recruitment of inflammatory cells, inflammation extends from the carotid to the aorta.
While in some studies, patients are treated with steroids, aspirin or NSAID (5); our patient didn’t receive therapy because symptoms evolved favorably without specific treatment.
In conclusion, we report the first case of G-CSF induced TIPIC syndrome with a favorable outcome. TIPIC syndrome is extremely rare. In this particular case, immunosuppressive therapy would have been at high risk of infection disease given the underlying neutropenia.