FDG Uptake in Large-Vessel Giant Cell Arteritis After Short-term, High-Dose Steroid Treatment

Fluorine-18-fluorodeoxyglucose Uptake in Large-Vessel Giant Cell Arteritis After Short-term, High-Dose Steroid Treatment - A Diagnostic Window of Opportunity?

Giant cell arteritis (GCA) affects large and medium sized vessels. Large vessel-GCA (LV-GCA) affecting aorta and/or its main branches is seen a) together with temporal arteritis (AT-GCA), b) as isolated LV-GCA but also c) with polymyalgia rheumatica.

There is a risk of vision loss and cerebral thromboembolic events or great vessel injury in GCA. With delayed or inadequate treatment mortality and morbidity increases. This highlights the need of fast diagnosis and early treatment.

The cornerstone in the diagnosis of GCA is a positive temporal artery biopsy. Patients with LV-GCA have more general, but less cephalic symptoms than patients with AT-GCA. Also, biopsy from large vessels can rarely be done and only 50% have a positive temporal artery biopsy (TAB). Hence, diagnosis often rely on imaging.

Fluorine-18-fluorodeoxyglucose positron-emission tomography (FDG PET)/CT has shown high diagnostic sensitivity and specificity and is believed to be superior to other imaging modalities in the diagnosis of LV-GCA . The impact of FDG PET/CT in the management of LV-GCA has been evaluated and has shown to increase the diagnostic accuracy in a significant proportion of patients. However, studies have indicated a lower sensitivity in steroid treated patients.

The aim of this study, was to evaluate the effect of steroid treatment on large-vessel FDG uptake in new-onset, treatment-naive LV-GCA by repetitive FDG PET/CT pre- and post therapeutic. With insights into the diagnostic capabilities after treatment is initiated, the possibility of timely treatment and confident diagnostic work up will improve.

As standard of care, patients suspected of GCA undergo clinical examination, laboratory screening, temporal artery biopsy, vascular ultrasound examination and FDG PET/CT.

All patients with a diagnosis of GCA will be treated with 60 mg af prednisolone and tapered according to a predefined algorithm.

In patients with FDG PET/CT verified LV-GCA, FDG PET/CT is repeated after either 3 (n=12) or 10 (n=12) days of steroid treatment.

An experienced nuclear medicine physician (LCG), blinded to clinical symptoms and findings, qualitatively assesses PET scans. A semiquantitative approach is applied (a.m. Meller) in which FDG uptake in vascular regions is graded on a 5-point scale (0 = no uptake, 1 = uptake below or equal to blood pool, 2 = above blood pool but below liver, 3 = above liver, 4 = 2 times above liver). Any score ≥3 is considered consistent with vasculitis. Sensitivity of post-therapeutic FDG PET/CT will be evaluated.

Moreover, standard uptake values (SUV) mean and maximum values in vascular regions will be calculated. A ratio SUV(wall)/SUV(blood pool) and a total metabolic burden (TMB) based on affected vascular volume and SUV mean values are obtained as measures of vascular wall inflammation.

Inclusion Criteria:

1. Clinical suspicion of GCA; Cranial symptoms, new-onset extremity claudication or protracted constitutional symptoms (weight loss > 5 kilograms or fever >38C for > 3 weeks).
2. C reactive protein >15 mg/l or erythrocyte sedimentation rate >40 mm/h
3. FDG PET/CT verified LV-GCA (steroid-naive) defined by FDG uptake in the aortic wall and/or supra-aortic branches with FDG uptake score ≥3.

Exclusion Criteria:

1. oral glucocorticoid treatment within the past month

2. subcutaneously, intramuscularly, intraarticularly or intravenously administered glucocorticoid within the past 2 months

3. treatment with DMARDs or other immunosuppressive therapy ongoing or within the past 3 months

4. ongoing treatment with interleukin2

5. any disease mimicking GCA, including

   • a) autoimmune diseases with possible aortitis; rheumatoid arthritis, Cogans syndrome, relapsing polychondritis, ankylosing spondylitis, systemic lupus erythematosus, Buerger's disease, Bechet's disease, inflammatory bowel disease
   • b) infections with possible aortitis: syphilis, known active current or history of recurrent tuberculosis, hepatitis or HIV
   • c) other large-vessel disease: sarcoidosis, neurofibromatosis, congenital coarctation, Marfans syndrome, Ehlers-Danlos syndrome, retroperitoneal fibrosis

6. body weight of >150 kg.

7. Previously diagnosed and treated for PMR or GCA