Novel Diagnostic and Prognostic Approaches to Systemic Vasculitides

Background. The management of giant cell arteritis (GCA) has gone through a number of paradigmatic changes in the last few years, including novel diagnostic approaches and treatment options. Objectives. We aimed at investigating and improving the management of GCA by: (i) assessing the impact of the fast track ultrasonographic clinic (FTA) of the Rheumatology Department, IRCCS Policlinico S. Matteo, University of Pavia on the risk of permanent visual loss and future relapse; (ii) evaluating the role of quantitative ultrasound assessment in terms of diagnostic and prognostic outcomes in GCA in an International study in collaboration with the University of Oxford; (iii) contributing to the update of the European recommendations on the management of large vessel vasculitis (LVV) by leading on the systematic literature review and participating in the recommendations development process. Methods. Patients referred for suspected GCA to the FTA were recruited if a diagnosis of GCA was confirmed. The role of quantitative ultrasound findings data was assessed, in collaboration with the University of Oxford, from the data of a large cohort study (TABUL Study) with the FTA cohort from the University of Pavia as an independent cohort. Quantitative ultrasound data [number of sites with halos, intima-media thickness (IMT), presence of bilateral halos] at the level of the temporal arteries (TA) and axillary arteries (AX) were assessed. Two systematic literature reviews (SLR) were performed by searching MEDLINE, EMBASE and Cochrane CENTRAL library to inform the European League Against Rheumatism (EULAR) update of the recommendations on the management of LVV. Results. The GCA cohort included 160 patients [female 120 (75%), mean age 72.4±8.2 years]. Sixty-three (39.4%) evaluated with FTA, 97 (60.6%) with conventional approach. Since the introduction of FTA the need for TAB reduced by 93%. Median follow-up duration was shorter in the FTA group compared to the conventional one (0.9 vs. 5.0 years; p<0.001). Permanent visual loss (PVL) occurred in 8 (12.7%) FTA patients and 26 (26.8%) conventional ones (p=0.03). During COVID-19 there was a significant increase in the occurrence of PVL (40%) including bilateral blindness despite a regularly operating FTA clinic. Cumulative incidence of relapses and time to first relapse did not change after FTA introduction. Quantitative ultrasound data were evaluated on 135 GCA patients from TABUL [female 92 (68%), age 73±8 years] and 72 patients from the independent cohort [female 33 (46%), age 75±7 years]. The best-fitting CDS model for TAB used maximum IMT and bilaterality of TA and AX halos. The best-fitting clinical model included raised inflammatory markers, polymyalgia rheumatica, headache and ischaemic symptoms. By combining CDS and clinical models a score to calculate the probability of having a positive TAB, given the ultrasonographic and clinical information, was derived. No significant association was found for prediction of clinical outcome at 6 months. The SLRs confirmed the need to urgently refer the patient to a specialised team, including FTA clinics. The main treatment for LVV remain high-dose GC, however, more evidence has been retrieved to support the use of adjunctive immunosuppressants, including novel biologic treatments for GCA. Conclusion. With our studies we have contributed to clarify the role of novel diagnostic approaches to the disease as part of fast track clinics and supported the role of ultrasound as a reliable diagnostic tool and to significantly reduce the risk of permanent blindness. A quantitative ultrasound analysis (extention and degree of vascular involvement) supported by clinical findings is useful to identify patients with a positive biopsy. Relapse rate and LV-complications did not change upon FTA introduction, highlighting the need for better disease activity monitoring and therapeutic strategies.