Ponte, Cristina

In the past decade, unprecedented progress has been made in understanding the pathogenesis, diagnosis, assessment, and treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs). International collaborations and input from several fields (e.g. immunology, rheumatology, and nephrology) have been critical for analyzing demographics, disease manifestations, and outcomes in clinical research studies. Such efforts opened new avenues for generating novel questions and rationale to design better clinical trials. In addition, clinical research has been a source of several biological discoveries and the starting point for knowledge seeking on the pathophysiology of AAV. Interestingly, the blending of clinical and basic research provides a platform for personalized medicine. Despite recent revisions on AAV classification, the incorporation of new findings on disease genetics and immunologic responses may soon result in changes in clinical practice. These advances will enhance the selection of more specific and targeted therapies. However, current unmet needs in the management of AAV are still sizable and heavily impact long-term survival. Especially, frequent relapses, damage accrual, and high morbidity contribute to poor outcomes. Finally, the lack of defined biomarkers for disease activity and the prognosis is a permanent challenge in AAV research. Our work provides an overview of the current state of the art in AAV literature and suggests bridges for the remaining knowledge gaps. It offers potential future directions for the clinical assessment, management, and research in the field toward a more personalized medicine approach.

Objective To identify and validate, using computer‐driven methods, patterns of arterial disease in Takayasu arteritis (TAK) and giant cell arteritis (GCA). Methods Patients with TAK or GCA were studied from the Diagnostic and Classification Criteria for Vasculitis (DCVAS) cohort and a combined North American cohort. Case inclusion required evidence of large‐vessel involvement, defined as stenosis, occlusion, or aneurysm by angiography/ultrasonography, or increased 18 F‐fluorodeoxyglucose (FDG) uptake by positron emission tomography (PET) in at least 1 of 11 specified arterial territories. K‐means cluster analysis identified groups of patients based on the pattern of arterial involvement. Cluster groups were identified in the DCVAS cohort and independently validated in the North American cohort. Results A total of 1,068 patients were included (DCVAS cohort: TAK = 461, GCA = 217; North American cohort: TAK = 225, GCA = 165). Six distinct clusters of patients were identified in DCVAS and validated in the North American cohort. Patients with TAK were more likely to have disease in the abdominal vasculature, bilateral disease of the subclavian and carotid arteries, or focal disease limited to the left subclavian artery than GCA ( P < 0.01). Patients with GCA were more likely to have diffuse disease, involvement of bilateral axillary/subclavian arteries, or minimal disease without a definable pattern than TAK ( P < 0.01). Patients with TAK were more likely to have damage by angiography, and patients with GCA were more likely to have arterial FDG uptake by PET without associated vascular damage. Conclusion Arterial patterns of disease highlight both shared and divergent vascular patterns between TAK and GCA and should be incorporated into classification criteria for large‐vessel vasculitis.

Objectives To define the elementary ultrasound (US) lesions in giant cell arteritis (GCA) and to evaluate the reliability of the assessment of US lesions according to these definitions in a web-based reliability exercise. Methods Potential definitions of normal and abnormal US findings of temporal and extracranial large arteries were retrieved by a systematic literature review. As a subsequent step, a structured Delphi exercise was conducted involving an expert panel of the Outcome Measures in Rheumatology (OMERACT) US Large Vessel Vasculitis Group to agree definitions of normal US appearance and key elementary US lesions of vasculitis of temporal and extracranial large arteries. The reliability of these definitions on normal and abnormal blood vessels was tested on 150 still images and videos in a web-based reliability exercise. Results Twenty-four experts participated in both Delphi rounds. From originally 25 statements, nine definitions were obtained for normal appearance, vasculitis and arteriosclerosis of cranial and extracranial vessels. The ‘halo’ and ‘compression’ signs were the key US lesions in GCA. The reliability of the definitions for normal temporal and axillary arteries, the ‘halo’ sign and the ‘compression’ sign was excellent with inter-rater agreements of 91–99% and mean kappa values of 0.83–0.98 for both inter-rater and intra-rater reliabilities of all 25 experts. Conclusions The ‘halo’ and the ‘compression’ signs are regarded as the most important US abnormalities for GCA. The inter-rater and intra-rater agreement of the new OMERACT definitions for US lesions in GCA was excellent.