Abstract

Vasculitis remains one of the major challenges in rheumatological practice. Our understandings of the causation, epidemiology, presentation, diagnosis, treatment and outcome have all improved substantially over the last two decades. The controversies in the definitions and classification of vasculitis, the role of structured clinical evaluation, the use of laboratory and imaging tests, the role of conventional immunotherapy and expected outcomes in vasculitis will all be discussed. Advances in unravelling the pathogenesis of anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis (AAV) and also of giant cell arteritis are being interpreted directly in clinical trials because more specific targets have been identified for treatment, moving away from an era of non-specific immunosuppression to much more selective, mechanism based therapies. AAV are complex multi-system disorders with many overlapping clinical features. Their outcome has been transformed by effective immunosuppression with cyclophosphamide and glucocorticoids, preventing death in over 70% of cases. The quality of survival is affected by the disease course, which is characterized by a significant likelihood of relapse in 38%, chronic effects from the disease and its treatment, as well as emerging or worsening comorbidity, all of which contribute to the patient's clinical condition and outcome. Although tumour necrosis factor receptor therapy with etanercept has been unsuccessful and problematic, rituximab has been comparable to cyclophosphamide in efficacy. Further studies of other forms of B cell inhibition, accessory molecule targeting and interference with the complement pathway are all underway as part of a strategy to define a range of safe, effective therapy in granulomatosis with polyangiitis and microscopic polyangiitis. Mepolizumab, and inhibitor of interleukin-5 appears to show promise in eosinophilic granulomatosis with polyangiitis. Our continued dependence on glucocorticoids as an important controlling mechanism in early as well as established disease is being increasingly challenged with new studies of low dose or even no dose glucocorticoids, as we improve the disease more rapidly with targeted interventions. Although giant cell arteritis and Takayasu arteritis are separate conditions, sub-types of GCA are being better defined in terms of pathogenesis and also in clinical features which overlap between GCA and TA. Improved imaging technology has allowed us to define aortitis as a potentially common feature of GCA, as well as occurring in isolation. The recognition of inerleukin-6 in mediating the inflammatory component of GCA has led to early studies using tocilizumab as a glucocorticoid sparing therapy. The development of reliable biomarkers to define groups of patients with different therapeutic requirements or to detect sub-clinical disease or a propensity to relapse remains a research aspiration, but could transform our ability to improve the effectiveness and limit the toxicity of current as well emerging therapies in vasculitis.