The systemic vasculitides are characterized by inflammation of blood vessels, which if untreated, results in tissue or end organ damage or death. Chapel Hill nomenclature is widely used to define different forms of vasculitis according to the size of the predominantly affected vessels. Other forms of vasculitis are not defined by a predominant vessel size (e.g. Behcet's syndrome). Vasculitis associated with the presence of anti-neutrophil cytoplasm antibody (ANCA), termed AAV, is less common than giant cell arteritis (GCA), but considerable advances have been made in understanding the pathogenesis and evidence based treatment for AAV. AAV is divided into three major forms: granulomatosis with polyangiitis (GPA) (Wegener's granulomatosis), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA) (Churg–Strauss syndrome). ANCA are implicated in their pathogenesis but not all patients with AAV are ANCA positive.
We will review recent EULAR guidelines on therapy for AAV, based on careful structured clinical evaluation of patients, with stratification according to severity. Cyclophosphamide or rituximab (plus glucocorticoid) is used for severe disease, followed by maintenance with azathioprine (AZA) or methotrexate (MTX), and reducing doses of glucocorticoids; or maintenance rituximab. Additional plasmapheresis is indicated for very severe disease; by contrast for less severe disease, MTX or AZA or mycophenolate (plus glucocorticoids) can be used. The evidence for effectiveness is clear for MPA and GPA. A number of studies are underway to improve our use of these existing agents and to test newer, mechanism based treatments such as inhibition CTLA4Ig or of the C5 complement pathway in GPA and MPA. For EGPA with severe manifestations, cyclophosphamide and glucocorticoids are recommended. A trial of mepolizumab (inhibitor of interleukin 5, a potent driver of eosinophil production) in EGPA has recently been completed. IL-6 inhibition with tocilizumab is a significant advance over glucocorticoid monotherapy in treatment of GCA. Apremilast is effective in treating mucocutaneous manifestations of Behcet's syndrome. Relapse is a common feature of many forms of vasculitis and needs to be monitored by structured clinical evaluation. Monitoring of ANCA titres in AAV or the acute phase response in most forms of vasculitis can be misleading and should not serve as sole guide to therapy in the absence of clinical evidence of active disease. Early survival is over 94% of patients with most forms of vasculitis. Five year survival is 70–75% for AAV with current therapy. However, if the condition is more severe disease, especially with significant renal impairment, mortality is worse.
Vasculitis remains a challenge. Whilst mortality has dramatically reduced as a result of effective immunosuppression, relapse and chronic damage are significant problems for all forms of vasculitis. We need a better understanding of how to manage and limit the long term chronic effects of vasculitis and its therapy.
Disclosure of Interest R. Luqmani Grant/research support from: Arthritis Research UK, GSK, MRC, UCSF/OIF, Canadian Institutes of Health Research, The Vasculitis Foundation; Consultant for: GSK, Medpace, MedImmune, Roche