October 23, 2014

State of the art in the treatment of systemic vasculitides

MINI REVIEW ARTICLE

  • NDORMS, Rheumatology Department, Nuffield Orthopaedic Centre, University of Oxford, Oxford, UK
Anti-neutrophil cytoplasm antibodies (ANCA) are associated with small vessel vasculitides (AASV) affecting the lungs and kidneys. Structured clinical assessment using the Birmingham Vasculitis Activity Score and Vasculitis Damage Index should form the basis of a treatment plan and be used to document progress, including relapse. Severe disease with organ or life threatening manifestations needs cyclophosphamide or rituximab, plus high dose glucocorticoids, followed by lower dose steroid plus azathioprine, or methotrexate. Additional plasmapheresis is effective for very severe disease, reducing dialysis dependence from 60 to 40% in the first year, but with no effect on mortality or long-term renal function, probably due to established renal damage. In milder forms of ANCA-associated vasculitis, methotrexate, leflunomide, or mycophenolate mofetil are effective. Mortality depends on initial severity: 25% in patients with renal failure or severe lung hemorrhage; 6% for generalized non-life threatening AASV but rising to 30–40% at 5 years. Mortality from GPA is four times higher than the background population. Early deaths are due to active vasculitis and infection. Subsequent deaths are more often due to cardiovascular events, infection, and cancer. We need to improve the long-term outcome, by controlling disease activity but also preventing damage and drug toxicity. By contrast, in large vessel vasculitis where mortality is much less but morbidity potentially greater, such as giant cell arteritis (GCA) and Takayasu arteritis, therapeutic options are limited. High dose glucocorticoid results in significant toxicity in over 80%. Advances in understanding the biology of the vasculitides are improving therapies. Novel, mechanism based therapies such as rituximab in AASV, mepolizumab in eosinophilic granulomatosis with polyangiitis, and tocilizumab in GCA, but the lack of reliable biomarkers remains a challenge to progress in these chronic relapsing diseases.
Keywords: vasculitis, cyclophosphamide, rituximab, ANCA, glucocorticoid, plasmapheresis, methotrexate, azathioprine
Citation: Luqmani RA (2014) State of the art in the treatment of systemic vasculitides. Front. Immunol. 5:471. doi: 10.3389/fimmu.2014.00471
Received: 25 July 2014; Accepted: 13 September 2014;
Published online: 13 October 2014.
Edited by:
Giuseppe Alvise Ramirez, Università Vita-Salute San Raffaele, Italy
Reviewed by:
Fulvio D’Acquisto, Queen Mary University of London, UK
Jaewoo Hong, National Institutes of Health, USA
Copyright: © 2014 Luqmani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Raashid Ahmed Luqmani, NDORMS, Rheumatology Department, Nuffield Orthopaedic Centre, University of Oxford, Windmill Road, Oxford OX3 7LD, UK e-mail: raashid.luqmani@ndorms.ox.ac.uk

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