Immune Vasculitis

Abstract

Vasculitides are a group of disorders characterised by inflammation and necrosis of the walls of blood vessels, resulting in narrowing or occlusion of the vessel lumen, leading to ischaemia and destruction of the tissues. They are usually classified according to the size of the vessels predominantly involved. The nomenclature of vasculitides was revised in 2012 at the second international Chapel Hill Consensus Conference (CHCC2012) to reflect the advances in our understanding of vasculitis. A wide range of immunopathological mechanisms have been implicated in the aetiology of vasculitis, and a subset of small‐vessel vasculitides are strongly associated with antineutrophil cytoplasmic antibodies (ANCA). The clinical presentation, often involving multiple organ systems, is heterogenous and depends on the size and site of the vessels involved. This makes both classification and diagnosis of these disorders challenging. Management of these conditions is fraught with the difficulty of balancing the benefits of immunosuppression with toxicity. However, with improved understanding of the immunopathogenesis, earlier diagnoses and newer targeted treatment options, improvements in morbidity and mortality have been reported.

Key Concepts

  • Vasculitis may be ‘idiopathic’ or ‘primary’ but it is important to rule out common mimics of vasculitis and the many underlying conditions that can induce a ‘secondary’ vasculitis.
  • Vasculitides are usually classified according to the predominant size of the vessels involved, but there is ongoing debate as to the most accurate and clinically useful way to classify the conditions.
  • Immunopathological mechanisms are diverse, with roles for both humoral and cellular immune mechanisms.
  • A subset of small‐vessel vasculitides are strongly associated with antineutrophil cytoplasmic antibody (ANCA), and this is often used as a biomarker to aid diagnosis.
  • There is strong evidence for a pathogenic role of ANCA in the ‘ANCA associated vasculitides’, but the extent of this continues to be debated.
  • Vasculitis is usually considered a ‘systemic’ disease with the propensity to affect blood vessels throughout the body, but individual clinical presentations may be limited to specific organ systems.
  • Many patients initially experience a prodrome of nonspecific symptoms such as malaise, fatigue, fever, night sweats or weight loss.
  • The prevalence of vasculitis is increasing. This may be due to the increased rates of diagnosis, due to clinical suspicion and use of biomarkers such as ANCA; increased survival postdiagnosis or a true increased incidence.
  • Further research into the underlying pathological processes is vital to identifying potential treatment targets.
  • Many trials are currently in progress and will contribute to the improving rates of morbidity and mortality in systemic vasculitis.

Keywords: inflammation; endothelium; autoantibodies; immunopathology; antineutrophil cytoplasmic antibody; vasculitis; diagnosis; treatment

Figure 1. Initial investigations may support a diagnosis of vasculitis or help to exclude common mimics or secondary vasculitis syndromes. Actual investigations performed will depend on the individual patient and the local expertise. Reproduced and adapted from Jayne (2009) © Elsevier.
close

References

Abdulahad WH et al. (2008) Skewed distribution of Th17 lymphocytes in patients with Wegener's granulomatosis in remission. Arthritis and Rheumatism 58 (7): 2196–2205.

Abdulahad WH et al. (2009) Urinary CD4+ effector memory T cells reflect renal disease activity in antineutrophil cytoplasmic antibody‐associated vasculitis. Arthritis and Rheumatism 60 (9): 2830–2838.

Abdulahad WH et al. (2013) Increased frequency of circulating IL‐21 producing Th‐cells in patients with granulomatosis with polyangiitis (GPA). Arthritis Research & Therapy 15 (3): R70.

Arida A et al. (2010) The diagnostic value of ultrasonography‐derived edema of the temporal artery wall in giant cell arteritis: a second meta‐analysis. BMC Musculoskeletal Disorders 11: 44.

Davatchi F et al. (2014) The International Criteria for Behçet's Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. Journal of the European Academy of Dermatology and Venereology 28: 338–347.

De Groot K et al. (2005) Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody‐associated vasculitis. Arthritis and Rheumatism 52 (8): 2461–2469.

Falk RJ et al. (1990) Anti‐neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proceedings of the National Academy of Sciences of the United States of America 87 (June): 4115–4119.

Fries JF, Hunder GG, Bloch DA, et al. (1990) The American College of Rheumatology 1990 criteria for the classification of vasculitis. Arthritis and Rheumatism 33 (8): 1065–1067. DOI: 10.1002/art.1780330802.

de Groot K et al. (2009) Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody‐associated vasculitis: a randomized trial. Annals of Internal Medicine 150 (10): 670–680.

Guillevin L and Dorner T (2007) Vasculitis: mechanisms involved and clinical manifestations. Arthritis Research and Therapy 9 (Suppl 2): S9.

Guillevin L et al. (2014) Rituximab versus azathioprine for maintenance in ANCA‐associated vasculitis. New England Journal of Medicine 371 (19): 1771–1780.

Hamzaoui K et al. (2011) Expression of Th‐17 and RORγt mRNA in Behçet's Disease. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research 17 (4): CR227–CR234.

Harper L et al. (2012) Pulse versus daily oral cyclophosphamide for induction of remission in ANCA‐associated vasculitis: long‐term follow‐up. Annals of the Rheumatic Diseases 71 (6): 955–960.

Hiemstra TF et al. (2011) Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody – associated vasculitis. JAMA : The Journal of the American Medical Association 304 (21): 2381–2388.

Inder S et al. (2000) Immunophenotypic analysis of the aortic wall in takayasu's arteritis: involvement of lymphocytes, dendritic cells and granulocytes in immuno‐inflammatory reactions. Vascular 8 (2): 141–148.

Jayne D et al. (2003) A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. New England Journal of Medicine 349 (1): 36–44.

Jayne D (2009) The diagnosis of vasculitis. Best Practice & Research. Clinical Rheumatology 23 (3): 445–453.

Jayne DR et al. (2007) Randomized trial of plasma exchange or high‐dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. Journal of the American Society of Nephrology 18 (7): 2180–2188.

Jennette JC et al. (1994) Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis and Rheumatism 37 (2): 187–192.

Jennette JC et al. (2013) 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Arthritis and Rheumatism 65 (1): 1–11.

Jones RB et al. (2010) Rituximab versus cyclophosphamide in ANCA‐associated renal vasculitis. New England Journal of Medicine 363 (3): 211–220.

Kain R et al. (2008) Molecular mimicry in pauci‐immune focal necrotizing glomerulonephritis. Nature Medicine 14 (10): 1088–1096.

Kessenbrock K et al. (2009) Netting neutrophils in autoimmune small‐vessel vasculitis. Nature Medicine 15 (6): 623–625.

(2012) Chapter 14: anti‐glomerular basement membrane antibody glomerulonephritis. Kidney International Supplements 2 (2): 240–242.

Levy JB et al. (2004) Clinical features and outcome of patients with both ANCA and anti‐GBM antibodies. Kidney International 66 (4): 1535–1540.

Lyons PA et al. (2012) Genetically distinct subsets within ANCA‐associated vasculitis. New England Journal of Medicine 367 (3): 214–223.

Mahr AD et al. (2007) Adjunctive methotrexate for treatment of giant cell arteritis: an individual patient data meta‐analysis. Arthritis and Rheumatism 56 (8): 2789–2797.

Mukhtyar C et al. (2009) EULAR recommendations for the management of large vessel vasculitis. Annals of the Rheumatic Diseases 68 (3): 318–323.

Navon Elkan P et al. (2014) Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. New England Journal of Medicine 370 (10): 921–931.

Newburger JW et al. (2004) Diagnosis, treatment, and long‐term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Circulation 110 (17): 2747–2771.

Oates‐Whitehead RM et al. (2003) Intravenous immunoglobulin for the treatment of Kawasaki disease in children. The Cochrane Database of Systematic Reviews 4: CD004000.

Osman M et al. (2014) The role of biological agents in the management of large vessel vasculitis (LVV): a systematic review and meta‐analysis. PLoS One 9 (12): e115026.

Ozen S, Ruperto N, Dillon M.J. et al. (2006) EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides. Annals of the Rheumatic Diseases 65 (7): 936–941. DOI: 10.1136/ard.2005.046300

Ozen S et al. (2010) EULAR/PRINTO/PRES criteria for Henoch‐Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: final classification criteria. Annals of the Rheumatic Diseases 69 (5): 798–806.

Pendergraft WF et al. (2004) Autoimmunity is triggered by cPR‐3(105–201), a protein complementary to human autoantigen proteinase‐3. Nature Medicine 10 (1): 72–79.

Saadoun D et al. (2010) Rituximab plus Peg‐interferon‐alpha/ribavirin compared with Peg‐interferon‐alpha/ribavirin in hepatitis C‐related mixed cryoglobulinemia. Blood 116 (3): 326–334; quiz 504–505.

Sangaletti S et al. (2012) Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells toward ANCA induction and associated autoimmunity. Blood 120 (15): 3007–3018.

Schmidt WA et al. (1997) Color duplex ultrasonography in the diagnosis of temporal arteritis. New England Journal of Medicine 337: 1336–1342.

Stone JH et al. (2010) Rituximab versus cyclophosphamide in ANCA‐associated renal vasculitis. New England Journal of Medicine 363: 221–232.

Walsh M et al. (2010) Effects of duration of glucocorticoid therapy on relapse rate in antineutrophil cytoplasmic antibody‐associated vasculitis: a meta‐analysis. Arthritis Care & Research (Hoboken) 62 (8): 1166–1173.

Wang H et al. (2011) Circulating B lymphocytes producing autoantibodies to endothelial cells play a role in the pathogenesis of Takayasu arteritis. Journal of Vascular Surgery 53 (1): 174–180.

Watts R et al. (2007) Development and validation of a consensus methodology for the classification of the ANCA‐associated vasculitides and polyarteritis nodosa for epidemiological studies. Annals of the Rheumatic Diseases 66 (2): 222–227.

Weyand CM and Goronzy JJ (2003) Medium‐ and large‐vessel vasculitis. New England Journal of Medicine 349: 160–169.

Weyand CM et al. (2005) Vascular dendritic cells in giant cell arteritis. Annals of the New York Academy of Sciences 1062: 195–208.

Zhu BH et al. (2012) A meta‐analysis on the effect of corticosteroid therapy in Kawasaki disease. European Journal of Pediatrics 171 (3): 571–578.

Further Reading

Hiemstra TF and Jayne D (2009) Newer therapies for vasculitis. Best Practice and Research Clinical Rheumatology 23: 379–389.

Jennette JC (2013) Overview of the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Clinical and Experimental Nephrology 17 (5): 603–606. DOI: 10.1007/s10157-013-0869-6.

Jennette JC and Falk RJ (2014) Pathogenesis of antineutrophil cytoplasmic autoantibody‐mediated disease. Nature Reviews. Rheumatology 10 (8): 463–473. DOI: 10.1038/nrrheum.2014.103.

Unizony S, Stone JH and Stone JR (2012) New treatment strategies in large‐vessel vasculitis. Current Opinion in Rheumatology 1. DOI: 10.1097/BOR.0b013e32835b133a.

Weyand CM and Goronzy JJ (2013) Immune mechanisms in medium and large‐vessel vasculitis. Nature Reviews. Rheumatology 9 (12): 731–740. DOI: 10.1038/nrrheum.2013.161.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Gopaluni, Seerapani, and Jayne, David(Oct 2015) Immune Vasculitis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002150.pub3]