Advertisement

Activity and Damage

  • Raashid A. LuqmaniEmail author
Chapter
Part of the Rare Diseases of the Immune System book series (RDIS)

Abstract

ANCA-associated vasculitides (AAVs) are a group of heterogeneous conditions with some overlapping patterns of clinical and laboratory manifestations. A major factor in defining optimal therapy and in measuring the success or failure of therapy is careful evaluation of each case. There are no simple measurements to define disease activity or response to treatment. A combination of a structured clinical assessment together with key laboratory measurements should guide the clinician in deciding on the most effective therapy with the minimal toxicity. Although ANCA measurement is potentially of value in predicting poor prognosis and could help to dictate therapy in high-risk groups (e.g., PR3-positive patients with nephritis), in general, its use as a biomarker has been disappointing. By contrast, structured clinical assessment of disease activity is an effective tool which with training can be used to define and document activity, response to therapy, and relapse in all cases of AAV. The Birmingham Vasculitis Activity Score is the most widely used instrument providing a record of disease manifestations as well as a weighted score which has been used to define change in clinical status in clinical trials of vasculitis. Although most patients survive with modern therapy, the long-term consequences of AAV include a high rate of relapse and accumulating comorbidity associated with scarring from the disease, drug toxicity, and worsening of existing comorbid conditions. Measurement of these outcomes, for example, by using the Vasculitis Damage Index provides a description of the outcomes for patients surviving their first presentation of vasculitis. There is a strong association between these outcomes and future mortality risk. The quality of survival can be measured by patients directly using self-assessment of their functional state with generic measures, such as SF 36, or more targeted instruments, such as the AAV-PRO, providing a further aspect to defining the outcome for patients with AAV.

Keywords

Birmingham Vasculitis Activity Score Vasculitis Damage Index Relapse Remission Response to therapy Patient-reported outcome measure 

References

  1. 1.
    Kalsch AI, Csernok E, Munch D, et al. Use of highly sensitive C-reactive protein for follow up of Wegener’s granulomatosis. J Rheumatol. 2010;37(11):2319–25.CrossRefGoogle Scholar
  2. 2.
    Monach PA. Biomarkers in vasculitis. Curr Opin Rheumatol. 2014;26(1):24–30.CrossRefGoogle Scholar
  3. 3.
    Bossuyt X, Cohen Tervaert JW, Arimura Y, et al. Position paper: revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis. Nat Rev Rheumatol. 2017;13(11):683–92.CrossRefGoogle Scholar
  4. 4.
    Luqmani RA. ANCA-associated vasculitides and polyarteritis nodosa. In: Bijlsma JWJ, Hachulla E, editors. EULAR textbook on rheumatic diseases. 2nd ed. Zurich: EULAR; 2015. p. 717–53.Google Scholar
  5. 5.
    Tervaert JW, van der Woude FJ, Fauci AS, et al. Association between active Wegener’s granulomatosis and anticytoplasmic antibodies. Arch Intern Med. 1989;149(11):2461–5.CrossRefGoogle Scholar
  6. 6.
    Specks U, Wheatley C, McDonald TJ, et al. Anticytoplasmic autoantibodies in the diagnosis and follow-up of Wegener’s granulomatosis. Mayo Clin Proc. 1989;64(1):28–36.CrossRefGoogle Scholar
  7. 7.
    Kerr GS, Fleisher TA, Hallahan CW, Leavitt RY, Fauci AS, Hoffman GS. Limited prognostic value of changes in antineutrophil cytoplasmic antibody titer in patients with Wegener’s granulomatosis. Arthritis Rheum. 1993;36(3):365–71.CrossRefGoogle Scholar
  8. 8.
    Davenport A, Lock RJ, Wallington T. Clinical significance of the serial measurement of autoantibodies to neutrophil cytoplasm using a standard indirect immunofluorescence test. Am J Nephrol. 1995;15(3):201–7.CrossRefGoogle Scholar
  9. 9.
    Tomasson G, Grayson PC, Mahr AD, Lavalley M, Merkel PA. Value of ANCA measurements during remission to predict a relapse of ANCA-associated vasculitis--a meta-analysis. Rheumatology (Oxford). 2012;51(1):100–9.CrossRefGoogle Scholar
  10. 10.
    Xiao H, Heeringa P, Hu P, et al. Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. J Clin Invest. 2002;110(7):955–63.CrossRefGoogle Scholar
  11. 11.
    Little MA, Al-Ani B, Ren S, et al. Anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune system. PLoS One. 2012;7(1):e28626.CrossRefGoogle Scholar
  12. 12.
    Kemna MJ, Damoiseaux J, Austen J, et al. ANCA as a predictor of relapse: useful in patients with renal involvement but not in patients with nonrenal disease. J Am Soc Nephrol. 2015;26(3):537–42.CrossRefGoogle Scholar
  13. 13.
    Fussner LA, Hummel A, Schroeder DR, et al. Specks factors determining the clinical utility of serial measurements of antineutrophil cytoplasmic antibodies targeting proteinase 3. Arthritis Rheum. 2016;68(7):1700–10.CrossRefGoogle Scholar
  14. 14.
    Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221–32.Google Scholar
  15. 15.
    Franssen C, Gans R, Kallenberg C, et al. Disease spectrum of patients with antineutrophil cytoplasmic autoantibodies of defined specificity: distinct differences between patients with antiproteinase 3 and antimyeloperoxidase autoantibodies. J Intern Med. 1998;244:209–16.CrossRefGoogle Scholar
  16. 16.
    Hogan SL, Falk RJ, Chin H, et al. Predictors of relapse and treatment resistance in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis. Ann Intern Med. 2005;143(9):621–31.CrossRefGoogle Scholar
  17. 17.
    Pagnoux C, Hogan SL, Chin H, et al. Predictors of treatment resistance and relapse in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis: comparison of two independent cohorts. Arthritis Rheum. 2008;58(9):2908–18.CrossRefGoogle Scholar
  18. 18.
    Lionaki S, Blyth ER, Hogan SL, et al. Classification of antineutrophil cytoplasmic autoantibody vasculitides: the role of antineutrophil cytoplasmic autoantibody specificity for myeloperoxidase or proteinase 3 in disease recognition and prognosis. Arthritis Rheum. 2012;64(10):3452–62.CrossRefGoogle Scholar
  19. 19.
    Specks U, Merkel PA, Seo P, et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med. 2013;369(5):417–27.Google Scholar
  20. 20.
    Cao Y, Tian Z, Li W, Ma L, Yu Y, Ren W. Predictors of treatment resistance and relapse in Chinese patients with antineutrophil cytoplasmic antibody-associated disease. J Rheumatol. 2014;41(5):916–22.CrossRefGoogle Scholar
  21. 21.
    Alberici F, Smith RM, Jones RB, et al. Long-term follow-up of patients who received repeat-dose rituximab as maintenance therapy for ANCA-associated vasculitis. Rheumatology (Oxford). 2015;54(7):1153–60.CrossRefGoogle Scholar
  22. 22.
    O’Reilly VP, Wong L, Kennedy C, et al. Urinary soluble CD163 in active renal vasculitis. J Am Soc Nephrol. 2016;27(9):2906–16.CrossRefGoogle Scholar
  23. 23.
    Kain R, Tadema H, McKinney EF, et al. High prevalence of autoantibodies to hLAMP-2 in anti-neutrophil cytoplasmic antibody-associated vasculitis. J Am Soc Nephrol. 2012;23(3):556–66.CrossRefGoogle Scholar
  24. 24.
    Berden AE, Nolan SL, Morris HL, et al. Anti-plasminogen antibodies compromise fibrinolysis and associate with renal histology in ANCA-associated vasculitis. J Am Soc Nephrol. 2010;21(12):2169–79.CrossRefGoogle Scholar
  25. 25.
    Suzuki K, Nagao T, Itabashi M, et al. A novel autoantibody against moesin in the serum of patients with MPO-ANCA-associated vasculitis. Nephrol Dial Transplant. 2014;29(6):1168–77.CrossRefGoogle Scholar
  26. 26.
    Monach PA, Warner RL, Tomasson G, et al. Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis. Ann Rheum Dis. 2013;72(8):1342–50.CrossRefGoogle Scholar
  27. 27.
    Luqmani RA, Bacon PA, Moots RJ, et al. Birmingham vasculitis activity score (BVAS) in systemic necrotizing vasculitis. QJM. 1994;87(11):671–8.PubMedGoogle Scholar
  28. 28.
    Mukhtyar C, Lee R, Brown D, et al. Modification and validation of the Birmingham vasculitis activity score (version 3). Ann Rheum Dis. 2009;68(12):1827–32.CrossRefGoogle Scholar
  29. 29.
    de Groot K, Gross W, Herlyn K, Reinhold-Keller E. Development and validation of a disease extent index for Wegener’s granulomatosis. Clin Nephrol. 2001;55(1):31–8.PubMedGoogle Scholar
  30. 30.
    Robson JDH, Suppiah R, Flossmann O, et al. Damage in the anca-associated vasculitides: long-term data from the European vasculitis study group (EUVAS) therapeutic trials. Ann Rheum Dis. 2015;74(1):177–84.CrossRefGoogle Scholar
  31. 31.
    Exley AR, Carruthers DM, Luqmani RA, et al. Damage occurs early in systemic vasculitis and is an index of outcome. QJM. 1997;90(6):391–9.CrossRefGoogle Scholar
  32. 32.
    Suppiah R, Flossman O, Mukhtyar C, et al. Measurement of damage in systemic vasculitis: a comparison of the vasculitis damage index with the combined damage assessment index. Ann Rheum Dis. 2011;70(1):80–5.CrossRefGoogle Scholar
  33. 33.
    Guillevin L, Pagnoux C, Seror R, et al. The five-factor score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French vasculitis study group (FVSG) cohort. Medicine (Baltimore). 2011;90(1):19–27.CrossRefGoogle Scholar
  34. 34.
    Koike K, Fukami K, Yonemoto K, et al. A new vasculitis activity score for predicting death in myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis patients. Am J Nephrol. 2012;35(1):1–6.CrossRefGoogle Scholar
  35. 35.
    Robson JC, Tomasson G, Milman N, et al. OMERACT endorsement of patient-reported outcome instruments in antineutrophil cytoplasmic antibody-associated vasculitis. J Rheumatol. 2017;44(10):1529–35.CrossRefGoogle Scholar
  36. 36.
    Dolezalova P, Price-Kuehne F, Özen S, et al. Disease activity assessment in childhood vasculitis: development and primary validation of the Paediatric Vasculitis activity score (PVAS). Ann Rheum Dis. 2013;72(10):1628–33.CrossRefGoogle Scholar
  37. 37.
    Luqmani R, Brown D, Hall C, O’Donoghue J, Robson J, Singh S. Clinical evaluation of systemic vasculitis. A practical guide to using BVAS and VDI. Oxford: University of Oxford; 2014. p. 32.Google Scholar
  38. 38.
    Robson J, Doll H, Suppiah R, et al. Damage in the anca-associated vasculitides: long-term data from the European vasculitis study group (EUVAS) therapeutic trials. Ann Rheum Dis. 2015;74(1):177–84.CrossRefGoogle Scholar
  39. 39.
    Merkel PA, Aydin SZ, Boers M, et al. The OMERACT core set of outcome measures for use in clinical trials of ANCA-associated vasculitis. J Rheumatol. 2011;38(7):1480–6.CrossRefGoogle Scholar
  40. 40.
    Hellmich B, Flossmann O, Gross WL, et al. EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis. Ann Rheum Dis. 2007;66(5):605–17.CrossRefGoogle Scholar
  41. 41.
    Exley AR, Bacon PA, Luqmani RA, et al. Development and initial validation of the vasculitis damage index for the standardized clinical assessment of damage in the systemic vasculitides. Arthritis Rheum. 1997;40(2):371–80.CrossRefGoogle Scholar
  42. 42.
    Exley AR, Bacon P, Luqmani RA, Kitas GD, Carruthers DM, Moots R. Examination of disease severity in systemic vasculitis from the novel perspective of damage using the vasculitis damage index (VDI). Br J Rheumatol. 1998;37(1):57–63.CrossRefGoogle Scholar
  43. 43.
    Rheumatology NESSCRGfS. Clinical commissioning policy: rituximab for the treatment of ANCA-associated vasculitis in adults. London: NHS England; 2015.Google Scholar
  44. 44.
    Herlyn K, Hellmich B, Seo P, Merkel PA. Patient-reported outcome assessment in vasculitis may provide important data and a unique perspective. Arthritis Care Res. 2010;62(11):1639–45.CrossRefGoogle Scholar
  45. 45.
    Koutantji M, Harrold E, Lane SE, Pearce S, Watts RA, Scott DG. Investigation of quality of life, mood, pain, disability, and disease status in primary systemic vasculitis. Arthritis Rheum. 2003;49(6):826–37.CrossRefGoogle Scholar
  46. 46.
    Faurschou M, Sigaard L, Bjorner JB, Baslund B. Impaired health-related quality of life in patients treated for Wegener’s granulomatosis. J Rheumatol. 2010;37(10):2081–5.CrossRefGoogle Scholar
  47. 47.
    Walsh M, Mukhtyar C, Mahr A, et al. Health related quality of life in patients with newly diagnosed anti-neutrophil cytoplasm antibody associated vasculitis. Arthritis Care Res. 2011;63(7):1055.CrossRefGoogle Scholar
  48. 48.
    Grayson PC, Amudala NA, McAlear CA, et al. Illness perceptions and fatigue in systemic vasculitis. Arthritis Care Res. 2013;65(11):1835–43.CrossRefGoogle Scholar
  49. 49.
    Basu N, McClean A, Harper L, et al. The characterisation and determinants of quality of life in ANCA associated vasculitis. Ann Rheum Dis. 2014;73(1):207–11.CrossRefGoogle Scholar
  50. 50.
    Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30(6):473–83.CrossRefGoogle Scholar
  51. 51.
    Tomasson G, Boers M, Walsh M, et al. Assessment of health-related quality of life as an outcome measure in granulomatosis with polyangiitis (Wegener’s). Arthritis Care Res. 2012;64(2):273–9.CrossRefGoogle Scholar
  52. 52.
    Annapureddy N, Elsallabi O, Baker J, Sreih AG. Patient-reported outcomes in ANCA-associated vasculitis. A comparison between Birmingham vasculitis activity score and routine assessment of patient index data 3. Clin Rheumatol. 2016;35(2):395–400.CrossRefGoogle Scholar
  53. 53.
    Robson JC, Milman N, Tomasson G, et al. Exploration, development, and validation of patient-reported outcomes in antineutrophil cytoplasmic antibody-associated vasculitis using the OMERACT process. J Rheumatol. 2015;42(11):2204–9.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal ScienceUniversity of OxfordOxfordUK
  2. 2.Rheumatology DepartmentNuffield Orthopaedic CentreOxfordUK

Personalised recommendations