AAV is a rare, severe small vessel vasculitis that affects multiple organs and has a high acute mortality risk.
AAV can result in damage to vital organs such as the lungs, kidneys, nervous system, gastrointestinal system, skin, eyes and heart.3 Both GPA and MPA show a lot of clinical commonality, whereas EGPA is distinctly different.2
As many as 23% of PR3- and MPO-ANCA positive patients who require RRT at the time of diagnosis die within 6 months and 29% do not regain renal function.4* In patients with renal involvement at diagnosis, ESRD occurs in 13% of PR3- and MPO-ANCA positive patients within 3 years of diagnosis.5† Compared with a short prodromal phase, patients with a long prodromal phase (>22 weeks between first AAV symptoms and diagnosis) are more likely to have proteinuria present at 6 months and are at double the risk of 3-year ESRD, which underlies the importance of early diagnosis in order to improve renal outcomes.5†
In the first year after a GPA or MPA diagnosis
(n=524), the mortality rate is 10.7% (n=561).1*
Half (50%) of mortality in the first year
is due to treatment-related infection.1
In clinical trial settings, the cumulative survival rate at 2 and 5 years in patients with newly diagnosed GPA and MPA is 85% and 78%, respectively.2†
Population-based data suggest that the long-term mortality rate in patients with AAV has improved considerably over the past two decades, but is still not as good as matched controls.3‡
In a study following individuals for a median 5.2 years, the mortality rate in incident GPA or MPA patients receiving conventional treatment was 2.6 times higher than an age- and sex-matched general population (p<0.0001).2†
Many patients have renal disease at presentation, but general non-specific referral symptoms predominate1
Renal disease: 64%
Fatigue: 58%
Fever: 54%
Weight loss: 53%
Joint pain: 47%
16% of patients have had their referral symptoms for over 3 months before receiving an AAV diagnosis1
Comorbidities at diagnosis are common (65% of patients)1
Hypertension: 45%
Type 2 diabetes: 16%
COPD/asthma: 15%
Coronary arterial disease: 10%
Arthritis: 9%
Osteoporosis: 7%
BMI >35: 6%
Cardiac failure: 6%
The relative rarity and non-specific presentation of AAV can lead to a delay in disease diagnosis of more than 6 months in one-third of patients.2
Diagnosis of AAV and differentiation into the GPA, MPA or EGPA subtype depends on the patient’s clinical symptom constellation, the results of imaging studies, and laboratory investigation.2,3
Due to the linkage of anti-PR3 with GPA and anti-MPO with MPA, ANCA testing is critical for diagnosis.2–6
Up to 20% of GPA and MPA patients and over 60% of EGPA patients are ANCA negative3
A positive ANCA test result can be found in other conditions, e.g. autoimmune hepatitis, ulcerative colitis, infection with hepatitis C virus or HIV, or infectious endocarditis, without associated vasculitis3
An organ biopsy, usually renal, is often performed to confirm the diagnosis.
EGPA is rarer than either GPA or MPA.2 In patients with EGPA, peripheral neuropathy is very frequent and almost all patients have asthma. ENT manifestations are frequent, but the kidneys are not commonly involved. In EGPA, ANCA are most commonly directed against MPO. However, over 60% of EGPA patients are ANCA negative.1
These individuals may have more frequent cardiac involvement, with less renal or peripheral nerve contribution.1 The absence of granuloma helps to differentiate MPA from GPA and EGPA.1,3 The presence of granuloma, the symptoms experienced, the organs involved and the type of ANCA differentiate GPA from EGPA.1,3
References & footnotes
AAV is a rare, severe small vessel vasculitis that affects multiple organs and has a high acute mortality risk
The interaction between the activated alternative complement pathway, neutrophils and C5a is at the heart of vasculitic damage in AAV
Treatment has improved but treatment-related complications remain common
Take the interactive challenge to assess your understanding of AAV. Fully interactive version available on desktop only
AAV, ANCA-associated vasculitis; ANCA, anti-neutrophil cytoplasmic autoantibody; GPA, granulomatosis with polyangiitis; MPA, microscopic polyangiitis
Watts RA, et al. Nephrol Dial Transplant 2015;30(Suppl 1):i14–22.
Omerod AS, Cook MC. Intern Med J 2008;38(11):816–23.
Watts RA, et al. Arthritis Rheum 2000;43(2):414–9.
Watts RA, et al. Rheumatology (Oxford) 2012;51(5):926–31.
Watts RA, et al. Rheumatology (Oxford) 2017;56(9):1439–40.
AAV, ANCA-associated vasculitis; ANCA, anti-neutrophil cytoplasmic autoantibody; EGPA, eosinophilic granulomatosis with polyangiitis; ENT, ear, nose and throat; ESRD, end-stage renal disease; GPA, granulomatosis with polyangiitis; MPA, microscopic polyangiitis; MPO, myeloperoxidase; PR3, proteinase 3; RRT, renal replacement therapy
*AAV patients with (n=212; mean age: 58 years; PR3-ANCA positive: n=138; MPO-ANCA positive: n=65; ANCA negative: n=9) and without (n=61; mean age: 52 years) renal involvement (active urinary sediment, proteinuria, impaired renal function or biopsy) diagnosed and treated with AAV at a single centre in the Netherlands between January 1990 and December 2007 who were followed until death, loss to follow-up, or December 2010;4 †Retrospective data collected from patients (n=72; mean age: 64 years) with a clinical AAV diagnosis (Chapel Hill disease definitions and PR3-/MPO-ANCA positive) and renal involvement at diagnosis (rise in serum creatinine >30% and/or erythrocyturia [≥10 red blood cells per high-power field and/or red blood cell casts]) in a single-centre cohort (Northwest Clinics, the Netherlands) between 1 February 2005 and 1 February 2015.5
Hutton HL, et al. Semin Nephrol 2017;37(5):418–35.
Pagnoux C. Eur J Rheumatol 2016;3(3):122–33.
Al-Hussain T, et al. Adv Anat Pathol 2017;24(4):226–34.
De Joode AAE, et al. Clin J Am Soc Nephrol 2013;8(10):1709–17.
Houben E, et al. BMC Nephrol 2017;18(1):378.
AAV, ANCA-associated vasculitis; ANCA, anti-neutrophil cytoplasmic autoantibody; EUVAS, European Vasculitis Study Group; GPA, granulomatosis with polyangiitis; MPA, microscopic polyangiitis; RCT, randomised controlled trial; UK, United Kingdom
*Patients (n=524) with newly diagnosed GPA or MPA (adapted Chapel Hill disease definitions) recruited into four EUVAS RCTs in 42 hospitals in 11 European countries and Mexico between 1995 and 2005, and followed for 1 year;1 †Patients (n=535; median age: 61 years) with newly diagnosed GPA (53%) or MPA (47%; adapted 1994 Chapel Hill disease definitions, clinical presentation, and positive ANCA serology and/or histology) recruited into four EUVAS RCTs in 70 general and university hospitals in 15 countries between 1995 and 2002 with a median 5.16 years of follow-up for all patients. A control cohort was matched for age, sex, year and country;2 ‡Data collected from patients with a first diagnosis of incident GPA (n=465; mean age: 60.3 years) and non-GPA matched (sex, age, year of birth, and GPA diagnosis year) controls (n=4613: mean age: 60.3 years) from the UK (The Health Improvement Network) between 1992 and 2013, and divided into two cohorts based on the year of diagnosis (1992–2002 and
2003–2013).3
Little MA, et al. Ann Rheum Dis 2010;69(6):1036−43.
Flossmann O, et al. Ann Rheum Dis 2011;70(3):488–94.
Wallace ZS, et al. Semin Arthritis Rheum 2016;45(4):483–9.
AAV, ANCA-associated vasculitis; ANCA, anti-neutrophil cytoplasmic autoantibody; BMI, body mass index; COPD, chronic obstructive pulmonary disease; EGPA, eosinophilic granulomatosis with polyangiitis; ENT, ear nose and throat; EU, European Union; GP, general practitioner; GPA, granulomatosis with polyangiitis; HIV, human immunodeficiency virus; ICU, intensive care unit; MPA, microscopic polyangiitis; MPO, myeloperoxidase; PR3, proteinase 3
*Retrospective study reviewing 929 incident AAV patients (GPA: 54%; MPA: 46%; mean age: 57 years; male: 53.7%) from four EU countries (399 physicians) who initiated remission induction therapy between November 2014 and February 2017 with data collected at baseline presentation, and after 1, 3, 6 and 12 months of treatment.1
Rutherford PA, et al. Real world experience in ANCA-associated vasculitis (AAV) – a complex pathway of patient referral, diagnosis, and management. Poster presented at: ASN 2018, 23–28 October 2018, San Diego, CA, USA (abstract SA-PO403).
Yates M, Watts R. Clin Med (Lond) 2017;17(1):60–4.
Pagnoux C. Eur J Rheumatol 2016;3(3):122–33.
Al-Hussain T, et al. Adv Anat Pathol 2017;24(4):226–34.
Chen M, et al. Medicine (Baltimore) 2008;87(4):203–9.
Lionaki S, et al. Arthritis Rheum 2012;64(10):3452–62.
ANCA, anti-neutrophil cytoplasmic autoantibody; EGPA, eosinophilic granulomatosis with polyangiitis; ENT, ear, nose and throat; GPA, granulomatosis with polyangiitis; MPA, microscopic polyangiitis; MPO, myeloperoxidase
Pagnoux C. Eur J Rheumatol 2016;3(3):122–33.
Watts RA, et al. Nephrol Dial Transplant 2015;30(Suppl 1):i14–22.
Mansi IA, et al. Am Fam Physician 2002;65(8):1615–20.
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