Introduction
Diagnosis and classification
Epidemiology
Reference | Country of study | Study period | Study population | Classification criteria | Incidence per 100,000 population | ||
---|---|---|---|---|---|---|---|
GPA | MPA | EGPA | |||||
Adult cohort data | |||||||
Watts et al. [12] | UK | 1988–1997 | All ages | CHCC/ACR | 8.7–10.3 | 6.8–8.9 | 1.5–3.7 |
Watts et al. [13] | UK | 1990–2005 | All ages | Clinical diagnosis | 8.4 | - | - |
Koldingsnes et al. [14] | Norway | 1984–1998 | Age >15 years | ACR | 6.0–14.4 | - | - |
Gonzales-Gay et al. [15] | Spain | 1998–2001 | Age >15 years | CHCC | 2.95 | 7.91 | 1.31 |
Reinhold-Keller et al. [16] | Germany | 1998–2002 | All ages | CHCC | 6–12 | 2–3 | 0–2 |
Ormerod et al. [17] | Australia | 1995–2004 | Age >15 years | ACR/CHCC | 8.4–8.8 | 2.3–5 | 2.2–2.3 |
Paediatric cohort data | |||||||
Gardner-Medwin et al. [18] | UK | 1996–1999 | Age <17 years | ACR | Primary systemic vasculitis incidence 10.6 per 100,000 patients (including ANCA-vasculitis) | ||
Grisaru et al. [19] | Canada | 1994–2009 | Age <18 years | ACR or EULAR/PRES | 6.39 | - | - |
Aetiology and pathogenesis
Clinical features
Granulomatosis with polyangiitis | ||||||
---|---|---|---|---|---|---|
Disease feature | Paediatric data | Adult data | ||||
Rottem et al. [25] (n = 23) | Stegmayr et al. [21] (n = 10) | Belostotsky et al. [2] (n = 17) | Akikusa et al. [1] (n = 25) | Cabral et al. [24] (n = 65) | Fauci et al. [26] (n = 18) | |
Criteria used for diagnosis | ACR 1990 | Triad of RPCGN, raised ANCA and upper/lower respiratory disease | ACR 1990 | ACR 1990 | ACR 1990 | NR |
Median age at onset (years) | 15.4 | 16.5 | 6 | 14.5 | 14.2 | 43.6 |
Male:female | 1:2.1 | 1:1 | 1:3.25 | 1:4 | NR | 1:0.6 |
Median duration of symptoms prior to admission, in months (range) | NR | 1 (0–2.5) | NR | 2 (0.3–12) | 2.7 (0–49) | NR |
Constitutional | NR | 10 (100) | NR | 24 (96) | 58 (89.2) | 14 (78) |
Pulmonary | 5 (22) | 9 (90) | 14 (82.4) | 20 (80) | 52 (80) | 18 (100) |
Upper airway | 20 (87) | 10 (100) | 17 (100) | 21 (84) | 52 (80) | 18 (100) |
Renal | 2 (9) | 10 (100) | 4 (23.5) | 22 (88) | 49 (75.4) | 15 (83) |
Requiring RRT | 0 (0) | NR | 1 (5.8) | 5 (20) | NR | NR |
Skin | NR | 4 (40) | 9 (53) | 8 (32) | 23 (35.4) | 8 (44) |
Neurological | NR | 2 (20) | 2 (12) | 2 (8) | 16 (24.6) | 4 (22) |
Gastrointestinal | NR | NR | NR | 3 (12) | 27 (41.5) | NR |
Joints | NR | 5 (50) | NR | NR | 37 (56.9) | 10 (56) |
Eyes | 3 (13) | 0 (0) | 9 (53) | 13 (52) | 24 (36.9) | 7 (39) |
Cardiovascular | NR | NR | NR | 3 (12) | 0 (0) | 5 (28) |
PR3-ANCA positive | NR | 8 (80) | 10 (59) | 13 (86.7) | 40 (93) | NR |
MPO-ANCA positive | NR | 1 (10) | NR | 2 (13.3) | 0 (0) | NR |
Microscopic polyangiitis | ||||||
Disease feature | Paediatric data | Adult data | ||||
Bakkaloglu et al. [27] (n = 10) | Hattori et al. [28] (n = 21) | Peco-Antic et al. [29] (n = 7) | Siomou et al. [30] (n = 6) | Nachman et al. [31] (n = 69) | ||
Criteria used for diagnosis | NR | Derived from 1994 CHCC classification criteria | Triad of clinical features of small-vessel vasculitis, biopsy proven pauci-immune necrotizing glomerulonephritis and raised MPO-ANCA titres | Derived from 1994 CHCC and EULAE/PRES classification criteria | Derived from 1994 CHCC classification criteria | |
Median age at onset (years) | 9.5 | 11.9 | 12 | 11.6 | 57.6 | |
Male:female | 1:1.5 | 1:6.8 | 0.16:1 | 0:6 | 1:0.83a,
b
| |
Median duration of symptoms prior to admission, in months (range) | NR | NR | 6.7 (3–15) | NR (1–12) | NR | |
Constitutional | 10 (100) | 18 | 7 (100) | NR | NR | |
Pulmonary | 3 (30) | 13 | 4 (57) | 3 (50) | 38 | |
Upper airway | NR | 2 | NR | 1 (16.7) | 14 | |
Renal | 7 (70) | 21 | 7 (100) | 6 (100) | 69 | |
Requiring RRT | 0 (0) | 7 ()* | 2 (29) | 1 (16.7) | 6 (5.6)a
| |
Skin | 7 (70) | 8 | 7 (100) | NR | 13 | |
Neurological | 2 (20) | 1 | 6 (86) | 1 (16.7) | 9 | |
Gastrointestinal | 2 (20) | 7 | 4 (57) | NR | 6 | |
Joints | 6 (60) | 2 | NR | NR | 10 | |
Eyes | NR | 2 | NR | 1 (16.7) | 2 | |
Cardiovascular | NR | NR | NR | NR | NR | |
PR3-ANCA positive | 0 (0) | 3 (9.7)* | 0 (0) | 0 (0) | 36 (37.1)a,
b
| |
MPO-ANCA positive | 9 (90) | 31 (90.3)* | 7 (100) | 5 (83.3) | 61 (62.9)a,
b
|
Granulomatosis with polyangiitis
Microscopic polyangiitis
Renal limited vasculitis
Eosinophilic granulomatosis with polyangiitis
Renal histology in AAV
Measurement of disease activity
Investigations
First-line investigations | Second-line investigations |
---|---|
Haematology -Full blood count with blood film -Erythrocyte sedimentation rate -Coagulation profile | Biochemistry/Immunology -Basic lymphocyte subsets -CD19 count (pre-rituximab) -Hepatitis B&C, parvovirus B19, human immunodeficiency virus -Mantoux and/or quantiferon tuberculosis testing -Ebstein–Barr virus, cytomegalovirus, enterovirus, adenovirus, JC virus |
Biochemistry -Urea & electrolytes -Liver function tests -Lactate dehydrogenase -Creatinine kinase -Thyroid function -Pancreatic function (amylase/lipase) -Urine albumin:creatinine ratio | Imaging -Computed tomography/magnetic resonance imaging (MRI) /X-ray sinuses and/or thorax -Renal dimercaptosuccinic acid scan -MRI/MR angiography head |
Infectious disease screen -Blood culture -Urine microscopy and cell culture -Mycoplasma serology -Anti-streptolysin titre -Anti-DNase B | Neurological -Nerve conduction studies |
Immunological tests -Anti-neutrophil cytoplasmic antibodies -Antinuclear antibodies -Anti-extractable nuclear antibodies -Rheumatoid factor -Anti-double stranded DNA antibodies -Anti-glomerular basement membrane antibodies -Coeliac screen -Complement (C) function: C3/4, CH100, Mannose binding lectin -Anti-cardiolipin antibodies -Lupus anticoagulant -Varicella status -Immunoglobulins (Ig): IgG, IgM, IgA, IgE -Serum angiotensin converting enzyme | Other -Histology: renal/lung biopsy -Ambulatory blood pressure monitoring -Formal glomerular filtration rate testing |
Other -Chest X-ray -Electrocardiography -Echocardiography |
Management
Category | Description |
---|---|
Localized | Upper and/or lower respiratory symptoms without other system involvement or constitutional symptoms |
Early systemic | Disease without threatened organ function or life-threatening disease (also known as ‘non-organ or life threatening’ |
Generalized | Renal, or other organ-threatening disease. Serum creatinine <500 μmol/l (or 5.6 mg/dl) |
Severe | Renal or other organ failure, serum creatinine >500 μmol/l (5.6 mg/dl). Also known as ‘immediately life threatening’ |
Refractory | Disease unresponsive to glucocorticoids and cyclophosphamide |