Journal List > J Korean Rheum Assoc > v.17(2) > 1003712

Uhm: ANCA Associated Vasculitis


Primary antineutrophil cytoplasmic antibody (ANCA) associated vasculitides (AAV) constitute a group of small vessel vasculitides that includes Wegener's granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome. Recently, many in vitro and in vivo studies have highlighted the role of ANCA as the main pathophysiological factor in the development of AAV. Two remarkable studies on ANCA pathogenesis were recently reported. One study examined anti-lysosomal membrane protein-2, which supports the ‘shared epitope’ theory. The other examined the neutrophil extracellular trap that is released by neutrophils primed by ANCA. Each disease of AAV shows a broad spectrum of the clinical features and severities, which makes it difficult to diagnose and treat them. Considerable effort has been made in the past decades to improve the treatment outcomes, reduce the incidence of relapse and avoid drug toxicity. This review describes the current understanding of AAV along with a few Korean reports.


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Table 1.
Summary of prevalence, incidence and onset age for ANCA associated vasculitis
Prevalence (/million) Incidence (/million/year) Onset age
Wegner's granulomatosis 24~160 (11-15) 3~11 (15, 20-22) 51~66 (11, 13-15)
Microscopic polyangiitis 25~94 (12-15) 2~8 (15, 20-24) 60~71 (11, 13-15)
Churg-Strauss syndrome 11~14 (11, 23, 25) 2~7 (23, 26) 50~61 (11, 13)
Table 2.
ACR classification criteria and CHCC nomenclature of ANCA associated vasculitis
ACR criteria (1990) (63) CHCC Nomenclature (1994) (8)
Wegner's granulomatosis 1. Nasal or oral inflammation
2. Chest X-ray showing nodules, infiltrates (fixed) or cavities
3. Microscopic hematuria or red cell casts in urine
4. Granulomatous inflammation on biopsy Two criteria classify WG with a sensitivity of 88.2% and specificity of 92.0%
▪ Granulomatous inflammation involving the upper and lower respiratory tract, and necrotizing vasculitis affecting small to medium-sized vessels
▪ Necrotizing GN is common
Microscopic polyangiitis ▪ Necrotizing vasculitis, with few or no immune deposits, affecting small vessels
▪ Necrotizing arteritis of small and medium-sized arteries may be present. Necrotizing GN is common. Pulmonary capillaritis often occurs.
Churg-Strauss syndrome 1. Asthma
2. Eosinophilia
3. Neuropathy
4. Pulmonary infiltrates (non-fixed)
5. Sinusitis
6. Positive biopsy
Four criteria classify CSS with a sensitivity of 85% and specificity of 99.7%
▪ Eosinophil-rich, granulmatous inflammation involving the respiratory tract, and necrotizing vasculitis affecting small to medium-sized vessels, associated with asthma and eosinophilia

ACR: American College of Rheumatology, CHCC: Chapel Hill Consensus Conference, WG: Wegner's granulomatosis, GN: glomerulonephritis, CSS: Churg-Strauss syndrome

Table 3.
Clinical manifestations of ANCA associated vasculitis
WG (100,101) MPA (102) CSS (62,103-106)
ANCA positivity ANCA antigen Specificity∗ (107) Fundamental histology 80~95%
PR3: 70~80%
MPO: 10~15%
Leukocytoclastic vasculitis; necrotizing granulomatous inflammation (rarely seen in renal biopsy specimen)
PR3: 15~30%
MPO: 50~70%
Leukocytoclastic vasculitis; no granulomatous inflammation
PR3: 15~20%
MPO: 30~40%
Eosinophilic tissue infiltrates and vasculitis: granulomas have eosinophilic necrosis
ENT 79~94%
Nasal septal perforation, saddle-nose deformity, sinusitis, conductive or sensorineural hearing loss, subglottic stenosis
Absent or mild
Nasal polyps, allergic rhinitis, sinusitis, conductive hearing loss
Eye 29~65%
Orbital pseudotumor, scleritis (risk of scleromalacia perforans), episcleritis, uveitis
Occasional eye disease, scleritis, episcleritis, uveitis
Occasional eye disease, scleritis, episcleritis, uveitis
Lung 53~83%
Nodules, infiltrates or cavitary lesions; alveolar hemorrhage
Alveolar hemorrhage
Asthma, fleeting infiltrates, alveolar hemorrhage
Kidney 23~77%
Segmental necrotizing GN, rare granulomatous features
Segmental necrotizing GN
Segmental necrotizing GN
Heart 13%
Occasional valvular lesions
Heart failure
Peripheral nerve 20%
Vasculitic neuropathy
Vasculitic neuropathy
Vasculitic neuropathy
Eosinophilia Mild eosinophilia occasionally None 90~100%

∗These percentages come from studies of Europe and the United States

Table 4.
Mimics and secondary causes of vasculitis (108)
Mimics of vasculitis Secondary causes of vasculitis
Atheroembolic disease Infections Tuberculosis
Atheromatous vascular disease Hepatitis B
Anti-phospholipid syndrome Hepatitis C
Multiple myeloma HIV
Infective endocarditis Parvovirus
Other chronic infections Cystic fibrosis
Para-neoplastic syndromes
Genetic vascular disorders (e.g. Marfan's syndrome) Malignancy Lymphoma
Autoinflammatory syndromes Solid organ malignancy
Hypersensitivity reactions Connective tissue disorders Rheumatoid arthritis
Cocaine and amphetamine abuse Systemic lupus erythematosus
Sjogren's syndrome
Drugs Penicillamine
Environmental exposure Dusts
Table 5.
Definitions for disease stages of ANCA associated vasculitis according to EULAR
Clinical subgroup Systemic vasculitis outside ENT tract and lung Threatened vital organ function Other definitions Serum creatinine (μ mol/L) Reference
Localized No No No constitutional symptoms, ANCA typically negative <120 (1.4 mg/dL)
Early systemic Yes Yes Constitutional symptoms present, ANCA-positive or -negative <120
Generalized Yes Yes ANCA-positive <500 (5.6 mg/dL) Jayne et al (128)
Severe Yes Organ failure ANCA-positive >500 Jayne (156)
Refractory Yes Yes Refractory to standard therapy Any Jayne (156)

ANCA: antineutrophil cytoplasmic antibody, ENT: ear, nose and throat

Table 6.
Recommendation for use and definition of activity states in vasculitis (155)
Activity state Definition
Remission Absence of disease activity attributable to active disease qualified by the need for ongoing stable maintenance immunosuppressive therapy. The term “active disease” is not restricted to vasculitis only, but also includes other inflammatory features like granulomatous inflammation in WG or tissue eosinophilia in CSS.
Response 50% reduction of disease activity score and absence of new manifestations
Relapse Re-occurrence or new onset of disease attributable to active vasculitis
Major Re-occurrence or new onset of potentially organ- or life-threatening disease
Minor Re-occurrence or new onset of disease which is neither potentially organ- nor life-threatening
Refractory disease Unchanged or increased disease activity in acute AAV after 4 weeks of treatment with standard therapy in acute AAV, or Lack of response, defined as ≤ 50% reduction in the disease activity score, after 6 weeks of treatment, or Chronic, persistent disease defined as presence of at least one major or three minor items on the disease activity score list (eg, BVAS or BVAS/WG) after ≥ 12 weeks of treatment
Low-activity disease state Persistence of minor symptoms (eg, arthalgia, myalgia) that respond to a modest increase of the GC dose and do not warrant an escalation of therapy beyond a modest dose increase inthe current medication

AAV: antineutrophil cytoplasmic antibody-associated vasculitis, BVAS: Birmingham Vasculitis Activity Score, BVAS/WG: Birmingham Vasculitis Activity Score for Wegener's granulomatosis, CSS: Chrug-Strauss syndrome, GC: glucocorticoid, WG: Wegener's granulomatosis

Table 7.
Dose modification of pulsed cyclophosphamide as used in a randomisedcontrolled trial comparing the efficacy of daily oral versus pulsed cyclophosphamide for renal vasculitis (
Pulsed CYC dose reductions for renal function and age
Age, years Creatinine (μ mol/litre)
<300 (3.4 mg/dL) 300~500 (3.4~5.6 mg/dL)
<60 15 mg/kg/pulse 12.5 mg/kg/pulse
60~70 12.5 mg/kg/pulse 10 mg/kg/pulse
>70 10 mg/kg/pulse 7.5 mg/kg/pulse

The trial did not include a separate regimen for patients with a creatinine of <150 μ mol/litre (1.7 mg/dL). CYC: cyclophosphamide

Table 8.
Alternative remission induction treatments in relapsing, refractory or persistent disease (155)
Drug Dose Reference
Intravenous immunoglobulin 2 g/kg over 5 days Muso et al, Jayne et al (176,177)
15-Deoxyspergualin 0.5 mg/kg/day till white cell count nadir of 3,000/ μ L, then wait until the white cell count returns to ≥ 4,000/ μ L and repeat the dose for six cycles Burke et al (185)
Anti-thymocyte globulin 2.5 mg/kg/day for 10 days adjusted according to lymphocyte count: no anti-thymocyte globulin if <150/ μ L, 1.5 mg/kg/day if 150~300/ μ L, full dose if >300/ μ L Schmitt et al (179)
Infliximab 3~5 mg/kg/infusion every 1 to 2 months Booth et al (180)
Mycophenolate mofetil 2 g/day Koukoulaki et al, Stassen et al (173,178)
Rituximab 375 mg/m2 body surface area weekly for 4 weeks Keogh et al, Keogh et al, Stasi et al, Brihaye et al, Eriksson et al (69,181-184)
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