ANCA Associated Vasculitis (Wegener, MPA, CS)

Question 1

Granulomatosis with polyangiitis is a granulomatous vasculitis of __ and __, with variable degree of disseminated vasculitis of __

Answer 1

Upper and lower respiratory tracts
Glomerulonephritis
Small arteries and veins

Question 2

Pathogenesis of GPA

Answer 2

Necrotising vasculitis of small arteries and veins with granuloma formation, either intravascular or extravascular
- Lung: multiple, bilateral, nodular cavitary infiltrates
- Upper airway: sinus, nasopharynx inflammation, necrosis and granuloma
- Rena: FSGS -> crescenteric GN

Question 3

What are the clinical manifestations of GPA?

Answer 3

A. Pulmonary involvement
- Cough, haemoptysis
- Dyspnoea, chest discomfort
- Obstruction, atelectasis

B. Renal disease
- Proteinuria, haematuria, red cell casts
- Rapid progressive renal failure

C. Upper airway involvement
- Paranasal sinus pain, purulent/bloody discharge
- Nasal mucosal ulceration, septal perforation, saddle nose deformity
- Serous otitis media, hearing loss, ear pain
- Subglottic stenosis, severe airway obstruction

D. Eye involvement
- Conjunctivitis, dacryocystitis, episcleritis, scleritis - eye pain, redness, visual loss
- Retro-orbital mass and proptosis

E. Skin involvement
- Papules, vesicles
- Palpable purpura and subcutaneous nodules
- Ulcers

F. Cardiac involvement
- Pericarditis, coronary vasculitis
- Cardiomyopathy

G. Neurology involvement
- Cranial neuritis
- Mononeuritis multiplex
- Cerebral vasculitis and granuloma

H. Others
- Arthralgia/arthritis
- Hyperthyroidism
- Non-specific symptoms: fever, malaise, weakness, anorexia, weight loss

Question 4

Investigations for GPA

Answer 4

1. Raised inflammatory markers - ESR, CRP
2. FBC - anaemia, leukocytosis, thrombocytosis
3. Hypergammaglobulinaemia - IgA
4. Mildly elevated RF
5. Predominant cANCA (PR3) (small percentage pANCA positive, 20% ANCA negative)
6. Biopsy and histology - granulomatous inflammation with necrosis +/- vasculitis

Question 5

Specific treatment for GPA
- induction, maintenance, biologics

Answer 5

Induction - corticosteroid and IST
A. Corticosteroids
1. Life threatening condition
- IV methylprednisolone 1g for 3 days
- Adjunctive plasmapharesis

2. Standard regime
   - Prednisolone 1mg/kg for 1 month then gradual tapering
   (recent trial - reduced dose steroid regime non-inferior to standard dose)

B. IST
- Cyclophosphamide 2mg/kg daily for 3 months
- Rituximab 375 mg/m2 once weekly for 4 weeks

Maintenance - either rituximab, azathioprine, MTX, MMF + low dose steroids
- Rituximab 500mg 6 monthly
- Azathioprine 2mg/kg daily
- MTX 15mg/week up to 20-25mg/week
- MMF 1000mg BD - higher rate of relapse
+
- Low dose prednisolone 5mg daily

Biologics and small molecule inhibitors
Ongoing trials as of 2024
- Abatacept (CTLA4-Ig)
- Avacopan (C5a receptor inhibitor)

Question 6

How would you manage GPA?

Answer 6

1. Multidisciplinary team involvement - respiratory, renal, rheumatology, ophthalmology, ENT
2. Specific treatment: induction and maintenance
   - High dose prednisolone
   - IST: cyclophosphamide or rituximab
   - Maintenance: rituximab, azathioprine, MTX, MMF and low dose steroids
   - Promising biologics
3. Bactrim prophylaxis - reduces relapse
4. Sinus moistuirisation and humidification
5. Subglottic dilatation and steroid injection

Question 7

Microscopic polyarthritis is a necrotising vasculitis with __ immune complexes of small vessels (capillaries, venules, arterioles), characterised by __ and __ in the absence of __

Answer 7

Few or no immune complexes
Glomerulonephrtitis and polyarteritis nodosa
Absence of granulomatous inflammation

Question 8

Pathogenesis of MPA

Answer 8

Involvement of small to medium sized arteries, capillaries and venules
Paucity (few to none) of immunoglobulin deposition
Highly associated with ANCA

Question 9

Clinical manifestation of MPA

Answer 9

Similar to Wegener’s granulomatosis
Except NO upper airway disease and pulmonary nodules

Question 10

Investigations for MPA

Answer 10

1. Elevated ESR, CRP
2. Anaemia, leukocytosis, thrombocytosis
3. Predominant pANCA (myeloperoxidase)
4. Histology: vasculitis with pauci-immune GN

Question 11

Treatment and prognosis of MPA

Answer 11

Similar to Wegener’s

5-year survival: 74% with treatment
Treatment relapse: 34%

Question 12

Churg-Strauss syndrome (Eosinophilic granulomatosis with polyangiitis) is characterised by __, __, __ and __

Answer 12

Asthma
Eosinophilia of peripheral/tissue
Granuloma formation extravascular
Vasculitis of multiple organ system

Question 13

Pathogenesis of CS

Answer 13

Involvement of small and medium sized vessels
Granuloma in tissue or within vessel walls
Eosinophil infiltration of tissues (lungs, skin, CVS, kidney, nervous system, GIT)

Question 14

Clinical manifestation of CS

Answer 14

Severe asthmatic attacks
Pulmonary infiltrates
Mononeuritis multiplex
Allergic rhinitis and sinusitis
Myocarditis, pericarditis, endocarditis
Coronary vasculitis
Palpable purpura, cutaneous or subcutaneous nodules

Often presents as non-specific symptoms of fever, anorexia, weight loss

Question 15

Investigations of CS

Answer 15

1. Clinical features of asthma, eosinophilia, vasculitis
2. FBC - eosinophilia > 1000 cells/uL
3. Elevated ESR, CRP
4. High fibrinogen
5. High alpha-2-globulin
6. pANCA positive (MPO)
7. Biopsy

Question 16

Treatment of CS

Answer 16

1. Similar to GPA
2. SC Mepolizumab (anti-IL5 Ab) 300mg once a month