ANCA Associated Vasculitis (GPA, MPA, EGPA) Flashcards
Granulomatosis with polyangiitis (GPA) is a granulomatous vasculitis of __ and __, with variable degree of disseminated vasculitis of __
Previously known as __
Upper and lower respiratory tracts
Glomerulonephritis
Small arteries and veins
Wegener’s granulomatosis
Epidemiology of GPA
- Affects men and women equally
- Peak age 65-74 years old with wide variation
EULAR Classification of GPA Severity
A. Localised - Upper or lower respiratory tract without systemic involvement or constitutional symptoms
B. Early systemic without organ/life threatening disease
C. Generalised - Renal or other organ threatening disease, Cr < 5.6mg/dL
D. Severe - Renal or other vital organ failure, Cr > 5.6mg/dL
E. Refractory - Progressive disease unresponsive to steroids alone and cyclophosphamide
Pathogenesis of GPA
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
What are the clinical manifestations of GPA?
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
ACR 1990 Criteria for GPA
2 of the following:
1. Nasal or oral inflammation - ulcers, nasal discharge
2. Abnormal CXR - nodules, infiltrates, cavities
3. Haematuria or red blood cell casts
4. Pathological evidence of granulomas, leukocytoclastic vasculitis, necrosis
Diagnostic investigations for GPA
Laboratory
1. Raised inflammatory markers - ESR, CRP
2. FBC - anaemia, leukocytosis, thrombocytosis
3. RP - urea and creatinine
4. UFEME - haematuria, RBC cast (GN)
5. Hypergammaglobulinaemia - IgA
6. Mildly elevated RF
7. Predominant cANCA (PR3) (small percentage pANCA positive, 20% ANCA negative)
8. Biopsy and histology (lung, kidney)- granulomatous inflammation with necrosis +/- vasculitis
Imaging
1. CXR or CT thorax - nodules and cavitations, ILD
2. CT sinus
Investigative evaluation for severity of GPA
- Pulmonary function test - obstruction
- Bronchoscopy in pulmonary haemorrhage
- Progressive bloody aliquot lavage
- Bronchial biopsy and inspection
Induction and maintenance treatment for GPA
Induction - corticosteroid and IST
A. Life threatening condition
1. IV methylprednisolone 1g for 3 days followed by oral prednisolone
2. Adjunctive plasmapharesis or IVIg - might remove RTX
(Not effective, but used for diffuse alveolar haemorrhage, renal vasculitis or anti-GBM)
3. PO Prednisolone 1mg/kg for 1 month then gradual tapering
(PEXIVAS trial - reduced dose steroid regime non-inferior to standard dose)
B. IST choice - CYC or RTX
1. Cyclophosphamide - IV 350-750 mg/m2 (max 1.2g) monthly with Mesna
- Reduced dose in kidney/liver failure, persistent lymphopenia/neutropenia, infections
- Rituximab - IV 750 mg/m2 (max 1g) 2 doses 2 weeks apart
Maintenance - either rituximab, azathioprine, MTX, MMF + low dose steroids
1. Maintenance IV Rituximab 750mg/m2 (max 1g) 6 monthly
- Check B lymphocytes subset (CD19 counts) and ANCA titres and re-dose when increasing
OR
If induction with cyclophosphamide - choice of either one or multiple:
1. Azathioprine 0.5-2mg/kg daily (start 0.5mg/kg/day max 50mg for 1 week and gradually increase)
- To start 14 days after last CYC dose
2. MTX 15mg/week up to 20-25mg/week
3. MMF 600mg/m2 Q12H (max 1000mg BD) - higher rate of relapse, but non-inferior to CYC
(change to Myfortic if persisetnt gastrointestinal side effect)
+
4. Progressive taper until low dose prednisolone 5mg daily
Biologics and small molecule inhibitors
Ongoing trials as of 2024
- Abatacept (CTLA4-Ig)
- Avacopan (C5a receptor inhibitor)
How would you manage GPA?
- Multidisciplinary team involvement - respiratory, renal, rheumatology, ophthalmology, ENT
- Specific treatment: induction and maintenance
- High dose prednisolone, with PEXIVAS tapering
- IST: cyclophosphamide or rituximab
- Maintenance: rituximab, azathioprine, MTX, MMF and low dose steroids
- Promising biologics - Vaccination, PJP and PTB prophylaxis, Glucocorticoid induced osteoporosis prevention
- Sinus moisturization and humidification
- Subglottic dilatation and steroid injection
Follow up on GPA
- cANCA (PR3) correlates with disease activity
- Monitor toxicity and opportunistic infections
- Scheduled ISTs
Prognosis of GPA
- Limited GPA better prognosis
- Worst prognosis in alveolar haemorrhage and renal failure
- Relapse in 50% patients
- Untreated 20% at 2 years, treated 90% at 2 years
Microscopic polyarthritis is a necrotising vasculitis with __ immune complexes of small vessels (capillaries, venules, arterioles), characterised by __ and __ in the absence of __
Few or no immune complexes
Glomerulonephrtitis and polyarteritis nodosa
Absence of granulomatous inflammation
Pathogenesis of MPA
Involvement of small to medium sized arteries, capillaries and venules
Paucity (few to none) of immunoglobulin deposition
Highly associated with ANCA
Clinical manifestation of MPA
Similar to Wegener’s granulomatosis
Except NO upper airway disease and pulmonary nodules
