1. DEFINITION
Small vessel vasculitides characterized by necrotizing inflammation of small vessels (capillaries, venules, arterioles) and a strong association with Antineutrophil Cytoplasmic Antibodies (ANCA). The group includes:
- Granulomatosis with Polyangiitis (GPA) – formerly Wegener’s.
- Microscopic Polyangiitis (MPA).
- Eosinophilic Granulomatosis with Polyangiitis (EGPA) – formerly Churg-Strauss.
2. PATHOPHYSIOLOGY
- ANCA Specificity: Directed against Proteinase 3 (PR3-ANCA/c-ANCA) or Myeloperoxidase (MPO-ANCA/p-ANCA).
- Mechanism: Cytokine-primed neutrophils express PR3/MPO on their surface. ANCA binding causes neutrophil activation, degranulation, and release of Reactive Oxygen Species (ROS), leading to endothelial damage and “Pauci-immune” necrotizing inflammation.
- Genetics: Strong association with HLA-DP (GPA) and HLA-DQ (MPA).
3. CLINICAL SPECTRUM
- GPA (Granulomatous):
- Upper Respiratory: Saddle nose deformity, chronic sinusitis, subglottic stenosis.
- Lower Respiratory: Cavitary nodules, alveolar hemorrhage.
- Renal: Necrotizing glomerulonephritis (pauci-immune).
- MPA (Non-granulomatous):
- Predominantly Renal: Rapidly Progressive Glomerulonephritis (RPGN).
- Pulmonary: Diffuse Alveolar Hemorrhage (DAH); lacks upper airway granulomas.
- EGPA (Eosinophilic):
- Triad: Asthma, peripheral eosinophilia (>1500/microL), and small-vessel vasculitis.
- Cardiac: Myocarditis (major cause of mortality).
4. INVESTIGATIONS
- Serology: Indirect Immunofluorescence (IIF) and ELISA for PR3-ANCA and MPO-ANCA.
- Histopathology (Gold Standard):
- Renal: Pauci-immune necrotizing crescentic glomerulonephritis.
- Lung/Tissue: Granulomatous inflammation (in GPA/EGPA).
- Radiology: HRCT chest for ground-glass opacities (DAH) or thick-walled cavities (GPA).
- Laboratory: Elevated ESR/CRP, Hematuria/Proteinuria, peripheral eosinophilia (EGPA).
5. CLASSIFICATION CRITERIA (EULAR/PRINTO/PRES 2022)
Incorporates clinical, radiological, and ANCA serology. Key features include:
- Positive ANCA.
- Upper/Lower airway involvement.
- Biopsy evidence of necrotizing vasculitis/granuloma.
6. MANAGEMENT (EULAR GUIDELINES)
A. Remission Induction (3–6 months)
- Organ/Life-threatening: High-dose Glucocorticoids (IV Methylprednisolone pulse followed by oral Prednisolone) + Cyclophosphamide (IV/Oral) OR Rituximab.
- Non-organ threatening: Glucocorticoids + Methotrexate or Mycophenolate Mofetil (MMF).
- Plasma Exchange (PLEX): Considered in severe RPGN (Creatinine >5.7 mg/dL) or DAH.
B. Remission Maintenance (18–24 months)
- Low-dose Glucocorticoids + Azathioprine, Rituximab (fixed intervals), or Methotrexate.
7. PROGNOSIS AND FOLLOW-UP
- Monitor ANCA titers (rising titers may predict relapse but don’t mandate treatment change alone).
- Monitor renal function (S. Creatinine, GFR) and urinalysis.
- Pneumocystis jirovecii (PJP) prophylaxis is mandatory during induction (Cotrimoxazole).