ANCA Associated Vasculitides

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).