ANCA-Associated Vasculitis

Lab Workup

• CBC with differential, chemistries, ESR/CRP (high), creatinine, urinalysis
• ANCA panel (most common association)
  • C-ANCA or PR3-ANCA = GPA (less commonly EGPA or MPA)
  • P-ANCA or MPO-ANCA = MPA 
  • P-ANCA/MPO-ANCA in EGPA ~30-50%
• Anemia of chronic disease
• AKI
• Urinalysis:
  • +blood
  • +protein
  • +RBC casts

Imaging

• CXR/CT chest (view images)
  • Diffuse infiltrates in diffuse alveolar hemorrhage (DAH)
  • Cavitating lung lesions in GPA

Bronchoscopy

• Confirm DAH
• Rule out infection (bacterial, fungal)
• Rule out malignancy

Kidney Biopsy

• Pauci-immune crescentic glomerulonephritis (GN)

Drug Induced

• PTU
• Hydralazine
• Minocycline
• Levamisole

Malignancy

Infection

• Infective endocarditis
• Organisms that can cause cavitary lung lesions and lung abscesses (tuberculosis, aspergillosis, pseudomonas, etc.)

Other Kidney Disease

• Lupus nephritis
• Membranous nephropathy
• IgA nephropathy
• Post-infectious glomerulonephritis (GN)
• Goodpasture (GBM disease)

Other Rheumatic Diseases

• Lupus
• Cryoglobulinemic vasculitis
• Antiphospholipid syndrome
• Complement-mediated disease

Other Vasculopathies

• Cocaine-associated vasculopathy
• Microthrombi leading to vasculopathy

• Should be managed in conjunction with a rheumatologist, nephrologist, or other specialist experienced with these diseases
• Two-part approach: induction and maintenance

Induction

• High doses of steroids (500-1000 mg IV for 3-5 days) followed by taper
  • Consider treatment for glucocorticoid-induced osteoporosis
• Cyclophosphamide
  • IV intermittent dosing or PO daily
  • Mesna to mitigate risk of hemorrhagic cystitis
  • Due to risk of infertility, prior to administration:
    • Women of child-bearing age: consider ovarian preservation
    • Men: sperm banking
• Rituximab
  • IV
  • Noninferior efficacy to cyclophosphamide but safer
• Methotrexate (for localized, milder disease – i.e., upper respiratory-limited GPA)
  • PO weekly or SQ
• +/- plasma exchange
  • Reserved for specific clinical scenarios
• Avacopan as add-on therapy for those with severe active disease

Maintenance Choices

• Azathioprine
• Methotrexate (works well for sinonasal/upper airway disease)
• Rituximab
  • IV
  • Associated with lower risk of relapse compared to azathioprine

Additional Therapy

• PJP prophylaxis for AAV and immunosuppressive therapy:
  • Especially lung involvement
  • Notably for RTX or CYC
• Vitamin D, calcium, and other concerns for patients with long-term systemic steroid therapy

Monitoring

• For patients with lung disease and/or receiving remission induction treatment (e.g., rituximab, cyclophosphamide)
  • Pneumocystis jiroveci pneumonia (PJP) prophylaxis needed
  • Monitor CBC every 1-2 wks with cyclophosphamide use
• Monitor renal function with metabolic panel and creatinine, urinalysis for proteinuria+hematuria
• Monitor pulmonary function with respiratory symptoms, physical exam and PFTs +/- imaging, as needed
• Monitor for infection from systemic immunosuppressive medications

Prognosis

• 80-90% mortality risk if untreated
• Need for dialysis in setting of renal disease can contribute significantly to mortality and morbidity

Disease Overview & Clinical Presentation

• Adult with new-onset asthma: consider eosinophilic granulomatosis with polyangiitis (EGPA)
• Keep granulomatosis with polyangiitis on DDx for:
  • New diagnosis of otitis media as adult
  • Recurrent sinusitis +/- epistaxis
  • Pseudotumor
  • Nasal septal perforation (view image)
  • Pulmonary renal syndrome
• Vasculities often presents with:
  • Constitutional symptoms
  • High CRP
  • ESR can be >100
• C-ANCA or PR3-ANCA = GPA (less commonly EGPA or MPA)
  P-ANCA or MPO-ANCA = MPA 
• Look for potential medications for drug-induced vasculitis
• ANCA negative does not rule out AAV
• ANCA usually negative in cardiac-associated EGPA or upper airway limited GPA

Treatment

• Need PJP prophylaxis for AAV lung disease and/or remission induction treatment (e.g., rituximab, cyclophosphamide)