Small Vessel Vasculitis

These diseases can be broken down into ANCA-associated vasculitis (AAV) and non-ANCA-associated vasculitis (ANCA: Anti-Neutrophil Cytoplasmic Antibodies)

cANCA = diffuse cytoplasmic staining of ANCA, most commonly associated with anti-PR3 (or anti-proteinase 3) ANCA

pANCA = perinuclear staining of ANCA, most commonly associated with anti-MPO (or anti-myeloperoxidase) ANCA

ANCA-associated vasculitis (AAV)

cANCA-associated

• Granulomatosis with polyangiitis (GPA, formerly Wegener’s Granulomatosis)
  • ENT: Hearing loss, nasal inflammation/ulceration/discharge, sinusitis ₍₁₎
  • Lungs: Cough +/- hemoptysis, shortness of breath, nodules/cavities on chest x-ray ₍₂₎
  • Kidneys: Glomerulonephritis ₍₃₎
  • Diagnosis
    • p-ANCA sensitivity: ~66%, specificity: ~98% ₍₄₎
    • Clinical disease in ≥2/3 systems (upper airways, lungs, or kidneys), as well as positive biopsy results (granulomatous inflammation) in at least one of these organ systems ₍₅₎
  • Treatment ₍₆₎
    • Non-severe disease: Methotrexate + glucocorticoids
    • Severe disease
      • Induction: Glucocorticoids + either cyclophosphamide or rituximab
      • Maintenance: Azathioprine, methotrexate, or rituximab
      • Relapse: Rituximab > Cyclophosphamide (RAVE Trial) ₍₂₃₎

pANCA-associated

• Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss)
  • Generally, patients have a history of asthma or nasal polyps, as well as peripheral eosinophilia ₍₇₎
  • Skin: Purpura
  • Lungs: Cough +/- hemoptysis, shortness of breath ₍₈₎
  • Kidneys: Glomerulonephritis
  • Diagnosis
    • ANCA sensitivity: 30-60%, of which 70-75% are p-ANCA positive ₍₉₎
    • ANCA specificity not well-reported
    • American College of Rheumatology diagnostic criteria ₍₁₀₎
      • ≥4/6 of the following: asthma, eosinophilia (>10%), neuropathy, pulmonary opacities, paranasal sinus abnormality, or blood vessel biopsy showing accumulation of eosinophils in extravascular areas
      • PLUS biopsy of tissue showing, classically, eosinophilic infiltration, extensive necrosis, and granulomas
  • Treatment ₍₁₁₎
    • Mild disease: Glucocorticoids
    • Severe disease:
      • Induction: Cyclophosphamide
      • Maintenance: Azathioprine, methotrexate, or leflunomide

• Microscopic polyangiitis (MPA)
  • Upper airway not as frequently as involved as in GPA
  • Lungs: Cough +/- hemoptysis, shortness of breath
  • Kidneys: Necrotizing glomerulonephritis ₍₁₂₎
  • Diagnosis
    • pANCA sensitivity: ~58% (and ~23% of patients will have cANCA) ₍₁₃₎
    • Relies on biopsy, which will show necrotizing glomerulonephritis in the kidney (similar to GPA and EGPA) as well as non-granulomatous (different from GPA and EGPA) inflammation on lung biopsy ₍₁₄₎
  • Treatment ₍₁₅₎
    • Induction
      • Non-severe: Glucocorticoids + methotrexate, or monotherapy with rituximab
      • Severe: Glucocorticoids + cyclophosphamide or rituximab
    • Maintenance: Azathioprine, methotrexate, or rituximab

non-ANCA-associated vasculitis

• IgA Vasculitis (formerly Henöch-Schonlein Purpura)
  • Most common in children ages 4-7, classically following a URI ₍₁₆₎
  • Skin: Palpable purpura
  • GI: Abdominal pain +/- GI bleed
  • MSK: Arthritis
  • Kidneys: Glomerulonephritis (This is different from IgA nephritis, however, the histopathologic findings are similar)
  • Diagnosis
    • Biopsy of skin or kidneys showing IgA deposition ₍₁₇₎
  • Treatment
    • Generally a self-resolving illness, so supportive treatment is the mainstay. However, moderate-severe abdominal pain can be managed with corticosteroids ₍₁₈₎
    • ACE Inhibitors or ARBs x 3–6 month course if proteinuria >0.5 g/day (including those with nephrotic syndrome). Glucocorticoids may be given if proteinuria is refractory to this treatment ₍₁₉₎

• Cryoglobulinemia: Disease that arises from antibodies that precipitate at cold temperatures (“Cryo” = cold) and has potential to cause a vasculitis
  • 3 classifications (Type I, II, and III – see below) ₍₂₀₎
  • Vasculitis manifestations include purpura (typically of lower extremities), neuropathy, and glomerulonephritis
  • Diagnosis: serum cryoglobulins and biopsy
  • Treatment: tailored toward underlying disease. Type I is associated with clonal hematologic diseases such as Multiple Myeloma. Type II and III (“mixed” cryoglobulinemias) are strongly associated with Hepatitis C and hematologic malignancies ₍₂₁₎
    • Methotrexate or glucocorticoids + cyclophosphamide depending on severity. Rituximab given in refractory cases. Plasmapheresis may be performed in life-threatening situations ₍₂₂₎

 

References:

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