Granulomatosis with polyangiitis

Background

• Formerly known as Wegener's granulomatosis
• c-ANCA associated systemic necrotizing vasculitis
• Small- and medium-sized blood vessels
• Predilection for upper and lower respiratory tracts and kidneys

Vasculitis Syndrome Types

• Large vessel
  • Takayasu arteritis
  • Giant cell arteritis (temporal arteritis)
• Medium-vessel
  • Kawasaki disease
  • Polyarteritis nodosa
  • Thromboangiitis obliterans (Buerger's disease)
  • Primary angiitis of the central nervous system
• Small-vessel
  • Henoch-Schönlein purpura
  • ANCA-associated vasculitides
    • Granulomatosis with polyangiitis (Wegner's)
    • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
    • Microscopic polyangiitis
  • Cutaneous leukocytoclastic angiitis (“hypersensitivity vasculitis”)
  • Essential cryoglobulinemia, cryoglobulinemic vasculitis due to hepatitis C
  • Behçet's disease]
• Secondary vasculitides and other/miscellaneous
  • Drug-induced vasculitis
  • Serum sickness
  • Vasculitis associated with other rheumatic diseases (e.g. SLE)

Clinical Features

• Upper respiratory, pulmonary and renal disease + constitutional symptoms
• White, older patients
• Constitutional symptoms: Fever, malaise, weight loss
• Upper airway: Serous otitis media, hearing loss, sinusitis, nasal mucosal ulcerations, septal perforation, epistaxis, laryngotracheal disease
  • Subglottic stenosis is most common laryngotracheal lesion (16% patients)
• Lower respiratory: Cough, dyspnea, pleuritis, hemoptysis, diffuse alveolar hemorrhage
• Renal failure, glomerulonephritis
• Ophthalmologic: scleritis, episcleritis, uveitis
• Cutaneous: Palpable purpura, nodules, ulcers
• Neurologic: Mononeuropathy and polyneuropathy, cerebral vasculitis, cerebral hemorrhage or thrombosis
• Cardiac: Pericarditis, myocarditis

Differential Diagnosis

• Polyarteritis nodosa, Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), SLE, Goodpasture syndrome
• Lymphoma, lung cancer
• Pneumonia, infective endocarditis, HUS
• Glomerulonephritis

Evaluation

Classification

• American College of Rheumatology: 88% sensitivity and 92% specificity for ≥2 criteria
• Nasal or oral inflammation
• Abnormal chest radiograph showing nodules, fixed infiltrate, or cavities
• Abnormal urinary sedimentation (microscopic hematuria)
• Granulomatous inflammation on biopsy of an artery or perivascular area

Workup

• Definitive diagnosis: Biopsy
• ANCA +, RF+
• CBC: Leukocytosis, normochromic anemia, thrombocytosis
• ESR/CRP elevated
• BUN/Cr
• Urinalysis (hematuria, proteinuria)
• CXR- Pulmonary infiltrates and nodules
• CT chest
• Consider ANA, C3 or C4, cryoglobulins, hepatitis serology, HIV, LFTs, blood culture to rule out other pathology
• Other tests: Bronchoscopy, PFT, sinus CT

Management

• Priority: Manage pulmonary hemorrhage and renal insufficiency
  • Difficult airway: Diffuse alveolar hemorrhage and subglottic stenosis
    • Fiberoptic intubation through LMA advocated
• Rheumatology consult + multidisciplinary consults
• Mild disease: Corticosteroids and methotrexate
  • No active glomerulonephritis or organ-threatening disease
• Mod-Severe disease: Corticosteroids and cyclophosphamide or rituximab
• Corticosteroids:
  • Methylprednisolone (7-15mg/kg/d with max 1000mg)
  • Prednisone 1mg/kg/d (max 80mg)
• Methotrexate: 20-25mg weekly PO or SC
• Cyclophosphamide: 2mg/kg/d PO or 15mg/kg q2 weeks x3 then q3 weeks
• Rituximab: 357mg/m² weekly x 4
• To consider plasma exchange: Severe/rapidly progressive renal disease, concurrent anti-GBM Ab disease, severe pulmonary hemorrhage