Granulomatosis with polyangiitis

Background

• "Granulomatosis with polyangiitis"
• c-ANCA associated systemic necrotizing vasculitis
• Small- and medium-sized blood vessels
• Predilection for upper and lower respiratory tracts and kidneys

Clinical Features

• Upper respiratory, pulmonary and renal disease + constitutional symptoms
• White, older patients
• Constitutional symptoms: Fever, malaise, weight loss
• Upper airway: Serous otits media, hearing loss, sinusitis, nasal mucosal ulcerations, septal perforation, epistaxis, laryngotracheal disease
  • Subglottic stenosis MC 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, Churg-Strauss syndrome, SLE, Goodpasture syndrome
• Lymphoma, lung cancer
• Pnuemonia, infective endocarditis, HUS
• Glomerulonephritis

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, normochronic anemia, thrombocytosis
• ESR/CRP elevated
• BUN/Cr
• UA (hematuria, proteinuria)
• CXR- Pulmonary infiltrates and nodules
• CT chest
• To consider ANA, C3 or C4, cryoglobulins, hepatitis serology, HIV, LFT, blood cx to r/o 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: 357 mg/m² weekly x 4
• To consider plasma exchange: Severe/rapidly progressive renal disease, concurrent anti-GBM Ab disease, severe pulmonary hemorrhage

Sources

• Rosen's Emergency Medicine 8th edition. 2013. Chapter: Erythematosus and the Vasculitides. p1536-1537.
• Falk RJ, et al. Clinical manifestations and diagnosis of granulomatosis with polyangiitis (Wegener's) and microscopic polyangiitis. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed December 22, 2014.
• Kaplan AA, et al. initial immunosuppressive therapy in granulomatosis with polyangiitis and microscopic polyangiitis. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed December 22, 2014.
• Tracy CL, et al. (2014, Sep 25). Granulomatosis with polyangiitis. eMedicine. Retrieved 12/22/2014 from http://emedicine.medscape.com/article/332622-overview