Definition
A multisystem disease characterized by granulomatous vasculitis involving multiple organs. • upper airway (otitis, sinusitis, nasal mucosa)
• lung
• kidney
Other organ systems involved include skin, joints, nervous system (peripheral or central).
EPIDEMIOLOGY
Incidence/Prevalence in USA: Incidence estimated at approximately 0.4/100,000; prevalence 3/100,000
Predominant age: Mean age of onset in mid-40's, but has been described in all age groups
Predominant sex: Male > Female (3:2)
SIGNS & SYMPTOMS
• Pulmonary infiltrates (71%) • Sinusitis (67%) • Arthralgia/arthritis (44%) • Fever (34%) • Cough (34%) • Otitis (25%) • Rhinitis (22%)
SIGNS & SYMPTOMS
• Hemoptysis (18%) • Ocular inflammation (16%) • Weight loss (16%) • Skin rash (13%) • Epistaxis (11%) • Renal failure (11%) • Chest pain, anorexia, proptosis, dyspnea, oral
ulcers, hearing loss, headache (all < 10%)
DIFFERENTIAL
• Infectious otitis and sinusitis (bacterial or fungal)
• Midline granuloma or other upper airway malignancy
• Fungal or tuberculous pulmonary infections, (Goodpasture's syndrome)
DIFFERENTIAL
• Other vasculitic syndromes (including polyarteritis nodosa, lymphomatoid granulomatosis, Churg-Strauss vasculitis, and overlap vasculitis syndromes)
• Any disease associated with necrotizing and crescentic glomerulonephritis
LABS
• Anemia, leukocytosis, and thrombocytosis common during active phases of disease
• Erythrocyte sedimentation rate (ESR) usually markedly elevated (75%)
• Rheumatoid factor present in low to moderate titer in up to 50%
LABS
• Hematuria and/or cellular casts with moderate range proteinuria
• Renal insufficiency, mild to moderate at first, but frequently progresses to end-stage renal disease
SPECIAL TESTS
Antibodies to neutrophilic cytoplasmic antigens with a cytoplasmic pattern of staining (c-ANCA) are detected in a majority (60-90%) of patients. Such pattern of staining is highly specific (90+%) for this diagnosis.
Special Tests
Perinuclear staining (p-ANCA), is nonspecific, but frequently seen in patients with other vasculitic syndromes or isolated necrotizing glomerulonephritis.
TREATMENT
Prednisone - given initially in high doses (60-100 mg/day). After initial 2-4 weeks may be tapered to alternate-day regimen. Then gradually discontinued over 2-6 months in most patients, depending on clinical course.
TREATMENT
Cyclophosphamide - in critically ill patient, may be given initially at a dose of 4 mg/kg/day IV for 2-3 days, then continued at 2 mg/kg/day orally. In stable patient, may be started at 2 mg/kg/day orally. Dosage may need to be adjusted, based on patient response and toxicity (usually bone marrow suppression).
Complications
Disease related
• Destructive nasal lesions with "saddle nose" deformity
• Deafness from refractory otitis • Necrotic pulmonary nodules with hemoptysis • Interstitial lung disease
Complications
• Renal failure • Foot drop from peripheral nerve disease • Skin ulcers, digital and limb gangrene from
peripheral vascular involvement
Prognosis• Without treatment, almost uniformly fatal with 10%
2 year survival and mean survival of 5 months • With aggressive treatment, survival improved to 75-
90% at 5 years • Treatment-related toxicity is significant, especially
from long-term cyclophosphamide. After 1-2 years of disease-free interval, cyclophosphamide is usually tapered, although some patients demonstrate disease re-activation during this phase.