WEGENER’S GRANULOMATOSIS

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)

Which one is seen in WG?

Which one is nasal crust?

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.