1. WEGENER’S GRANULOMATOSIS

2. 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).

3. 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)

4. Which one is seen in WG?

6. Which one is nasal crust?

11. SIGNS & SYMPTOMS Pulmonary infiltrates (71%) Sinusitis (67%)
Arthralgia/arthritis (44%)
Fever (34%)
Cough (34%)
Otitis (25%)
Rhinitis (22%)

12. 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%)

13. DIFFERENTIAL Infectious otitis and sinusitis (bacterial or fungal)
Midline granuloma or other upper airway malignancy
Fungal or tuberculous pulmonary infections, (Goodpasture's syndrome)

14. DIFFERENTIAL
Other vasculitic syndromes (including polyarteritis nodosa, lymphomatoid granulomatosis, Churg-Strauss vasculitis, and overlap vasculitis syndromes)
Any disease associated with necrotizing and crescentic glomerulonephritis

16. 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%

17. 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

18. 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.

19. Special Tests
Perinuclear staining (p-ANCA), is nonspecific, but frequently seen in patients with other vasculitic syndromes or isolated necrotizing glomerulonephritis.

20. TREATMENT
Prednisone - given initially in high doses ( mg/day). After initial 2-4 weeks may be tapered to alternate-day regimen. Then gradually discontinued over months in most patients, depending on clinical course.

21. 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).

22. Complications Disease related
Destructive nasal lesions with "saddle nose" deformity
Deafness from refractory otitis
Necrotic pulmonary nodules with hemoptysis
Interstitial lung disease

23. Complications Renal failure Foot drop from peripheral nerve disease
Skin ulcers, digital and limb gangrene from peripheral vascular involvement

24. 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.