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.