Presentation• Upper Airway (95%)
• Persistent rhinorhea• Purulent/bloody nasal discharge• Oral and/or nasal ulcers• Sinus pain• Other: Hoarseness, stridor, earache,
conductive and/or sensorineural hearing loss, otorrhea
• Lower Airway (85-90%)• Cough• Dyspnea• Hemoptysis• Pleuritic pain• Pulmonary consolidation and/or Pleural
effusion• Renal (77%)
• Glomerulonephritis • Proteinuria• Hematuria, RBC casts
• Eyes (52%)• Conjunctivitis• Dacryocystitis• Episcleritis/scleritis• Granulomatous sclerouveitis• Ciliary vessel vasculitis• Retroorbital mass lesions ->
Proptosis• Skin (46%)
• Papules, vesicles, palpable purpura, ulcers, or subcutaneous nodules
• CNS (23%)• Cranial neuritis, mononeuritis
multiplex, cerebral vasculitis and/or granuloma
• Cardiac (8%)• Pericarditis, coronary vasculitis,
cardiomyopathy• Other (common)
• Malaise, weakness, arthralgias, anorexia, weight loss, fever.
Epidemiology
• 3/100,000 patients• Much more common
in Caucasians• M:F = 1:1• Mean age of onset
~40 yrs• Occurs at any age• 15% at <19 yrs, but
rare before adolescence
Diagnosis
• Clinical Criteria:• Nasal or oral inflammation• Abnormal CXR showing nodules, fixed infiltrates, or
cavities• Abnormal urinary sediment (microscopic hematuria
+/- RBC casts)• Granulomatous inflammation on biopsy of an artery
or perivascular area• 2+ yields sens. of 88%, spec. of 92%
• Laboratory Evaluation:• Leukocytosis• Thrombocytosis (>400,000/mm3)• Elevated ESR, CRP• Normochromic, normocytic anemia
Diagnosis, cont.
• Biopsy• Taken from site of active disease• Leukocytoclastic, necrotizing vasculitis with little
or no complement and IgG on immunoflorescence
• Granulomatous inflammation differentiates from MPA
• Kidney: segmental necrotizing GN, pauci-immune on immunofluorescence or EM
• ANCA• Indirect immunofluorescence assay:
• c-ANCA or p-ANCA• 90-95% sensitive
• ELISA:• PR3 or MPO
Differential Diagnosis
• Medium Vessel• Polyarteritis nodosa
• Renal infarcts, renal vasculitis, visceral microaneurysms
• ANCA -• Kawasaki’s disease
• Coronary artery involvement
• Mucocutaneous lesions, LAD
• Large Vessel• Giant cell (temporal)
arteritis• Takayasu’s arteritis
• Small Vessel• Churg-Strauss syndrome
• Asthma, eosinophilia• ANCA +
• Microscopic polyangiitis• ANCA +• Pulm-Renal syndrome• No granulomatous disease
• Henoch-Schonlein purpura• Dermal-Renal syndrome
• Cryoglobulinemic vasculitis• Cutaneous leukocytoclastic
angiitis• Behcet’s disease• Goodpasture’s syndrome
• Pulm-Renal syndrome• Anti-GBM
Pulmonary Hemorrhagic Alveolar Capillaritis Neutrophils in the alveolar septa and hemorrhage into the alveolar spaces
Jennette, et al. NEJM. November 1997.www.merck.com
Treatment Recommendations
• Induction of Remission• Daily oral cyclophosphamide + glucocorticoids (most
aggressive Rx)• Monthly cyclophosphamide + glucocorticoids• Low-dose weekly oral MTX + glucocorticoids (mild
disease)• No role for PLEX unless DAH present
• Maintenance of Remission (12-18 mos)• Weekly oral MTX• Daily oral Azathioprine• Cyclophosphamide not advised 2/2 toxicity• Glucocorticoids should be quickly tapered off
• Treatment of Relapse - Reinduction
Prognosis
• Morbidities of disease:• Renal insufficiency• Hearing loss• Tracheal stenosis• Saddle nose deformity• Chronic sinus dysfunction
• Morbidities of treatment:• Glucocorticoids – DM,
infection, cataracts, osteoporosis, cushingoid features
• Cyclophosphamide – Cystitis (30%), bladder cancer (6%), myelodysplasia (2%), permanent infertility
• Disease was universally fatal prior to established treatment regimens
• With above therapies, improvement seen in >90%, CR in 75%
• Relapse seen in 50% of CR
• Reinduction almost always successful
References
• Jennette JC, Falk RJ. Small-Vessel Vasculitis. N Engl J Med. 1997 Nov 20; 337 (21): 1512-23.
• Kasper, et al. Harrison’s Principles of Internal Medicine, 16th Ed.
• King, et al. Up To Date. Clinical manifestations and diagnosis of Wegener's granulomatosis and microscopic polyangiitis. 2009 Apr 21.
• Stone JH, et al. Initial and maintenance therapy of Wegener's granulomatosis and microscopic polyangiitis. Up To Date. 2009 Jun 19.