Wegener’s Granulomatosis

Kristine ScruggsAM Report

14 September 2009

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

Jennette, et al. NEJM. November 1997.

Jennette, et al. NEJM. November 1997.

+

+ +

Jennette, et al. NEJM. November 1997.

809090

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.