This disorder is characterized by a necrotizing granulomatous vasculitis of the upper and lower respiratory tract with variable renal involvement ranging from a focal or segmental glomerulonephritis to a fulminant necrotizing glomerulonephritis. Varying degrees of a small vessel vasculitis affecting arterioles and venules from various organ systems are present with a wide array of symptoms. The upper airways are most commonly affected followed by the lungs and renal parenchyma. Limited forms of the disease in which involvement is limited to one organ system, usually the upper airways, are not uncommon. Pulmonary involvement usually precedes renal manifestations by weeks to years. Therefore, the diagnosis should be considered in patients suffering from prolonged sinusitis or rhinitis refractory to therapy, and the differential diagnosis should include syphilis, tuberculosis, fungal infections, malignancies, Churg-Strauss syndrome, sarcoidosis, midline granuloma, and immunodeficiency states. Systemic lupus erythematosus, Goodpastures syndrome, Churg Strauss syndrome, Behcets syndrome, mitral stenosis, bronchitis, bronchiectasis, pneumonia, lung abscess, pulmonary infarction, and cystic fibrosis should also be considered when patients present with hemoptysis.
Symptoms are usually nonspecific and include fever, malaise, weight loss, arthralgias, myalgias, chronic rhinitis, sinusitis (with pain or purulent, bloody discharge), otitis media, arthritis, nasal or oral mucosal ulcerations, hearing loss, or a saddle nose deformity. Tracheal stenosis may occur. Ocular involvement may manifest as episcleritis or uveitis; however, proptosis secondary to orbital granulomas is the most common ocular manifestation. Peripheral or cranial neuropathies may also result. Cutaneous manifestations include nodules, purpura, or the above-mentioned nasal or oral mucosal ulcerations.
Pulmonary involvement usually precedes renal disease. However, renal involvement may often be overlooked because the serum BUN and creatinine levels may be normal when there is underlying renal disease. It is for this reason that a urinalysis with microscopic examination of the urine should be performed on all patients suspected of having this disorder. Common findings on urinalysis include proteinuria and hematuria. Microscopic exam often reveals dysmorphic red blood cells or red blood cell casts, indicating a glomerular source for the hematuria.
Pulmonary involvement is variable and may range from either a fulminant diffuse proliferative alveolitis, capillaritis or alveolar hemorrhage to the classic granulomatous lesions. Radiographic abnormalities include infiltrates or nodules in the mid to lower lung zones. Pleural effusion is an uncommon finding and is only present in approximately 20% of cases. Thrombotic disease is also common and patients should be screened for venous thrombosis or pulmonary emboli in appropriate cases.
Laboratory abnormalities include a normochromic, normocytic anemia (anemia of chronic disease), thrombocytosis, leukocytosis, proteinuria, and hematuria with the findings noted above on microscopic examination of the urine specimen. An elevated BUN and creatinine indicate renal impairment. The ESR and CRP are frequently elevated, and rheumatoid factor is present in the serum of 50% of afflicted patients. However, complement levels are normal, and serum studies for ANA and cryoglobulins are negative. C-ANCAs(PR3) are elevated in approximately 80% of cases and are 90% specific for this disease. A minority of cases may be C-ANCA (PR3) negative and P-ANCA (MPO) positive although this is uncommon. ANCA negative disease requires a diagnostic biopsy. ANCA titers should not be used to follow disease activity or screen for disease flares.
Diagnosis is best established by biopsy of affected tissues. Lesions of the upper airways are often nondiagnostic. Therefore, open lung biopsy is generally recommended. Since the discovery of C-ANCA , some authorities now believe that in patients with the classic clinical presentation, a positive C-ANCA (PR3) eliminates the need for biopsy. If the presentation and C-ANCA (PR3) are both consistent with Wegeners, therapy may be initiated. If a patient does not respond to induction therapy, then the diagnosis should be questioned and a biopsy performed at that time. The initial evaluation should also include chest radiography (CXR, CT or MRI), urinalysis with microscopic evaluation, and an audiogram.
Therapy entails administering glucocorticoids along with cyclophosphamide for induction therapy for three to six months. Rituximab is also an option in conjunction with glucocorticoids for induction therapy. In less severe cases, methotrexate may be used for induction therapy. Following successful induction, maintenance therapy may be initiated with either azathioprine, methotrexate or mycophenolate. Once remission occurs and patients have been tapered off treatment, they must undergo close follow-up with routine monitoring for recurrence. One-third of patients who obtain complete remission may experience recurrence of disease. Plasma exchange therapy may be used in disease with a marked elevation of the creatinine (greater than 5.7 mg/dL).