Antineutrophil cytoplasmic antibodies (ANCA)
There are two primary types of ANCA, differentiated on the basis of their pattern of immunofluorescence on ethanol-fixed neutrophils.
Antibodies directed against serine protease proteinase 3 (PR3).
These give a cytoplasmic pattern.
Antibodies directed against the enzyme myeloperoxidase (MPO).
These give a perinuclear pattern.
The ANCA typing can be combined with antigen-specific testing for PR3 and MPO to increase specificity.
Table 8.8. Distribution of ANCA among the small vessel vasculitides organ systems: the upper respiratory tract, the lungs, and the kidneys. Greater than 90% of patients seek help for symptoms related to the respiratory tract.
Patients suffer initially from severe rhinor-rhea. This is followed by nasal and sinus inflammation, which eventually leads to cartilaginous ischemia, the sequelae of which are perforation of the nasal septum and saddlenose deformity of the nasal bridge. Tracheal inflammation and sclerosis lead to stridor and potentially dangerous airway stenosis. This particular complication is more common in children who are affected. Disease activity in the lower respiratory tract leads to cough, hemoptysis, and pleuritic pain. Renal tract disease manifests as glomerulonephritis. This is present in only 20% of patients at the time of diagnosis, but appears overall in 80% eventually.
A chest radiograph may show nodular masses, which can be multiple. There may also be ground-glass infiltration and cavitation. Over time, the lesions show a migratory pattern, disappearing in one area only for new lesions to appear in others.
The typical histology of Wegener's is best seen in the kidney. A renal biopsy demonstrates necrotizing microvascular glomerulonephritis. However, diagnosis is often by nonrenal biopsy, which demonstrates the granulomatous necro-tizing inflammation with neutrophil aggregation and vasculitis. The site of biopsy is important. An upper airway biopsy, although easy to perform, demonstrates diagnostic changes in only 20% of cases. A more invasive biopsy of the lung parenchyma shows the diagnosis in 90%.
Before treatment became available, patients suffering from Wegener's granulomatosis would have a mean survival time of only 5 months before succumbing to pulmonary or renal failure. Even with treatment, relapse is seen in around 50% of cases. The presence of lung or kidney involvement at diagnosis is a poor prognostic indicator. Wegener's also has an especially mutilating form, known as midline granuloma, which carries a particularly poor outlook.
Therapy is with a combination of glucocorti-coids and other immunosuppressants. Treatment with prednisolone alone is ineffective, and the decision on which further agent to use is based on a number of factors. In active Wegener's where the disease is life threatening, treatment with prednisolone is combined with cyclophosphamide. This leads to a 90% improvement rate, achieving complete remission in around 75% and giving a survival rate of 80%. The main drawback with this regimen is the significant toxicity associated with cyclophosphamide use. To avoid it, a progressive approach may be needed, using cyclophos-phamide until the disease is in remission, then changing to another agent such as methotrexate or azathioprine, which can then be tapered out. In active disease that is not life threatening, combination treatment with prednisolone and methotrexate is equally as good at maintaining remission compared with a cyclophos-phamide, and a similar regimen may also be used in those patients who are intolerant of cyclophosphamide.
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