Wegener granulomatosis is a multisystem autoimmune disorder characterized by the classic triad of necrotizing granulomatous vasculitis of the upper and lower respiratory tract, focal segmental glomerulonephritis, and necrotizing vasculitis of small arteries and veins. Involvement of the paranasal sinuses is the most characteristic clinical feature of this disorder, followed by pulmonary and renal disease. Renal involvement may or may not be evident at presentation, but its early detection is important, as up to 85% of patients develop glomerulonephritis during the course of the disease, which, if left untreated, carries significant mortality. A limited form of this disease has also been described, consisting of granulomatous inflammation involving the respiratory tract without overt involvement of the kidneys; however, subclinical renal disease may be present on tissue biopsy.
Patients may present with constitutional symptoms, sinusitis associated with bloody nasal discharge, pulmonary symptomatology, and arthritis. Dermatologic involvement is seen in approximately one-half of patients, with purpura involving the lower extremities occurring most frequently; less common are ulcers and subcutaneous nodules. Nervous system involvement may be seen in approximately one-third of patients with peripheral neuropathies, the most common being mononeuritis multiplex; less frequently observed are cranial neuropathies, seizures, stroke syndromes, and cerebral vasculitis.
Ocular or orbital involvement is seen in 15% of patients at presentation and in up to 50% of patients during the course of the disease. Orbital involvement, one of the most frequently reported ocular findings, is usually secondary to contiguous extension of the granulomatous inflammatory process from the paranasal sinuses into the orbit. Orbital pseudotumor, distinct from the sinus inflammation; orbital cellulitis; and dacryocystitis may arise from the involved and secondarily infected nasal mucosa. Scleritis of any type, particularly diffuse anterior or necrotizing disease, with or without peripheral ulcerative keratitis, affects up to 40% of patients. Posterior scleritis has also been reported.
Approximately 10% of patients with Wegener granulomatosis and ocular involvement have been reported to have an associated nonspecific unilateral or bilateral anterior, intermediate, or posterior uveitis, with varying degrees of vitritis. Retinal involvement is relatively uncommon, occurring in up to 10% of patients. Retinal vascular manifestations range from relatively benign cotton-wool spots, with or without associated intraretinal hemorrhages, to more severe vaso-occlusive disease, including branch or central retinal artery or vein occlusion. Retinitis has been reported in up to 20% of patients; those with accompanying retinal vasculitis may develop retinal neovascularization, vitreous hemorrhage, and neovascular glaucoma (Fig 6-22). Optic nerve involvement, especially ischemic optic neuropathy, is not uncommon. Vision loss in Wegener granulomatosis may occur in up to 40% of patients, especially among those with long-standing or inadequately treated disease.
Tissue biopsy establishes the histologic diagnosis; chest x-ray may disclose nodular, diffuse, or cavitary lesions; and laboratory evaluation may note proteinuria or hematuria, elevated ESR, and the presence of C-reactive protein and ANCAs.
ANCAs are antibodies directed against cytoplasmic azurophilic granules of neutrophils and monocytes, which are specific markers for a group of related systemic vasculitides that include Wegener granulomatosis, PAN, microscopic polyarteritis nodosa, Churg-Strauss syndrome, and pauci-immunoglomerulonephritis. Two main classes of ANCA have been described based on the immunofluorescence staining pattern on ethanol-fixed neutrophils and the main target antigen. The cytoplasmic pattern, or c-ANCA, is both sensitive and specific for Wegener granulomatosis and is present in up to 95% of patients; proteinase 3 is the most common target antigen. The perinuclear pattern, or p-ANCA, is associated with PAN, microscopic polyarteritis nodosa, relapsing polychondritis, and renal vasculitis. Myeloperoxidase is the most common antigenic target. In contrast to the results found in Wegener granulomatosis, the diagnostic sensitivities of c-ANCA and p-ANCA for PAN are only 5% and 15%, respectively; in patients with microscopic polyarteritis nodosa, p-ANCA (myeloperoxidase) positivity is more common (50%–80%), with a smaller percentage (40%) having the c-ANCA (proteinase 3) marker.
As with PAN, appropriate treatment mandates combination therapy with oral corticosteroids and IMT, specifically cyclophosphamide. Without therapy, the 1-year mortality rate is 80%. However, 93% of patients treated with cyclophosphamide and corticosteroids successfully achieve remission with resolution of ocular manifestations. As with PAN, ophthalmologists must be intimately familiar with Wegener granulomatosis, as ocular inflammatory manifestations are frequently present, and timely diagnosis and treatment are essential in reducing not only ocular morbidity but overall patient mortality.
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