ANCA-associated vasculitis

Granulomatosis with polyangiitis Formerly known as Wegener granulomatosis, granulomatosis with polyangiitis (GPA) is an immune-mediated necrotizing granulomatous vasculitis affecting small vessels. The disease strikes older adults and both sexes equally, with white individuals more commonly affected. The clinical features of GPA include granulomatous inflammation of the paranasal sinuses or nasopharyngeal tissues in a majority of cases. Glomerulonephritis occurs in up to 85% of patients and can be asymptomatic until later stages. Other findings include cutaneous vasculitis and, less commonly, neurovasculitis. Limited forms of the disease may occur without significant systemic involvement, making diagnosis difficult. Ocular disease, found in up to 50% of patients, may be the presenting feature. Ocular findings include scleritis with or without peripheral keratitis, idiopathic orbital inflammatory disease, and vasculitis-mediated retinal vascular or neuro-ophthalmic lesions. Over 85% of patients with GPA are seropositive for ANCA. Histopathology remains the definitive way to confirm the diagnosis. (See also BCSC Section 7, Oculofacial Plastic and Orbital Surgery, and BCSC Section 9, Uveitis and Ocular Inflammation.)

Early and aggressive treatment of systemic GPA is critical, as the mortality rate of untreated severe disease approaches 90% within 2 years of onset. Glucocorticoids in combination with either cyclophosphamide or rituximab are highly effective in inducing and maintaining remission of disease. Trimethoprim-sulfamethoxazole prophylaxis is sometimes used to help prevent opportunistic infections during treatment. Plasma exchange may be beneficial in severe cases with rapidly deteriorating renal or pulmonary function.

Eosinophilic granulomatosis with polyangiitis Formerly known as Churg-Strauss syndrome, eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis of small- to medium-sized arteries characterized by chronic rhinosinusitis, asthma, and eosinophilia. The cause is unknown. Average age of onset is between 50 and 60 years, with no sex predominance.

Any organ can be affected, but the lungs and skin (tender subcutaneous nodules) are most commonly involved. Cardiovascular involvement is responsible for half of the deaths among affected patients. Peripheral mononeuropathy or polyneuropathy is common. Renal and gastrointestinal involvement is sometimes evident. Ophthalmic manifestations include conjunctival granulomas, retinal vasculitis and occlusion, uveitis, and cranial nerve palsies.

Diagnosis of EGPA depends on the presence of several criteria, including asthma, eosinophilia, eosinophilic vasculitis, transient pulmonary infiltrates, and neuropathy. Biopsy of tissue from the lung or a skin nodule is helpful in establishing the diagnosis; pathologic examination often shows granulomas with eosinophilic tissue infiltration of smaller vessels. ANCA titers are positive in about 50% of patients. Many patients achieve remission with glucocorticoids alone, although additional immunosuppressive therapy may be necessary in more severe cases.

Microscopic polyangiitis Microscopic polyangiitis (MPA) is a systemic necrotizing vasculitis that is similar to GPA in targeting small vessels, and it is sometimes difficult to differentiate between the 2 entities. On histologic examination, however, MPA lacks the necrotizing granulomatous formation seen in GPA. Patients with MPA are also less likely to relapse. In both conditions, the majority of patients are ANCA-positive; but patients with GPA tend to have high proteinase 3 (PR3)-ANCA levels, whereas patients with MPA tend to have higher myeloperoxidase (MPO)-ANCA levels. Treatment of MPA is similar to that of GPA.

Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.