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ESSENTIALS OF DIAGNOSIS

  • Three pathologic hallmarks: granulomatous inflammation, vasculitis, and necrosis.

  • Classic clinical features are found in multiple organ systems:

    • Nonspecific constitutional symptoms, such as fatigue, myalgias, weight loss, and fevers.

    • Migratory pauciarticular or polyarticular arthritis.

    • Persistent upper respiratory tract and ear “infections” that do not respond to antibiotic therapy.

    • Orbital pseudotumor, nearly always associated with chronic nasosinus conditions.

    • Nodular or cavitary lung lesions that are misdiagnosed initially as malignancies or infections.

    • Rapidly progressive glomerulonephritis.

  • Antineutrophil cytoplasmic antibody (ANCA) assays are extremely helpful in diagnosis but have significant shortcomings as indicators of disease activity or guides to when to treat. A significant minority of patients with granulomatosis with polyangiitis are ANCA negative, particularly those with “limited” disease.

General Considerations

Granulomatosis with polyangiitis (GPA; formerly called Wegener granulomatosis) is one of the most common forms of systemic vasculitis, with a reported annual incidence of 10 cases per million. The disease involves small- to medium-sized blood vessels (small more often than medium). GPA affects both the arterial and venous circulations, in contrast to polyarteritis nodosa, a disorder in which only arteries and muscular arterioles are affected. The cause of GPA is not known, but the prominence of upper and lower airway involvement suggests a response to an inhaled antigen. The disease is the prototype of conditions associated with antineutrophil cytoplasmic antibodies (ANCAs), autoantibodies generally believed to amplify rather than to initiate the inflammatory process. GPA occurs in people of all ethnic backgrounds but demonstrates a predilection for whites, particularly those of northern European ancestry. The male:female ratio is approximately 1:1. The mean age at diagnosis is 50 years. The elderly are often affected. The disease is less common but known to occur in children.

GPA typically presents in a subacute fashion. Patients complain of symptoms that appear to be innocuous at first, such as nasal stuffiness, “sinusitis,” and decreases in hearing. During this “prodrome,” attentive clinicians may suspect and diagnose GPA before the onset of generalized disease. Such early recognition of GPA may prevent the disabling and disfiguring end-organ complications of this disorder such as collapse of the nasal bridge, renal failure, diffuse alveolar hemorrhage, and widespread infarctions of peripheral nerves. Because of the remitting and relapsing nature of many GPA cases and the disease’s tendency to recur during or after the stopping of treatment, remission maintenance strategies and early detection of disease flares are important.

Therapies for GPA are associated with substantial treatment-induced morbidity in both the short and long term. The long-term impact of chronic glucocorticoid therapy is frequently underappreciated. Careful follow-up and monitoring of basic laboratory tests (eg, regularly obtaining complete blood cell counts) may prevent some adverse effects of treatment or minimize their impact. More widespread use of rituximab in lieu of cyclophosphamide has also reduced some of the long-term side effects once seen commonly with cyclophosphamide, particularly infertility, malignancy, and opportunistic infection.

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