- 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.
- Persistent upper respiratory tract and ear “infections” that do not respond to antibiotic therapy.
- Orbital pseudotumor, nearly always associated with chronic nasosinus conditions.
- Migratory pauciarticular or polyarticular arthritis.
- Nodular or cavitary lung lesions that are misdiagnosed initially as malignancies or infections.
- Rapidly progressive glomerulonephritis.
- Antineutrophil cytoplasmic antibody (ANCA) assays are helpful in diagnosis if positive by both immunofluorescence and enzyme immunoassay. A significant minority of patients with granulomatosis with polyangiitis are ANCA-negative, particularly those with “limited” disease.
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 ANCAs, an autoantibody generally believed to amplify rather than to initiate the inflammatory process. GPA occurs in people of all ethnic backgrounds but demonstrates a strong 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 primary care providers 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.
Therapies for GPA are associated with substantial treatment-induced morbidity in both the short- and long-term. 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 may diminish some of the long-term side effects associated with GPA treatment, particularly infertility and malignancy.
Because of the remitting and relapsing nature of many GPA cases and the disease’s tendency to recur during or after the taper of treatment, primary care providers play an important role in the early detection of disease flares.
Approximately 90% of patients with GPA have nasal involvement. This is often the first disease manifestation. The ...