Clinical Pearls & Morning Reports
Published August 2, 2017
Eosinophilic granulomatosis with polyangiitis is a vasculitis of small and medium-sized arteries that is characterized by chronic rhinosinusitis, peripheral and tissue eosinophilia, and asthma. A negative test result for antineutrophil cytoplasmic antibodies (ANCAs) does not rule out eosinophilic granulomatosis with polyangiitis, since this test is negative in approximately 60% of patients with this condition. Glucocorticoids are considered to be the first-line therapy. Read the Clinical Problem-Solving article on the subject.
Q. What are the major clinical manifestations of eosinophilic granulomatosis with polyangiitis?
A. In addition to pulmonary disease, the major manifestations of eosinophilic granulomatosis with polyangiitis include peripheral neuropathy, skin lesions, cardiomyopathy, and involvement of the ear, nose, and throat. Other manifestations can include eosinophilic gastroenteritis, peritonitis, or colitis, necrotizing glomerulonephritis, hypertension, and venous thromboembolic disease.
Q. Is there a correlation between ANCA status and clinical disease manifestations in patients with eosinophilic granulomatosis with polyangiitis?
A. ANCA positivity, present in approximately 40% of patients with eosinophilic granulomatosis with polyangiitis, may correlate with disease manifestations and prognosis. In one study, patients with positive test results for ANCAs were more likely to have manifestations related to the ear, nose, and throat, peripheral neuropathy, and renal involvement but less likely to have cardiac manifestations than patients with negative results for ANCAs. In that study, patients with ANCA positivity were also more likely to have a relapse of vasculitis. In another study, ANCA positivity was not related to a higher rate of relapse but was associated with more severe disease, including the presence of mononeuritis and renal involvement.
A: The American College of Rheumatology has established that eosinophilic granulomatosis with polyangiitis is probable when four of the following six criteria are present: asthma, peripheral eosinophilia greater than 10% on the differential white-cell count, mononeuropathy (including mononeuropathy multiplex) or polyneuropathy, migratory or transient radiographic pulmonary opacities, paranasal sinus abnormality, and extravascular eosinophil infiltration on biopsy. In a study involving 20 patients with eosinophilic granulomatosis with polyangiitis and 787 control patients with other forms of vasculitis, the presence of four or more of the six criteria yielded a sensitivity of 85% and a specificity of 99.7% for the diagnosis of this condition.
A: The use of omalizumab, a monoclonal antibody that inhibits IgE binding to the IgE receptor on mast cells and basophils, has been associated with the abatement of symptoms of asthma, a decrease in eosinophilia, and reduction in requirements for glucocorticoids in patients with eosinophilic granulomatosis with polyangiitis and moderate-to-severe asthma. Mepolizumab, an inhibitor of interleukin 5 (a driver of eosinophilic inflammation), was associated with a significantly lower frequency of asthma exacerbations than placebo in a randomized trial of patients with severe eosinophilic asthma. Recently, in a multicenter phase 3 trial involving mepolizumab in patients with eosinophilic granulomatosis with polyangiitis, mepolizumab was associated with a remission of longer duration than placebo, and a higher proportion of patients receiving mepolizumab had remission.