Eosinophilic Granulomatosis with Polyangiitis

Eosinophilic granulomatosis with polyangiitis (formerly known as the Churg–Strauss syndrome) is a vasculitis of small and medium-sized arteries. This condition typically occurs in men older than 40 years of age who have adult-onset asthma, allergic symptoms (e.g., rhinitis, chronic sinusitis, or nasal polyps), neuropathy, and pulmonary symptoms. Some patients have kidney or skin involvement, which can make this diagnosis challenging to distinguish from granulomatosis with polyangiitis or microscopic polyangiitis.

Eosinophilic granulomatosis with polyangiitis has three characteristic stages: the allergic phase, eosinophilic stage, and vasculitic stage. The allergic stage includes symptoms resembling those of asthma, allergic rhinitis, and atopic disease. It is later followed by peripheral blood eosinophilia and eosinophilic infiltration of organs. The final stage is characterized by necrotizing vasculitis of small and medium-sized vessels with granuloma formation.

Eosinophils are thought to induce pathogenic effects in patients with eosinophilic granulomatosis with polyangiitis by means of tissue and vascular infiltration and inflammation through a variety of mediators. Cytokine interleukin-5 regulates eosinophil proliferation, maturation, and differentiation and is present at increased levels in patients with eosinophilic granulomatosis with polyangiitis.

The American College of Rheumatology (ACR) has defined six classification criteria for eosinophilic granulomatosis with polyangiitis; asthma, peripheral eosinophilia greater than 10% on the differential white cell count, mononeuropathy or polyneuropathy, migratory or transient radiographic pulmonary opacities, paranasal sinus abnormality, and extravascular eosinophil infiltration on biopsy. When four or more ACR criteria are present, a diagnosis of eosinophilic granulomatosis with polyangiitis has 85% sensitivity and 99.7% specificity

Approximately 40% of patients with eosinophilic granulomatosis with polyangiitis have a positive test for anti-neutrophil cytoplasmic antibody (ANCA), typically myeloperoxidase (MPO) antibody. The presence of ANCA is not included in the ACR diagnostic criteria for eosinophilic granulomatosis with polyangiitis because more than half of patients do not have detectable antibody. However, ANCA positivity does appear to correlate with disease manifestations and prognosis. Patients with ANCA are more likely to have manifestations related to the ear, nose, and throat, peripheral neuropathy, and renal involvement but less likely to have cardiac disease than patients with negative results for ANCA. A negative test result for antineutrophil cytoplasmic antibodies (ANCAs) does not rule out eosinophilic granulomatosis with polyangiitis.

Glucocorticoids are considered to be the first-line therapy for eosinophilic granulomatosis with polyangiitis. Cyclophosphamide can be added to the treatment regimen when patients have a relapse or as an adjuvant therapy when there is substantial vasculitic end-organ involvement. Azathioprine is typically used after the induction of remission with cyclophosphamide or as a glucocorticoid-sparing agent in patients requiring long-term treatment with prednisone at a dose of 15 mg per day or more. 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 is an anti–interleukin 5 monoclonal antibody that binds to interleukin-5 and prevents its interaction with its receptor on the eosinophil surface. Mepolizumab therapy is 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.

References

Divakaran S. etal. All that Wheezes....N Engl J Med 2017;377:477-484.

Agarwal R, Chakrabarti A, Shah A, et al. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy 2013;43:850-873.

Masi AT, Hunder GG, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 1990;33:1094-1100.

Sinico RA, Di Toma L, Maggiore U, et al. Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg-Strauss syndrome. Arthritis Rheum 2005;52:2926-2935.

Agarwal R, Chakrabarti A, Shah A, et al. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy 2013;43:850-873.

Masi AT, Hunder GG, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 1990;33:1094-1100.

Sinico RA, Di Toma L, Maggiore U, et al. Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg-Strauss syndrome. Arthritis Rheum 2005;52:2926-2935.

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