(See also Overview of Vasculitis Overview of Vasculitis Vasculitis is inflammation of blood vessels, often with ischemia, necrosis, and organ inflammation. Vasculitis can affect any blood vessel—arteries, arterioles, veins, venules, or capillaries... read more .)
Eosinophilic granulomatosis with polyangiitis (EGPA) occurs in about 3 people/million. Mean age at onset is 48.
EGPA is characterized by extravascular necrotizing granulomas (usually rich in eosinophils), eosinophilia, and tissue infiltration by eosinophils. However, these abnormalities do not always coexist. The vasculitis typically affects small- and medium-sized arteries. Any organ can be affected, but the lungs, skin, sinuses, cardiovascular system, kidneys, peripheral nervous system, central nervous system, joints, and gastrointestinal (GI) tract are most commonly affected. Rarely, pulmonary capillaritis may cause alveolar hemorrhage.
Etiology of EGPA
The cause of eosinophilic granulomatosis with polyangiitis is unknown. However, an allergic mechanism, with tissue directly injured by eosinophils and neutrophil degranulation products, may be involved. Activation of T lymphocytes seems to help maintain eosinophilic inflammation. The syndrome occurs in patients who have adult-onset asthma Asthma Asthma is a disease of diffuse airway inflammation caused by a variety of triggering stimuli resulting in partially or completely reversible bronchoconstriction. Symptoms and signs include dyspnea... read more , allergic rhinitis Allergic Rhinitis Allergic rhinitis is seasonal or perennial itching, sneezing, rhinorrhea, nasal congestion, and sometimes conjunctivitis, caused by exposure to pollens or other allergens. Diagnosis is by history... read more , nasal polyposis Nasal Polyps Nasal polyps are fleshy outgrowths of the nasal mucosa that form at the site of dependent edema in the lamina propria of the mucous membrane, usually around the ostia of the maxillary sinuses... read more , or a combination. Antineutrophil cytoplasmic autoantibodies (ANCA) are present in 30% to 40% of cases.
Symptoms and Signs of EGPA
The syndrome has 3 phases, which may overlap:
Prodromal: This phase may persist for years. Patients have allergic rhinitis, nasal polyposis, asthma, or a combination.
2nd phase: Peripheral blood and tissue eosinophilia is typical. Clinical presentation, which may resemble Löffler syndrome, includes chronic eosinophilic pneumonia and eosinophilic gastroenteritis.
3rd phase: Potentially life-threatening vasculitis develops. Organ dysfunction and systemic symptoms (eg, fever, malaise, weight loss, fatigue) are common in this phase.
However, the phases do not necessarily follow one another consecutively, and the time interval between them varies greatly.
Various organs and systems may be affected:
Respiratory: Asthma, often with onset during adulthood, occurs in most patients and tends to be severe and corticosteroid-dependent. Sinusitis is common, but not destructive, without severe necrotizing inflammation. Patients may be short of breath. Transient patchy pulmonary infiltrates are common.
Neurologic: Neurologic manifestations are very common. Multiple mononeuropathy (mononeuritis multiplex) Multiple Mononeuropathy Multiple mononeuropathies are characterized by sensory disturbances and weakness in the distribution of ≥ 2 affected peripheral nerves. (See also Overview of Peripheral Nervous System Disorders... read more occurs in up to three fourths of patients. Central nervous system involvement is rare but can include hemiparesis, confusion, seizures, and coma, with or without cranial nerve palsies or evidence of cerebral infarction.
Cutaneous: The skin is affected in about one half of patients. Nodules and papules appear on extensor surfaces of extremities. They are caused by extravascular palisading granulomatous lesions with central necrosis. Purpura or erythematous papules, due to leukocytoclastic vasculitis with or without prominent eosinophilic infiltration, may develop.
Musculoskeletal: Arthralgias, myalgias, or even arthritis can occur.
Cardiac: Cardiac involvement, a major cause of mortality, includes heart failure due to myocarditis and endomyocardial fibrosis, coronary artery vasculitis (possibly with myocardial infarction), valvular disorders, and pericarditis. The predominant histopathologic finding is eosinophilic myocarditis.
Gastrointestinal: Up to one third of patients present with gastrointestinal symptoms (eg, abdominal pain, diarrhea, bleeding, acalculous cholecystitis) due to eosinophilic gastroenteritis or mesenteric ischemia due to vasculitis.
Renal: The kidneys are affected less often than in other vasculitic disorders associated with antineutrophil cytoplasmic autoantibodies. Typically, pauci-immune (few if any immune complexes), focal segmental necrotizing glomerulonephritis with crescent formation is present; eosinophilic or granulomatous inflammation of the kidneys is rare.
Renal, cardiac, or neurologic involvement indicates a worse prognosis.
Diagnosis of EGPA
Routine laboratory tests
The 2012 Chapel Hill Consensus Conference (1 Diagnosis reference Eosinophilic granulomatosis with polyangiitis is a systemic small- and medium-vessel necrotizing vasculitis, characterized by extravascular granulomas, eosinophilia, and tissue infiltration... read more ) defined eosinophilic granulomatosis with polyangiitis (EGPA) as an eosinophil-rich and necrotizing granulomatous inflammation involving the respiratory tract with necrotizing vasculitis of small- and medium-sized vessels in association with asthma and eosinophilia. Criteria for classification from the American College of Rheumatology consist of the following:
Eosinophilia of > 10% in peripheral blood
Pulmonary infiltrates, sometimes transient
Histologic evidence of vasculitis with extravascular eosinophils
Multiple mononeuropathy or polyneuropathy
If ≥ 4 criteria are present, sensitivity is 85%, and specificity is 99.7%.
Testing aims to establish the diagnosis and the extent of organ involvement and to distinguish EGPA from other eosinophilic disorders (eg, parasitic infections Approach to Parasitic Infections Human parasites are organisms that live on or in a person and derive nutrients from that person (its host). There are 3 types of parasites: Single-cell organisms (protozoa, microsporidia) Multicellular... read more , drug reactions Adverse Drug Reactions Adverse drug reaction (ADR, or adverse drug effect) is a broad term referring to unwanted, uncomfortable, or dangerous effects that drugs (including medications ) may have. Adverse drug reactions... read more , acute eosinophilic pneumonia Acute Eosinophilic Pneumonia Acute eosinophilic pneumonia (AEP) is a disorder of unknown etiology characterized by rapid eosinophilic infiltration of the lung interstitium. (See also Overview of Eosinophilic Pulmonary Diseases... read more and chronic eosinophilic pneumonia Chronic Eosinophilic Pneumonia Chronic eosinophilic pneumonia (CEP) is a disorder of unknown etiology characterized by an abnormal, chronic accumulation of eosinophils in the lung. (See also Overview of Eosinophilic Pulmonary... read more , allergic bronchopulmonary aspergillosis Allergic Bronchopulmonary Aspergillosis (ABPA) Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus species (generally A. fumigatus) that occurs almost exclusively in patients with asthma... read more , hypereosinophilic syndrome Hypereosinophilic Syndrome Hypereosinophilic syndrome is a condition characterized by peripheral blood eosinophilia with manifestations of organ system involvement or dysfunction directly related to eosinophilia in the... read more ). Diagnosis of EGPA is suggested by clinical findings and results of routine laboratory tests but should usually be confirmed by biopsy of lung or other affected tissue.
Blood tests and chest x-rays are done, but results are not diagnostic. Complete blood count with differential is done to check for eosinophilia, which in some patients may be a marker of disease activity. IgE and C-reactive protein levels and erythrocyte sedimentation rate (ESR) are determined periodically to evaluate inflammatory activity. Urinalysis and creatinine are done to screen for renal disease and monitor its severity. Electrolyte levels are measured.
Serologic testing is done and detects antineutrophil cytoplasmic autoantibodies (ANCA) in up to 40% of patients; if ANCA is detected, enzyme-linked immunosorbent assay (ELISA) is done to check for specific antibodies. Perinuclear ANCA (p-ANCA) with antibodies against myeloperoxidase is the most common result, but ANCA is not a specific or sensitive test for EGPA.
Although used as markers of disease activity, eosinophilia, IgE, ANCA, ESR, and C-reactive protein levels accomplish this and predict flare-ups only with significant limitations.
Chest x-ray often shows transient patchy pulmonary infiltrates.
A 2D echocardiogram of the heart should be obtained in all patients at baseline and repeated over time if symptoms and/or signs of heart failure develop.
Biopsy of the most accessible affected tissue should be done if possible.
1. Jennette JC, Falk RJ, Bacon PA, et al: 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 65(1):1-11, 2013. doi: 10.1002/art.37715
Treatment of EGPA
Systemic corticosteroids plus an immunosuppressant are the mainstay of treatment of eosinophilic granulomatosis with polyangiitis (EGPA) because corticosteroids alone often do not sustain remission, even if there are no poor prognostic factors. Other immunosuppressants (eg, cyclophosphamide, rituximab, methotrexate, azathioprine) are added, the choice of which depends on the severity and the type of organ involvement, using the same general criteria for treatment of granulomatosis with polyangiitis Granulomatosis with Polyangiitis (GPA) Granulomatosis with polyangiitis is characterized by necrotizing granulomatous inflammation, small- and medium-sized vessel vasculitis, and focal necrotizing glomerulonephritis, often with crescent... read more or microscopic polyangiitis Treatment Microscopic polyangiitis is a systemic necrotizing vasculitis without immune globulin deposition (pauci-immune) that affects mainly small vessels. It may begin as a pulmonary-renal syndrome... read more . In a retrospective study of 41 patients with EGPA treated with rituximab, 49% were in remission at 12 months and rituximab decreased the need for corticosteroids. These results compare favorably to other treatments. Mepolizumab, 300 mg subcutaneously every 4 weeks, has been shown to lower the relapse rate in mild to moderate, relapsing or refractory EGPA. The benefit was predominantly in the upper and lower respiratory tract, including active asthma (1 Treatment reference Eosinophilic granulomatosis with polyangiitis is a systemic small- and medium-vessel necrotizing vasculitis, characterized by extravascular granulomas, eosinophilia, and tissue infiltration... read more ). The effect of mepolizumab is unknown in patients with severe manifestations, including cardiac disease.
Cardiac involvement as manifested by myocarditis with heart failure is the main cause of death in EGPA.
Wechsler ME, Akuthota P, Jayne D, et al: Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N Engl J Med 376(20):1921-1932, 2017. doi:10.1056/NEJMoa1702079
Eosinophilic granulomatosis with polyangiitis is a rare small- and medium-sized vessel vasculitis.
Phases include upper respiratory symptoms and wheezing, eosinophilic pneumonia and gastroenteritis, and life-threatening vasculitis.
Phases may occur in or out of order and may overlap.
Cardiac or neurologic involvement can occur and indicate a poor prognosis.
Diagnose by clinical criteria, routine laboratory testing, and sometimes biopsy.
Do a 2D echocardiogram in all patients.
Treat with corticosteroids and other immunosuppressants, based on severity of disease, and use the same criteria for treatment of granulomatosis with polyangiitis or microscopic polyangiitis.
Consider treatment with rituximab for its possible high rates of response and reduced requirement for corticosteroids.
Consider mepolizumab in relapsing or refractory disease with primarily upper and/or lower respiratory tract manifestations.
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
American College of Rheumatology (ACR): Lists a number of ACR-approved classification criteria sets and provides information about the purpose of criteria sets, their development and validation, and the role of the ACR in adopting them.
Drugs Mentioned In This Article
|Drug Name||Select Trade|
|Cyclophosphamide, Cytoxan, Neosar|
|RIABNI, Rituxan, RUXIENCE, truxima|