Eosinophilic Granulomatosis with Polyangiitis (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, allergic rhinitis, nasal polyposis, or a combination. Antineutrophil cytoplasmic autoantibodies (ANCA) are present in 30% to 40% of cases.

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) 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.

Cutaneous Vasculitis (Lower Extremity)

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Renal, cardiac, or neurologic involvement indicates a worse prognosis.

• Clinical criteria

• Routine laboratory tests

• Echocardiography

• Biopsy

The 2012 Chapel Hill Consensus Conference (1) 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:

• Asthma

• Eosinophilia of > 10% in peripheral blood

• Paranasal sinusitis

• 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, drug reactions, acute eosinophilic pneumonia and chronic eosinophilic pneumonia, allergic bronchopulmonary aspergillosis, hypereosinophilic syndrome). 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.

• Corticosteroids

granulomatosis with polyangiitis or microscopic polyangiitis1

Cardiac involvement as manifested by myocarditis with heart failure is the main cause of death in EGPA.

The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

1. 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.