Practice Essentials
Eosinophilic granulomatosis with polyangiitis (EGPA) (alternatively termed Churg-Strauss syndrome or allergic granulomatosis and angiitis) is a rare disorder characterized by a small- and medium-sized vessel vasculitis with severe asthma and tissue eosinophilia. [1] The combination of allergic granulomatosis and angiitis associated with asthma, typically of adult onset, and allergic rhinitis [2] was first described by Churg and Strauss in 1951, when they reviewed 13 autopsy cases that were previously classified as polyarteritis nodosa. [3] These cases were atypical in that asthma and eosinophilia preceded the systemic vasculitis. They named the syndrome "allergic angiitis and allergic granulomatosis," which came to be known as Churg-Strauss syndrome (CSS) and is now EGPA. [3] Since the identification of antineutrophil cytoplasmic antibodies (ANCA) in the early nineties, EGPA is part of a group of diseases known as the ANCA-associated vasculitides (AAV) that includes granulomatosis with polyangiitis (previously known as Wegener granulomatosis) and microscopic polyangiitis. [4]
Also see Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome) and Churg-Strauss Disease.
Signs and symptoms
Also see Physical Examination.
The 3 phases—allergic, eosinophilic, and vasculitic—of EGPA do not necessarily follow one another in any particular order and frequently overlap. Symptoms depend on the phase and organ systems involved. A careful history should include medication usage, infectious symptoms, and/or preexisting disease. [5, 6]
The allergic phase (also called prodromal) may last months to years and is characterized by the following:
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Rhinitis, sinus pain, headache
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Cough
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Wheezing or asthma is one of the main manifestations, with an estimated 96-100% of patients affected
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Arthralgias, myalgias
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Malaise
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Fever
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Weight loss
The eosinophilic phase (or second phase) is characterized by the following:
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Peripheral eosinophilia (usually greater than 1,500/µL) and possible organ involvement
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Gastrointestinal - Abdominal pain, diarrhea, bleeding, nausea, vomiting, bleeding
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Pulmonary - Cough
The vasculitic phase (or third phase) is characterized by the following:
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General - Malaise, fever
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Cardiac - Chest pain, dyspnea
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Cutaneous - Purpura, papules
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Pulmonary - Cough, hemoptysis
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Rheumatologic - Arthralgia, arthritis, myalgia
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Neurologic - Weakness, numbness
Complications
Although many organ systems can be affected by EGPA, patients are most likely to have pulmonary or cardiac disease. In rare cases, cardiac complications can include eosinophilic myocarditis. [7]
Diagnostics
See Workup.
Management
For a full discussion, see Medical Care.
Corticosteroids are the mainstay of treatment in EGPA. The addition of other medications may be necessary in cases of life- or organ-threatening vasculitis. [8]
Because EGPA is a systemic disorder, consultation with an internist, rheumatologist, cardiologist, pulmonologist, neurologist, or other medical subspecialist should be obtained as warranted.
The major long-term complications of the vasculitic phase of EGPA are hypertension and permanent peripheral nerve damage.
Myocardial involvement may be so severe as to require valve replacement.
Watch for CNS involvement.
Atrophic scars are the main complication of skin lesions.
Long-term asthma management is required.
Pathophysiology
The diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) is challenging because of the highly variable presentation and course of the disease. Some patients have only mild manifestations, while others are affected by life-threatening conditions. Some investigators have divided EGPA into 3 phases, as follows [9] :
- A prodromal phase characterized by allergic manifestations followed by asthma
- A second phase of marked peripheral blood eosinophilia and eosinophilic tissue infiltration that produces a picture similar to that of Loeffler syndrome, chronic eosinophilic pneumonia, or eosinophilic gastroenteritis
- A third phase with systemic vasculitis
Pulmonary involvement, neuropathy, and skin lesions are common with each occurring in at least two thirds or more of affected patients. Other systemic features include polyneuropathy (symmetric or mononeuritis multiplex), ischemic bowel disease, nasal perforation, glomerulonephritis, ocular inflammation, coronary arteritis, and cardiomyopathy. [10] Myocardial involvement or congestive heart failure is the most common cause of death. A high eosinophilia count is present in all patients, averaging 1 X 109/L, and approximately two thirds have a positive perinuclear ANCA titer, which targets primarily myeloperoxidase. [11]
More than one classification scheme exists for EGPA, including Lanham’s criteria, which emphasize clinical features, and the Chapel Hill Consensus Conference criteria, which emphasize pathology. A third option is the American College of Rheumatology (ACR) criteria, originally created for epidemiologic and therapeutic studies.
Etiology
The etiology of eosinophilic granulomatosis with polyangiitis (EGPA) remains unclear. Several triggers are suspected, including environmental factors such as inhaled allergens, infections (bacterial or parasitic), vaccinations, and medications (eg, carbamazepine, quinine, macrolides, corticosteroid-sparing drugs used to treat asthma) all have been implicated. A class of medications that has received particular attention is leukotriene receptor antagonists, which are typically used to treat asthma. It is postulated that the use of these medications may lead to a reduction in patients’ corticosteroid exposure, unmasking EGPA features such as vasculitis. It remains unclear if they are a direct cause or simply associated with the disease. [12] Another possible drug association with EGPA is omalizumab, an anti-immunoglobulin E (IgE) antibody used to treat asthma. Once again, whether omalizumab use is truly responsible for EGPA or simply unmasks it after corticosteroid tapering remains unclear. [13, 14]
A foreign or infectious agent has been suggested to initiate an inflammatory cascade in an individual with a susceptible genetic background. Small sample sizes complicate EGPA genetic association studies. Two studies from Italy and Germany found HLA-DRB1 alleles and HLA-DRB3 and HLA-DR4 associated with EGPA. HLA-DR4 was found to correlate with vasculitic symptoms of the antineutrophil cytoplasmic antibodies (ANCA)‒positive subset. [6]
Epidemiology
Frequency
United States
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare and likely underreported disease.
International
EGPA is a rare disease. The annual incidence of the disorder is estimated at 2.4-4 cases per million general population, while among asthma patients, an average of 34.6 cases per million asthma population as been reported. [15]
Race-, sex-, and age-related information
No racial predilection is currently recognized for EGPA.
Sexual predilection for EGPA varies according to the source, with most sources citing a male predominance. The male-to-female ratio is 1.3:1.
EGPA may affect both children and elderly persons. The age of onset is wide (4-75 y), with a mean age of 38 years. [16]
Prognosis
Since the introduction of immunosuppressive therapy, considerable improvement has been gained in patient survival. Five-year survival rates for eosinophilic granulomatosis with polyangiitis (EGPA) range from 68-100% depending on the study. Deaths occurring early in the course of disease are usually attributable to active systemic vasculitis resulting multiorgan failure and/or infection. Long-term adverse effects of therapy and the development of comorbidities account for deaths later in the course of disease. [17]
Treatment with corticosteroids improves patient survival, with long-term overall remission rates nearly 82%. However, 26-28% of patients in remission have relapses. The overall mortality rate in treated patients who relapse is only 3.1%.
A short interval from the onset of asthma to the development of the systemic vasculitis indicates an unfavorable prognosis.
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Granuloma with a central core of eosinophilic debris surrounded by a peripheral palisade of epithelioid histiocytes and eosinophils.
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Bilateral papules and nodules with central necrosis.
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Magnified view of papules and nodules with central necrosis.
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Distal digital purpuric papule.
