Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome)

Updated: Dec 02, 2020
  • Author: Spencer T Lowe, MD; Chief Editor: Herbert S Diamond, MD  more...
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Overview

Practice Essentials

Eosinophilic granulomatosis with polyangiitis (EGPA)—or, as it was traditionally termed, Churg-Strauss syndrome—is a rare systemic necrotizing vasculitis that affects small-to-medium-sized vessels and is associated with severe asthma and blood and tissue eosinophilia. [1, 2] Like granulomatosis with polyangiitis (Wegener granulomatosis), and the microscopic form of periarteritis (ie, microscopic polyangiitis), EGPA is an antineutrophil cytoplasmic antibody (ANCA)–associated vasculitide. [3, 4, 5, 6]

In 1951, Churg and Strauss first described the syndrome in 13 patients who had asthma, eosinophilia, granulomatous inflammation, necrotizing systemic vasculitis, and necrotizing glomerulonephritis. [4] In 1990, the American College of Rheumatology (ACR) proposed the following six criteria for the diagnosis of Churg-Strauss syndrome [7] :

  • Asthma (wheezing, expiratory rhonchi)
  • Eosinophilia of more than 10% in peripheral blood
  • Paranasal sinusitis
  • Pulmonary infiltrates (may be transient)
  • Histological proof of vasculitis with extravascular eosinophils
  • Mononeuritis multiplex or polyneuropathy

The presence of four or more criteria yields a sensitivity of 85% and a specificity of 99.7%. The 1994 Chapel Hill consensus conference on the classification of vasculitides did not modify the ACR criteria. [8]

A new set of classification criteria for EGPA, based on the Diagnosis and Classification of Vasculitis Study (DCVAS) dataset of 226 EGPA patients, has been proposed and awaits final endorsement by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). The new criteria set is intended for use when a diagnosis of small-vessel or medium-vessel vasculitis has been made, and has sensitivity of 88% and specificity of 98%.  A total score of 5 or higher (positive points minus negative points) is needed for classification of EGPA. Criteria and scores are as follows [9] :

  • Obstructive airways disease: +3 points
  • Nasal polyps: +3 points
  • Mononeuritis multiplex or motor neuropathy: +1 point
  • Eosinophil count ≥1x10 9/L: +5 points
  • Extravascular eosinophilic-predominant inflammation/eosinophils in bone marrow: +2 points
  • cANCA or PR3-antibody positive: -3 points
  • Microscopic hematuria: -1 point

A 2017 study by the Groupe d'Etudes et de Recherche sur les Maladies Orphelines Pulmonaires—conducted in 157 patients with asthma, eosinophilia, and at least one systemic organ manifestation attributable to systemic disease—found that 41% of patients had definite vasculitis manifestations (37%) or strong surrogates of vasculitis (4%), of whom only 53% had ANCA. This group proposed a new entity termed hypereosinophilic asthma with systemic (non-vasculitic) manifestations. The image below depicts transient pulmonary infiltrates. [10]

Transient pulmonary infiltrates in a patient with Transient pulmonary infiltrates in a patient with Churg-Strauss syndrome (CSS).

See Vasculitis: Case Presentations, a Critical Images slideshow, for more information on clinical, histologic and radiographic imaging findings in various forms of vasculitis.

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Pathophysiology

EGPA is a granulomatous small-vessel vasculitis. The cause of this allergic angiitis and granulomatosis is unknown. [11] No data have been reported regarding the role of immune complexes or cell-mediated mechanisms in this disease, although autoimmunity is evident with the presence of hypergammaglobulinemia, increased levels of immunoglobulin E (IgE), rheumatoid factor, and ANCA. However, only a minority (30%) of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). [12]

An EGPA-like syndrome is a rare complication that develops in steroid-dependent patients with asthma who have their oral steroid dose reduced after they start treatment with a leukotriene receptor antagonist (eg, montelukast, zafirlukast). [13] It has also been reported in patients in whom withdrawal of oral steroids is facilitated by use of inhaled steroids.

This complication is probably related to steroid withdrawal, which unmasks underlying EGPA, [14, 15, 16] rather than to the drugs themselves. However, in rare cases, this syndrome has developed when a leukotriene receptor antagonist has been substituted for inhaled steroids ini patients without a history of oral steroid withdrawal. [17]

HLA-DRB4 positivity may be a genetic risk factor for the development of EGPA, and may increase the likelihood of vasculitic manifestations of the disease. [18]  

A genome-wide association study (GWAS) of 676 EGPA cases identified 11 loci associated with EGPA. When the patients were differentiated by MPO ANCA status, the researchers reported that EGPA has two genetically and clinically distinct subtypes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease with clinical features and an HLA-DQ association similar to MPO+ ANCA-associated vasculitis. In individuals with ANCA- EGPA, the association with genes affecting barrier function (including GPA33) implies a role for mucosal dysfunction. [12]

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Etiology

Causes of EGPA are unknown. [11]  EGPA is possibly an allergic or autoimmune reaction to an environmental agent or drug.

Several case reports have described drug-induced forms of EGPA. Mesalazine-induced EGPA has been reported in a patient with Crohn disease and sclerosing cholangitis. [19]  Publications have addressed the association between propylthiouracil, methimazole, and vasculitides, including EGPA. One report is available on the association of freebase cocaine and EGPA. [20]

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Epidemiology

The incidence of EGPA in the United States is 1-3 cases per 100,000 adults per year. [21] The international incidence of EGPA is approximately 2.5 cases per 100,000 adults per year.

EGPA is slightly more common in males than in females. The age at onset varies from 15-70 years, with a mean age of approximately 38 years. EGPA in pediatric patients is well described, but mostly as case reports. [22] The mean age at diagnosis is around 50 years.

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Prognosis

Overall, without treatment, the 5-year survival rate in EGPA is about 25%. With treatment, the 1-year survival rate is 90% and the 5-year survival rate is 62%. [3, 23]

The principal causes of morbidity and mortality in EGPA are myocarditis and myocardial infarction secondary to coronary arteritis. [24]   Other causes of death associated with EGPA include the following:

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