Dermatologic Manifestations of Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss Syndrome)

Updated: Dec 15, 2017
  • Author: Claudia Hernandez, MD, FAAD; Chief Editor: William D James, MD  more...
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Overview

Background

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.

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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 [5] :

  1. A prodromal phase characterized by allergic manifestations followed by asthma
  2. 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
  3. 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. [6] 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. [7]

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.

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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. [8] 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. [9, 10]

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. [11]

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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. [12]

Race

No racial predilection is currently recognized for EGPA.

Sex

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.

Age

EGPA may affect both children and elderly persons. The age of onset is wide (4-75 y), with a mean age of 38 years. [13]

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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. [14]

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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