What is the pathophysiology of EGPA (Churg-Strauss syndrome)?

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

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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