Version July 2025
INTRODUCTION —
Eosinophilic granulomatosis with polyangiitis (EGPA), which was previously called the Churg-Strauss syndrome (CSS) or allergic granulomatosis and angiitis, is a multisystem disorder characterized most commonly by asthma, rhinitis, nasal polyps, and prominent peripheral blood and tissue eosinophilia [1-9]. EGPA is classified as a vasculitis of the small and medium sized arteries, although the vasculitis is often not apparent in the initial phases of the disease.
Other than the allergic manifestations, the most commonly involved organs are the lungs, the skin, and the nervous system. However, EGPA can affect almost any organ system, including the upper respiratory, cardiovascular, gastrointestinal, kidney, and central nervous systems. Vasculitis of extrapulmonary organs can result in significant morbidity and mortality.
The epidemiology, pathogenesis, and pathology of EGPA will be reviewed here. The clinical features, diagnosis, treatment and prognosis of this disorder, as well as the approach to patients with vasculitis and/or eosinophilia are discussed separately.
●(See "Overview of and approach to the vasculitides in adults".)
●(See "Clinical features and diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA)".)
●(See "Eosinophilic granulomatosis with polyangiitis: Treatment and prognosis".)
●(See "Overview of pulmonary eosinophilia".)
●(See "Approach to the patient with unexplained eosinophilia".)
EPIDEMIOLOGY —
The epidemiology of EGPA remains unclear because of the uncertainties related to diagnosis [10], however estimates suggest incident cases of 1.1 to 1.2 cases per million-years depending on geography, and estimated prevalence of 12 to 15 cases per million individuals [11]. Though estimating the epidemiology of rare conditions remains difficult, in general, the incidence and prevalence of all vasculitides have been increasing worldwide. Among the antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV), EGPA is one of the more rare subtypes, comprising approximately 10 percent of AAVs [5]. (See "Overview of and approach to the vasculitides in adults".)
The mean age at diagnosis of EGPA is 40 to 50 years [12,13]. An initial diagnosis of EGPA is more rare in individuals >65 years [14,15]. EGPA is also rare in children and adolescents; when it does occur in this age group, it appears to follow a more aggressive course with prominent pulmonary and cardiovascular manifestations [16-18].
EGPA does not exhibit sex predominance [11,12,19].
PATHOGENESIS
Abnormal immune function — The exact pathogenesis of EGPA is unknown. Antineutrophil cytoplasmic antibodies (ANCA) are detected in about 30 to 40 percent of patients, and EGPA is classified among the ANCA-positive vasculitides [12,20-23]. ANCAs likely have a pathogenic role for some of the manifestations of vasculitis in EGPA, as has been shown in animal models and human models of other vasculitides. For patients without neutrophil autoantibodies (ANCA), whether other as yet undetected autoantibodies or eosinophils themselves play a predominant role in pathogenesis is not known. (See "Clinical features and diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA)", section on 'Antineutrophil cytoplasmic antibodies' and "Pathogenesis of antineutrophil cytoplasmic autoantibody-associated vasculitis".)
In addition, EGPA is characterized by several other abnormalities in immune function [24-27]:
●The prominence of allergic features (allergic rhinitis, eosinophilic pulmonary inflammation, asthma, and positive skin tests) suggests heightened Type 2 (T2) immunity [26].
●Th1 cells have been implicated in granuloma formation [27].
●Th17 cells have been associated with development of active EGPA and evidence of submucosal eosinophilia as well as crypt change in eosinophilic colitis [28].
●Reduction of IL-10 producing peripheral blood CD4+CD25+ T cells (Tregs) in patients with EGPA compared with asthma or chronic eosinophilic pneumonia. Tregs were increased in patients with EGPA in remission [29].
●Abnormal eosinophil function is likely due to a combination of increased eosinophil recruitment by Th2 cytokines and decreased eosinophil apoptosis [24].
●Altered humoral immunity is suggested by hypergammaglobulinemia, especially IgE, and rheumatoid factor positivity in some patients.
Genetic factors — Genetic factors may also play a role. In a study of 48 patients and 350 healthy controls, both HLA-DRB1*07 and HLA-DRB4 were more prevalent among patients with EGPA and HLA-DRB4 correlated with the number of vasculitic manifestations [30].
A genome wide association study (GWAS) that included 676 patients with EGPA and 6809 healthy controls identified genetic distinctions between ANCA-myeloperoxidase positive (MPO+) and ANCA-negative disease, correlating with different clinical features [22]. Variants in the regions of BCL2L11, LPP, C5orf56-IRF1-IL5, and 10p14 were associated with EGPA, consistent with a polygenic disease and suggesting a role for susceptibility to eosinophilia in EGPA pathogenesis. When comparing MPO+ patients with MPO- patients, the study noted an association with HLA-DQ in MPO+ EGPA that was not present in MPO- EGPA, suggesting two potential subtypes of EGPA: an eosinophilic autoimmune (MPO+) disease and a mucosal barrier dysfunction (MPO-) subtype.
Polymorphisms in the interleukin (IL)-10 gene have been associated with EGPA. In a study of 103 patients with EGPA, genotyping identified three single nucleotide polymorphisms (SNPs) relating to the interleukin (IL)-10 gene [31]. The IL-10 -3575/-1082/-592 TAC haplotype (part of IL 10.2) was strongly associated with EGPA (OR=2.16) and negatively associated with granulomatosis with polyangiitis (GPA). Three-fourths of the patients were ANCA negative. (See "Genetics of asthma".)
ASSOCIATION WITH MEDICATIONS AND TOXINS —
Several medications have been associated with the appearance of EGPA. In the case of asthma therapies such as leukotriene receptor antagonists, inhaled glucocorticoids, and omalizumab, this is believed to be due to unmasking of underlying EGPA due to asthma controller medications allowing glucocorticoid tapering, rather than a direct causal relationship as evidenced by this phenomenon occurring with addition of multiple medication classes [32-52].
An unusual EGPA-like vasculitis has been associated with the use of free base cocaine-levamisole [53]. The diagnosis of EGPA in patients who use cocaine adulterated with levamisole is a complicated issue because both acute and chronic eosinophilic pneumonia are manifestations of cocaine toxicity, and antineutrophil cytoplasmic antibodies are detected in the majority of patients with cocaine-induced midline destructive lesions of the nose [54]. Positive antinuclear antibodies, low complement level, and positive testing for antiphospholipid antibodies are also common [55]. (See "Pulmonary complications of cocaine use", section on 'Acute pulmonary toxicity and crack lung' and "Pulmonary complications of cocaine use", section on 'Chronic toxicity'.)
PATHOLOGY
The major histopathologic findings of EGPA from any affected organ include the following, although they may not all be present (especially in patients who have been partially treated) [56-58]:
●Eosinophilic infiltration
●Prominent and sometimes quite extensive areas of necrosis
●An eosinophilic, giant cell vasculitis, especially of the small arteries and veins
●Interstitial and perivascular necrotizing granulomas (picture 1)
Pathologic findings in different organs include:
●In the lung, asthmatic bronchitis, eosinophilic pneumonia, extravascular granulomas, or vasculitis (affecting arteries, veins, or capillaries) may be seen. In some cases, the inflammatory lesions extend along the pleura and interlobular septa. The granulomas in EGPA typically have a border of palisading histiocytes and multinucleated giant cells surrounding a central necrotic zone consisting of eosinophils. The vascular infiltrates often contain chronic inflammatory cells, eosinophilic infiltrates, epithelioid histiocytes, multinucleated giant cells and/or neutrophils. Diffuse pulmonary hemorrhage and capillaritis may be seen.
●In the kidney, necrotizing crescentic glomerulonephritis is the most common finding, but eosinophilic interstitial nephritis, mesangial glomerulonephritis, and focal segmental glomerulosclerosis are also seen [59,60].
●Endomyocardial biopsies typically reveal eosinophilic infiltration and endomyocarditis, but not vasculitis [61].
●Skin biopsy typically reveals a leukocytoclastic vasculitis with eosinophil infiltration [62]. Palisading granulomas and/or eosinophilic infiltration of dermal nerve fibers may also be noted.
●Nerve biopsies typically show evidence of vasculitis in and around the epineural vessels. Eosinophils may also infiltrate the endoneurium [63].
The histopathologic findings may vary with the phase of disease [64,65]. (See "Clinical features and diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA)", section on 'Natural history'.)
●During the prodromal or eosinophilic phases, tissue infiltration by eosinophils may be present without overt vasculitis.
●During the vasculitic phase, a nondestructive infiltration of vessel walls is noted and may be more common than necrotizing vasculitis.
Some conditions may be confused with EGPA on biopsies due to overlapping features on histopathology. Clinical judgement and presentations should guide diagnosis when biopsies are inconclusive. Examples of some conditions with similar biopsy features include:
●IgG4-related disease (IgG4-RD) – Both IgG4-RD and EGPA can have heightened IgG4 staining; however, characteristic fibrosis features are lacking on EGPA biopsies [66].
●Granulomatosis with polyangiitis (GPA) may have eosinophils present in tissues in addition to vasculitis.
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Vasculitis" and "Society guideline links: Pulmonary eosinophilia".)
SUMMARY AND RECOMMENDATIONS
●Nomenclature and definition – Eosinophilic granulomatosis with polyangiitis (EGPA), which was previously called the Churg-Strauss syndrome (CSS) or allergic granulomatosis and angiitis, is a multisystem disorder characterized by allergic rhinitis, asthma, and prominent peripheral blood eosinophilia. (See 'Introduction' above.)
●Pathogenesis and potential etiologies – The exact etiology of EGPA is unknown.
•Immune system abnormalities – Antineutrophil cytoplasmic antibodies (ANCA) are detected in about 30 to 40 percent of patients and EGPA is classified among the ANCA-positive vasculitides. Several other abnormalities in immunologic function occur in EGPA, including heightened Th1 and Th2 lymphocyte function, increased eosinophil recruitment and decreased eosinophil apoptosis. (See 'Pathogenesis' above.)
•Genetic factors – Genetic factors such as human leukocyte antigen (HLA) class and certain interleukin-10 polymorphisms may play a role in EGPA pathogenesis. (See 'Genetic factors' above.)
•Medications – Several asthma medications, such as the leukotriene modifying agents, inhaled glucocorticoids, and omalizumab, have been associated with the appearance of EGPA. The association is due to unmasking of underlying EGPA or initiation of additional controller therapies for a patient who has progressive disease rather than a causal relationship secondary to drugs. (See 'Association with medications and toxins' above.)
•Toxins – An EGPA-like illness can rarely occur after the use of freebase cocaine-levamisole. However, the autoimmune features often differ considerably. (See 'Association with medications and toxins' above.)
●Pathology – The major histopathologic findings of EGPA from any affected organ include the following, although they may not all be present: eosinophilic infiltration; prominent and sometimes extensive areas of fibrinoid necrosis; an eosinophilic, giant cell vasculitis, especially of the small arteries and veins; and also interstitial and perivascular necrotizing granulomas (picture 1). (See 'Pathology' above.)
ACKNOWLEDGMENT —
The UpToDate editorial staff acknowledges Talmadge E King, Jr, MD, who contributed to earlier versions of this topic review.
