Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing vasculitis of small to medium-sized vessels accompanied by asthma and eosinophilia. It was first reported by Churg and Strauss in 1951. The former name was Churg-Strauss syndrome.
EGPA, along with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), is classified as an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, it differs clinically and therapeutically from other AAVs and is classified separately in the American College of Rheumatology (ACR) guidelines.
The estimated annual incidence is 4 per million population. The prevalence is estimated at 18 per million. In patients with asthma, the annual incidence rises to approximately 67 per million. The mean age at diagnosis is 38–54 years, with no significant sex or ethnic differences. Onset in children is extremely rare, but when it occurs, the course is more severe, with a higher frequency of lung and cardiac involvement 2).
EGPA is characterized by asthma and eosinophilia, and differs from other AAV in that tissue damage by eosinophils is central to the pathogenesis. The ANCA positivity rate is also lower, at about 40%, compared to granulomatosis with polyangiitis and MPA. Treatment choices also differ; the anti-IL-5 antibody mepolizumab is used specifically for EGPA.
The clinical course of EGPA can be divided into three phases.
Adult-onset asthma is present in over 90% of patients. Neurological involvement occurs in approximately 70% of patients. Upper respiratory tract symptoms (nasal polyps, rhinitis, otitis media, facial nerve palsy, etc.) appear in up to 96% of patients.
In 1984, Lanham et al. proposed the following three phases.
Ocular findings are observed in 6–20% of patients. They are mainly classified into the following two patterns.
Orbital inflammatory type
Dacryoadenitis: Inflammatory swelling of the lacrimal gland.
Myositis: Ocular movement disorder due to inflammation of the extraocular muscles.
Episcleritis and perineuritis: Tend to follow a chronic course.
ANCA status: Tends to be negative.
Ischemic vasculitis type
Central retinal artery occlusion (CRAO): The most common ocular manifestation of EGPA.
Ischemic optic neuropathy (ION): Causes acute vision loss.
Amaurosis fugax: Presents with transient vision loss.
ANCA status: Tends to be associated with positivity.
However, the correlation between ANCA status and ocular symptoms is not always consistent, and CRAO has been reported even in ANCA-negative patients.
According to longitudinal studies, ocular findings are observed in 6–20% of patients. CRAO is the most common, followed by ischemic optic neuropathy. Since eye symptoms appear on average 6 years after the diagnosis of asthma, baseline ophthalmologic examination is recommended when suspicious symptoms arise.
The exact cause of EGPA is unknown. As with other autoimmune vasculitides, a combination of environmental factors and genetic predisposition is suggested.
A 2018 genome-wide association study (GWAS) revealed different genetic associations between MPO-ANCA-positive and MPO-ANCA-negative EGPA. This finding partly explains why clinical features differ depending on ANCA status.
The use of leukotriene receptor antagonists has been reported to be associated with the onset of EGPA, but it is thought that the drug itself is not the cause; rather, steroid reduction may have unmasked latent EGPA. Additionally, onset or exacerbation of EGPA has been reported after dupilumab use, but a causal relationship has not been established1).
According to the 2022 ACR/EULAR guidelines, EGPA is classified when a score of 6 or more is obtained based on the following scoring system.
The classification criteria score for EGPA is shown below.
| Criterion | Score |
|---|---|
| Obstructive airway disease | +3 |
| Nasal polyps | +3 |
| Mononeuritis multiplex | +1 |
| Blood eosinophil count ≥ 1×10⁹/L | +5 |
| Extravascular eosinophil-predominant inflammation | +2 |
| cANCA or anti-PR3 antibody positive | -3 |
| Hematuria | -1 |
In the validation dataset, sensitivity was 85% (95% CI: 77-91%) and specificity was 99% (95% CI: 98-100%).
The main finding on biopsy is eosinophilic infiltration. The following findings are characteristic:
Histological findings vary by organ; peripheral nerve and renal lesions often lack eosinophil infiltration.
The following diseases must be excluded.
The basic algorithm for EGPA treatment is induction therapy followed by maintenance therapy.
Severity is assessed using the Five Factor Score (FFS) developed by the French Vasculitis Study Group. Age, creatinine level, and organ involvement are considered to classify as severe or non-severe.
As a treatment principle for ANCA-associated vasculitis, treatment is initiated with a combination of corticosteroids and immunosuppressive agents.
Mepolizumab, an anti-IL-5 antibody, suppresses eosinophil proliferation, activation, and survival. In the MIRRA trial (2017), mepolizumab plus tapering steroids significantly prolonged the cumulative remission period compared to placebo. This made mepolizumab the first FDA-approved drug for EGPA. It is recommended as an excellent treatment for ANCA-negative EGPA.
For severe cardiac lesions presenting with complete atrioventricular block, temporary pacing and high-dose methylprednisolone pulse therapy are initiated simultaneously. Subsequent transition to mepolizumab has been reported 4).
Mepolizumab targets eosinophils and is highly effective for ANCA-negative EGPA. In contrast, rituximab targets B cells and shows a high remission rate (80%) in ANCA-positive EGPA. It is important to consider ANCA status and make individualized treatment choices. For details, see the “Standard Treatment” section.
The pathology of EGPA is based on the promotion of T cell differentiation into the Th2 type. Inflammatory cytokines (IL-4, IL-13, IL-5) increase, leading to eosinophil recruitment, activation, and inhibition of apoptosis.
Activated eosinophils release the following cytotoxic granules, causing tissue damage.
Production of IL-25 by eosinophils further exacerbates this process and plays a key role in tissue destruction.
ANCA-negative EGPA is predominantly a Th2-driven immune response and eosinophil-mediated inflammation, and is prone to myocardial damage and eosinophilic pneumonia 3). In contrast, ANCA-positive EGPA presents with classic AAV-type vasculitis, often manifesting as peripheral neuropathy and glomerulonephritis.
Activated eosinophils infiltrate the myocardium and conduction system, releasing cytotoxic proteins such as MBP and ECP. This leads to myocardial necrosis, edema, and arteritis, resulting in conduction disturbances and heart failure4).
The increased risk of arterial and venous thromboembolism in EGPA is thought to involve eosinophil-mediated endothelial damage, decreased fibrinolytic activity, and immunothrombosis via eosinophil extracellular traps (EETs)2).
Dupilumab (IL-4 receptor alpha chain inhibitor) is used to treat asthma and nasal polyps, but cases of EGPA onset or exacerbation after its use have been reported.
Kai et al. (2023) reported a 67-year-old woman who developed EGPA with peri-aortitis 11 months after starting dupilumab. Switching to mepolizumab plus oral prednisone achieved complete remission after 6 months. Dupilumab suppresses eosinophil migration into tissues but does not suppress eosinophil hematopoiesis, partially explaining the mechanism of eosinophil accumulation in the blood1).
Central nervous system complications due to EGPA are rare, but central diabetes insipidus secondary to hypophysitis has been reported.
Zhang et al. (2025) reported a case of a 19-year-old male with EGPA presenting with polydipsia and polyuria. Pituitary MRI showed enlargement of the pituitary stalk. After adding mepolizumab 300 mg/month to prednisone plus rituximab, the diabetes insipidus symptoms and hypophysitis improved. This is considered the first report showing that mepolizumab is effective for pituitary dysfunction in EGPA 3).
Patients with EGPA have a high risk of arterial and venous thromboembolism, and the efficacy of eosinophil-targeted therapy is being investigated.
Kucukali et al. (2025) reported a 17-year-old male who developed massive pulmonary thromboembolism during an EGPA relapse. A good outcome was achieved with combined anticoagulation and immunosuppressive therapy. Future studies are needed to determine whether anti-IL-5 therapies such as mepolizumab are also effective in preventing thromboembolism 2).
