Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis with hypereosinophilia that is preceded by asthma and chronic rhinosinusitis with nasal polyps. Since multiple organs may be involved in this disease, early treatment is required. In this regard, glucocorticoid (GC) therapy is often initiated before a definitive diagnosis is made. A biopsy of an injured organ is useful for a diagnosis but is not performed in all cases due to its invasiveness and, at times, diagnostic accuracy. Therefore, a comprehensive diagnosis is often made based on symptoms and clinical course of disease. However, it is sometimes difficult to distinguish EGPA from other hypereosinophilic diseases or vasculitides. In recent years, in addition to GC and immunosuppressive agents, anti-interleukin (IL)-5/IL-5 receptor alpha (IL-5Rα) antibodies targeting eosinophils have become increasingly important in the treatment of EGPA. However, accumulating data suggest that such anti-IL-5/IL-5Rα antibody therapy may have effects beyond those observed in eosinophils. This paper outlines the clinical features, diagnosis, pathogenesis, and current treatment of EGPA, a hypereosinophilic disease.

Our objective was to review the available literature on cardiac magnetic resonance imaging (cMRI) findings in patients with antineutrophil cytoplasmic antibody-associated vasculitides (AAV), evaluate its diagnostic utility, and assess its potential as a screening tool.

We systematically searched PubMed, Embase, Scopus, and Web of Science from inception to March 29, 2023, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines. English-language studies involving adult patients diagnosed with AAV-eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA), or microscopic polyangiitis (MPA)-using recognized classification criteria were included. Studies had to report specific cMRI parameters in at least three patients. Three independent reviewers conducted study selection, data extraction, and quality assessment.

Of 2,251 studies, 30 met the inclusion criteria, encompassing 1,149 patients with AAV (87% with EGPA, 13% with GPA, and 0.3% with MPA). The mean patient age was 52 ± 5 years, with 50.4% being female. The mean left ventricular ejection fraction (LVEF) was 55.6% ± 11.3%, and 29% of patients had an LVEF less than 50%. Myocardial fibrosis, indicated by late gadolinium enhancement (LGE), was present in 49% of patients, with predominantly subendocardial or endocardial (23%), intramyocardial (14%), and subepicardial (10%) patterns. Patients in remission (26%), when compared to those not in remission (74%), exhibited higher proportions of LGE (55% vs 47%) and glucocorticoid use (77% vs 68%), despite similar rates of abnormal electrocardiograms (44% vs 42%).

This systematic review reveals a high prevalence of myocardial fibrosis detected by cMRI in patients with AAV, even during remission. Significant subclinical cardiac involvement may be missed by conventional diagnostic methods, underscoring the utility of cMRI during routine evaluation.

Currently, cardiac involvement is used to describe all eosinophilic granulomatosis with polyangiitis (EGPA) cardiac problems. However, heterogeneity exists among them. We aimed to depict the disease spectrum of EGPA cardiac involvement and identify the high-risk population.

We included EGPA patients hospitalized in our centre from 2012 to 2023 and in public databases. Based on the cardiac enzymes, cardiac MRI and endomyocardial biopsy results, the patients were divided into three groups: eosinophilic myocarditis (EGPA-EM), chronic inflammatory cardiomyopathy (EGPA-ICM) and EGPA-Control. Their clinical, laboratory, imaging results and prognoses were collected and compared.

A total of 193 EGPA patients were included, 118 with cardiac involvement (74 EGPA-EM, 44 EGPA-ICM) and 75 control. Among EGPA-Control, EGPA-ICM and EGPA-EM, eosinophil increased (6.12/8.71/10.42 × 109/l, P < 0.01), ANCA positivity decreased (41.33/31.82/14.86%, P < 0.01) and lung involvement was reduced (73.33/72.73/43.24%, P = 0.02). In EGPA-EM, cardiac troponin was further elevated (0.27 vs 6.00 ng/ml, P < 0.01), ejection fractions decreased (57.79 vs 33.20%, P < 0.01) while more ST-T abnormality was observed (41.89 vs 20.45%, P = 0.02). The prognosis of EGPA-EM was significantly worse, with a 14.86% death rate and 2-year event-free survival rate below 50%. Furthermore, we proposed a LATE-EAST diagnostic score (7 items, 9 points) to discriminate EGPA-EM from EGPA-ICM using 4 points as threshold [area under the receiver operating characteristic curve 0.85 (95% CI 0.78-0.92), sensitivity 0.78, specificity 0.86].

We first proposed different subtypes of cardiac involvement in EGPA. Identification and treatment of EGPA-EM needs improvement. LATE-EAST score could recognize the high-risk EGPA-EM effectively. Multi-disciplinary treatment is warranted, immunosuppressive therapy should be given in a timely manner and anti-IL-5 antibodies should be be tested in trials.

Eosinophilic myocarditis (EM) is a rare and heterogeneous form of inflammatory heart disease that can present with a wide range of severity. Current literature is limited to case reports or small case series that outline the evaluation process, disease course, and the nonstandardized treatments trialed. This review aims to concisely summarize the current literature on EM including an update on maintenance therapy for refractory or recurrent disease.

In the last several years, several observational studies have reported the clinical benefit of mepolizumab and benralizumab in refractory EM. EM is a complex and heterogenous cause of inflammatory heart disease with a wide range of etiologies and presentations. Treatment of this disease has not been standardized as there are no large scale trials quantifying benefit of any specific therapy regimen. Targeted biologics show promise in observational studies; therefore, prospective studies are needed to quantify this benefit in EM.

Eosinophilic granulomatosis with polyangiitis (EGPA), as a heterogeneous component of antineutrophil cytoplasmic antibody-associated vasculitis, may be induced by a series of environmental and genetic factors, involved with a variety of immune cells and immune components, and presented with various clinical manifestations, with multiple organs and systems (respiratory, skin, heart, kidney, nerve, etc.) involved. The choice of glucocorticoid (GC) dosage and immunosuppressant in traditional treatment strategies varies greatly from individual to individual and is not universally applicable in all the EGPA phenotype spectrum, especially in relapsing or refractory diseases. With the understanding of the heterogeneity of EGPA, a variety of therapeutic approaches are emerging and improving the traditional treatment model. In this review, we summarized the heterogeneity of EGPA etiology and pathogenesis. Clinical and pathological manifestations of the same organ involved also show significant differences and there are even gender differences. Biological treatments that mainly target type 2 inflammatory pathways are widely used in clinical practice for remission induction and maintenance of EGPA. Targeted biological therapy has shown excellent performance in reducing GC dosage and controlling symptoms and recurrence. However, a large number of high-quality randomized controlled studies are still under research for relapsing or refractory EGPA with special organ involvement. We believe that EGPA has a highly heterogeneous phenotype spectrum, and the treatment patterns targeting key molecules in the pathogenesis are of great value for individual treatment of EGPA.

We describe the case of a 45-year-old female affected by asthma and nasal polyposis who presented to the emergency department because of worsening dyspnea and paresthesia of the left lower limb. Comprehensive instrumental examinations revealed the presence of severe left ventricle dysfunction, intra-cardiac thrombus, deep vein thrombosis, pulmonary embolism, lung infiltrates, polyserositis, and neurological involvements. Finally, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg-Strauss syndrome, a rare vasculitis of small-medium blood vessels with several organ involvements. Treatment with anticoagulants, corticosteroids, and cyclophosphamide led to a significant clinical improvement. However, a subcutaneous cardiac defibrillator was implanted because of the persistence of severe left ventricular dysfunction and the high cardiovascular risk phenotype. Indeed, several cardiac manifestations may occur in EGPA, particularly in patients with anti-neutrophil cytoplasmic antibody-negative disease. Therefore, clinicians should have high clinical suspicion because cardiac involvement in EGPA results in a poor prognosis if not diagnosed and adequately treated.

Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update.

Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations.

Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4-5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV.

In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.

Hypereosinophilic syndromes are a group of disorders secondary to the accumulation of eosinophils leading to the injury of one or more organs. Among them, eosinophilic myocarditis (EM) is a rare form of inflammatory cardiomyopathy characterized by eosinophilic infiltration into myocardial tissue and subsequent release of substances with cell membrane damage and cell destruction. The degree of infiltration is thought to depend on the underlying condition, as well as the degree and duration of eosinophil exposure and ranges from mild localized disease to diffuse multifocal infiltrates associated with myocardial necrosis, thrombotic complications and endomyocardial fibrosis. The main causes of EM are hypersensitivity reactions, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome variants, infections and cancer. Clinical presentation can be variable, ranging from asymptomatic forms to life-threatening conditions, to chronic heart failure due to progression to chronic restrictive cardiomyopathy. Marked eosinophilia in peripheral blood, elevated serum eosinophilic cationic protein concentration and multimodality imaging may suggest the etiology of EM, but in most cases an endomyocardial biopsy must be performed to establish a definitive diagnosis. Systemic treatment varies greatly depending on the underlying cause, however the evidence of an eosinophilic infiltrate allows initiation of immunosuppressive therapy, which is the mainstay of treatment in idiopathic and in most forms of EM. Patients with helminthic infection benefit from anti-parasitic therapy, those with myeloid clone often need a tyrosine kinase inhibitor, while anticoagulant therapy should be undertaken in case of possible thrombotic complications.

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare form of anti-neutrophil cytoplasmic antibody-associated vasculitis characterized by asthma, vasculitis, and eosinophilia.

We report an atypical case of EGPA in a 20-year-old female patient. Unlike previously reported cases of EGPA, this patient's initial symptom was asthma associated with a respiratory infection. This was followed by Loeffler endocarditis and cardiac insufficiency. She received treatment with methylprednisolone sodium succinate, low molecular weight heparin, recombinant human brain natriuretic peptide, furosemide, cefoperazone sodium/sulbactam sodium, and acyclovir. Despite prophylactic anticoagulation, she developed a large right ventricular thrombus. EGPA diagnosis was confirmed based on ancillary test results and specialty consultations. Subsequent treatment included mycophenolate mofetil. Her overall condition improved significantly after treatment, as evidenced by decreased peripheral blood eosinophils and cardiac markers. She was discharged after 17 d. Her most recent follow-up showed normal peripheral blood eosinophil levels, restored cardiac function, and a reduced cardiac mural thrombus size.

This case illustrates the swift progression of EGPA and underscores the significance of early detection and immediate intervention to ensure a favorable prognosis.

Eosinophilic granulomatosis with polyangiitis (EGPA) causes necrotizing vasculitis and eosinophil-rich granulomatous inflammation in small- to medium-sized vessels, resulting in multiple organ damage. EGPA is classified as an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, with myeloperoxidase-ANCA detected in approximately one-third of the patients. Conventional treatment of EGPA relies on systemic glucocorticoids (GCs) in combination with cyclophosphamide when poor prognostic factors are present; however, the dilemma between disease control and drug-related adverse effects has long been a challenge. Recent studies have revealed that the genetic background, pathophysiology, and clinical manifestations differ between ANCA-positive and ANCA-negative patients; however, mepolizumab, an interleukin (IL)-5 inhibitor, is effective in both groups, suggesting that the IL-5-eosinophil axis is deeply involved in the pathogenesis of both ANCA-positive and ANCA-negative EGPA. This review summarizes the latest knowledge on the pathophysiology of EGPA and focuses on the roles of eosinophils and ANCA. We then introduce the current treatment recommendations and accumulated evidence for mepolizumab on EGPA. Based on current unmet clinical needs, we discuss potential future therapeutic strategies for EGPA.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease characterized by eosinophil-rich granulomatous inflammation and necrotizing vasculitis, pre-dominantly affecting small-to-medium-sized vessels. It is categorized as a primary antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) but also shares features of hypereosinophilic syndrome (HES); therefore, both vessel inflammation and eosinophilic infiltration are suggested to cause organ damage. This dual nature of the disease causes variable clinical presentation. As a result, careful differentiation from mimicking conditions is needed, especially from HES, given the overlapping clinical, radiologic, and histologic features, and biomarker profile. EGPA also remains a diagnostic challenge, in part because of asthma, which may pre-dominate for years, and often requires chronic corticosteroids (CS), which can mask other disease features. The pathogenesis is still not fully understood, however, the interaction between eosinophils and lymphocytes B and T seems to play an important role. Furthermore, the role of ANCA is not clear, and only up to 40% of patients are ANCA-positive. Moreover, two ANCA-dependent clinically and genetically distinct subgroups have been identified. However, a gold standard test for establishing a diagnosis is not available. In practice, the disease is mainly diagnosed based on the clinical symptoms and results of non-invasive tests. The unmet needs include uniform diagnostic criteria and biomarkers to help distinguish EGPA from HESs. Despite its rarity, notable progress has been made in understanding the disease and in its management. A better understanding of the pathophysiology has provided new insights into the pathogenesis and therapeutic targets, which are reflected in novel biological agents. However, there remains an ongoing reliance on corticosteroid therapy. Therefore, there is a significant need for more effective and better-tolerated steroid-sparing treatment schemes.

Despite significant advances in managing systemic vasculitides, cardiovascular morbidity and mortality are still of primary concern. Advances in non-invasive imaging have broadened our understanding of the clinical heterogeneity of cardiac involvement in vasculitides. Common cardiovascular complications in primary or secondary vasculitides are; coronary artery aneurysms, acute coronary syndromes, myocarditis, pericarditis, endocarditis, and valvular dysfunction. Echocardiography, cardiac magnetic resonance (CMR), positron emission tomography (PET), and CT angiography are essential in identifying cardiac involvement and guiding treatment. Here, we present our experiences of cardiac involvement in systemic vasculitides, covering most aspects of common cardiac complications based on a multi-modality approach to challenging (real-world) cases. As many cardiac manifestations are clinically silent, heart function should be systemically assessed by a multi-modality imaging-based approach, including ECG, serial echocardiograms with strain imaging and 3D, and CMR to detect early signs of cardiac manifestations. This enables timely intervention and optimal medical treatment, which is essential for a better prognosis. There is a need for better and closer collaboration in clinical practice and research fields between Cardiologists and Rheumatologists.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare autoimmune disease that can affect multiple organ systems in the body. A majority of patients with EGPA present with asthma-like symptoms and may be misdiagnosed with refractory asthma. It is necessary to distinguish EGPA from asthma and provide a theoretical basis for effective future prevention and treatment. Objective: This study aimed to compare the clinical features of EGPA and the clinical features of allergic asthma in an effort to make an early diagnosis possible. Methods: We reviewed the basic information, test results, pre-onset conditions, and prognosis of 44 adult patients with EGPA who were admitted to our hospital between January 2013 and June 2021, and conducted a 1:1 matched case-control study to compare patients with EGPA and patients with allergic asthma. Results: The 44 patients with EGPA were older than those with allergic asthma, but more than half of the patients with EGPA had been diagnosed with bronchial asthma, with a history of 10 months to 40 years, and had previously used inhalers or systemic steroids. The proportion of male-to-female cases was ∼1:1, with seven antineutrophil cytoplasmic antibodies (ANCA) positive cases (15.9%), 20 limited EGPA cases (45.45%), and 24 systemic EGPA cases (54.55%). Although the peripheral blood eosinophil count and percentage were lower in the male patients than in the female patients, male patients with higher five-factor scores might indicate worse prognosis. The fractional exhaled nitric oxide (FeNO) level, eosinophil percentage and count, and total immunoglobulin E (IgE) level were higher in the EGPA group than in the allergic asthma group. Unlike in allergic asthma, the FeNO level is not correlated with the blood eosinophil count or percentage in EGPA. Seven patients received cardiac emission computed tomography (ECT) tests, with abnormalities suggested in six patients. Results of an electrocardiogram, color-Doppler echocardiography, myocardial enzyme level, and troponin level suggested no obvious abnormality. Conclusion: The proportion of patients with EGPA who tested positive for ANCA is not high, and patients with high eosinophil counts should be alert to the possibility of having EGPA. For patients with infiltration of eosinophils into the airway, a diagnosis should not be based on peripheral blood eosinophil counts. It is recommended that the FeNO level and pulmonary function should also be monitored for patients who present with symptoms in other body systems. The sensitivity of cardiac ECT tests is higher than routine tests, so timely screening by cardiac ECT is recommended for all patients with EGPA.

To provide an overview of existing literature on pathogenetic and clinical aspects of cardiac and vascular involvement in eosinophilic granulomatosis with polyangiitis (EGPA).

In EGPA, cardiac and vascular involvement are more common than previously thought. However, no international recommendations on the topic are available yet. Herein, we summarize the existing evidence on the topic and propose a diagnostic approach for cardiac involvement in EGPA. The prevalence of cardiovascular involvement in patients with EGPA varies greatly among published studies, ranging between 3.1-18.7% for occlusive arterial disease, 5.8-30% for venous thrombosis and 17-92% for heart involvement. Cardiac involvement in EGPA is associated with high mortality even though manifestations are heterogeneous. In principle, every anatomical structure of the heart can be involved, and EGPA-related heart disease may be completely asymptomatic at first. A careful diagnostic work-up for early detection and prompt treatment initiation is therefore required. While cardiac manifestations are more common in anti-neutrophil cytoplasmic antibodies (ANCA)-negative patients, arterial and venous thrombotic events are not linked to ANCA status but correlate closely with disease activity and accumulate at disease onset. Thrombotic events (mainly venous) are considerably more frequent in EGPA than in the general population contributing substantially to morbidity and highlighting the importance of developing specific prevention strategies for patients who are diagnosed with EGPA.

Autoimmune diseases (ADs) encompass multisystem disorders, and cardiovascular involvement is a well-known feature of autoimmune and inflammatory rheumatic conditions. Unfortunately, subclinical and early cardiovascular involvement remains clinically silent and often undetected, despite its well-documented impact on patient management and prognostication with an even more significant effect on severe and future MACE events as the disease progresses. Cardiac magnetic resonance imaging (MRI), today, commands a unique position of supremacy versus its competition in cardiac assessment and is the gold standard for the non-invasive evaluation of cardiac function, structure, morphology, tissue characterization, and flow with the capability of evaluating biventricular function; myocardium for edema, ischemia, fibrosis, infarction; valves for thickening, large masses; pericardial inflammation, pericardial effusions, and tamponade; cardiac cavities for thrombosis; conduction related abnormalities and features of microvascular and large vessel involvement. As precise and early detection of cardiovascular involvement plays a critical role in improving the outcome of rheumatic and autoimmune conditions, our review aims to highlight the evolving role of CMR in systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), rheumatoid arthritis (RA), systemic sclerosis (SSc), limited sclerosis (LSc), adult-onset Still's disease (AOSD), polymyositis (PM), dermatomyositis (DM), eosinophilic granulomatosis with polyangiitis (EGPA) (formerly Churg-Strauss syndrome), and DRESS syndrome (DS). It draws attention to the need for concerted, systematic global interdisciplinary research to improve future outcomes in autoimmune-related rheumatic conditions with multiorgan, multisystem, and cardiovascular involvement.