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Kamide Y, Taniguchi M. Eosinophilic granulomatosis with polyangiitis: current status and future perspectives. Respir Investig 2025; 63:639-650. [PMID: 40383090 DOI: 10.1016/j.resinv.2025.04.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 04/18/2025] [Accepted: 04/24/2025] [Indexed: 05/20/2025]
Abstract
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.
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Affiliation(s)
- Yosuke Kamide
- Clinical Research Center for Allergy and Rheumatology, NHO Sagamihara National Hospital, 18-1 Sakuradai, Minamiku, Sagamihara, Kanagawa, Japan.
| | - Masami Taniguchi
- Clinical Research Center for Allergy and Rheumatology, NHO Sagamihara National Hospital, 18-1 Sakuradai, Minamiku, Sagamihara, Kanagawa, Japan
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Li K, Jia Y, Ruan G, Xu T, Tang H, Zhou J, Li J, Fei Y. Similarities and differences of clinical manifestations and prognosis between eosinophilic gastroenteritis and eosinophilic granulomatosis with polyangiitis complicating gastrointestinal involvement. Clin Rheumatol 2025; 44:1259-1268. [PMID: 39821126 DOI: 10.1007/s10067-024-07286-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 12/11/2024] [Accepted: 12/18/2024] [Indexed: 01/19/2025]
Abstract
OBJECTIVE To investigate the similarities and differences of clinical manifestations and long-term prognosis between eosinophilic gastroenteritis (EGE) and eosinophilic granulomatosis with polyangiitis (EGPA) complicating GI involvement (EGPA-GI). METHODS Sixty-two EGE and 30 EGPA-GI patients were retrospectively enrolled in PUMCH from 2008 to 2023. Baseline clinical records were collected. Kaplan-Meier curves and log-rank tests were used to analyzed the relapse-free and non-adverse-outcome survival rate. Logistic regression was used to construct a predictive model for diagnosing EGE and EGPA-GI. RESULTS Both diseases had a middle age onset. EGE had a shorter disease duration (3.5 vs. 11.0 months, p = 0.023), higher prevalence of distension (50.0% vs 20.0%, p = 0.007) and intestinal obstruction (32.3% vs 3.3%, p = 0.001), and lower prevalence of fever (6.5% vs 50.0%, p < 0.001) than EGPA-GI. EGPA-GI had higher prevalence of allergic diseases (86.7% vs 46.8%, p < 0.001) and higher IgE level (445.0 KU/L vs 153.0 KU/L, p = 0.003). Meanwhile, in EGPA-GI, higher ESR (25.0 mm/h vs 4.0 mm/h, p = 0.001) and hsCRP (48.9 mg/L vs 1.8 mg/L, p < 0.001) were observed. Asthma (OR 572.043, 95% CI 21.729-176,210.429, p = 0.0043), fever (OR 25.221, 95% CI 2.334-585.159, p = 0.0157), rash (OR 28.671, 95% CI 1.898-2274.543, p = 0.454), intestinal obstruction (OR 0.015, 95% CI 0.000-0.357, p = 0.0318), higher ESR (OR 1.101, 95% CI 1.035-1.208, p = 0.0099), and hsCRP (OR 1.038, 95% CI 1.010-1.081, p = 0.0208) were found to be independent discriminating factors for EGPA-GI. Both diseases presented recurrent courses. Adverse outcomes including GI perforation, organ failure, and all-cause death occurred in seven EGPA-GI patients while none in EGE (p = 0.00011). CONCLUSION Both diseases have chronic and recurrent disease courses. Clinical manifestations and laboratory tests help to discriminate them. EGPA-GI have more unfavorable prognosis compared with EGE during long-term follow-up. Key Points •Baseline characteristics and long-term prognosis of 62 EGE and 30 EGPA patients with GI involvement (EGPA-GI) were compared in this study. •Both diseases had chronic and recurrent disease duration, eosinophilia, and increased IgE level. •EGPA-GI had higher prevalence of asthma, fever, rash, higher IgE, ESR, and CRP compared with EGE. •EGPA-GI had higher risk for severe adverse outcomes.
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Affiliation(s)
- Kaiwen Li
- Department of Gastroenterology, Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Yimeng Jia
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Peking Union Medical College Hospital, Beijing, 100730, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China
| | - Gechong Ruan
- Department of Gastroenterology, Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Tianming Xu
- Department of Gastroenterology, Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Hao Tang
- Department of Gastroenterology, Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Jiaxin Zhou
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Peking Union Medical College Hospital, Beijing, 100730, China.
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China.
| | - Ji Li
- Department of Gastroenterology, Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
| | - Yunyun Fei
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Peking Union Medical College Hospital, Beijing, 100730, China.
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China.
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Rua-Figueroa I, Solans-Laqué R, Blanco-Aparicio M, Cid MC. Ten clinical conundrums in the management of eosinophilic granulomatosis with polyangiitis. Expert Rev Clin Immunol 2025; 21:153-167. [PMID: 39499220 DOI: 10.1080/1744666x.2024.2423700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Accepted: 10/28/2024] [Indexed: 11/07/2024]
Abstract
INTRODUCTION Eosinophilic granulomatosis with polyangiitis (EGPA) is an immune-mediated, inflammatory, multisystemic disease that is considered a form of ANCA-associated vasculitis and whose association with asthma and blood and tissue eosinophilia differentiate it from other types of vasculitis. Nevertheless, diagnosis of EGPA may be difficult or delayed not only because of the rarity of the disease, but also because other diseases can present with similar manifestations. AREAS COVERED We review a series of key areas in EGPA, namely, laboratory and clinical indicators of disease, diagnosis, role of biomarkers, induction and maintenance therapy, and use of traditional and novel drugs. This narrative review was based on a thorough search of PubMed. EXPERT OPINION Clinicians should be aware of the limitations of available tools for diagnosing EGPA, and more efforts should be made to identify clinical and laboratory red flags, with the purpose of achieving an early diagnosis before irreversible damage occurs. New effective therapies are available, although future research should target an approach that spares glucocorticoids, reduces the risk of flares and organ damage, and maintains long-term remission with minimum adverse effects.
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Affiliation(s)
- Iñigo Rua-Figueroa
- Rheumatology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
| | - Roser Solans-Laqué
- Internal Medicine Department, H. Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | | | - Maria C Cid
- Autoimmune Diseases Department, Hospital Clínic Barcelona, FRCB-IDIBAPS, Universitat de Barcelona, Barcelona, Spain
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Kai Y, Kataoka R, Suzuki K, Nakamura E, Takano M, Muro S. Successful discontinuation of corticosteroids through remission induction therapy with benralizumab for chronic eosinophilic pneumonia. Respirol Case Rep 2024; 12:e01279. [PMID: 38239332 PMCID: PMC10794867 DOI: 10.1002/rcr2.1279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 01/04/2024] [Indexed: 01/22/2024] Open
Abstract
Chronic eosinophilic pneumonia (CEP) is an eosinophilic lung disease. Treatment for CEP includes corticosteroids; however, CEP often recurs. A 53-year-old woman was referred to our hospital because of poorly controlled asthma. She was treated with combination of moderate-dose inhaled corticosteroid (ICS), a long-acting β2-agonist (LABA), and betamethasone/dexchlorpheniramine. She was switched to single-inhaler triple therapy, after which her asthma control improved; thus, betamethasone/dexchlorpheniramine was discontinued. Ten weeks later, she was diagnosed with CEP due to marked eosinophilia and pulmonary eosinophilic infiltrates. Oral corticosteroid treatment was initiated, symptoms improved, and peripheral blood eosinophilia decreased with improved infiltrative shadows. Remission induction therapy was initiated with benralizumab combined with corticosteroid therapy. Eosinophilia and inflammatory responses decreased. After 7 months, corticosteroid was discontinued, and she was treated with benralizumab alone. She remained in remission for 4 months. This case suggests that benralizumab may be useful as a remission induction therapy in patients with CEP.
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Affiliation(s)
- Yoshiro Kai
- Department of Respiratory MedicineMinami‐Nara General Medical CenterNaraJapan
| | - Ryosuke Kataoka
- Department of Respiratory MedicineMinami‐Nara General Medical CenterNaraJapan
| | - Kentaro Suzuki
- Department of Respiratory MedicineMinami‐Nara General Medical CenterNaraJapan
| | - Eriko Nakamura
- Department of Respiratory MedicineNara Medical UniversityNaraJapan
| | - Masato Takano
- Department of Diagnostic PathologyMinami‐Nara General Medical CenterNaraJapan
| | - Shigeo Muro
- Department of Respiratory MedicineNara Medical UniversityNaraJapan
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Mouliou DS. C-Reactive Protein: Pathophysiology, Diagnosis, False Test Results and a Novel Diagnostic Algorithm for Clinicians. Diseases 2023; 11:132. [PMID: 37873776 PMCID: PMC10594506 DOI: 10.3390/diseases11040132] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 09/15/2023] [Accepted: 09/19/2023] [Indexed: 10/25/2023] Open
Abstract
The current literature provides a body of evidence on C-Reactive Protein (CRP) and its potential role in inflammation. However, most pieces of evidence are sparse and controversial. This critical state-of-the-art monography provides all the crucial data on the potential biochemical properties of the protein, along with further evidence on its potential pathobiology, both for its pentameric and monomeric forms, including information for its ligands as well as the possible function of autoantibodies against the protein. Furthermore, the current evidence on its potential utility as a biomarker of various diseases is presented, of all cardiovascular, respiratory, hepatobiliary, gastrointestinal, pancreatic, renal, gynecological, andrological, dental, oral, otorhinolaryngological, ophthalmological, dermatological, musculoskeletal, neurological, mental, splenic, thyroid conditions, as well as infections, autoimmune-supposed conditions and neoplasms, including other possible factors that have been linked with elevated concentrations of that protein. Moreover, data on molecular diagnostics on CRP are discussed, and possible etiologies of false test results are highlighted. Additionally, this review evaluates all current pieces of evidence on CRP and systemic inflammation, and highlights future goals. Finally, a novel diagnostic algorithm to carefully assess the CRP level for a precise diagnosis of a medical condition is illustrated.
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He JL, Liu XY, Zhang Y, Niu L, Li XL, Xie XY, Kang YT, Yang LQ, Cai ZY, Long H, Ye GF, Zou JX. Eosinophilic granulomatosis with polyangiitis, asthma as the first symptom, and subsequent Loeffler endocarditis: A case report. World J Clin Cases 2023; 11:6523-6530. [PMID: 37900222 PMCID: PMC10601009 DOI: 10.12998/wjcc.v11.i27.6523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 08/18/2023] [Accepted: 09/01/2023] [Indexed: 09/20/2023] Open
Abstract
BACKGROUND 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. CASE SUMMARY 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. CONCLUSION This case illustrates the swift progression of EGPA and underscores the significance of early detection and immediate intervention to ensure a favorable prognosis.
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Affiliation(s)
- Jia-Ling He
- Department of Emergency, Affiliated Hospital of Guizhou Medical University, Guiyang 550001, Guizhou Province, China
| | - Xing-Yu Liu
- Department of Orthopedic Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang 550001, Guizhou Province, China
| | - Yi Zhang
- Department of Emergency, Affiliated Hospital of Guizhou Medical University, Guiyang 550001, Guizhou Province, China
| | - Li Niu
- Department of Internal Cardiovascular Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang 550001, Guizhou Province, China
| | - Xin-Lin Li
- Department of Medical Cosmetology, Beijing Puxiang Traditional Chinese Medicine Hospital, Beijing 100080, China
| | - Xing-Yu Xie
- Department of Emergency, Affiliated Hospital of Guizhou Medical University, Guiyang 550001, Guizhou Province, China
| | - Yang-Ting Kang
- Department of Emergency, Affiliated Hospital of Guizhou Medical University, Guiyang 550001, Guizhou Province, China
| | - Lan-Qing Yang
- College of Pediatrics, Guizhou Medical University, Guiyang 550001, Guizhou Province, China
| | - Zheng-Yang Cai
- Department of Emergency, Affiliated Hospital of Guizhou Medical University, Guiyang 550001, Guizhou Province, China
| | - Hui Long
- Department of Internal Cardiovascular Medicine, People’s Hospital of Baiyun District, Guiyang 550014, Guizhou Province, China
| | - Guang-Fei Ye
- Department of Orthopedic Surgery, Hospital of Guizhou Panjiang Coal Power Group Limited Liability Company, Liupanshui 553537, Guizhou Province, China
| | - Jun-Xin Zou
- Department of Imaging, Affiliated Hospital of Guizhou Medical University, Guiyang 550001, Guizhou Province, China
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Watanabe R, Hashimoto M. Eosinophilic Granulomatosis with Polyangiitis: Latest Findings and Updated Treatment Recommendations. J Clin Med 2023; 12:5996. [PMID: 37762936 PMCID: PMC10532073 DOI: 10.3390/jcm12185996] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 09/08/2023] [Accepted: 09/13/2023] [Indexed: 09/29/2023] Open
Abstract
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.
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Affiliation(s)
- Ryu Watanabe
- Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan
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Fijolek J, Radzikowska E. Eosinophilic granulomatosis with polyangiitis - Advances in pathogenesis, diagnosis, and treatment. Front Med (Lausanne) 2023; 10:1145257. [PMID: 37215720 PMCID: PMC10193253 DOI: 10.3389/fmed.2023.1145257] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 03/13/2023] [Indexed: 05/24/2023] Open
Abstract
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.
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