Clinical Features of Patients with Active Eosinophilic Granulomatosis with Polyangiitis Successfully Treated with Mepolizumab

2021 ◽  
pp. 1-13
Author(s):  
Naomi Tsurikisawa ◽  
Chiyako Oshikata ◽  
Maiko Watanabe ◽  
Nobuhiko Fukuda ◽  
Takanori Yamaguchi ◽  
...  
Keyword(s):  
Clinical Features ◽  
Granulomatosis With Polyangiitis ◽  
Marked Effect ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Blood Eosinophil ◽  
City Hospital ◽  
Weak Effect ◽  
Peripheral Blood Eosinophil ◽  
Serum Igg ◽  
Eosinophilic Granulomatosis

<b><i>Background:</i></b> In some patients with eosinophilic granulomatosis with polyangiitis (EGPA), remission cannot be induced, despite treatment with corticosteroids and immunosuppressants. We evaluated the clinical features of patients with EGPA in whom mepolizumab was effective. <b><i>Methods:</i></b> There were 59 EGPA patients treated at Hiratsuka City Hospital, Japan, between April 2018 and September 2020, and 30 of them received mepolizumab. Twenty (66.7%) experienced a “marked effect” (the daily dose of corticosteroid or immunosuppressant could be decreased, or the interval between intravenous immunoglobulin (IVIG) treatments could be prolonged) and 10 (33.3%) experienced a “weak effect” (these measures were not achieved). Eosinophil numbers, serum IgG levels, daily doses of corticosteroids and immunosuppressants, and the interval between IVIG treatments at diagnosis and before and after mepolizumab initiation were determined. <b><i>Results:</i></b> Eosinophil numbers at diagnosis were significantly higher in the marked-effect group than in the weak-effect group (<i>p</i> &#x3c; 0.05) but not before mepolizumab initiation or at the last visit. Birmingham Vasculitis Activity Scores (BVASs) before mepolizumab initiation (<i>p</i> &#x3c; 0.05) and at last visit (<i>p</i> &#x3c; 0.01), and frequency of relapse before treatment initiation (<i>p</i> &#x3c; 0.05) were significantly higher, and the serum IgG level before mepolizumab treatment was significantly lower in the weak-effect group than in the marked-effect group. The weak-effect group received higher doses of corticosteroids, even if the corticosteroid dose could be reduced for a while after mepolizumab initiation. <b><i>Conclusion:</i></b> High peripheral blood eosinophil numbers at EGPA diagnosis were suggestive of a positive clinical response to mepolizumab.

scholarly journals Serum Cytokine Profiling Identifies Axl as a New Biomarker Candidate for Active Eosinophilic Granulomatosis With Polyangiitis

2021 ◽  
Vol 8 ◽  
Author(s):  
Jianjuan Ma ◽  
Cong Dong ◽  
Shushan Wei ◽  
Minzhi Qiu ◽  
Penghui Wu ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Expression Patterns ◽  
Serum Levels ◽  
Serum Biomarkers ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Blood Eosinophil ◽  
Peripheral Blood Eosinophil ◽  
Kegg Pathways ◽  
Eosinophilic Granulomatosis ◽  
Eosinophil Counts

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) prognosis is generally favorable and is treated with combined corticosteroids/immunosuppressor(s) therapy. However, disease flares increase the number of clinical visits. Therefore, discovering new serum biomarkers for early identification of active EGPA is crucial.Objective: To identify reliable serum biomarkers to measure EGPA activity.Methods: The expression of 160 proteins was compared in sera from 15 inactive and 13 active EGPA patients by antibody-based microarray. Network-based analysis identified patterns in the different groups. Differentially expressed proteins (DEPs) in active disease were identified, and the correlation between their serum levels and clinical parameters was assessed. DEPs were further analyzed for GO enrichment and KEGG pathways. Finally, DEP marker candidates were validated by ELISA and Bio-plex as well as against a second cohort of 22 inactive and 18 active EGPA patients.Results: The active group presented higher peripheral and sputum eosinophil counts, FeNO, and FEV1 (% predicted) (P &lt; 0.05). Network-based analysis showed scattered expression patterns in active subjects, but no significant bias in inactive subjects. Significant differences were observed in serum levels of 19 candidate markers, all of which were higher in active EGPA (P &lt; 0.05). KEGG analysis indicated that DEPs were mainly involved in the MAPK, PI3K-Akt, RAS and Rap1 related pathways. Nine out of 19 candidate markers were positively correlated with peripheral eosinophil counts including FGF-7, SCF, GDNF, β-NGF, IGFBP-4, Axl, PIGF, Insulin, NT-4, ErbB3, OPN and BMP-4 (r = 0.693, r = 0.692, r = 0.687, r = 0.683, r = 0.671, r = 0.606, r = 0.571, r = 0.570, r = 0.516, respectively; P &lt; 0.05), while two, CD14 and MCP-3, were negatively correlated (r = −0.644 and r = −0.515; P &lt; 0.05). The higher expression of Axl, OPN, HCC-4, GDNF, and MCP-3 in active EGPA subjects was confirmed by ELISA and Custom Multiplex Bio-plex analyses.Conclusion: The serum protein profiles were significantly different between active and inactive EGPA. The expression of the candidate proteins correlated with peripheral blood eosinophil count. Serum Axl, OPN, HCC-4, GDNF, and MCP-3 levels were consistently higher in active EGPA, independent of the assessment methods. Finally, Axl had the largest AUC, indicating that this cytokine may serve as novel biomarker for the diagnosis of active EGPA.

scholarly journals Clinical features of central nervous system involvement in patients with eosinophilic granulomatosis with polyangiitis: a retrospective cohort study in China

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Suying Liu ◽  
Ling Guo ◽  
Xiaoyuan Fan ◽  
Zhaocui Zhang ◽  
Jiaxin Zhou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Features ◽  
Associated Factors ◽  
Granulomatosis With Polyangiitis ◽  
Disease Duration ◽  
Gastrointestinal Perforation ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Cns Involvement ◽  
Eosinophilic Granulomatosis

Abstract Background Central nervous system (CNS) involvement is extremely rare in eosinophilic granulomatosis with polyangiitis (EGPA), but is associated with a poor prognosis in the five-factor score. This study aims to elucidate the clinical features and independently associated factors of EGPA with CNS involvement. Results CNS involvement was observed in 17.3% (19/110) of EGPA patients from Peking Union Medical College Hospital between 2007 and 2019. We retrospectively reviewed their clinical data and analyzed the independently associated factors. Their mean age was 51.7 ± 11.56 years with no male/female predominance. Ischemic lesions were the most common manifestations, accounting for 63.2% of the 19 cases, followed by posterior reversible encephalopathy syndrome (36.8%), spinal cord involvement (15.8%), medulla oblongata involvement (15.8%), and intracranial hemorrhages (15.8%). Compared to the control group, patients with CNS involvement were of older age (51.7 ± 11.56 vs. 43.7 ± 13.78 years, p = 0.019) and had a higher ratio in the digestive tract involvement (52.6% vs. 28.6%, p = 0.042). Further multivariate analysis revealed that age, disease duration, and fever were the potential independent risk factors for CNS involvement of EGPA. Glucocorticoids combined with cyclophosphamide were the strategic therapy (94.7%). Intrathecal injections of dexamethasone and methotrexate were administered to 21.1% of the patients. Although seven patients relapsed during glucocorticoid reduction, seventeen patients finally achieved clinical remission. One patient died of acute intracerebral hemorrhage within one month, and another died of gastrointestinal perforation. Outcomes and cumulative survival show no significant differences between the two groups. Conclusions CNS involvement is uncommon in EGPA with various manifestations, and ischemic lesions are the most frequent. Age, disease duration, and fever are independent factors associated with CNS involvement in EGPA. The therapy of glucocorticoids combined with cyclophosphamide and intrathecal injections yields favorable responses. Acute intracranial hemorrhage and gastrointestinal perforation may be the principal causes of death.

scholarly journals Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg–Strauss)

2016 ◽  
Vol 48 (5) ◽  
pp. 1429-1441 ◽  
Author(s):  
Vincent Cottin ◽  
Elisabeth Bel ◽  
Paolo Bottero ◽  
Klaus Dalhoff ◽  
Marc Humbert ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Airflow Obstruction ◽  
Corticosteroid Treatment ◽  
Final Visit ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Blood Eosinophil ◽  
First Onset ◽  
Systemic Manifestations ◽  
Eosinophilic Granulomatosis

The respiratory manifestations of eosinophilic granulomatosis with polyangiitis (EGPA) have not been studied in detail.In this retrospective multicentre study, EGPA was defined by asthma, eosinophilia and at least one new onset extra-bronchopulmonary organ manifestation of disease.The study population included 157 patients (mean±sd age 49.4±14.1 years), with a mean±sd blood eosinophil count of 7.4±6.4×109 L−1 at diagnosis. There was a mean±sd of 11.8±18.2 years from the onset of asthma to the diagnosis of EGPA, of 1.4±8.4 years from the first onset of peripheral eosinophilia to the diagnosis of EGPA, and of 7.4±6.4 years from EGPA diagnosis to the final visit. Despite inhaled and oral corticosteroid treatment, the severity of asthma increased 3–6 months before the onset of the systemic manifestations. Asthma was severe in 57%, 48%, and 56% of patients at diagnosis, at 3 years, and at the final visit, respectively. Persistent airflow obstruction was present in 38%, 30%, and 46% at diagnosis, at 3 years, and at the final visit, respectively.In EGPA, asthma is severe, antedates systemic manifestations by a mean of 12 years, and progresses to long-term persistent airflow obstruction despite corticosteroids in a large proportion of patients, which affects long-term management and morbidity.

scholarly journals Rapid effect of benralizumab in exacerbation of severe eosinophilic asthma associated with eosinophilic granulomatosis with polyangiitis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Carlos Martínez-Rivera ◽  
Ignasi Garcia-Olivé ◽  
Blanca Urrutia-Royo ◽  
Maria Basagaña-Torrento ◽  
Antoni Rosell ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Forced Expiratory Volume ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Blood Eosinophil ◽  
Rapid Improvement ◽  
Eosinophilic Asthma ◽  
Α Subunit ◽  
Severe Eosinophilic Asthma ◽  
First Case ◽  
Eosinophilic Granulomatosis

Abstract Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a disease that is associated with severe uncontrolled eosinophilic asthma. Eosinophils play an important pathogenic role in the development of both diseases. Benralizumab is an antieosinophilic monoclonal antibody that binds to the α subunit of the human interleukin 5 receptor that is expressed on the surface of the eosinophil and basophil. We present the first case of rapid improvement in symptoms and lung function during admission for exacerbation of a severe eosinophilic asthma associated with EGPA. Case presentation A 57-year-old man diagnosed with severe eosinophilic asthma associated to EGPA was admitted to the Pulmonology Department due to severe bronchospasm. At admission he presented 2300 eosinophils/µl. Despite intensive bronchodilator treatment, intravenous methylprednisolone at a dose of 80 mg/d, oxygen therapy, and budesonide nebulization, the patient continued to present daily episodes of bronchospasm. Ten days after admission, with blood eosinophil levels of 1700 cells/µl, benralizumab 30 mg sc was administered. That day, the Forced Expiratory Volume in the first second (FEV1) was 28% of the theoretical value (1150 ml). AT three days, FEV1 increased to 110 ml (31%). On the 9th day FEV1 was 51% (2100 ml). The blood eosinophil level on the 9th day was 0 cells/µl. Conclusions The rapid improvement of FEV1 is in line with studies based on clinical trials that found improvement after two days in peak flow and one phase II study that showed rapid response in exacerbation of asthma in the emergency room. The antieosinophilic effect at 24 h and the effect in different tissues determine the rapid improvement and the potential advantage of benralizumab in the treatment of EGPA. This case suggests the usefulness of benralizumab in patients with EGPA and eosinophilic severe asthma who show bronchospasm refractory to conventional treatment during a hospitalization due to asthma exacerbation.

scholarly journals Eosinophilic Granulomatosis with Polyangiitis Presenting with Myocarditis as an Initial Symptom: A Case Report and Review of the Literature

2021 ◽  
pp. 329-333
Author(s):  
Kanako Kurihara ◽  
Jun Tsugawa ◽  
Shinji Ouma ◽  
Toshiyasu Ogata ◽  
Mikiko Aoki ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Nerve Biopsy ◽  
Pulse Therapy ◽  
Sural Nerve Biopsy ◽  
Lower Limbs ◽  
Rapid Progression ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Initial Symptom ◽  
Steroid Pulse ◽  
Eosinophilic Granulomatosis

A 66-year-old woman with a history of bronchial asthma had shortness of breath and fatigue upon mild exercise. She was diagnosed as congestive heart failure. A blood test showed eosinophilia without the presence of anti-neutrophil cytoplasmic antibody (ANCA), and a myocardial biopsy specimen revealed eosinophilic infiltration in the myocardium. Eosinophilia was improved when she was administered short-term methylprednisolone. After that, she had numbness and pain in her lower limbs with re-elevation of eosinophils. She had dysesthesia and hypalgesia in the distal part of the limbs. Sural nerve biopsy revealed axonal degeneration and thickness of the arterial wall, indicating a diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA). Two courses of steroid pulse therapy were performed, resulting in marked improvement of her sensory symptoms. ANCA-negative EGPA might be associated with myocarditis and peripheral neuropathy. A sufficient immunotherapy should have been considered to prevent rapid progression.

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