scholarly journals B-Cell-Depleting Therapy Improves Myocarditis in Seronegative Eosinophilic Granulomatosis with Polyangiitis

2021 ◽  
Vol 10 (19) ◽  
pp. 4577
Author(s):  
Chrong-Reen Wang ◽  
Yi-Shan Tsai ◽  
Hung-Wen Tsai ◽  
Cheng-Han Lee
Keyword(s):  
B Cell ◽  
Clinical Remission ◽  
Granulomatosis With Polyangiitis ◽  
Disease Onset ◽  
Cardiac Insufficiency ◽  
Induction Treatment ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Asthma Attack ◽  
Eosinophilic Granulomatosis ◽  
Eosinophil Counts

Cardiac involvement is a major mortality cause in eosinophilic granulomatosis with polyangiitis (EGPA), requiring novel therapeutics to spare the use of cyclophosphamide with known cardiotoxicity. Despite the observed efficacy of B-cell-depleting therapy in myocarditis of seropositive microscopic polyangiitis, it remains to be elucidated in seronegative EGPA. A retrospective study was performed in 21 hospitalized active patients aged 20 to 70 years with five-factor score 1 or 2, eosinophil counts 10,034 ± 6641/μL and vasculitis scores 27 ± 6. Overt myocarditis was identified in 10 cases, at disease onset in 6 and relapse in 4, with endomyocarditis in 4 and myopericarditis in 4. Five seronegative and one seropositive patient received rituximab with an induction regimen 375 mg/m2 weekly × 4 for refractory or relapse disease, and the same regimen for annual maintenance therapy. All cases had lower eosinophil counts, improved cardiac dysfunction and clinical remission with a relapse-free follow-up, 48 ± 15 months after the induction treatment. One seronegative endomyocarditis patient had eosinophilia and disease relapse with asthma attack and worsening cardiac insufficiency 24 months after induction, achieving clinical remission under anti-IL-5 therapy. Our findings suggest the suppression of IL-5-mediated eosinophilia as an action mechanism of B-cell-depleting therapy in seronegative EGPA myocarditis.

scholarly journals Longterm Outcomes of 188 Japanese Patients with Eosinophilic Granulomatosis with Polyangiitis

2018 ◽  
Vol 45 (8) ◽  
pp. 1159-1166 ◽  
Author(s):  
Aiko Saku ◽  
Shunsuke Furuta ◽  
Masaki Hiraguri ◽  
Kei Ikeda ◽  
Yoshihisa Kobayashi ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Disease Onset ◽  
Japanese Patients ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Factors Associated ◽  
Hazards Model ◽  
Eosinophilic Granulomatosis ◽  
Eosinophil Counts

Objective.Patients with eosinophilic granulomatosis with polyangiitis (EGPA) frequently experience relapses, which lead to cumulative organ damage. In this retrospective observational study, we aimed to reveal the risk factors for relapse in EGPA.Methods.A total of 188 Japanese patients with EGPA diagnosed between 1996 and 2015 were identified from medical records in 10 hospitals. The diagnosis was based on the American College of Rheumatology 1990 criteria or Lanham’s criteria. Baseline characteristics, treatments, asthma exacerbation, and relapses were evaluated by retrospective chart review.Results.The median followup period was 56 months. The median age at disease onset was 59.7 years. At the disease onset, 95.2% of the patients had a history of bronchial asthma and 44.7% were positive for antineutrophil cytoplasmic antibodies. The cumulative survival and relapse-free survival rates at 5 years were 89.6% and 64.0%, respectively. Multivariate analysis with 2 models, proportional hazards, and competing risk models, was performed to identify the factors associated with relapse. The proportional hazards model identified azathioprine (AZA) maintenance therapy and high eosinophil counts at onset as independent factors with lower relapse risks, and high immunoglobulin E (IgE) levels at onset as a risk factor for relapse. The competing risk model identified no statistically significant factors.Conclusion.Although potential benefit of AZA maintenance therapy in preventing relapse of EGPA was suggested by the proportional hazards model, there was a discrepancy in the results between the models. Eosinophil counts and IgE levels at onset were also identified as candidates of factors associated with relapse in EGPA.

scholarly journals Biological therapy improves myocarditis and disease activity in eosinophilic granulomatosis with polyangiitis patients

2020 ◽  
Author(s):  
Chrong-Reen Wang ◽  
Yi-Shan Tsai ◽  
Jiu-Yao Wang ◽  
Hung-Wen Tsai ◽  
Cheng-Han Lee
Keyword(s):  
Retrospective Study ◽  
Disease Activity ◽  
Cardiac Dysfunction ◽  
Granulomatosis With Polyangiitis ◽  
Biological Therapy ◽  
Cardiac Insufficiency ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Heart Involvement ◽  
Eosinophilic Granulomatosis ◽  
Eosinophil Counts

Abstract Background Cardiac insufficiency is a major cause of mortality in eosinophilic granulomatosis with polyangiitis (EGPA). Despite the dosages-related cardiotoxicity, cyclophosphamide is usually prescribed to induce disease remission in the presence of myocarditis with heart involvement. There is an imperative need of novel medications to efficiently control disease activity and spare the use of cyclophosphamide. Methods A retrospective study was carried out in hospitalized EGPA patients from January 1, 2008 to December 31, 2019, focusing on the use of biologics including benralizumab (BEN, anti-IL-5 receptor), mepolizumab (MEP, anti-IL-5), omalizumab (OMA, anti-IgE) and rituximab (RTX, anti-CD20). Results Sixteen admitted patients, 8 females aged 10 to 70 years (40.4 ± 15.5), had higher disease activities (Birmingham Vasculitis Activity Score 16 to 39, 26.8 ± 6.9), poorer prognostic factors (five-factor score 1 or 2, 1.4 ± 0.5) and elevated eosinophil counts (2,314 to 26,781/µL, 11,108 ± 7,060). BEN, MEP, OMA and RTX were prescribed in one, 2, one and 6 patients, respectively. Ten patients (63%) had myocarditis with impaired left ventricle ejection fraction and cardiac arrhythmia, and 7 received biological therapy without a combined use of cyclophosphamide. One patient obtained MEP with a 100 mg quadri-weekly × 13 regimen at induction for disease relapse. Six patients acquired RTX with a 375 mg/m2 weekly × 4 regimen at induction for refractory activity or relapsing disease, or plus a yearly maintenance schedule in 5. All patients received serial cardiac magnetic resonance imaging, transthoracic echocardiography and 24-hour Holter monitor to evaluate the therapeutic responses in heart involvement. After biological therapy, there were improved cardiac dysfunction, lower eosinophil counts and clinical remission (4 complete, 3 partial) with a relapse-free follow-up (13 to 61 months, 39.1 ± 16.0) after induction. Conclusions In this single-center retrospective study, we observed improved cardiac dysfunction and disease activity after biological therapy in EGPA patients with myocarditis.

Rituximab and Dupilumab Improve Eosinophilic Granulomatosis With Polyangiitis With Multiple Pulmonary Thrombi

2021 ◽  
Author(s):  
Sei Adachi ◽  
Chiyako Oshikata ◽  
Takeshi Kaneko ◽  
Naomi Tsurikisawa
Keyword(s):  
Heart Failure ◽  
Granulomatosis With Polyangiitis ◽  
Disease Onset ◽  
Gastrointestinal Symptoms ◽  
Patient Treatment ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Oxygen Inhalation ◽  
First Case ◽  
Venous Thromboembolic Events ◽  
Eosinophilic Granulomatosis

Abstract BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is characterized by a necrotizing vasculitis with tissue and peripheral blood eosinophilia affecting small and medium-sized arteries, capillaries, and veins. Venous thromboembolic events have occurred in 19 of 232 (8.2%) patients with EGPA. However, there are only a few reported cases of EGPA complicated by pulmonary embolism or infarction. Case presentationWe report the case of a 43-year-old woman with eosinophilic granulomatosis with polyangiitis patient with acute respiratory and heart failure due to bilateral pulmonary artery thrombosis and left femoral vein thrombosis in addition to cardiac involvement as myocarditis, pericardial effusion, and diastolic dysfunction, gastrointestinal symptoms and peripheral neuropathy 12 years after disease onset. The condition was refractory to treatment with systemic corticosteroids, intravenous cyclophosphamide, and mepolizumab, but the acute cardiac failure associated with the thrombosis, cardiac and gastrointestinal symptoms, and multiple polyneuropathy improved after a switch to rituximab. But her heart failure did not improve sufficiently, she continued to need oxygen inhalation at 1 L/min and asthma exacerbations occurred. We changed the patient’s treatment with mepolizumab to dupilumab. Not only did she have no asthma attacks after switching to dupilumab, but also her vasculitis symptoms improved. Oxygen therapy was discontinued as heart failure improved five months after starting the dupilumab. ConclusionsThis may be the first case report of the successful treatment of pulmonary thromboembolism associated with EGPA by rituximab. In addition, in this patient, treatment with dupilumab was effective not only for the asthma symptoms but also for the symptoms of vasculitis.

scholarly journals Eosinophilic Granulomatosis with Polyangiitis Manifesting as Recurrent Nasal Polyps and Hemorrhagic Necrotic Bullae: A Rare Disease Successfully Treated with Azathioprine

2019 ◽  
Vol 11 (1) ◽  
pp. 28-35
Author(s):  
Abdulaziz Alotaibi ◽  
Stefan W. Schneider
Keyword(s):  
Case Report ◽  
Granulomatosis With Polyangiitis ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Induction Treatment ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Oral Steroids ◽  
Strauss Syndrome ◽  
Low Incidence ◽  
Eosinophilic Granulomatosis ◽  
Allergic Granulomatosis

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare multisystemic vasculitis which was previously called Churg-Strauss syndrome or allergic granulomatosis. It has an unknown pathogenesis, possibly autoimmune in nature. As it has a low incidence, there is only scant published literature. This case report is valuable to dermatologists, since skin involvement is one of the most common features of the vasculitic phase. This report represents one of the possible presentations of EGPA according to the antineutrophil cytoplasmic antibody status – which in our case was negative, with a low prognostic Five-Factor Score – that was successfully treated with oral steroids and azathioprine as a steroid-sparing agent. Our objective was to add a case report to the scarce existing literature in order to learn more about therapeutic options for EGPA. This case report demonstrates that oral steroids, as induction treatment, and azathioprine, as maintenance treatment, are effective in elderly patients with EGPA without involvement of any other organs. Nevertheless, additional studies are necessary to achieve appropriate management.

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 < 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 < 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 < 0.05), while two, CD14 and MCP-3, were negatively correlated (r = −0.644 and r = −0.515; P < 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 Safety and Effectiveness of Mepolizumab Therapy in Remission Induction Therapy for Eosinophilic Granulomatosis with Polyangiitis: A Retrospective Study

2021 ◽  
Author(s):  
Masanobu Ueno ◽  
Ippei Miyagawa ◽  
Takafumi Aritomi ◽  
Koichi Kimura ◽  
Shigeru Iwata ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Granulomatosis With Polyangiitis ◽  
Retention Rate ◽  
Remission Induction ◽  
High Dose ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Eosinophilic Granulomatosis ◽  
Eosinophil Counts

Abstract Objectives: To investigate the safety and effectiveness of mepolizumab (MPZ), an anti-interleukin-5 antibody, as remission induction therapy for severe eosinophilic granulomatosis with polyangiitis (EGPA).Methods: The clinical courses of patients with severe EGPA over 6 months were retrospectively investigated and compared between patients treated with high-dose corticosteroid (CS) plus MPZ therapy (MPZ group, n=7) and those treated with high-dose CS plus intravenous cyclophosphamide (IVCY) pulse therapy (IVCY group, n=13). The primary endpoints were the MPZ retention rate and the IVCY completion rate. The secondary endpoints were adverse events and changes in the Birmingham Vasculitis Activity Score (BVAS), Vascular Damage Index (VDI), eosinophil counts, and concomitant CS doses, and the extent and rates of these changes were compared between the MPZ and IVCY groups.Results: Regarding the primary endpoints, the MPZ retention rate was 100%, and the IVCY completion rate was 61.5%. Regarding the secondary endpoints, adverse events were detected in 2/7 patients (28.6%) in the MPZ group and 7/13 patients (53.8%) in the IVCY group. BVAS and eosinophil counts significantly decreased in both groups at and after month 1, but there was no significant difference in the magnitude of changes between the two groups. VDI scores did not significantly increase in either group, and the degree of changes did not significantly differ between the two groups. Although concomitant CS doses significantly decreased at and after month 1 in both groups, the rates of decrease in CS doses at and after month 3 were significantly higher in the MPZ group.Conclusions: This study suggested that the use of MPZ as remission induction therapy for severe EGPA might be safe and effective for controlling disease activity and reducing CS doses.

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