Coronary vasospasm in eosinophilic granulomatosis with polyangiitis.
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ABSTRACT:
SUBMITTER: Chapman FA
PROVIDER: S-EPMC7733721 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Vasculitis refers to inflammation of the systemic vessels. Eosinophilic granulomatosis with polyangiitis (EGPA) is a medium and small vessel vasculitis characterized by hypereosinophilia, pulmonary infiltrates, difficult to treat asthma and polyneuropathies. Diagnosis can often be challenging. In this article, we present a case of a young lady who was diagnosed ANCA negative EGPA.
| S-EPMC6446216 | biostudies-literature
Project description:BackgroundEosinophilic granulomatosis with polyangiitis is an eosinophilic vasculitis. Mepolizumab, an anti-interleukin-5 monoclonal antibody, reduces blood eosinophil counts and may have value in the treatment of eosinophilic granulomatosis with polyangiitis.MethodsIn this multicenter, double-blind, parallel-group, phase 3 trial, we randomly assigned participants with relapsing or refractory eosinophilic granulomatosis with polyangiitis who had received treatment for at least 4 weeks and were taking a stable prednisolone or prednisone dose to receive 300 mg of mepolizumab or placebo, administered subcutaneously every 4 weeks, plus standard care, for 52 weeks. The two primary end points were the accrued weeks of remission over a 52-week period, according to categorical quantification, and the proportion of participants in remission at both week 36 and week 48. Secondary end points included the time to first relapse and the average daily glucocorticoid dose (during weeks 48 through 52). The annualized relapse rate and safety were assessed.ResultsA total of 136 participants underwent randomization, with 68 participants assigned to receive mepolizumab and 68 to receive placebo. Mepolizumab treatment led to significantly more accrued weeks of remission than placebo (28% vs. 3% of the participants had ≥24 weeks of accrued remission; odds ratio, 5.91; 95% confidence interval [CI], 2.68 to 13.03; P<0.001) and a higher percentage of participants in remission at both week 36 and week 48 (32% vs. 3%; odds ratio, 16.74; 95% CI, 3.61 to 77.56; P<0.001). Remission did not occur in 47% of the participants in the mepolizumab group versus 81% of those in the placebo group. The annualized relapse rate was 1.14 in the mepolizumab group, as compared with 2.27 in the placebo group (rate ratio, 0.50; 95% CI, 0.36 to 0.70; P<0.001). A total of 44% of the participants in the mepolizumab group, as compared with 7% of those in the placebo group, had an average daily dose of prednisolone or prednisone of 4.0 mg or less per day during weeks 48 through 52 (odds ratio, 0.20; 95% CI, 0.09 to 0.41; P<0.001). The safety profile of mepolizumab was similar to that observed in previous studies.ConclusionsIn participants with eosinophilic granulomatosis with polyangiitis, mepolizumab resulted in significantly more weeks in remission and a higher proportion of participants in remission than did placebo, thus allowing for reduced glucocorticoid use. Even so, only approximately half the participants treated with mepolizumab had protocol-defined remission. (Funded by GlaxoSmithKline and the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT02020889 .).
| S-EPMC5548295 | biostudies-literature
Project description:BackgroundEosinophilic myocarditis (EM) is a rare and potentially life-threatening form of myocarditis, frequently (but not always) associated with eosinophilia, and presents with acute chest pain, or signs and symptoms of acute or chronic heart failure. Eosinophilic myocarditis has various aetiologies, including eosinophilic granulomatosis with polyangiitis (EGPA).Case summaryA 52-year-old female with a long-standing history of asthma, acral paraesthesia, subcutaneous nodules, and recurrent chest pain treated with anti-inflammatory drugs was admitted to our hospital with chest pain, repolarization disturbances, eosinophilia, and increased troponin levels. After an initial evaluation by coronary angiography, echocardiography and cardiac magnetic resonance, a definitive diagnosis of EM was made with the help of an endomyocardial biopsy. The aetiological diagnosis of EM as a manifestation of tissue involvement in EGPA was concluded after ruling out other possible causes of eosinophilia and with the help of other diagnostic criteria for EGPA (asthma, eosinophilia, and neuropathy). Therefore, we started with a high dosage of glucocorticoids, and attained relief of symptoms and normalization of eosinophilic count after a few days.DiscussionIn cases of myocarditis (particularly if associated with eosinophilia), EM is a manifestation of EGPA and should be considered for a prompt differential diagnosis. Endomyocardial biopsy represents the gold standard for the diagnosis of EM. The mainstay of therapy for EM is immunosuppressive drugs to help prevent its evolution to a fulminant form and chronic progression towards restrictive cardiomyopathy.
| S-EPMC8564711 | biostudies-literature
Project description:Conventional immunosuppressants are ineffective for the management of EGPA-related asthma. Tezepelumab is a human monoclonal antibody that inhibits thymic stromal lymphopoietin (TLSP) that has proven efficacy in several phase 3 studies for the treatment of asthma. We treated with off-label tezepelumab the first two patients with severe refractory EPGA-related asthma. These preliminary findings suggest that targeting upstream signaling of the T2 inflammatory pathway can improve symptoms, reduce BVAS and increase Asthma Control Test scores, even in patients with refractory asthma who have failed several previous lines of treatment. Nevertheless, by analogy with dupilumab-induced IL-4/13 blockade, the persistence of sputum eosinophilia (reported in both patients) raises questions as to whether TSLP inhibition could lead to a rebound of eosinophilia and potentially to eosinophil-related symptoms in patients with EGPA.
| S-EPMC11242001 | biostudies-literature
Project description:Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare autoimmune disease characterized by medium and small vessels inflammation. Cardiac vasculitic involvement is one of the most severe manifestations with a significant impact on patients' long-term prognosis: anyway, a specific therapeutic approach for heart involvement in EGPA has not been explored yet. Current regimen consists of a long-term therapy with high dose of glucocorticoids, causing the well-known related-adverse events; immunosuppressive drugs are used in patients with severe manifestations, with some limitations. New therapeutic approaches are needed for patients with refractory disease or contraindications to conventional therapies. The quest for the ideal therapy is going toward a more and more personalized approach: on the one hand, efforts are made to use already existing therapies in the most appropriate way; on the other hand, new insights into EGPA pathogenesis allow the discovery of new targets, as demonstrated by mepolizumab and rituximab, targeting eosinophils, and B-cell compartments. This review summarizes the emerging therapies used in EGPA, focusing on the most recent studies on biologics and analyzing their efficacy and safety.
| S-EPMC8593004 | biostudies-literature
Project description:ObjectiveIdentification of a biomarker for disease activity in eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss) remains an unmet need. This study examined the value of serum periostin, a marker of type 2 inflammation, as a measure of disease activity in patients with EGPA.MethodsParticipants enrolled in a multicenter, prospective cohort of patients with EGPA were included in this study if they had disease activity (defined as Birmingham Vasculitis Activity Score [BVAS] > 0) during follow-up. Serum levels of periostin were measured at flare visit as well as two pre- and two post-flare visits, if available. The outcome of disease activity was assessed either with BVAS or Physician Global Assessment (PGA). Mixed-effect models were used to examine the association between periostin levels and disease activity. Comparisons were made with a historical cohort of healthy individuals and patients with asthma.ResultsIn the 49 patients included in the study, the median periostin level was 60 ng/ml (IQR 50 to 73) in all visits and did not significantly change across visits. Multivariate analyses found no association between periostin level and presence or absence of flare according to the BVAS (adjusted OR 1.00 [95% CI 0.98 to 1.02], p = 0.98) but an increase in periostin level was significantly associated with greater disease severity during a flare according to the PGA (adjusted beta-coefficient 0.02 [95% CI 0.004 to 0.03], p = 0.01). Periostin levels in EGPA were significantly higher than previously studied healthy controls and patients with asthma.ConclusionIn EGPA serum periostin level is modestly associated with greater disease severity during a flare but does not discriminate active from inactive disease. Periostin levels in EGPA are higher than in other previously studied cohorts, including healthy populations and patients with asthma, and are relatively stable over time.
| S-EPMC6181402 | biostudies-literature
Project description: Not available
| S-EPMC9929370 | biostudies-literature
Project description: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.
| S-EPMC10193253 | biostudies-literature
Project description:ObjectiveMepolizumab proved to be an efficacious treatment for eosinophilic granulomatosis with polyangiitis (EGPA) at a dose of 300 mg every 4 weeks in the randomized, controlled MIRRA trial. In a few recently reported studies, successful real-life experiences with the approved dose for treating severe eosinophilic asthma (100 mg every 4 weeks) were observed. We undertook this study to assess the effectiveness and safety of mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks in a large European EGPA cohort.MethodsWe included all patients with EGPA treated with mepolizumab at the recruiting centers in 2015-2020. Treatment response was evaluated from 3 months to 24 months after initiation of mepolizumab. Complete response to treatment was defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] = 0) and a prednisolone or prednisone dose (or equivalent) of ≤4 mg/day. Respiratory outcomes included asthma and ear, nose, and throat (ENT) exacerbations.ResultsTwo hundred three patients, of whom 191 received a stable dose of mepolizumab (158 received 100 mg every 4 weeks and 33 received 300 mg every 4 weeks) were included. Twenty-five patients (12.3%) had a complete response to treatment at 3 months. Complete response rates increased to 30.4% and 35.7% at 12 months and 24 months, respectively, and rates were comparable between mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks. Mepolizumab led to a significant reduction in BVAS score, prednisone dose, and eosinophil counts from 3 months to 24 months, with no significant differences observed between 100 mg every 4 weeks and 300 mg every 4 weeks. Eighty-two patients (40.4%) experienced asthma exacerbations (57 of 158 [36%] who received 100 mg every 4 weeks; 17 of 33 [52%] who received 300 mg every 4 weeks), and 31 patients (15.3%) experienced ENT exacerbations. Forty-four patients (21.7%) experienced adverse events (AEs), most of which were nonserious AEs (38 of 44).ConclusionMepolizumab at both 100 mg every 4 weeks and 300 mg every 4 weeks is effective for the treatment of EGPA. The 2 doses should be compared in the setting of a controlled trial.
| S-EPMC9305132 | biostudies-literature
Project description:BackgroundEosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare multisystem disease characterized by asthma, rhinosinusitis, and eosinophilia. Cardiac involvement, present in half the patients, may be life threatening.Case summaryA young woman with long-standing asthma and nasal polyposis was admitted with new-onset dyspnoea, sinus tachycardia, and eosinophilia. She had severe biventricular thrombosis and severe tricuspid regurgitation (TR) on echocardiography, with preserved ejection fraction of both ventricles. Cardiac magnetic resonance (CMR) imaging showed diffuse subendocardial late gadolinium enhancement (LGE). She had a positive test for perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) confirming the diagnosis of ANCA positive EGPA. She was treated with anticoagulation, high-dose corticosteroids, cyclophosphamide, and rituximab with gradual resolution of her symptoms. Follow-up echocardiography showed significant improvement in ventricular thrombi and TR but could not reliably exclude residual ventricular thrombus. Repeat CMR at 11 months confirmed complete resolution of both ventricular thrombi and near complete resolution of LGE.DiscussionCardiac involvement in EGPA, a rare cause of heart failure, can manifest as severe biventricular thrombosis and severe TR, resulting in heart failure with preserved ejection fraction. Combined immunosuppression and anticoagulation can lead to complete remission within a year. CMR is instrumental for both diagnosis and follow-up of EGPA, allowing for safe discontinuation of oral anticoagulation.
| S-EPMC7793161 | biostudies-literature