Dysphonia and dyspnea in idiopathic hypereosinophilic syndrome treated with Mepolizumab.
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SUBMITTER: Kay D
PROVIDER: S-EPMC6038714 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC7780009 | biostudies-literature
Project description:BackgroundMepolizumab, a monoclonal anti-IL-5 antibody, is an effective corticosteroid-sparing agent for patients with Fip1-like 1/platelet-derived growth factor receptor ? fusion (F/P)-negative hypereosinophilic syndrome (HES). Lymphocytic variant hypereosinophilic syndrome (L-HES) is characterized by marked overproduction of IL-5 by dysregulated T cells.ObjectiveTo determine whether patients with L-HES respond to mepolizumab in terms of corticosteroid tapering and eosinophil depletion to the same extent as corticosteroid-responsive F/P-negative patients with HES and a normal T-cell profile.MethodsPatients enrolled in the mepolizumab trial were evaluated for L-HES on the basis of T-cell phenotyping and T-cell receptor gene rearrangement patterns, and their serum thymus-and-activation-regulated chemokine (TARC) levels were measured. Response to treatment was compared in patient subgroups based on results of these analyses.ResultsLymphocytic variant HES was diagnosed in 13 of 63 patients with HES with complete T-cell assessments. The ability to taper corticosteroids on mepolizumab was similar in patients with L-HES and those with a normal T-cell profile, although a lower proportion of patients with L-HES maintained eosinophil levels below 600/?L. Increased serum TARC levels (>1000 pg/mL) had no significant impact on the ability to reduce corticosteroid doses, but a lower proportion of patients with elevated TARC achieved eosinophil control on mepolizumab.ConclusionMepolizumab is an effective corticosteroid-sparing agent for patients with L-HES. In some cases however, eosinophil levels remain above 600/?L, suggesting incomplete neutralization of overproduced IL-5 or involvement of other eosinophilopoietic factors.
| S-EPMC2950246 | biostudies-literature
Project description:BackgroundHypereosinophilic syndromes (HESs) are chronic disorders that require long-term therapy to suppress eosinophilia and clinical manifestations. Corticosteroids are usually effective, yet many patients become corticosteroid refractory or develop corticosteroid toxicity. Mepolizumab, a humanized monoclonal anti-IL-5 antibody, showed corticosteroid-sparing effects in a double-blind, placebo-controlled study of FIP1L1/PDGFRA-negative, corticosteroid-responsive subjects with HESs.ObjectiveWe evaluated long-term safety and efficacy of mepolizumab (750 mg) in HES.MethodsMHE100901 is an open-label extension study. The primary end point was the frequency of adverse events (AEs). Optimal dosing frequency, corticosteroid-sparing effect of mepolizumab, and development of antimepolizumab antibodies were also explored.ResultsSeventy-eight subjects received 1 to 66 mepolizumab infusions each (including mepolizumab infusions received in the placebo-controlled trial). Mean exposure was 251 weeks (range, 4-302 weeks). The most common dosing interval was 9 to 12 weeks. The incidence of AEs was 932 events per 100 subject-years in the first year, declining to 461 events per 100 subject-years after 48 months. Serious AEs, including 1 death, were reported by the investigator as possibly due to mepolizumab in 3 subjects. The median daily prednisone dose decreased from 20.0 to 0 mg in the first 24 weeks. The median average daily dose for all subjects over the course of the study was 1.8 mg. Sixty-two percent of subjects were prednisone free without other HES medications for ? 12 consecutive weeks. No neutralizing antibodies were detected. Twenty-four subjects withdrew before study completion for death (n = 4), lack of efficacy (n = 6), or other reasons.ConclusionMepolizumab was well tolerated and effective as a long-term corticosteroid-sparing agent in PDGFRA-negative HES.
| S-EPMC3558744 | biostudies-literature
Project description:Idiopathic hypereosinophilic syndrome (HES) is a myeloproliferative disease of unknown etiology. Recently, it has been reported that imatinib mesylate (Gleevec), an inhibitor of Bcr-Abl kinase useful in the treatment of chronic myeloid leukemia, is also effective in treating HES; however, the molecular target of imatinib in HES is unknown. This report identifies a genetic rearrangement in the eosinophilic cell line EOL-1 that results in the expression of a fusion protein comprising an N-terminal region encoded by a gene of unknown function with the GenBank accession number NM_030917 and a C-terminal region derived from the intracellular domain of the platelet-derived growth factor receptor alpha (PDGFRalpha). The fusion gene was also detected in blood cells from two patients with HES. We propose naming NM_030917 Rhe for Rearranged in hypereosinophilia. Rhe-PDGFRalpha fusions result from an apparent interstitial deletion that links Rhe to exon 12 of PDGFRalpha on chromosome 4q12. The fusion kinase Rhe-PDGFRalpha is constitutively phosphorylated and supports IL-3-independent growth when expressed in BaF3 cells. Proliferation and viability of EOL-1 and BaF3 cells expressing Rhe-PDGFRalpha are ablated by the PDGFRalpha inhibitors imatinib, vatalanib, and THRX-165724.
| S-EPMC164673 | biostudies-literature
Project description:Knowledge of the multi-organ involvement in hypereosinophilic syndrome (HES) is important for the diagnosis and care of patients with this condition, even in cases with atypical presentation. This report aims to describe cerebral embolic infarction and intracardiac atypical linear-shaped thrombus in a patient with idiopathic HES and to discuss the approach of appropriate diagnosis and timely interventional management. A 55-year-old man presented with general weakness, including left-sided weakness, mild cognitive dysfunction, and mild exertional dyspnea for about 2 weeks. Initial magnetic resonance imaging for evaluating the brain showed multifocal acute to subacute infarction of both cerebral hemispheres and both cerebellums. Laboratory findings revealed leukocytosis (25,620 cells/mm3) and eosinophilia (54.9%). To evaluate the intracardiac embolic source, the patient underwent echocardiography, and a 1.5 cm linear thread-like and mobile mass was detected. Consequently, the patient was diagnosed with idiopathic HES. After bone marrow biopsy, corticosteroid and hydroxyurea were administered to control the eosinophilia. This case indicates that HES can present as a floating intracardiac atypical linear-shaped thrombus attached to the left ventricle. After appropriate diagnostic approaches, proper treatment could be given for the patient. <Learning objective: Idiopathic hypereosinophilic syndrome (HES) is a disorder characterized by persistent eosinophilia with heterogeneous clinical manifestations. Knowledge of the multi-organ involvement in HES is important for the diagnosis and care of patients with this condition, even in cases with atypical shaped thrombus as clinical presentation. Close monitoring combined with early treatment and diagnosis may help reduce mortality in HES patients.>.
| S-EPMC8103353 | biostudies-literature
Project description:A 9-year-old boy with hypereosinophilic syndrome (HES) was referred for cardiac magnetic resonance (CMR) imaging following an abnormal echocardiogram that showed a large mass layered on the inferolateral wall of the left ventricle, causing secondary severe mitral regurgitation. Cardiac involvement in HES usually affects the ventricular apex. In our case, CMR confirmed the presence of a large mural thrombus of 0.9 cm × 4.2 cm. This unusual cardiac involvement in HES was diagnosed in its intermediate thrombotic stage. CMR is very sensitive and specific in staging the disease. It explained the etiology of mitral regurgitation and guided therapy, especially when echocardiography was nonconclusive.
| S-EPMC5963242 | biostudies-literature
Project description: Not available
| S-EPMC2801956 | biostudies-literature
Project description:Asthma is a complex disorder frequently associated with a poor symptom control, concomitant morbidity, mortality, and significant health care costs due to lack of compliance or inadequate therapeutic options. Interleukin-5 (IL-5) plays a key role in the pathogenesis of eosinophilic disorders, and in the latest years has become a definite target for treatment. Besides asthma, other hypereosinophilic disorders include the hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, sinonasal polyposis, COPD with eosinophilic airway inflammation, allergic rhinitis, atopic dermatitis, eosinophilic esophagitis. The introduction of mepolizumab, a fully humanized monoclonal antibody that binds to IL-5, may represent a useful therapeutic option to control exacerbations and improve asthma-related quality of life in a subgroup of patients with persistent airway eosinophilia and moderate to severe asthma. Several studies carried out in recent years allow, at present, a careful patient selection for appropriate individualized treatment in severe asthma. Further research is anyway needed in order to better understand the pathogenetic mechanisms of asthma and to find new biomarkers. The high costs of biological agents as compared with standard drugs may be largely offset by increased clinical efficacy and good safety profile in selected patients.
| S-EPMC4603708 | biostudies-other
Project description:Highlights•Loeffler endocarditis is a systemic manifestation of HE.•Laboratory studies include CBC and cytogenetics for the FIP1L1-PDGFRA fusion gene.•Imaging studies include echocardiography, cardiac catheterization, and CMR.•The cornerstone of treatment includes steroids and anticoagulation.•Medications, such as antipsychotics, can cause secondary HE.
| S-EPMC7175807 | biostudies-literature
Project description:Hypereosinophilic syndrome (HES) is defined by persistently elevated blood eosinophil levels and is associated with evidence of organ damage. Cardiovascular involvement in HES is most commonly associated with Loffler endocarditis (cardiac HES). Cardiac HES is typically characterized by progressive subendocardial fibrosis with overlying mural thrombus formation, leading to restrictive dysfunction of the left ventricle. The thrombus from cardiac HES could result in cardiogenic stroke; however, most of the stroke cases with HES were not associated with huge thromboembolism rather multiple infarcts in the watershed area. The major clinical features of 97 previously reported cases of stroke with HES are as follows: the median age was 52 years, of which 61 (63%) were men; the initial presenting symptoms were neurological (73%), followed by headache (16%), respiratory symptoms (9%), and visual symptoms (9%). Almost half of the cases were diagnosed with cardiac HES. The characteristics of cardiac findings were mural thrombi, endomyocardial fibrosis, and a restrictive pattern of heart failure. Cerebral findings revealed 78 cases (80%) were described as multiple infarctions and 55 cases (57 %) were involved with watershed areas, whereas 11 cases (11％) were described as embolic stroke for one proximal large-vessel occlusion. Regarding treatment, 71 (73%), 28 (29%), and 16 (16%) patients were treated with steroids, anticoagulants, and antiplatelets, respectively. The overall mortality and recovery rates were 11% and 89%, respectively. Physicians should know most cases of stroke with HES are characterized by multiple infarctions in the watershed area, and cardiac HES is not always associated with stroke.
| S-EPMC8636825 | biostudies-literature