Background: Hypereosinophilic syndromes (HES) are marked by persistent eosinophilia, absence of a primary cause, and evidence of eosinophil-mediated organ damage. HES presents a spectrum of clinical manifestations, with prognosis and treatment varying based on the subtype, including myeloid/lymphoid neoplasms and chronic eosinophilic leukemia, not otherwise specified. The primary treatment goal is to reduce eosinophil levels to prevent organ damage, typically by using glucocorticoids and immunosuppressive agents. However, these treatments often have limited efficacy and considerable adverse effects. Objective: Given the central role of interleukin (IL) 5 in eosinophil development and survival, this study aimed to assess the efficacy and safety of anti-IL-5 therapies in patients with HES. Methods: A systematic literature search was conducted on two data bases. The primary outcome was the reduction in absolute eosinophil count, and secondary outcomes included the incidence of flares and adverse events. Data Analysis was conducted, and forest plots were made for each outcome. Results: Four trials were included in the analysis. Ninety-five percent of the patients in the anti-IL-5 group showed a reduction in the absolute eosinophil count compared with 41% in the placebo group (risk ratio [RR] 2.32 [95% confidence interval {CI}, 1.67-3.22]; p = <0.00001; tau statistic (I²) = 0%). Anti-IL-5 therapy was associated with a lower incidence of disease flares, with 15% of the patients in the anti-IL-5 group who experienced flares compared with 30% in the placebo group (RR 0.50 [95% CI, 0.31-0.86]; p = 0.01; I² = 0%). The incidence of adverse events was similar between the two groups (RR 0.99 [95% CI, 0.91-1.07]; p = 0.81; I² = 0%). Conclusion: Anti-IL-5 therapies are effective in reducing eosinophil count and preventing disease flares in patients with HES.

Eosinophils are essential innate immune cells in allergic responses. Accumulating evidence indicates that eosinophils also participate in the pathogenesis of cardiovascular diseases (CVDs). In clinical studies, high blood eosinophil counts and eosinophil cationic protein levels have been associated with an increased risk of CVD, including myocardial infarction (MI), cardiac hypertrophy, atrial fibrillation, abdominal aortic aneurysm (AAA) and atherosclerosis. However, low blood eosinophil counts have also been reported to be a risk factor for MI, heart failure, aortic dissection, AAA, deep vein thrombosis, pulmonary embolism and ischaemic stroke. Although these conflicting clinical observations remain unexplained, CVD status, timing of eosinophil data collection, and tissue eosinophil phenotypic and functional heterogeneities might account for these discrepancies. Preclinical studies suggest that eosinophils have protective actions in MI, cardiac hypertrophy, heart failure and AAA. By contrast, cationic proteins and platelet-activating factor from eosinophils have been shown to promote vascular smooth muscle cell proliferation, vascular calcification, thrombomodulin inactivation and platelet activation and aggregation, thereby exacerbating atherosclerosis, atrial fibrillation, thrombosis and associated complications. Therefore, eosinophils seem to promote calcification and thrombosis in chronic CVD but are protective in acute cardiovascular settings. In this Review, we summarize the available clinical and preclinical data on the different roles of eosinophils in CVD.

Objectives: To investigate the role of blood eosinophils in predicting PH in end-stage lung disease. Methods: We conducted a retrospective study of adults with CF, COPD, and ILD who underwent RHC during lung transplant evaluations (2010-2022). Patients were classified by the 2022 ECS/ERS PH guidelines with pulmonary function and laboratory tests, including hemograms. The eosinophil threshold was set at 0.30 G/L. Results: We analyzed 663 patients (n = 89 CF, n = 294 COPD, and n = 280 ILD). Severe PH was more common in ILD (16%) than in CF (4%) and COPD (7%) (p = 0.0002), with higher eosinophil levels in ILD (p = 0.0002). No significant correlation was found between eosinophil levels and hemodynamic parameters (PAPm, PVR, and CI) across CF, COPD, and ILD (PAPm: p = 0.3974, p = 0.4400 and p = 0.2757, respectively; PVR: p = 0.6966, p = 0.1489 and p = 0.1630, respectively; CI: p = 0.9474, p = 0.5705 and p = 0.5945, respectively), nor was a correlation observed in patients not receiving OCS. Linear regression analysis confirmed the lack of association (PAPm: p = 0.3355, p = 0.8552 and p = 0.4146, respectively; PVR: p = 0.6924, p = 0.8935 and p = 0.5459, respectively; CI: p = 0.4260, p = 0.9289 and p = 0.5364, respectively), controlling for 6-MWD, Nt-proBNP, and ICS/OCS dosages. ROC analysis indicated eosinophils were ineffective in distinguishing PH severity levels across these diseases (AUC 0.54, 0.51, and 0.53, respectively). The analysis of eosinophil levels measured 18 ± 6 months prior to baseline found no predictive correlation with the presence of PH either. Eosinophil levels did not differ significantly among PH groups, but eosinophilic COPD was linked to more unclassified PH, higher CO, and greater lung volumes than non-eosinophilic COPD. Conclusions: In our cohort of end-stage CF, COPD, and ILD patients, blood eosinophilia did not predict the presence of PH but was associated with hemodynamic parameters and lung volumes in COPD.

Idiopathic hypereosinophilic syndrome is a group of unexplained diseases characterized by a persistent increase in eosinophils with multiple organs damage. Herein, we describe the 68Ga-FAPI PET/CT findings of idiopathic hypereosinophilic syndrome in a 56-year-old woman. 68Ga-FAPI PET/CT showed multiple aneurysms with increased FAPI uptake. In addition, myocardial uptake of FAPI was observed.

Caseous calcification of the mitral annulus (CCMA) and hypereosinophilic syndrome (HES) are both associated with thrombotic tendencies. Caseous calcification of the mitral annulus may cause mitral valve regurgitation (MR), which may necessitate surgical intervention, depending on its severity. Given the absence of reported cases combining CCMA and HES, the optimal target range for anticoagulation therapy after mitral valve replacement remains to be established.

A 64-year-old man with CCMA complicated by HES was admitted due to heart failure and severe MR. The patient underwent mitral valve replacement with a mechanical valve. Despite standard anticoagulation therapy, prosthetic valve dysfunction had developed because of thrombosis. Intraoperative transoesophageal echocardiography revealed a closed stuck valve, necessitating valve re-replacement. A bioprosthetic valve was selected.

In cases of CCMA complicated by HES, the target of anticoagulation therapy is unclear. This case demonstrated that more intensive anticoagulation is required because of the thrombogenic risk of CCMA and HES. The mechanism of calcification due to eosinophilia has been suggested, and the relationship between eosinophilia and CCMA remains a subject for future research.

We describe the case of a 73-year-old man who had been followed up by our clinic for pulmonary hypertension and asthma. He was later hospitalized and found to have significant and persistent eosinophilia compatible with hypereosinophilic syndrome. Various other conditions such as drug reaction with eosinophilia and systemic symptoms (DRESS), malignancy, and eosinophilic granulomatosis with polyangiitis (EGPA) were considered but largely excluded after further investigation. He responded well to steroids and was transitioned to mepolizumab for long-term control.

Gut microbiota and infectious diseases affect neurological disorders, brain development, and function. Compounds generated in the gastrointestinal system by gut microbiota and infectious pathogens may mediate gut-brain interactions, which may circulate throughout the body and spread to numerous organs, including the brain. Studies shown that gut bacteria and disease-causing organisms may pass molecular signals to the brain, affecting neurological function, neurodevelopment, and neurodegenerative diseases. This article discusses microorganism-producing metabolites with neuromodulator activity, signaling routes from microbial flora to the brain, and the potential direct effects of gut bacteria and infectious pathogens on brain cells. The review also considered the neurological aspects of infectious diseases. The infectious diseases affecting neurological functions and the disease modifications have been discussed thoroughly. Recent discoveries and unique insights in this perspective need further validation. Research on the complex molecular interactions between gut bacteria, infectious pathogens, and the CNS provides valuable insights into the pathogenesis of neurodegenerative, behavioral, and psychiatric illnesses. This study may provide insights into advanced drug discovery processes for neurological disorders by considering the influence of microbial communities inside the human body.

Hypereosinophilic syndrome (HES) represents a group of disorders with eosinophil-mediated end-organ damage. Eosinophilic myocarditis (EM) represents cardiac involvement in HES. Data are limited regarding this rare condition. To better understand contemporary clinical characteristics of EM in HES, we reviewed demographics, cardiac imaging, and outcomes of this condition at our center.

We performed a cross-sectional study of all patients aged >18 years with diagnosis of EM in HES at our center between September 1986 and January 2023. Relevant clinical data, including clinical presentation, medical history, medication use, comorbidities, imaging findings, and outcomes, were collected and analyzed.

Of 1,664 patients identified with hypereosinophilia (HE), 36 cases of clinically diagnosed HES were identified. Of the 36 patients diagnosed with HES, 11 patients (30.6%) were diagnosed with EM. Of these, six patients underwent endomyocardial biopsy (EMB). The mean age was 57±12 years and 63.6% were female. Asthma was the most common comorbidity (54.5%). Patients with EM had significantly more dyspnea (63.6%), fatigue (54.5%), and neuropathy (36.4%) compared to those without cardiac involvement. Echocardiography was performed in all patients and cardiac magnetic resonance (CMR) imaging was performed in eight patients. Left ventricular (LV) thrombus was detected more frequently by CMR (5/8, 62.5%) compared to echocardiography (3/10, 30%). Subendocardial pattern of late gadolinium enhancement (LGE) was observed in the majority of patients on CMR (6/7, 85.7%). Steroids were utilized in 90.9% of cases, and aspirin in all patients. Compared to HES patients without cardiac involvement, thromboembolic events occurred significantly more frequently (63.6% vs. 24.0%, P=0.02).

In a 37-year cohort of HES-associated EM, echocardiography was the first-line imaging modality, while CMR was an essential but still under-utilized imaging modality. Patients with EM had significantly more thromboembolic events compared to HES without cardiac involvement.

In this review, we aim to explore the optimal approach to patients presenting with eosinophilia, considering recent advances in diagnostic and therapeutic strategies. Specifically, we focus on the integration of novel therapies into clinical practice to improve patient outcomes.

Advanced insights into the clinical and genetic features of eosinophilic disorders have prompted revisions in diagnostic criteria by the World Health Organization classification (WHO-HAEM5) and the International Consensus Classification (ICC). These changes reflect a growing understanding of disease pathogenesis and the development of targeted treatment options. The therapeutic landscape now encompasses a range of established and novel therapies. For reactive conditions, drugs targeting the eosinophilopoiesis, such as those aimed at interleukin-5 or its receptor, have demonstrated significant potential in decreasing blood eosinophil levels and minimizing disease flare-ups and relapse. These therapies have the potential to mitigate the side effects commonly associated with prolonged use of oral corticosteroids or immunosuppressants. Myeloid and lymphoid neoplasms with eosinophilia and tyrosine kinase (TK) gene fusions are managed by various TK inhibitors with variable efficacy. Diagnosis and treatment rely on a multidisciplinary approach. By incorporating novel treatment options into clinical practice, physicians across different disciplines involved in the management of eosinophilic disorders can offer more personalized and effective care to patients. However, challenges remain in accurately diagnosing and risk-stratifying patients, as well as in navigating the complexities of treatment selection.

Hypereosinophilic syndromes (HES) comprise a group of rare disorders characterized by persistent blood eosinophilia, accompanied by eosinophil-associated organ damage. Nearly every organ can be affected, with the skin, lungs, heart, and gastrointestinal tract being the most common. Unspecific presenting symptoms hinder timely management, facilitating disease progression. Treatment is aimed at the underlying disease, reducing disease progression and controlling symptoms. We present the case of a 39-year-old female admitted with an acute venous thromboembolic event who developed acute hypereosinophilic-related heart failure and encephalopathy. After a thorough investigation, the diagnosis of idiopathic HES with multiorgan involvement was established, and the patient was medicated with high-dose corticosteroids, resulting in a good clinical and laboratory response. Due to non-compliance with medical treatment, disease progression culminated in death. This case highlights the multiorgan involvement in HES and the importance of treatment adherence for these patients.

A 46-year-old Japanese man was referred to our hospital because of a marked increase in his eosinophil count (22,870/μL) and elevated liver enzyme levels. Computed tomography (CT) showed thrombi measuring approximately 8 cm in both femoral veins. A liver biopsy revealed eosinophilic infiltration, hepatocyte necrosis, fibrosis, and multiple thrombi. We suspected acute liver injury and deep vein thrombosis associated with hypereosinophilic syndrome and initiated steroids and heparin treatment. Four days after starting treatment, the patient experienced sudden chest pain and cardiopulmonary arrest. CT revealed bilateral pulmonary artery thrombosis, and despite administration of a tissue plasminogen activator, the patient died.

Transthoracic echocardiography is usually the first non-invasive imaging modality for the detection of Loeffler endocarditis at thrombotic stage. In the recent decade 3D echocardiography and deformation imaging already proved as a helpful tool for the monitoring of left and right ventricular heart disease.

The present case illustrates the diagnostic role of 3D echocardiography and deformation imaging in the acute stage of right sided Loeffler endocarditis in a 70-year-old Western European (German) woman. This case proves that myocardial involvement due to inflammation can be detected at subclinical stages by speckle tracking echocardiography. Acute deterioration of left and right ventricular function and the early response to prednisolone therapy can objectively be monitored. In addition, alterations of effective stroke volume can quantitatively be assessed by 3D right ventricular volumetry with exclusion of thrombus formation in the volume measurements.

This case underlines the importance of 3D echocardiography and deformation imaging as a helpful diagnostic tool in disease management in the acute phase of Loeffler endocarditis at thrombotic stage.

Hypereosinophilic syndrome (HES) is a disorder characterized by elevated levels of eosinophils, which may be associated with multi-organ involvement depending on severity. The recent diagnostic criteria for idiopathic HES require an elevated absolute eosinophil count (AEC) above 1500 cells/mcL with evidence of tissue damage. We present a case of a 37-year-old male firefighter with a purported history of eosinophilic bronchitis who was referred to the hospital with syncopal episodes and a persistent productive cough. The patient showed an AEC of 4500 cells/mcL on admission associated with high inflammatory markers. Cardiac imaging demonstrated acute myocarditis with heart failure and a reduced ejection fraction. Chest imaging was initially suggestive of community-acquired pneumonia. Workup was negative for a malignant etiology; infectious causes similarly were excluded. After a multidisciplinary evaluation, a diagnosis of idiopathic HES was made and steroids were instituted with rapid resolution of symptoms. Our case illustrates the importance of considering hypereosinophilia as a precipitating factor for acute heart failure in an otherwise healthy adult. An expeditious diagnosis can lead to early initiation of steroids to avoid progression toward multi-organ failure.

Hypereosinophilic syndrome comprises a diverse and intricate array of rare disorders, exhibiting clinical manifestations that extend across various medical subspecialties. Within its myeloid form, chronic eosinophilic leukemia represents a rare myeloid malignancy characterized by severe hematological complications and distinctive organ dysfunction, notably affecting the cardiovascular system. This report presents a rare case of chronic eosinophilic leukemia and Loeffler syndrome with an initial presentation of ventricular tachycardia.

Hypereosinophilic syndrome can produce cardiac involvement and endomyocardial fibrosis, which have a poor prognosis. However, there is limited information regarding cardiac involvement among migrants from Latin America with eosinophilia related to helminthiasis.

We conducted a pilot observational study where an echocardiography was performed on migrants from Latin America with both eosinophilia (>450 cells/μL) and a diagnosis of helminth infection, and on migrants from Latin America without eosinophilia or helminth infection. Microbiological techniques included a stool microscopic examination using the Ritchie's formalin-ether technique, and a specific serology to detect Strongyloides stercoralis antibodies.

37 participants were included, 20 with eosinophilia and 17 without eosinophilia. Twenty (54.1%) were men with a mean age of 41.3 (SD 14.3) years. Helminthic infections diagnosed in the group with eosinophilia were: 17 cases of S. stercoralis infection, 1 case of hookworm infection, and 2 cases of S. stercoralis and hookworm coinfection. Among participants with eosinophilia, echocardiographic findings revealed a greater right ventricle thickness (p = 0.001) and left atrial area and volume index (p = 0.003 and p = 0.004, respectively), while showing a lower left atrial strain (p = 0.006) and E-wave deceleration time (p = 0.008). An increase was shown in both posterior and anterior mitral leaflet thickness (p = 0.0014 and p = 0.004, respectively) when compared with participants without eosinophilia.

Migrants from Latin America with eosinophilia related to helminthic infections might present incipient echocardiographic alterations suggestive of early diastolic dysfunction, that could be related to eosinophilia-induced changes in the endomyocardium.

Hypereosinophilic syndrome (HES) encompasses a heterogeneous and complex group of different subtypes within the wider group of hypereosinophilic disorders. Despite increasing research interest, several unmet needs in terms of disease identification, pathobiology, phenotyping, and personalized treatment remain to be addressed. Also, the prospective burden of non-malignant HES and, more in general, HE disorders is currently unknown. On a practical note, shortening the diagnostic delay and the time to an appropriate treatment approach probably represents the most urgent issue, even in light of the great impact of HES on the quality of life of affected patients. The present document represents the first action that the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC) has finalized within a wider project aiming to establish a collaborative national network on HES (InHES-Italian Network on HES) for patients and physicians. The first step of the project could not but focus on defining a common language as well as sharing with all of the medical community an update on the most recent advances in the field. In fact, the existing literature has been carefully reviewed in order to critically integrate the different views on the topic and derive practical recommendations on disease identification and treatment approaches.

Cardiac complications in patients with hypereosinophilia cause significant morbidity and mortality. However, mechanisms of how eosinophilic inflammation causes heart damage are poorly understood.

We developed a model of hypereosinophilia-associated heart disease by challenging hypereosinophilic mice with peptide from the cardiac myosin heavy chain. Disease outcomes were measured by histology, immunohistochemistry, flow cytometry, and measurement of cells and biomarkers in peripheral blood. Eosinophil dependence was determined by using eosinophil-deficient mice (ΔdblGATA). Single cells from heart were subjected to single cell RNA sequencing to assess cell composition, subtypes and expression profiles.

Mice challenged with myocarditic and control peptide had peripheral blood leukocytosis, but only those challenged with myocarditic peptide had heart inflammation. Heart tissue was infiltrated by eosinophil-rich inflammatory infiltrates associated with cardiomyocyte damage. Disease penetrance and severity were dependent on the presence of eosinophils. Single cell RNA sequencing showed enrichment of myeloid cells, T-cells and granulocytes (neutrophils and eosinophils) in the myocarditic mice. Macrophages were M2 skewed, and eosinophils had an activated phenotype. Gene enrichment analysis identified several pathways potentially involved in pathophysiology of disease.

Eosinophils are required for heart damage in hypereosinophilia-associated heart disease. Additionally, myeloid cells, granulocytes and T-cell cooperatively or independently participate in the pathogenesis of hypereosinophilia-associated heart disease.

Inflammatory diseases have been associated with an increased cardiovascular risk. However, data on incident major adverse cardiovascular events (MACE) from large population-based cohorts of patients with eosinophilic esophagitis (EoE) is lacking.

This study included all Swedish adults with EoE without a record of previous cardiovascular disease (CVD) (1990-2017, N = 1546) with follow-up until 2019. Individuals with EoE were identified from prospectively recorded histopathology reports from all Swedish pathology departments (n = 28). EoE patients were matched at index date for age, sex, calendar year and county with up to five general population reference individuals (N = 7281) without EoE or CVD. Multivariable-adjusted hazard ratios (aHRs) for MACE (ischemic heart disease, congestive heart failure, stroke and cardiovascular mortality) were calculated using Cox proportional hazards models. Full sibling comparisons and adjustment for cardiovascular medication were performed.

During a median follow-up of 6.0 years, we observed 65 incident MACE in patients with EoE (6.4/1000 person-years (PY)) and 225 in reference individuals (4.7/1000 PY). EoE was not associated with a higher risk of MACE (aHR = 1.14, 95% CI = 0.86-1.51) or any of its components. No differences between age, sex and follow-up time were observed. The results remained stable in sensitivity analyses, including when adjusting for relevant cardiovascular medications and a full sibling comparison.

In this large population-based cohort study, patients with EoE had no increased risk of MACE compared to reference individuals and full siblings. The results are reassuring for patients with EoE.

Hypereosinophilic syndrome is a rare systemic condition characterized by eosinophil-mediated organ damage. Cardiac involvement is common and typically occurs in sequential stages. We present two cases that demonstrate these different stages and presentations of eosinophilia-mediated myocardial disease, where multimodality imaging was essential for the diagnosis. More importantly, they demonstrate, for the first time, the dissociation between the eosinophil count and patients' clinical evolution, suggesting the need for close follow up even after the eosinophilia has been controlled.

Cardiac involvement in hypereosinophilic syndrome typically occurs in three stages - necrotic, thrombotic, and fibrotic. Although cardiac damage is mediated by eosinophils, the blood eosinophil count and patients' clinical evolution are dissociated. Therefore, eosinophil count on its own is not an adequate marker of clinical evolution, and cardiac follow up should be continued even after the eosinophilia has been controlled.

Hypereosinophilia is a rare condition, defined as a persistent elevation of absolute eosinophil count greater than 1.5x109/L and/or tissue eosinophilia. This condition can be caused by numerous different etiologies, both hematological (clonal) and non-hematological (reactive). Reactive hypereosinophilia encompasses all disorders, including infections. Patients with hypereosinophilia may experience a spectrum of clinical consequences due to multiple organ damage, including neurologic and thrombotic complications, associated with organ dysfunction and potentially life-threatening sequelae. Cerebral venous thrombosis (CVT) is the term used to describe thrombotic occlusion of veins and/or venous sinuses in the brain. This condition can occur at all ages and CVT related to hypereosinophilia is a rare disease. Diagnosis of the disease must be done quickly because thrombosis causes blockage of cerebral drainage, venous congestion, disruption of cerebrospinal fluid reabsorption, ischemic neuronal damage, cerebral edema, and hemorrhage, leading to severe neurological complications. Management of intracranial hemorrhage from CVT due to hypereosinophilia is a challenging task for clinicians, based on anticoagulation therapy, systemic corticosteroid, management of elevated intracranial pressure, and potentially progressive hemorrhage due to anticoagulant. The outcome of the patient generally relies on early detection, prompt, and appropriate treatment. In this case report, we discuss a rare case of CVT with hypereosinophilia and positive dengue serology in a child, in the context of intracranial hemorrhage, enlightening the importance of considering a personalized strategy in the management of this complex scenario.

Autoimmunity significantly contributes to the pathogenesis of myocarditis, underscored by its increased frequency in autoimmune diseases such as systemic lupus erythematosus and polymyositis. Even in cases of myocarditis caused by viral infections, dysregulated immune responses contribute to pathogenesis. However, whether triggered by existing autoimmune conditions or viral infections, the precise antigens and immunologic pathways driving myocarditis remain incompletely understood. The emergence of myocarditis associated with immune checkpoint inhibitor therapy, commonly used for treating cancer, has afforded an opportunity to understand autoimmune mechanisms in myocarditis, with autoreactive T cells specific for cardiac myosin playing a pivotal role. Despite their self-antigen recognition, cardiac myosin-specific T cells can be present in healthy individuals due to bypassing the thymic selection stage. In recent studies, novel modalities in suppressing the activity of pathogenic T cells including cardiac myosin-specific T cells have proven effective in treating autoimmune myocarditis. This review offers an overview of the current understanding of heart antigens, autoantibodies, and immune cells as the autoimmune mechanisms underlying various forms of myocarditis, along with the latest updates on clinical management and prospects for future research.

Hypereosinophilic Syndrome (HES) is a rare disorder characterized by persistent elevation of eosinophils, leading to multi-organ infiltration and damage. Eosinophilic Myocarditis (EM) is one of its severe complications contributing significantly to morbidity and mortality. Herein, we describe the diagnostic and therapeutic challenges of EM, emphasizing the significance of early recognition and multidisciplinary management.

A 51-year-old female with a history of EM, heart failure, and peripheral eosinophilia presented with NYHA class 3b symptoms. Laboratory findings revealed elevated peripheral eosinophil count, NT-Pro BNP, and characteristic electrocardiogram abnormalities. Imaging studies confirmed biventricular thrombi and myocardial abnormalities consistent with EM. Treatment involved Solu-Medrol for HES and heparin for ventricular thrombi, leading to initial clinical improvement. However, refractory heart failure necessitated urgent heart transplantation.

EM, an under-recognized complication of HES, poses diagnostic and management challenges. Management includes standard heart failure treatments, steroids, and emerging therapies like Mepolizumab. Early diagnosis and aggressive management are pivotal for improving outcomes in this rare and potentially fatal condition.

Advancements in the detection of complications, surgical management, and therapeutic options have improved outcomes in HES. Ongoing research is essential to further understand and address the diagnostic and therapeutic challenges of HES and EM.

The report explores a case of cerebral sinus venous thrombosis associated with hypereosinophilia, presenting a unique clinical scenario. A 22-year-old male presented with persistent headache for eight days, escalating in intensity, along with projectile vomiting and blurred vision. Despite the absence of typical indicators such as fever or respiratory symptoms, comprehensive evaluations revealed hypereosinophilia in the complete blood count. Imaging studies, including magnetic resonance angiography and venography, confirmed cerebral sinus venous thrombosis. The patient was successfully treated with a multidimensional approach, including anticoagulation therapy, corticosteroids, and supportive measures. This report highlights the concealed nature of hypereosinophilia in the context of cerebral sinus venous thrombosis and underscores the importance of a vigilant diagnostic approach in unravelling this silent association.

Hypereosinophilic syndrome (HES) is a rare condition characterized by elevated eosinophil counts (>1.5 x 109 on two consecutive measurements), which are of myeloid clonal in origin or are driven by excess cytokines. One subtype of HES exhibits the Fip1-like 1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRA) fusion gene, a gain-of-function mutation resulting in a hyperactive tyrosine kinase. HES, especially the FIP1L1-PDGFRA variant, exhibits an excellent response to chemotherapy with imatinib. In this report, we present a 38-year-old patient with no contributory past medical history who experienced sudden-onset fatigue, ataxia, visual changes, and headaches. He was found to have multiple small acute infarcts in his cerebrum and cerebellum. A stroke work-up, including transthoracic echocardiogram (TTE), transesophageal echocardiogram (TEE), and computed tomography angiography (CTA), did not yield insight into the origin of his infarcts. On CBC, he was consistently hypereosinophilic, and a bone marrow biopsy revealed hypercellularity and the FIP1L1-PDGFRA fusion gene, confirming the diagnosis of HES. The patient was treated first with methylprednisolone and then imatinib with excellent response. It appears that, in our patient, strokes were not of a thromboembolic nature but rather due to hypercoagulability. In this report, we advocate for considering HES and emphasize the importance of revisiting basic laboratory studies such as a CBC if the standard stroke workup fails to elucidate the mechanism behind ischemic strokes with an embolic pattern.

Eosinophils have widespread procoagulant effects. In daily practice, eosinophil-related cardiovascular toxicity consists of endomyocardial damage, eosinophilic vasculitis and arterial or venous thrombosis. Here we aim to report on the clinical features and treatment outcomes of patients with unexplained ophthalmic vascular manifestations and eosinophilia.

We conducted a retrospective, multicenter, observational study and a literature review of patients with eosinophilia (≥0.5 x109/L) and concomitant ophthalmic vascular manifestations independent of the underlying eosinophilic disease but with no alternative cause for ophthalmic manifestations.

Fifty-seven patients were included (20 from the observational study and 37 from the literature review). Ophthalmic vascular features were the initial manifestation of eosinophil-related disease in 34 (59%) patients and consisted of 29 central retinal artery occlusions, six branch retinal artery occlusions, five central retinal vein occlusions, two branch retinal vein occlusions, seven retinal vasculitides, two retinal vasospasms, 12 Purtscher's retinopathies, 13 anterior ischemic optic neuropathies and two posterior ischemic optic neuropathies. The median [IQR] absolute eosinophil count at onset of ophthalmic vascular manifestations was 3.5 [1.7-7.8] x109/L. Underlying eosinophil-related diseases included eosinophilic granulomatosis with polyangiitis (n=32), clonal hypereosinophilic syndrome (HES) (n=1), idiopathic HES (n=13), lymphocytic HES (n=2), adverse drug reactions (n=3), parasitosis (n=2), polyarteritis nodosa (n=1), IgG4-related disease (n=1), eosinophilic fasciitis (n=1) and primary sclerosing cholangitis (n=1). Other extra-ophthalmologic arterial or venous thromboses related to eosinophilia were reported in four (7%) and nine (16%) patients, respectively. Visual prognosis was poor: only eight (10%) patients achieved full recovery of ophthalmologic symptoms. After a median follow-up of 10.5 [1-18] months, one patient (3%) had a recurrence of an ophthalmic vascular manifestation, and three patients (10%) had a recurrence of other vascular symptoms (deep vein thrombosis in two and pulmonary embolism in one patient). At the time of recurrence, absolute eosinophil counts were above 0.5 x109/L in all cases (n=4).

This study broadens the spectrum of vascular manifestations associated with hypereosinophilia by adding ophthalmic vascular manifestations. In patients with ophthalmological vascular manifestations and hypereosinophilia, aggressive treatment of the underlying pathology (and normalization of blood count) should be implemented.

We present a case of a man in his 30s presenting with ST-segment elevation myocardial infarction and eosinophilia. The patient underwent thrombus aspiration and initially echocardiographic evaluation was normal. The patient was discharged after 2 days, but was hospitalised again after 6 days. Echocardiographic evaluation now revealed a thrombus formation on the aortic valve. Laboratory data revealed increasing eosinophilia, and treatment with high-dosage corticosteroids and hydroxyurea was initiated as eosinophilic disease with organ manifestations could not be precluded. Eosinophils normalised and the patient was discharged again. The combination of hypereosinophilia and absence of infection, rheumatological disorders and malignancy, led to reactive or idiopathic hypereosinophilic syndrome being the most plausible diagnoses. The patient was closely monitored in the cardiology and haematology outpatient clinics. Echocardiographic evaluation, performed 6 weeks after the patient was discharged, showed significant regression in the size of the thrombus mass.

Loeffler endocarditis, eosinophilic endocarditis or eosinophilic endomyocardial disease are conditions associated with hypereosinophilia and they affect the heart function. Loeffler endocarditis is a rare endomyocardial disorder thought to be caused by eosinophilic damage. The disorder is characterized by inflammatory infiltration, formation of thrombus within cardiovascular system, and ultimately fibrosis of the afflicted area. It can lead to multiple severe complications, including thromboembolic disease, thickening of fibrous tissue in the endocardium of ventricles, valve involvement, apical obliteration, and various heart disorders. Although early clinical intervention can lead to remission, the underlying mechanisms of the disorder remain unresolved. In the present article, we summarise the existing literature concerning Loeffler endocarditis based on PubMed, Web of Science, and other medical databases to conduct an in-depth review of the epidemiology, etiology, pathophysiological mechanisms, staging, diagnosis, treatment and prognosis of Loeffler endocarditis. Meanwhile, we provide novel patients data and clinical figures of Loeffler endocarditis to supplement the understanding of this cardiac disorder. The findings presented in this article provide a basis for further studies and can be used to improve management of the disorder.

Hypereosinophilic syndrome (HES) is defined as the presence of (1) peripheral blood eosinophilia >1.5 x 109/L for at least one month, (2) evidence of eosinophil-mediated organ damage and/or dysfunction, and (3) exclusion of other potential causes of eosinophilia. In hemodialysis patients, HES has been associated with manifestations because of low blood pressure or gastrointestinal symptoms that result in dialysis intolerance. Very few cases of HES co-occurrence in dialysis patients have been reported in the literature, and their clinical characteristics are not fully understood. Here, we report two end-stage renal disease patients diagnosed with idiopathic HES while undergoing maintenance hemodialysis. The first patient presented with unexplained persistent pruritus and intradialytic hypotension, which started 10 minutes after the dialysis session initiation. Hematologic studies revealed hypereosinophilia which remarkably improved on steroid therapy. The second patient was accidentally discovered with asymptomatic persistent hypereosinophilia. His blood counts improved initially on interferon treatment before achieving full remission on steroid therapy. Neither of the two patients reported any history of allergy or atopic manifestations. Our case report sheds light on the possible occurrence of HES in hemodialysis patients which may be confused with other dialysis-related complications. Although steroids remain the mainstay of treatment, the optimal dose and duration of treatment remain unknown.

Chronic hypereosinophilia, defined as persistent elevated blood levels of eosinophils ≥1,500/μL, is associated with tissue infiltration of eosinophils and consequent organ damage by eosinophil release of toxic mediators. The current therapies for chronic hypereosinophilia have limited success, require repetitive administration, and are associated with a variety of adverse effects. As a novel approach to treat chronic hypereosinophilia, we hypothesized that adeno-associated virus (AAV)-mediated delivery of an anti-human eosinophil antibody would provide one-time therapy that would mediate persistent suppression of blood eosinophil levels. To assess this hypothesis, we first generated a human monoclonal antibody (mAb) directed against Siglec8, a sialic-acid binding immunoglobulin-like lectin, expressed at high levels on the cell surface of human eosinophils. Transgenic mice with a human immunoglobulin repertoire were immunized with human Siglec8 protein or DNA encoding human Siglec8. Based on target binding assessments, the 08C07 mAb was chosen for further study. The human variable regions of 08C07 were joined to the human Ig constant region, creating H08C07 (hAntiEos), a fully human anti-human eosinophil mAb. Using the gene sequence of hAntiEos, we created AAVrh.10hAntiEos, an AAVrh.10-based vector expressing the heavy and light chains of H08C07. Intravenous administration of AAVrh.10hAntiEos (1011 genome copies or gc) to C57Bl/6 mice resulted in persistent elevated serum levels of hAntiEos. In vivo gene therapy generated hAntiEos bound to recombinant human Siglec8 protein in a dose-dependent manner and to human eosinophils, mediated apoptosis of human eosinophils, and antibody-dependent cellular cytotoxicity activity against human eosinophils. Consistent with these data, administration of AAVrh.10hAntiEos to human CD34+ transplanted NSG-SGM3 immunodeficient mice suppressed levels of human eosinophils in vivo. AAVrh.10hAntiEos holds the potential to offer therapeutic benefit to patients with chronic hypereosinophilia.

Restrictive cardiomyopathy (RCM) is characterized by restrictive ventricular pathophysiology determined by increased myocardial stiffness. While suspicion of RCM is initially raised by clinical evaluation and supported by electrocardiographic and echocardiographic findings, invasive hemodynamic evaluation is often required for diagnosis and management of patients during follow-up. RCM is commonly associated with a poor prognosis and a high incidence of heart failure, and PH is reported in paediatric patients with RCM. Currently, only a few therapies are available for specific RCM aetiologies. Early referral to centres for advanced heart failure treatment is often necessary. The aim of this review is to address questions frequently asked when facing paediatric patients with RCM, including issues related to aetiologies, clinical presentation, diagnostic process and prognosis.

This narrative review examines the complex connection between infectious diseases and their neurological effects. It provides a detailed analysis of recent instances and insights derived from various pathogens. As we explore the realm of infectious agents, including viruses, bacteria, parasites, and fungi, a thorough and diverse analysis reveals the intricacies of neurological problems. The review begins by examining viral infections, specifically focusing on how viruses invade the neurological system and its subsequent effects. Significant instances from recent widespread disease outbreaks function as instructive benchmarks, highlighting the progressing comprehension of these ever-changing interconnections. The article examines the complex pathophysiology of neurological problems caused by bacterial infections. It presents current cases that illustrate the various ways these complications might manifest and the difficulties faced in their therapeutic management. Parasitic and fungal infections, which are typically overlooked, are being carefully examined to emphasize their distinct role in causing neurological complications. The mentioned cases highlight the importance of being thoroughly aware of these less-explored areas ranging from protozoan parasites to opportunistic fungal infections. In addition to the immediate effects caused by infectious agents, the review investigates autoimmune responses activated by infections. It provides a detailed examination of specific instances that shed light on the complex relationship between viral triggers and future neurological problems. This text elaborates on the intricacy of autoimmune-related neurological issues, highlighting the necessity for a comprehensive approach to diagnosing and treating them. The narrative next redirects its attention to the diagnostic difficulties that arise when interpreting the neurological symptoms of viral disorders. This article provides a thorough examination of existing diagnostic tools, along with an investigation into new technologies that have the potential to improve our capacity to identify and comprehend complex presentations. This debate connects to the following examination of treatment methods, where current cases that showcase successful interventions are carefully examined to extract valuable insights into good clinical management. The discussion focuses on the public health implications of preventive efforts against infectious infections, including their neurological consequences. The story emphasizes the link between infectious diseases and overall societal health, advocating for a proactive strategy to reduce the impact of neurological complications. The abstract concludes by providing a prospective viewpoint, highlighting areas of research that still need to be addressed, and suggesting potential future avenues. This narrative review seeks to provide a comprehensive resource for physicians, researchers, and public health professionals dealing with the complex field of neurological manifestations in infectious diseases. It combines recent examples, synthesizes current information, and offers a holistic perspective.

Hypereosinophilic syndrome is a progressive disease with extensive eosinophilia that results in organ damage. Cardiac pathologies are the main reason for its high mortality rate. A better understanding of the mechanisms of eosinophil-mediated tissue damage would benefit therapeutic development. Here, we describe the cardiac pathologies that developed in a mouse model of hypereosinophilic syndrome. These IL-5 transgenic mice exhibited decreased left ventricular function at a young age which worsened with age. Mechanistically, we demonstrated infiltration of activated eosinophils into the heart tissue that led to an inflammatory environment. Gene expression signatures showed tissue damage as well as repair and remodeling processes. Cardiomyocytes from IL-5Tg mice exhibited significantly reduced contractility relative to wild type (WT) controls. This impairment may result from the inflammatory stress experienced by the cardiomyocytes and suggest that dysregulation of contractility and Ca2+ reuptake in cardiomyocytes contributes to cardiac dysfunction at the whole organ level in hypereosinophilic mice.

Hypereosinophilic syndrome (HES) is a leucoproliferative disorder, characterized by marked blood eosinophilia and organ damage due to tissue eosinophilia. Pulmonary involvement may lead to life-threatening acute respiratory failure and intensive care unit (ICU) admission. Association between eosinophilia and thromboembolism has been previously described. However, simultaneous venous and arterial thromboses are less reported. We report a case of a 25-year-old man, admitted to the ICU and developed acute respiratory failure, laboratory tests revealed hyperleukocytosis (39,700 /µL) with high eosinophil count (27393 /µl), Computed tomographic (CT) pulmonary angiography on admission showed a right pulmonary embolism and foci of splenic infarctions. Echocardiography showed a thrombus in the ascending aorta. On day 3, the patient presented worsening polypnea with increase of oxygen requirements. Chest CT scan showed pulmonary parenchymal involvement with bilateral condensations surrounded by "tree-in-bud" micronodules. The diagnosis of eosinophilic pneumonia was established. Bone marrow biopsy showed hyperplasia of the 3 lineages, predominant on the granulocyte lineage made mostly of eosinophilic polynuclear mature cells, suggesting myeloproliferative syndrome. The patient was treated with corticosteroids and anticoagulation. Physicians should consider HES diagnosis in case of hypereosinophilia and evolving life threatening organ damage to avoid therapy delay and complications.

The landscape of polyarteritis nodosa (PAN) has substantially changed during the last decades. Recent data regarding causes, characteristics, and prognosis of systemic PAN in the modern era are lacking.

This retrospective study included patients with systemic PAN referred to the French Vasculitis Study Group between 2005 and 2019. Characteristics, associated conditions and outcomes were collected, and predictors of relapse and death were analyzed.

196 patients were included. Main clinical symptoms were constitutional (84%), neurological (59%), skin (58%) and musculoskeletal (58%) manifestations. Secondary PAN accounted for 55 (28%) patients, including myelodysplastic syndrome (9%), solid cancer (7%), lymphoma (4%) and autoinflammatory diseases (4%). No patient had active HBV infection. All treated patients (98.5%) received glucocorticoids (GCs), alone (41%) or in combination with immunosuppressants (59%), with remission achieved in 90%. Relapses were independently associated with age >65 years (HR 1.85; 95% CI1.12-3.08), gastrointestinal involvement (1.95; 95% CI1.09-3.52) and skin necrotic lesions (HR 1.95; 95%CI 1.24-3.05). One-, 5- and 10-year overall survival rates were 93%, 87% and 81%, respectively. In multivariate analyses, age >65 years (HR 2.80; 95%CI 1.23-6.37), necrotic purpura (HR 4.16; 95%CI 1.62-10.70), acute kidney injury (HR 4.89; 95% 1.71-13.99) and secondary PAN (HR 2.98; 95%CI 1.29-6.85) were independently associated with mortality.

Landscape of PAN has changed during the last decades, with the disappearance of HBV-PAN and the emergence of secondary PAN. Relapse rate remains high, especially in aged patients with gastrointestinal and cutaneous necrosis, as well as mortality.