Probable idiopathic hypereosinophilic syndrome: A case report of severe multi-organ eosinophilic involvement in a young male presenting with heart failure.

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.

An Unusual Case of Immune Complex-Mediated Membranoproliferative Glomerulonephritis as Renal Manifestation of Idiopathic Hypereosinophilic Syndrome: A Case Report and Literature Review.

BACKGROUND: Idiopathic hypereosinophilic syndrome (IHES) is a disorder characterized by abnormal and persistent peripheral blood hypereosinophilia (eosinophil count ≥ 1.5 × 109/L and ≥10% eosinophils) with duration ≥ 6 months, associated organ damage, and/or dysfunction attributable to tissue eosinophilic infiltrate of unknown cause. IHES affects different organs such as the heart, lungs, nervous system, and skin, with renal involvement being rare in this condition. CASE PRESENTATION: We present a case of a young patient with IHES and immune complex-mediated membranoproliferative glomerulonephritis with nephrotic syndrome, as a rare renal manifestation. We discuss the clinical, analytical, and histopathologic renal and hematologic features, comparing them with other reported cases in the literature.

Prognostic factors of idiopathic hypereosinophilic syndrome: A nationwide survey in Japan.

Idiopathic hypereosinophilic syndrome (iHES) is a condition wherein persistent hypereosinophilia associated with end-organ damage occurs without any known causes. Due to the rarity of the disease, insufficient knowledge has been accumulated. We therefore conducted a retrospective, multicentre, nationwide survey on iHES in Japan. A total of 57 patients were identified. For 43 patients who received any treatment, all cases were first treated with corticosteroids. An eosinophil percentage of less than 30% in the bone marrow and the absence of oedema were identified as factors associated with steroid dependency. The 5-year overall survival was 88.2%, and five patients died during follow-up; factors associated with worse overall survival were age >50, haemoglobin <12 g/dL, activated partial thromboplastin time >34 s, the presence of dyspnoea, the presence of thrombotic tendency and the presence of renal failure. Given the rarity of fatalities in our cohort, time-to-next-treatment (TTNT) was further analysed; the presence of renal failure, splenomegaly and lung abnormalities were associated with worse TTNT. Our nationwide study not only demonstrated clinical characteristics and the outcome of patients with iHES but also for the first time revealed clinical factors associated with steroid dependency and duration of first-line corticosteroid efficacy.

Cardiac Magnetic Resonance Imaging Used to Determine a Rare Etiology of a Layered Left Ventricular Apical Thrombus.

Eosinophilic myocarditis (EM) is a rare disease, often associated with hypereosinophilic syndrome (HES). Historically, the diagnostic gold standard was endomyocardial biopsy (EMB). We present a unique case of a 58-year-old female who presents after a syncopal episode and was found to have a layered left ventricular (LV) thrombus. Using laboratory studies and cardiac magnetic resonance imaging (MRI), we were able to delineate the etiology, avoiding any invasive testing.

A Rare Presentation of Hypereosinophilic Syndrome With Loffler's Endomyocarditis, Encephalopathy, and Multiple Thromboembolic Strokes.

Idiopathic hypereosinophilic syndrome is a disorder with a high eosinophilic count for which no identifiable cause is evident. Herein we report a case of a 47-year-old male with a background history of hypereosinophilia, who presented with sudden onset altered level of consciousness and drowsiness for 1-day duration associated with a gradual onset progressive memory loss for 1-month duration. Based on clinical, biochemical, and imaging studies, a diagnosis of Loffler's endomyocarditis was made for which he was treated with albendazole with diethylcarbamazine along with high-dose steroids. He made a successful recovery after 2 months of treatment.

Hypereosinophilic Syndrome Endocarditis With Severe Biventricular Failure Complicated by Sepsis: A Challenging Case.

Hypereosinophilic syndrome (HES) is a myeloproliferative disorder characterized by persistent hypereosinophilia that is associated with multi-organ damage. Eosinophilic endocarditis is a serious complication of HES. The exact prevalence of the disease is unknown, and it is characterized by a persistently elevated eosinophil count, resulting in multi-organ involvement due to eosinophilic infiltration. We present a case of a 65-year-old Caucasian male patient who presented with one-week symptoms of feeling unwell and intermittent pleuritic chest pain. His medical history was significant for the idiopathic hypereosinophilic syndrome, eosinophilic myocarditis, hypertension (HTN), type 2 diabetes mellitus (T2DM), and chronic obstructive pulmonary disease (COPD). Inflammatory markers were raised, including eosinophil count, and a transthoracic echocardiogram (TTE) showed a mass attached to the mitral valve (MV) leaflets, suggesting vegetation or thrombus. The patient was commenced on intravenous antibiotics, inotropes for septic shock, and low molecular weight heparin (LMWH) for a possible thrombus. He showed mild biochemical improvement initially without any clinical improvement before further deterioration secondary to aspiration pneumonia. He was seen by the palliative care team and mental health team for confusion and agitation and was put on the palliative care pathway. All active medical treatment was stopped, and the patient succumbed to his illness three weeks into his admission.

Successful use of mepolizumab for severe hypereosinophilic vasculitis with c-ANCA positivity in a previously healthy 7-year-old boy.

An unusual case of a pediatric patient with severe eosinophilic vasculitis causing digital ischemia is reported. The patient responded well to the anti-IL-5 agent mepolizumab, lending support for use of mepolizumab in pediatric patients with hypereosinophilic syndromes.

Idiopathic Hypereosinophilic Syndrome: A Case Report.

Idiopathic hypereosinophilic syndrome is a rare condition characterized by persistent severe eosinophilia and organ damage without any apparent cause. A 20-year-old male patient with no significant medical history was admitted to the Emergency Department with retrosternal chest pain, fatigue and asthenia. EKG showed ST elevation I, II, III, aVF, V4-V6 and blood tests showed elevated troponin levels. An echocardiogram was performed revealing severe global left ventricular systolic dysfunction. Further evaluations included cardiac magnetic resonance imaging and endomyocardial biopsy, confirming the diagnosis of eosinophilic myocarditis. The patient was started on systemic corticosteroid therapy, resulting in clinical improvement. The patient was discharged after 12 days of hospitalization, following a recovery of biventricular function and he was told to continue oral corticosteroid therapy at home. Further investigation ruled out other causes of hypereosinophilic syndromes, therefore the diagnosis of idiopathic hypereosinophilic syndrome was assumed. Despite the attempt to reduce corticosteroid therapy, the eosinophil count became elevated again, so the dosage was increased and associated with azathioprine with subsequent favorable analytical evolution. This case highlights the challenges in diagnosing and managing idiopathic hypereosinophilic syndrome and emphasizes the importance of prompt treatment initiation to prevent complications.

Case Report: Off-label treatment of idiopathic hypereosinophilic syndrome with Omalizumab.

Idiopathic hypereosinophilic syndrome (IHES) is a rare disease characterized by causeless persistent hypereosinophilia and eosinophilia-associated end-organ damage. Current treatment modalities don't meet the needs due to adverse events of steroids as first-line therapy and the limited efficacy of second-line treatments, underscoring the need for new therapeutic strategies. Here we presented two cases of IHES with different clinical manifestations that were both refractory to corticosteroids. Patient #1 experienced rashes, cough, pneumonia, and steroid-induced side effects. Patient #2 had severe gastrointestinal symptoms attributed to hypereosinophilia. They both had high levels of serum IgE, didn't respond well to second-line treatments of interferon-α (IFN-α) and imatinib, and Mepolizumab was not accessible. We then innovatively switched to Omalizumab, an anti-IgE monoclonal antibody approved for allergic asthma and chronic idiopathic urticaria. Patient #1 was treated with Omalizumab 600 mg per month for 20 months; his absolute eosinophil count (AEC) decreased significantly and has stabilized at around 1.0×109/L for 17 months, with complete relief from erythra and cough. Patient #2 recovered promptly from severe diarrhea with a sharp drop in AEC after 3 months of treatment with omalizumab at 600 mg per month. Therefore, we concluded that Omalizumab may be a seminal therapeutic strategy for IHES patients who are refractory to corticosteroids, whether as long-term management of AEC or as an urgent intervention to address severe symptoms caused by eosinophilia.

Updates on eosinophilic disorders.

This review addresses changes and updates in eosinophilic disorders under the International Consensus Classification (ICC). The previous category of myeloid/lymphoid neoplasm with eosinophilia (M/LN-eo) and a specific gene rearrangement is changed to M/LN-eo with tyrosine kinase gene fusions to reflect the underlying genetic lesions. Two new members, M/LN-eo with ETV6::ABL1 fusion and M/LN-eo with various FLT3 fusions, have been added to the category; and M/LN-eo with PCM1::JAK2 and its genetic variants ETV6::JAK2 and BCR::JAK2 are recognized as a formal entity from their former provisional status. The updated understanding of the clinical and molecular genetic features of PDGFRA, PDGFRB and FGFR1 neoplasms is summarized. Clear guidance as to how to distinguish these fusion gene-associated disorders from the overlapping entities of Ph-like B-acute lymphoblastic leukemia (ALL), de novo T-ALL, and systemic mastocytosis is provided. Bone marrow morphology now constitutes one of the diagnostic criteria of chronic eosinophilic leukemia, NOS (CEL, NOS), and idiopathic hypereosinophilia/hypereosinophilic syndrome (HE/HES), facilitating the separation of a true myeloid neoplasm with characteristic eosinophilic proliferation from those of unknown etiology and not attributable to a myeloid neoplasm.

Idiopathic Hypereosinophilia: A Multicenter Retrospective Analysis.

Purpose: Physicians can sometimes encounter idiopathic hypereosinophilia (HE), but little is known about it. In this multicenter study, we analyzed the clinical characteristics, treatment, and outcomes of patients with idiopathic HE. Patients and Methods: Patients diagnosed with idiopathic HE (idiopathic hypereosinophilic syndrome: iHES or hypereosinophilia with undetermined significance: HEus) at six tertiary hospitals between January 2010 and June 2021 were included in this retrospective observational study. Demographics, clinical and laboratory data, and treatment responses were obtained from the electronic medical records of the study subjects. Results: A total of 73 patients with idiopathic HE (45 with iHES and 28 with HEus) were included in the present study. Overall, 12 (26.7%) and 5 (17.9%) were women, and mean age of patients at diagnosis was 51.84 ± 17.29 years and 60.21 ± 18.01 years in iHES and HEus groups, respectively. Forty-three (95.6%) patients of iHES and 15 (53.6%) patients of HEus received corticosteroids as 1st-line treatment. Treatment response to corticosteroids in patients with iHES was generally good: complete response (n=25, 58.1%), partial response (n=12, 27.9%), no response (n=6, 14.0%). Treatment response to corticosteroids in HEus was complete response (n=7, 46.7%), partial response (n=6, 40.0%), and no response (n=2, 13.3%). There were 13 patients (46.4%) with HEus who were not treated. Conclusion: Corticosteroid treatment is generally effective and well tolerated by patients with iHES. Some patients with HEus are treated with corticosteroids in clinical practice. Extensive research is needed to establish a standardized management guidelines for iHES and determine whether treatment for HEus is required.

Case report: Application of non-VKA oral anticoagulants in patient of idiopathic hypereosinophilic syndrome with intracardiac thrombus.

Idiopathic hypereosinophilic syndrome (IHES) is a rare but life-threatening disease related to a group of myeloproliferative disorders characterized by prolonged eosinophilia of unknown cause and inflammatory damage to multiple organs. Here, we present a 44-year-old female patient complaining of shortness of breath and palpitations for 1 month. Her history and presentation were unremarkable, except for a 3-years history of rheumatoid arthritis treated with ibuprofen (0.3 g per day). Initial examination showed heart rate (HR) 120 bpm, respiratory rate (RR) 20 bpm, temperature (T) 36°C, blood pressure (BP) 130/70 mmHg, ventricular gallop rhythm, rales at the lung bases, soft abdomen, nonpalpable liver and spleen, and slight edema in both lower extremities. Bone marrow aspirate and biopsy confirmed the diagnosis of IHES, while cardiac MRI showed intracardiac thrombus. The symptoms of shortness of breath and palpitation disappeared, the eosinophil counts in routine blood tests were normal, and the thrombus in the cardiac cavity gradually disappeared after combined therapy of anti-hypereosinophilic, anti-coagulant and anti-heart failure treatments.

The Neutrophil/Lymphocyte Ratio is an Independent Predictor of All-Cause Mortality in Patients with Idiopathic Hypereosinophilic Syndrome.

Background: Idiopathic hypereosinophilic syndrome (IHES) often causes inflammatory damage to multiple organs. However, whether immune/inflammatory indicators and other factors are associated with mortality in patients with IHES remains unclear. Patients and Methods: The clinical data and follow-up results of 167 patients with IHES were retrospectively analyzed using Cox regression analysis and receiver operating characteristic curve (ROC). Results: Of 167 patients, 120 were men (71.9%) and 47 were women (28.1%). The median age was 52 (36.0, 68.0) years. The median follow-up period was 42.8 (18.5, 75.1) months, during which all-cause mortality occurred in 26 patients (15.6%). Age (HR: 1.041, 95% CI: 1.015-1.068; p = 0.002), lymphocyte counts (109/L, HR: 0.866, 95% CI: 0.816-0.907; p = 0.013), platelet counts (109/L, HR: 0.994, 95% CI: 0.989-0.999; p = 0.012) and NLR (HR: 1.161, 95% CI: 1.054-1.280; p = 0.003) were independent risk factors for all-cause mortality. There was no relationship between PLR, and SII and all-cause mortality (p = 0.181 and 0.202, respectively). ROC analysis showed that the AUCs of age, lymphocyte count (109/L), platelet count (109/L) and NLR were 0.712 (95% CI: 0.601-0.824), 0.584 (95% CI: 0.448-0.719), 0.686 (95% CI: 0.560-0.812), and 0.797 (95% CI: 0.695-0.899), respectively, with sensitivities of 0.5, 0.462, 0.769, and 0.792, respectively, and specificities of 0.765, 0.745, 0.617, and 0.845, respectively. Kaplan-Meier analysis (Log rank test) showed that patients with age ≥73.5 years, lymphocyte count (109/L) <1.45, platelet count (109/L) <225 and NLR ≥2.54 had high mortality. Patients with high NLR (≥2.54) usually have multiorgan involvement, with cardiac involvement and skin involvement being the most common. Patients with NLR ≥2.54 had significantly higher absolute eosinophil counts (p = 0.047) and percentages (p = 0.041). Conclusion: We identified NLR for the first time as an independent predictive factor for all-cause mortality in patients with IHES, necessitating its further application in clinical practice.

Hyperleucocytosis as an unusual presentation of hypereosinophilic pneumonitis with acute respiratory distress syndrome.

Idiopathic hypereosinophilic syndrome in children is a rare disease. Even with improved understanding of eosinophilic disorders and recent advances in diagnostic modalities, evaluation of hypereosinophilia remains challenging due to heterogeneous etiologic factors. In acute clinical settings, the management plan is often unclear as the condition is not encountered frequently. It is often associated with leucocytosis, but hyperleucocytosis causing multiorgan dysfunction in the absence of malignancy is rarely seen. A previously well 5-year-old boy presented to our emergency room with a 2-week history of fever, progressive cough and dyspnoea, rapidly progressing to respiratory failure and acute respiratory distress syndrome. Hyperleucocytosis with hypereosinophilia on peripheral blood film, bilateral pulmonary infiltrates on X-ray and ground glass opacities suggested hypereosinophilic syndrome with secondary acute respiratory distress syndrome. Owing to severe and rapidly increasing leucocytosis, malignancy was highly suspected, but it was ruled out along with secondary hypereosinophilic syndrome after extensive investigations, and acute respiratory distress syndrome in this child was attributed to Idiopathic Hypereosinophilic Syndrome. Eosinophilia had a dramatic response to high dose corticosteroid therapy. To conclude, in patients with hypereosinophilic syndrome, possibility of progression to acute respiratory distress syndrome should be anticipated and managed accordingly.

Eosinophilia characterized by a rare CCT6B mutation and responsive to tyrosine kinase inhibition: Case report and literature review.

Hypereosinophilic syndrome is a rare disorder arising from neoplastic, or idiopathic causes. The availability of NGS panels has increasingly identified rare mutations as underlying pathogenic events and have led to reclassification of cases of idiopathic hypereosinophilic syndrome as chronic eosinophilic leukemia(CEL). In this report, we describe a case of a young man with hypereosinophilia whose disease initially did not fit the WHO criteria for CEL but harbored a rare mutation in CCT6B gene. We report our experience in successfully treating this patient with multiple tyrosine kinase inhibitors and provide literature review of this rare entity including potential treatment strategies.

Recurrent prosthetic valve dysfunction in a patient with idiopathic hypereosinophilic syndrome: A case report and literature review.

Idiopathic hypereosinophilic syndrome with cardiac involvement is characterized by endocardial fibrosis and thrombosis. Here, we report a case of mitral valve prosthetic dysfunction in a patient with idiopathic hypereosinophilic syndrome and review related cases in the literature. Valve replacement with a 27-mm St. Jude bioprosthetic mitral valve improved his symptoms and hypereosinophilia. A 4-year follow-up revealed that the prosthetic valve was intact without thrombosis. Because mechanical prosthesis implantation yields poor surgical outcomes, bioprosthesis is the preferred choice for patients with idiopathic hypereosinophilic syndrome. Medications for controlling eosinophilia may improve the long-term outcomes of valve replacement surgeries.

Idiopathic hypereosinophilic syndrome with intracardiac atypical linear-shaped and floating thrombus presenting as embolic cerebral infarction.

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. .

[Multiple cerebral infarctions in the deep perforator regions in a case of idiopathic hypereosinophilic syndrome].

A 61-year-old man was admitted to our hospital due to cerebral infarction in the pons and the right putamen. On admission (day 3 from symptom onset), laboratory testing showed a white blood cell count of 13,100/µl with hypereosinophilia of 3,734/µl. As deep vein thrombosis was detected on contrast-enhanced CT, we started anticoagulation therapy. There were no cardio-embolic sources, including right-to-left shunt, but eosinophil infiltration was found in biopsy specimens of the gastric mucosa. These findings allowed us to diagnose multiple perforator infarction due to idiopathic hypereosinophilic syndrome (idiopathic HES). After the administration of oral prednisolone was started on day 10, his hypereosinophilia rapidly improved, and no recurrence of deep perforator infarction occurred other than a symptomatic infarction in the left putamen at day 19. There are a few reports of idiopathic HES with multiple infarctions developing in deep perforator regions. The current case suggests that idiopathic HES could cause multiple cerebral infarction restricted to deep perforator areas.

Idiopathic Hypereosinophilic Syndrome with Multiple Organ Involvement.

Idiopathic hypereosinophilic syndrome is a rare disease which is diagnosed after excluding other conditions. The syndrome is characterized by multiple organ involvement including the heart, nervous system, lungs, and gastrointestinal tract. The disease is suspected if there is peripheral blood eosinophilia and no clear etiology. The main treatment is corticosteroids. Patients who do not respond to corticosteroids can be treated with imatinib, immunomodulatory agents, myelosuppressive therapy, or mepolizumab. Alemtuzumab can be considered in severe cases that are unresponsive to other therapies. In this paper, we describe a case of idiopathic hypereosinophilic syndrome with mainly cardiac system involvement and left ventricular thrombus formation which was complicated by cerebral thromboemboli while on warfarin with international normalized ratio in the therapeutic range. Our patient responded well to steroids appreciated by improvement in clinical symptoms and decrease in eosinophil count.

Acute progressive stroke with middle cerebral artery occlusion caused by idiopathic hypereosinophilic syndrome: a case report.

BACKGROUND: Idiopathic hypereosinophilic syndrome (IHES) is associated with various organ system dysfunctions. Neurologic abnormalities have been previously noted in this syndrome. Cerebral infarction secondary to occlusion of large cerebral artery is rarely reported. Here we described a patient with IHES presented progressive multiple cerebral infarctions caused by bilateral middle cerebral artery occlusion. CASE PRESENTATION: A 55-year-old Chinese woman presented to our hospital with acute onset of right limbs weakness and slurred speech. Laboratory tests showed a significant eosinophilia of 5.29 × 109/L (normal, < 0.5), 49.9% of leukocytes. Brain magnetic resonance imaging (MRI) revealed multiple acute cerebral ischemic lesions. Magnetic resonance angiography (MRA) demonstrated stenosis in horizontal segment of right middle cerebral artery. A pretibial skin biopsy revealed eosinophilic infiltration around the capillaries in deep dermis and adipose tissue. The patient was given oral dual anti platelet agents and intravenous methylprednisolone. However, one week later, the patient presented significant neurological deterioration with right-sided hemiparesis and totally motor aphasia. Brain MRI and computed tomography perfusion (CTP) demonstrated new acute cerebral ischemia in left hemisphere. Digital subtraction angiography (DSA) revealed left middle cerebral artery completely occluded. The patient received a high-dose of intravenous methylprednisolone 500 mg per day and the eosinophil count quickly fell to normal within 2 days. She was transferred to a rehabilitation center and her neurological symptoms improved with modified Ranking Scale from 4 to 2. CONCLUSIONS: IHES is one of the rare causes of acute ischemic stroke with large cerebral artery occlusion. An early high-dose of corticosteroids therapy should be considered in cases of IHES patients. Our case study is benefit to clinical diagnosis and treatment of cerebral infarction with IHES.