Idiopathic hypereosinophilic syndrome presenting with stroke.

Hypereosinophilic syndrome (HES) is characterized by eosinophilia associated with organ damage. The disorder has substantial clinical heterogeneity and a highly variable prognosis. This report describes an interesting autopsy case of a 62-year-old lady presenting with itching and stroke-like symptoms. She was diagnosed with an "idiopathic" variant of HES after a thorough exclusion of all known causes. Despite adequate measures, she deteriorated rapidly. At autopsy, acute cerebral infarcts were identified in multiple vascular territories including infarcts in watershed areas. Additionally, her heart showed classic pathological features of eosinophilic myocarditis spanning all three stages.

Loeffler's Endocarditis- A cause of endomyocardial fibrosis in a patient of juvenile idiopathic arthritis: A Case Report.

Endomyocardial fibrosis secondary to hyper-eosinophilic syndrome also known as Loeffler's Endocarditis is a rare cause of restrictive cardiomyopathy. If left untreated, it carries a very high morbidity and mortality rate. The case of a 20 years old girl, a known case of polyarticular juvenile idiopathic arthritis since the age of 13 years was reported at Federal Government Polyclinic Hospital, Islamabad on 14th May 2022. She presented with an acute history of shortness of breath and cough for two weeks. Her initial echocardiogram showed suspicion of Loeffler's Endocarditis, which is attributed to be an adverse effect of etanercept- a tumour necrosis factor (TNF) inhibitor, which she had been prescribed for her arthritis. The patient is currently being managed with high doses of steroids, therapeutic anticoagulation with rivaroxaban, carvedilol for tachycardia and mycophenolate mofetil as an immunosuppressant.

Proposed refined diagnostic criteria and classification of eosinophil disorders and related syndromes.

Eosinophilia and eosinophil activation are recurrent features in various reactive states and certain hematologic malignancies. In patients with hypereosinophilia (HE), HE-induced organ damage is often encountered and may lead to the diagnosis of a hypereosinophilic syndrome (HES). A number of known mechanisms and etiologies contribute to the development of HE and HES. Based on these etiologies and the origin of eosinophils, HE and HES are divided into primary forms where eosinophils are clonal cells, reactive forms where an underlying reactive or neoplastic condition is detected and eosinophils are considered to be "non-clonal" cells, and idiopathic HE and HES in which neither a clonal nor a reactive underlying pathology is detected. Since 2012, this classification and the related criteria have been widely accepted and regarded as standard. However, during the past few years, new developments in the field and an increasing number of markers and targets have created a need to update these criteria and the classification of HE and HES. To address this challenge, a Working Conference on eosinophil disorders was organized in 2021. In this conference, a panel of experts representing the relevant fields, including allergy, dermatology, hematology, immunology, laboratory medicine, and pathology, met and discussed new markers and concepts as well as refinements in definitions, criteria and classifications of HE and HES. The outcomes of this conference are presented in this article and should assist in the diagnosis and management of patients with HE and HES in daily practice and in the preparation and conduct of clinical trials.

Pediatric hypereosinophilic syndrome associated with liver damage, portal vein, splenic vein and superior mesenteric vein thromboses: a case report.

BACKGROUND: The hypereosinophilic syndrome (HES) is a group of rare blood disorders characterized by persistent eosinophilia and damage to multiple organs. HES can be either primary, secondary or idiopathic. Secondary HES are commonly caused by parasitic infections, allergic reactions or cancer. We described a pediatric case of HES associated with liver damage and multiple thrombi. A 12-year-old boy with eosinophilia was complicated with severe thrombocytopenia, liver damage, portal vein, splenic vein, and superior mesenteric vein thromboses. The thrombi recanalized after treatment with methylprednisolone succinate and low molecular weight heparin. No side effects appeared after 1-month. CONCLUSIONS: Corticosteroids should be used at an early stage of HES to prevent further damage to vital organs. Anticoagulants should be recommended only in cases with thrombosis which should be actively screened as a part of evaluation of end organ damage.

Hypereosinophilic syndrome with cutaneous manifestations successfully treated with Dupilumab as a sole agent: A case report.

Hypereosinophilic syndrome describes a process in which eosinophils in the peripheral blood are persistently increased, with variable clinical manifestations. Finding efficacious treatments for this disease can be challenging. This case describes a 72-year-old man with idiopathic hypereosinophilic syndrome with cutaneous manifestations who was successfully treated with dupilumab as a single agent therapy. There was complete clinical and biochemical resolution of disease (eosinophils levels decreased from 4.13 to 0.92) without complications.

[Chronic neutrophilic leukemia/chronic eosinophilic leukemia].

Chronic neutrophilic leukemia (CNL) is a clonal disorder that is characterized by increasing mature neutrophils. Colony stimulating factor 3 receptor (CSF3R) T618I mutation was frequently identified in patients with CNL and is defined as a molecular marker of the disease. Ruxolitinib, a JAK2 inhibitor, provided a promising therapeutic effect in a phase II study. In particular, ruxolitinib was more efficient for patients with CSF3R mutation. Allogeneic stem cell transplantation (Allo-SCT) may be a curative treatment for CNL. On the other hand, further studies are needed to define the optimal method of transplantation, source of donor, conditioning therapy, and timing of transplantation. Chronic eosinophilic leukemia (CEL) is a clonal disorder that is characterized by increasing eosinophils. In the World Health Organization Classification 5th edition, diagnostic criteria for CEL are renewed. Because the new criteria will be more specific for CEL than criteria in the older edition, "not otherwise specified (NOS) " is removed from the name of the disease. Anti-CD52 antibody, alemtuzumab, or anti-IL-5 antibody, mepolizumab, are promising drugs to control symptoms that are associated with hypereosinophilic syndrome. Allo-SCT is anticipated as a curative treatment for CEL, but the evidence of Allo-SCT for CEL is still limited. Further study is required to define the treatment strategy.

Case 305: Loeffler Endocarditis.

HISTORY: A 27-year-old man was admitted to the emergency department with fever and thoracic pain. In the previous 6 months, the patient lost a substantial amount of weight (12 kg). His family history was negative for cardiac disease. Electrocardiography revealed sinus rhythm and diffuse T-wave inversion. Two-dimensional echocardiography was performed and revealed normal left systolic function (ejection fraction, 60%). Laboratory tests showed elevated levels of high-sensitivity cardiac troponin (1.07 ng/mL; normal value, <0.015 ng/mL), high levels of C-reactive protein (16 mg/dL; normal range, 0-5 mg/dL), and leukocytosis with an eosinophilia level of 8710/µL (normal level, <400/µL). Parasitic and infectious diseases (Toxocara canis, strongyloides, filariasis, cysticercosis, fasciola, trichinella, echinococcosis) were excluded based on blood and fecal test results. Corticosteroid therapy was started, and the patient was dismissed. A few days later, he was readmitted to the emergency department with a headache and suddenly blurred vision. Neurologic and ophthalmologic findings were normal, and MRI of the brain was performed. Cardiac MRI was performed 2 days later and revealed the following quantitative results: (a) left ventricular end-diastolic volume (LVDV) of 165 mL (LVDV/body surface area [BSA], 89 mL/m2; normal range, 64-100 mL/m2), left ventricular end-systolic volume (LVSV) of 80 mL (LVSV/BSA, 43 mL/m2; normal range, 17-39 mL/m2), stroke volume (SV) of 85 mL (SV/BSA, 46 mL/m2; normal range, 43-67 mL/m2), and ejection fraction of 52% and (b) right ventricular end-diastolic volume (RVDV) of 163 mL (RVDV/BSA, 88 mL/m2; normal range, 63-111 mL/m2), right ventricular end-systolic volume (RVSV) of 81 mL (RVSV/BSA, 44 mL/m2; normal range, 32-92 mL/m2), stroke volume (SV) of 82 mL (SV/BSA, 44 mL/m2; normal range, 39-71 mL/m2), and ejection fraction of 50%.

Systemic thrombo-embolic events in a middle-aged male with Loeffler endocarditis without peripheral eosinophilia-a case report.

BACKGROUND: Loeffler-endocarditis (LE) is considered a chronic restrictive cardiomyopathy and manifestation of eosinophilic myocarditis characterized by eosinophilic infiltration. LE is a rare underdiagnosed disease and associated with high morbidity and mortality. CASE PRESENTATION: We report a case of a 46-year-old man suffering from LE associated with thromboembolic events without peripheral eosinophilia. The patient presented with typical clinical signs of acute onset of limb ischaemia, predominantly on the right limb, indicating immediate iliacal thrombectomy and due to a severe compartment syndrome additional fasciotomy. Total occlusion also of left popliteal artery suggesting an impaired chronic and aggravated impaired perfusion indicated also urgent left sided revascularization. Subsequent echocardiography revealed severe left ventricular dysfunction with a striking amount of spontaneous echo-contrast, noticeable in the left ventricular cavity. Furthermore the initial CT scan demonstrated asymptomatic left kidney- and brain infarctions. Diagnostic workup including endomyocardial biopsy (EMB) of the left ventricle, uncovered an underlying LE without peripheral eosinophilia. CONCLUSIONS: This case demonstrates and highlights the findings, treatment and outcome of a patient with LE and associated thrombo-embolic events without peripheral eosinophilia and emphazises the importance of awareness for LE in patients presenting with an acute cardiac decompensation and thrombo-embolic events. EMB should be performed early in unstable patients unsuitable for cardiovascular magnetic resonance imaging.

Idiopathic Hypereosinophilic Syndrome Associated With Pulmonary Hypertension in an Infant.

Hypereosinophilic syndrome (HES) is a very rare disease during childhood. It involves the different organs like skin, gastrointestinal system, heart and lungs, besides pulmonary hypertension (PHT) is a very rare morbidity of HES that may cause life-threatening complications. PHT improves with the treatment of hypereosinophilia, without the need for pulmonary vasodilator therapy. Here, we present a case of PHT developed after recovery of pulmonary infiltration in an infant with idiopathic HES. We revealed that pulmonary pressure returned to normal range in parallel with the decrease in eosinophil count with steroid treatment.

Imaging patterns of cerebral ischemia in hypereosinophilic syndrome: case report and systematic review.

INTRODUCTION: Ischemic stroke is a potential complication of hypereosinophilic syndromes (HES), and little is known about underlying pathophysiological mechanisms. We aimed to describe the imaging patterns of cerebral ischemia in patients with HES. METHODS: An individual case is reported. A systematic PubMed review of all records reporting adult patients with HES who suffered ischemic stroke and for whom neuroimaging details of ischemic lesions were available was performed. RESULTS: A 60-year-old man presented with progressive subacute gait difficulty and psychomotor slowing as well as an absolute eosinophilia (2.2 × 109/L) at admission. Brain magnetic resonance tomography revealed multiple acute and subacute internal and external border zone infarcts. Cardiac diagnostic suggested the presence of endomyocarditis. After extensive diagnostic workup, idiopathic HES was diagnosed. The systematic review yielded 183 studies, of which 40 fulfilled the inclusion criteria: a total of 64 patients (31.3% female), with mean age 51.1 years and a median absolute eosinophile count at diagnosis of 10.2 × 109/L were included in the analyses. A border zone pattern of cerebral ischemic lesions was reported in 41 patients (64.1%). Isolated peripheral infarcts were reported in 7 patients (10.9%). Sixteen patients had multiple acute infarcts with no border zone distribution (25.0%). An intracardiac thrombus was reported in 15/60 patients (25%), and findings suggestive of endomyocarditis or endomyocardial fibrosis were found in 31/60 patients (51.7%). CONCLUSIONS: Border zone distribution of cerebral ischemia without hemodynamic compromise is the most frequent imaging pattern in patients with HES, occurring in 2/3 of patients who develop ischemic stroke.

Tumefactive eosinophil-rich non-granulomatous small vessel vasculitis in the cerebrum in a patient with idiopathic hypereosinophilic syndrome.

The definite diagnosis of central nervous system vasculitis requires pathological verification by biopsy or surgical resection of the lesion, which may not always be feasible. A 74-year-old woman with a history of allergic rhinitis, but not asthma, presented with slowly progressive left hemiparesis. Magnetic resonance imaging of the head revealed a heterogeneously enhancing mass involving the right internal capsule and corona radiata. Histological examination of the resected specimen revealed eosinophil-rich non-granulomatous small vessel vasculitis with no neutrophil infiltration or foci of microbial infection. Epstein-Barr virus in situ hybridization was negative, and polymerase chain reaction tests for both T-cell receptor gamma and immunoglobulin heavy-chain variable region genes did not show rearrangements, excluding the possibility of lymphoma and lymphoproliferative disorders. Blood hypereosinophilia and elevated erythrocyte sedimentation rate were observed; however, anti-neutrophil cytoplasmic antibodies were not detected. A biopsy of the erythema in the hips and thighs revealed perivasculitis with eosinophilic infiltration within the dermis. Chest computed tomography revealed multiple small nodules in the lungs. Her symptoms, aside from hemiparesis, disappeared after corticosteroid administration. The clinicopathological features were similar to eosinophilic granulomatosis with polyangiitis but did not meet its current classification criteria and definition. This patient is the first reported case of idiopathic eosinophilic vasculitis or idiopathic hypereosinophilic syndrome-associated vasculitis affecting the small vessels in the brain. Further clinicopathological studies enrolling similar cases are necessary to establish the disease concept and unravel the underlying pathogenesis.

Bioprosthetic mitral valve stenosis secondary to hypereosinophilic syndrome.

Herein we present a case of hypereosinophilic syndrome (HES) with recurrent involvement of mitral valve. The patient developed mitral regurgitation secondary to HES. Surgical mitral valve replacement was performed successfully. The prosthetic valve dysfunction occurred 3 years later and echocardiography showed severe mitral valve stenosis. Extensive mural thrombi were discovered on both sides of the stenotic valve with eosinophilic infiltration. The patient underwent a repeated mechanical prosthesis replacement and recovered uneventfully.

An unusual neurological presentation in a patient with primary hypereosinophilic syndrome.

Hypereosinophilic syndromes are characterized by an increased number of blood eosinophils (usually more than 1.5 × 109) infiltrating tissues and causing organ damage through over-production of pro-inflammatory cytokines with heterogeneous clinical presentation. Here we present a case of a 47 years old male, with an unremarkable previous medical history, with a sudden onset of subungual hemorrhage and low back pain. Admitted for right arm weakness and vomiting, was raised the suspicion of acute cerebrovascular syndrome, but a brain CT scan with angiogram and perfusion sequences did not show any signs of early ischaemic lesions; conversely, lab tests revealed an increased peripheral eosinophil blood count. Clinical conditions rapidly worsened and a brain MRI showed multiple sub-acute ischaemic lesions compatible with vasculitis while EEG was in favor of widespread cortical distress. Diagnosis of the hypereosinophilic syndrome was made through peripheral blood smear and osteo-medullar biopsy, which showed a rich prevalence of eosinophils. The molecular biology testing showed FIP1L1-PDGRA gene mutation. Despite the prompt therapy beginning with intravenous corticosteroids and tyrosine-kinase inhibitors with normalization of cell blood count in a few days, the patient remained in minimal consciousness. When facing unusual symptoms onset (low back pain with weakness in one limb) and a highly impaired WBC not consistent with other courses (such as infections, vasculitis, allergies, and other diseases involving the immune system) clinicians should take into account the possibility of a hematological disorder and treat it as soon as possible to avoid a poor prognosis.

[ACUTE VISION LOSS ASSOCIATED WITH HYPEREOSINOPHILIC SYNDROME].

INTRODUCTION: Hypereosinophilic syndrome (HES) is a rare disorder, in which eosinophilic toxins damage capillary and coronary endothelium and neuronal axons, at different target organs; 12% of patients experience stroke as a result of endothelial dysfunction, cardiomyopathy with secondary embolism, hyperviscosity and hypercoagulability. The treatment target is to lower the eosinophil count and shorten its tissue survival time. Supportive care and anticoagulants are given as required. We report a case of myocarditis, respiratory failure and cortical blindness due to rapidly deteriorating HES. The case demonstrates how early recognition and appropriate treatment can reduce tissue toxicity and functional loss due to hypereosinophilic syndrome.

FIP1L1-PDGFRA-Associated Hypereosinophilic Syndrome as a Treatable Cause of Watershed Infarction.

Background and Purpose: Ischemic stroke has been reported in various conditions associated with eosinophilia. FIP1L1-PDGFRA fusion ([Fip1-like 1-platelet-derived growth factor receptor alpha]; F/P) leads to the proliferation of the eosinophilic lineage and thus to a clonal hypereosinophilic syndrome that is highly responsive to imatinib. Methods: We previously reported on a nationwide retrospective study of 151 patients with F/P-associated clonal hypereosinophilic syndrome. Patients from this cohort with a clinical history of ischemic stroke (as well as 2 additional cases) were further analyzed to better define their clinical picture and outcomes. Results: Sixteen male patients (median age, 51 [43­59] years) with low-to-intermediate cardiovascular risk were included. Median National Institutes of Health Stroke Scale was 4 (range, 1­6). Most cerebral imaging disclosed multiple bilateral infarctions of watershed distribution (69%). Despite frequent cardiac involvement (50%), cardiac thrombus was evidenced in a single patient and, according to the TOAST classification (Trial of ORG 10172 in Acute Stroke Treatment), 62.5% of strokes were presumably of undetermined etiology. Among the 15 patients treated with imatinib, and after a median follow-up of 4.5 years, stroke recurred in only 3 patients (consisting of either cardio embolic or hemorrhagic events, unrelated to the first episode). Conclusions: F/P+ clonal hypereosinophilic syndrome is a diagnosis to consider in patients with unexplained ischemic stroke and hypereosinophilia (especially in the setting of multiple cortical borderzone distribution) and warrants prompt initiation of imatinib.

Loeffler endocarditis with intracardiac thrombus: case report and literature review.

BACKGROUND: Loeffler endocarditis is a relatively rare and potentially life-threatening heart disease. This study aimed to identify the characteristic features of Loeffler endocarditis with intracardiac thrombus on a background of hypereosinophilic syndrome (HES). CASE PRESENTATION: We described a 57-year-old woman with Loeffler endocarditis and intracardiac thrombus initially presenting with neurological symptoms, who had an embolic stroke in the setting of HES. After cardiac magnetic resonance (CMR), corticosteroids and warfarin were administered to control eosinophilia and thrombi, respectively. During a 10-month follow-up, the patient performed relatively well, with no adverse events. We also systematically searched PubMed and Embase for cases of Loeffler endocarditis with intracardiac thrombus published until July 2021. A total of 32 studies were eligible and included in our analysis. Further, 36.4% of recruited patients developed thromboembolic complications, and the mortality rate was relatively high (27.3%). CMR was a powerful noninvasive modality in providing diagnostic and follow-up information in these patients. Steroids were administered in 81.8% of patients, achieving a rapid decrease in the eosinophil count. Also, 69.7% of patients were treated with anticoagulant therapy, and the thrombus was completely resolved in 42.4% of patients. Heart failure and patients not treated with anticoagulation were associated with poor outcomes. CONCLUSIONS: Cardiac involvement in HES, especially Loeffler endocarditis with intracardiac thrombus, carries a pessimistic prognosis and significant mortality. Early steroids and anticoagulation therapy may be beneficial once a working diagnosis is established. Further studies are needed to provide evidence-based evidence for managing this uncommon manifestation of HES.

Clinical and morphologic spectrum of renal involvement in idiopathic hypereosinophilic syndrome.

BACKGROUND: To explore the clinical and pathological features of renal lesions in patients with kidney involvement in idiopathic hypereosinophilic syndrome (IHES). METHODS: The demographic, clinical, and pathological characteristics and the treatment and follow-up data were analyzed. RESULTS: We identified 18 patients with IHES and renal involvement. Eleven patients presented with nephrotic syndrome, and 6 patients had impaired renal function. 15 patients underwent renal biopsy, and the pathological findings included the following: membranoproliferative glomerulonephritis in 3 patients; minimal-change disease in 3; mesangial proliferative nephritis in two; IgA nephropathy in 2; membranous nephropathy in two; chronic interstitial nephritis in two; focal segmental sclerosis in one; and eosinophil infiltration into the renal interstitium in 11 and into the glomerulus in 3. After treatment with glucocorticoids, the eosinophil count decreased. 15 patients were followed up, and 14 showed a decrease in urinary protein or renal function recovery. When glucocorticoids were discontinued, eosinophil increased (8 cases), urine protein increased (1 case), and 1 patient progressed to end-stage renal disease. CONCLUSIONS: Nephrotic syndrome with or without renal insufficiency is the main clinical manifestation. A wide spectrum of renal lesions can be observed in patients with IHES. Eosinophil infiltration into the renal interstitium was common in these patients. Most patients have a good prognosis after glucocorticoid therapy.

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.

Irreversible coronary aneurysm presenting as acute coronary syndrome in a child with hypereosinophilic syndrome: a case report.

Hypereosinophilic syndrome is defined as persistent eosinophilia in the blood for more than 6 months, without any identifiable cause and with end-organ involvement evidence. Cardiac manifestations of HES include heart failure due to restrictive cardiomyopathy, arrhythmia, intraventricular thrombosis, and coronary artery involvement occurs frequently. In rare instances, coronary ectasia, aneurysms, or dissection can occur and cause morbidity and mortality in these patients.A coronary aneurysm occurs rarely in adult patients with HES but to our knowledge, this is the first report of this association in a 14-year-old boy who was presented to us as coronary aneurysm due to hypereosinophilic syndrome.

Episodic angioedema with eosinophilia (Gleich syndrome) in children: A clinical review.

BACKGROUND: Episodic angioedema with eosinophilia (EAE, Gleich syndrome) is a rare disease, consisting of recurrent angioedema with hypereosinophilia and frequent increased serum immunoglobulin M levels. Less than 100 patients have been reported, mainly adults, sometimes with underlying lymphocytic variant of hypereosinophilic syndrome (HESL ). The aim of this study was to identify and describe pediatric cases. METHODS: We performed a retrospective study of all pediatric cases of EAE referred within the French National Referral Center for Hypereosinophilic Syndrome (CEREO). Next, the PRISMA guidelines were applied in order to perform a systematic review (data sources: PubMed, Web of Science). RESULTS: Among the two reported and 15 previously published cases of EAE occurring in children, the main clinical findings mimicked those of adults, including recurrent angioedema, hives, and weight gain. The median time between the first angioedema flare and the diagnosis of EAE was 5 years in published cases. Hypereosinophilia was constant, usually worsening with each attack, but seldom disappeared between flares. Total IgM serum levels were elevated in 16 patients. Four children had evidence of abnormal CD3- CD4+ T cells. First-line therapy relied on oral corticosteroids in all patients, and further lines (used in five patients) included interferon-α, methotrexate, and cyclosporin. Two children developed eosinophilic myocarditis during follow-up. CONCLUSION: Pediatricians should be aware that EAE is a diagnosis to consider in children. T-cell immunophenotyping is warranted in this setting. Prognosis seems fair, yet eosinophil-related organ damage may occur in patients with persistent eosinophilia.