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%.

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.

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.

Transient left ventricular clot in COVID-19-related myocarditis is associated with hypereosinophilic syndrome: a case report.

Frequent clinical presentations have been reported in patients with Coronavirus disease 2019 (COVID-19). It may be associated with multi-organ and cardiovascular involvements such as myocarditis and clot formation. Hypereosinophilic syndrome (HES) is a rare disease diagnosed with idiopathic eosinophilia and organ involvement. Here, we report a patient with COVID-19 who presented with clot formation and myocarditis. One month after discharge, regarding persistent peripheral/bone marrow hypereosinophilia and clot in echocardiography, fluorescent in situ hybridization (FISH) analysis was done that showed FIP1L1-CHIC2 fusion (PDGFRɑ rearrangement) in 18% of scored cells and PDGFRß rearrangement in 12% of scored cells, which confirmed HES diagnosis. Clot formation may be a late manifestation of COVID-19 or myocarditis due to COVID-19, or the first manifestation of HES that COVID-19 might provoke in this rare syndrome.

Hypereosinophilic syndrome with central nervous system involvement treated with anti-IL-5 therapy.

Hypereosinophilic syndrome (HES) is a rare disorder characterized by a persistent eosinophilia with a multi-organ involvement including neurological manifestation. A 59-year-old man was referred from a neurosurgery unit with a spastic triparesis with predominant left side involvement, dissociated sensory loss to Th7, and metastasis-like lesions in a brain CT. MRI examination of the thoracic spine revealed an intraspinal T2-hyperintensive lesion with a subtle central gadolinium enhancement at Th4-Th8 level. MRI of the cervical spine showed a C1-Th1 long T2-hyperintensive lesion with a partial gadolinium enhancement and MRI of the brain revealed a large tumefactive T2-hyperintensive lesion in the right hemisphere. Blood tests showed an increased number of eosinophils (1790 cells/µl; 18.3%). Common causes of the eosinophilia were excluded. After corticosteroid treatment moderate neurological improvement was observed however in the brain MRI new T2-hyperintensive lesions were revealed. The patient was referred to the Department of Allergology and qualified for a treatment with mepolizumab, a monoclonal antibody against IL-5, with subsequent clinical and radiological improvement. To the best of our knowledge, this is the first case of hypereosinophilic syndrome with brain and spinal cord involvement treated with mepolizumab.

Central Nervous System and Cardiac Involvement in the Hypereosinophilic Syndrome: A Case Report.

Hypereosinophilic syndrome is a rare entity and heterogeneous group of disorders characterized by hypereosinophilia and organ involvement. In this study, we presented a 49-year-old woman with cardiac tamponade in the context of Hypereosinophilic syndrome. Identifying hypereosinophilia as the underlying cause can have tremendous clinical implications for rapid initiation of appropriate treatment to minimize further end organ damage.

Idiopathic hypereosinophilic syndrome with formation of multiple liver mass lesions.

We report a case of idiopathic hypereosinophilic syndrome (IHES) characterized by multiple liver mass lesions in an 82-year-old man. Numerous hypoechoic lesions were observed on ultrasonography and were mainly distributed in the S4, S6, and S7 segments. Plain computed tomography (CT) scans revealed low-density lesions. Dynamic CT images revealed arterial and portal vein branches passing through these lesions, with marginal areas enhanced during the arterial phase. The enhanced areas were extended during the portal venous phase. Contrast-enhanced ultrasonography (CEUS) images revealed enhanced vasculature in the early vascular phase. CEUS images obtained in the late vascular phase revealed enhanced areas containing microbubbles extended into the parenchyma; a prolonged enhancement pattern was observed. Kupffer-phase images revealed large portions of the lesion filled with microbubbles and a star-like defect at the center of the nodule. F18-2-fluoro-2-deoxyglucose (FDG) positron emission tomography/CT scans revealed intense FDG uptake by these lesions, which was similar to that by the segments S4, S6, and S7. Liver biopsy revealed diffused eosinophils infiltrated. The patient was closely followed up and was completely cured 11 weeks later without any treatment. This is a rare case of IHES with multiple liver mass lesions, which was well researched using multi-imaging equipment and cured without any treatment.

When multimodality cardiac imaging saves the day: rare cause of embolic strokes.

Hypereosinophilic syndrome (HES) is a rare disorder characterised by eosinophilic infiltration of tissues. Myocardial infiltration occurs in 50%-60% of HES and leads to a condition called Loeffler's endocarditis. This can lead to endomyocardial injury with resultant superimposed thrombus formation and embolic stroke. We describe the case of a 57-year-old female patient presenting with neurological symptoms who was found to have multiple embolic strokes on a background of long-standing eosinophilia. Following a series of investigations, including transthoracic and transoesophageal echocardiographies and cardiovascular MRI, she was confirmed to have Loeffler's endocarditis with left ventricular thrombus. She was treated successfully with steroids and anticoagulation. We describe the pathophysiology of HES and Loeffler's endocarditis and stress the crucial role of multimodality cardiac imaging in establishing its diagnosis and treatment monitoring.

Raman imaging highlights biochemical heterogeneity of human eosinophils versus human eosinophilic leukaemia cell line.

Eosinophils are acidophilic granulocytes that develop in the bone marrow. Although their population contributes only to approximately 1-6% of all leucocytes present in the human blood, they possess a wide range of specific functions. They play a key role in inflammation-regulating processes, when their numbers can increased to above 5 × 109 /l of peripheral blood. Their characteristic feature is the presence of granules containing eosinophil peroxidase (EPO), the release of which can trigger a cascade of events promoting oxidative stress, apoptosis or necrosis, leading finally to cell death. Raman spectroscopy is a powerful technique to detect EPO, which comprises a chromophore protoporphyrin IX. Another cell structure associated with inflammation processes are lipid bodies (lipid-rich organelles), also well recognized and imaged using high resolution confocal Raman spectroscopy. In this work, eosinophils isolated from the blood of a human donor were analysed versus their model, EoL-1 human eosinophilic leukaemia cell line, by Raman spectroscopic imaging. We showed that EPO was present only in primary cells and not found in the cell line. Eosinophils were activated using phorbol 12-myristate 13-acetate, which resulted in lipid bodies formation. An effect of cells stimulation was studied and compared for eosinophils and EoL-1.

Loeffler's endocarditis with isolated left ventricular involvement on cardiac MRI.

Loeffler endocarditis is an uncommon restrictive cardiomyopathy associated with eosinophilia and endomyocardial fibrosis causing diastolic restriction, predominantly involving the right ventricle. Cardiac MRI plays a crucial role in early detection of disease. Early disease usually responds well to corticosteroids. We describe a case of Loeffler endocarditis with isolated left ventricular involvement on MRI in a young male having hypereosinophilia.

The right atrium in idiopathic hypereosinophilic syndrome : Insights from the 3D speckle tracking echocardiographic MAGYAR-Path Study.

BACKGROUND: Idiopathic hypereosinophilic syndrome is characterized by a persistent eosinophil blood count of >1.5 × 109 cells/l and organ damage, independent of the primary and secondary causes of eosinophilia. The purpose of the present study was to assess the three-dimensional speckle tracking echocardiography-derived right atrial volumetric and functional properties between hypereosinophilic syndrome patients and matched controls. METHODS: A total of 11 patients with idiopathic hypereosinophilic syndrome and 22 age- and gender-matched healthy controls were enrolled in the study. Three-dimensional speckle tracking echocardiography was used for calculation of right atrial volumes, volume-based functional properties, and strain parameters. RESULTS: Significantly increased right atrial maximum (68.7 ± 33.1 ml vs. 40.3 ± 12.1 ml, respectively; p = 0.001) and minimum volumes (48.3 ± 31.0 ml vs. 28.3 ± 9.4 ml, respectively; p = 0.009), as well as right atrial volume before atrial contraction (58.6 ± 27.3 ml vs. 34.5 ± 11.8 ml, respectively; p = 0.001), were found in hypereosinophilic syndrome patients compared with controls. Total and passive right atrial stroke volumes proved to be significantly increased in hypereosinophilic syndrome patients. However, global and mean segmental strain parameters did not differ significantly between the groups. CONCLUSION: Increased cyclic right atrial volumes and mild alterations in right atrial functional properties could be demonstrated in idiopathic hypereosinophilic syndrome patients.