Causes Of Hypereosinophilia Research Articles

Idiopathic hypereosinophilic syndrome with gastrointestinal involvement

Idiopathic hypereosinophilic syndrome with gastrointestinal involvement

Retrospective Single Center Descriptive Analysis of a Cohort with Hypereosinophilia Evaluated in the Last Decade

BACKGROUND: Hypereosinophilia (HE) (>1,5x109/L eosinophils in peripheral blood (pb)) is an occasional cause of consultation in hematology. The etiologies are varied, the diagnostic process is wide and may include other specialties. In addition, the absence of prospective studies and large cohorts makes the diagnosis and management of these patients very challenging. OBJECTIVE: To describe the diagnostic process of a series of patients with HE evaluated in our center between 2013-2023. METHODS: Clinical-biological characteristics and diagnostic evaluations performed were registered. Clonal HE and reactive HE were compared using Fisher exact test and Mann-Whitney U. RESULTS: Sixty patients with HE (n=59) or tyrosine-kinase fusion genes eosinophilia related (n=1) were selected out of 109 patients with eosinophilia (>0.5x109/L and <1,5x109/L eosinophils in pb), detected in the last decade in our center. Characteristics of the study population and diagnostic tests conducted are summarized in Table 1. Interestingly, bone marrow data with cytogenetic study was made in up to 70% of patients. Despite extensive analysis of the PDGFRα rearrangement by FISH, other fusion genes were less evaluated and NGS studies were little used. Diagnostic studies for exclusion of secondary causes were carried out in more than 40% of patients ( Table 1). Fifteen percent of HE attended were a primary clonal entity whereas 73% were secondary/reactive: 5% due to allergy, 7% to asthma, 2% to drugs 2%,13% parasites, 25% other, 2% lymphoma, 8% were hypereosinophilic syndrome (HES)-lymphocytic variants, 8% HES-overlap, 3% associated hematologic neoplasm. Twelve of the patients couldn't be classified, which evidences the diagnostic complexity. Among the variables used in differential diagnosis of HE, those significantly associated with clonal HE compared to reactive HE in our series were: BM dysplasia (85.7% vs 14.3%, p<0.001), BM fibrosis (100% vs 0, p<0.001), abnormal karyotype (83.3% vs 16.7%, p<0.001), LDH (328 vs 188.5 U/L, p=0.028), cobalamins (>1476 vs 279 pmol/L, p=0.003), tryptase (16.6 vs 6.7 ug/L, p=0.019) and leucocytes (39.2 vs 10.2 x109/L, p=0.014). Other analytical parameters were significantly lower in clonal vs. reactive HE: hemoglobin (125 vs. 136 g/L, p=0.020) and platelets (121 vs. 260x109/L, p=0.004). It was noteworthy that the number of eosinophils did not help always to distinguish clonal vs. non-clonal entities. Patients diagnosed with a primary clonal HE were 9 (15%): 7 patients with rearrangement of PDGFRα, 1 patient with ETV6 and 1 with BCR::JAK2. The group of PDGFRα patients, all asymptomatic, showed a median diagnostic delay of 45 months (5.1-103) since the first hematological evaluation. Four out of 7 patients with PDGFRα showed hematological and cytogenetic response after a median of 3.37 months (0.95-78.2) from imatinib initiation. Two patients started imatinib recently (not evaluable) and one patient presented clonal evolution and transformation to the blastic phase after 10 years of disease. He has been treated with imatinib 400mg achieving hematological response. The overall survival of this subgroup was 80% CI 95% (62.8-97.2), with a median follow-up of 25.8 months. One patient with ETV6 rearrangement presented as acute leukemia and died after few days from diagnosis and the patient with BCR::JAK2 fusion gen also presented with acute leukemia is in complete remission after being treated with intensive induction chemotherapy and allogeneic hematopoietic cell transplantation. CONCLUSIONS: HE requires a wide diagnostic evaluation with a multidisciplinary approach and the development of working groups in order to avoid these inconclusive diagnosis (12% in our series) and the missing diagnostic tests. Our study suggests the association between elevated LDH, cobalamins and tryptase and clonal cause of HE, as well as a higher rate of fibrosis, medullary dysplasia and altered karyotypes in these patients, indicating the need to include these evaluations in the diagnostic process. The group of PDGFRα patients had good prognosis with imatinib, but one patient presented clonal evolution and blastic transformation, showing the clinical challenge of these entities.

Diagnostic spectrum of hypereosinophilia based on bone marrow pathology: 10 years' experience at a tertiary care hospital.

Hypereosinophilia (HE) is defined as peripheral blood (PB) eosinophil count exceeding 1.5 × 109 /L. As the causes of HE can be diverse, the work-up of patients was complicated. In this study, we aimed to categorize the underlying diseases associated with HE and demonstrate minimum diagnostic approach. Cases presenting with HE within 7 days of bone marrow (BM) examination conducted between 2008 and 2019 were selected. Cases were classified by the revised 2022 WHO and ICC classification. We also assessed morphologic features of unclassified persisting HE (>4 weeks) patients according to the morphologic criteria suggested a previous study by Wang et al. RESULTS: A total of 364 patients were included. The work-up confirmed primary HE in 38.7%, secondary HE in 48.9%, HE patients with insufficient evaluation in 13.7%. When conducted a slide review of HE patients with sustained HE more than 4 weeks among HE patients with insufficient evaluation, the morphological features showed abnormal eosinophils in PB/BM (69.0%/81.0%), hypercellularity (26.2%), myelofibrosis (7.1%), increased M:E ratio (5.3%), and dysmegakaryopoiesis (4.8%). Of these patients, 14 patients who met all morphologic criteria were suspected of CEL. This study demonstrates that HE is associated with variable conditions. BM morphological assessment based on a robust criterion can help to confirm a MN irrespective of the presence of clonal markers. The work-up of patients in whom ruled out the common secondary causes of HE requires a systematic but sufficient approach including at a minimum BM karyotyping, PDGFRA testing, lymphocyte immunophenotyping and TCR gene rearrangement.

636 LOOKING AT THE BIGGER PICTURE: FROM ACUTE MYOCARDITIS TO THE DIAGNOSIS OF A MULTISYSTEMIC DISEASE

Abstract A 49-year-old man without cardiovascular risk factors, recently diagnosed of asthma and rino-sinusal polyposis, entered the Emergency Department for chest pain, shortness of breath and non-productive cough. The patient was in stable conditions. Laboratory exams showed eosinophilic leucocytosis (WBC 33.000/sqmm, 60% eosinophils) and a mild elevation of C-reactive protein (CRP 2,2 mg/dL). ECG showed a sinus rhythm with flat T-waves in the antero-lateral leads. Troponin values were high but not suggestive of acute myocardial damage (9900 - 9700 ng/L). Echocardiography showed normal biventricular volumes with moderately depressed left ventricular ejection fraction (40%), hypokinesia of the antero-lateral wall in the mid-apical segments and mild pericardial effusion. During the hospital stay he developed progressive respiratory failure, and he was transferred to a tertiary center to perform an endomyocardial biopsy (EMB) in the suspicion of acute myocarditis. EMB showed multifocal interstitial and sub-endocardial inflammatory infiltrates (predominantly eosinophils) with foci of myocellular damage, small vessels wall inflammation with hypertrophy of the muscular tunica. The overall picture was consistent with diffuse moderate eosinophilic myocarditis with small vessels vasculitis. The right heart cath performed in the same procedure and during diuretic therapy showed a normal hemodynamic profile (RAP 5 mmHg, PCWP 13 mmHg, CI 3,7 L/min/sqm). The patient was treated with high dose steroids, first intravenously (methylprednisolone 125 mg/day for three days), then orally (prednisone 80 mg/day) in slow decalage until a maintenance dose of 12.5 mg daily. The recent-onset of asthma with hyper-eosinophilia and rhino-sinus-bronchial syndrome in the light of the present cardiac condition was consistent with eosinophilic granulomatosis with polyangiitis (EGPA). Chest CT showed two areas of ground glass at the left superior and right superior lobes. Other potential haematological and infective causes of hyper eosinophilia and viral causes of myocarditis were ruled out. After the treatment, his clinical conditions improved, ECG was completely normalized, left ventricular systolic function improved (LVEF 50%) and eosinophil count was significantly reduced (Eosinophils 830/sqmm, 8,9%), whereas CT showed resolution of the lung infiltrates. One month after discharge, the patient was still asymptomatic. Cardiac MRI showed normal biventricular ejection fraction (LVEF 55%) with circumferential subendocardial fibrosis involving only the left ventricle. EMB showed a complete resolution of the inflammatory infiltrates and of the vasculitic aspects. Eosinophil count was elevated (5660/sqmm, 36%). Therefore, steroidal dose was raised to 50 mg/day. After rheumatologic evaluation, a steroidal sparing strategy with cyclophosphamide and anti-IL5 antibody Mepolizumab was adopted, with good laboratory response. Three months later, cardiac MRI showed no signs of active disease. No further EMB was scheduled. Through the presentation of this unusual cause of acute myocarditis, we want to underscore the importance of an early referral to a tertiary level center of patients with suspected myocarditis and reduced systolic function and the usefulness of histology to guide medical therapy in specific forms of myocarditis that can lead to a potential complete recovery.

A CASE OF HYPEREOSINOPHILIA IN A PATIENT WITH EVANS SYNDROME

<h3>Introduction</h3> Hypereosinophilia has numerous potential etiologies with the risk of end-organ damage and significant morbidity. The workup can be challenging in the setting of complicated medical and social histories and requires a broad differential. <h3>Case Description</h3> A 26 year-old woman with a history of Evans Syndrome (autoimmune hemolytic anemia with immune thrombocytopenia), juvenile dermatomyositis, moderate persistent asthma, and allergic rhinitis presented to Allergy clinic for evaluation of hypereosinophilia. Approximately 6 months prior to presentation to Allergy clinic, the patient experienced a sharp sustained rise in absolute eosinophil count (AEC), increasing from a baseline of 300 cells/mcL to a peak of 3100 cells/mcL. The timing of eosinophilia coincided with ongoing Evans Syndrome management requiring obinutuzumab and romiplostim as well as routine marijuana usage. The patient was asymptomatic during this time apart from a self-limited flare in asthma symptoms following inhaled marijuana. The differential included standard etiologies as well as consideration of marijuana (or contaminant) hypersensitivity and/or drug reaction to a novel biologic medication. Laboratory and radiographic evaluations were extensive, though ultimately inconclusive, and the patient's AEC spontaneously normalized with ongoing inhaled marijuana avoidance and deferral of obinutuzumab and romiplostim. <h3>Discussion</h3> We present this case to demonstrate novel exposures which may have precipitated an uncommon cause of hypereosinophilia. We hope this may provide insight into evaluating patients with unclear causes of hypereosinophilia, especially as exposures to marijuana and biologic medications continue to grow.

IDIOPATHIC HYPEREOSINOPHILIC SYNDROME DIAGNOSED IN AN INFANT: A CASE REPORT

<h3>Introduction</h3> Idiopathic hypereosinophilic syndrome (IHES) is a rare disorder characterized by persistent eosinophilia (>1.5 × 10⁹/L) for ≥6 months, tissue infiltration with end-organ damage, and exclusion of known causes for hypereosinophilia. It is mainly observed in adults, and rarely in children. We report, to our knowledge, the first case report of IHES in an infant. <h3>Case Description</h3> A 5-month-old male presented with severe failure to thrive and malnutrition. His hospitalization was complicated by acute kidney injury, pulmonary edema requiring intubation, pseudomonas bacteremia with concomitant tibial osteomyelitis, COVID-19 infection, and bradycardic arrest requiring CPR. Notably, patient had persistent eosinophilia (maximum 11.4 × 10⁹/L) (Table 1). Parasite testing was negative. Immune work-up was normal (Table 1). Primary immunodeficiency panel testing of 407 geneswas negative. Endoscopy revealed eosinophilia in the sigmoid colon and rectum. Bone marrow biopsy revealed a low normocellular bone marrow (70%) with maturing trilineage hematopoiesis and increased eosinophils and eosinophil precursors (approximately 50% of nucleated cells). A FISH panel was negative for PDGRFRA/4q12, PDGRFRB/5q33, FGFR1/8p12, and ETV6/12p13 gene regions. The patient was diagnosed with IHES and started on steroids at 0.5 mg/kg/day. Hydroxyurea was added due to up-trending eosinophil count despite steroid therapy. Three months post-diagnosis, he is doing well off medications, with most recent eosinophil count being 2.1 × 10⁹/L. <h3>Discussion</h3> Hypereosinophilia in children is most commonly due to secondary causes such as atopic dermatitis, parasitic infections, neoplasms, graft-versus-host disease, sickle cell disease, and immunodeficiency. Once the above diagnoses have been excluded, IHES should be considered, especially in patients with evidence of end-organ damage.

TREATMENT OF HYPEREOSINOPHILIA WITH MEPOLIZUMAB IN A 6-YEAR-OLD BOY

<h3>Introduction</h3> Hypereosinophilic syndrome (HES) is a rare cause of hypereosinophilia among pediatric patients. Mepolizumab, an IL-5 antagonist, is an effective treatment for hypereosinophilia approved for patients ≥12 years of age, but for younger children treatment remains limited to corticosteroids or other cytoreductive agents. This case illustrates successful treatment of hypereosinophilia with mepolizumab in a child. <h3>Case Description</h3> A previously heathy 6-year-old male presented with three days of fatigue, fever, and right cervical lymphadenopathy with an elevated absolute eosinophil count (AEC) that peaked at 83,350 cells/microliter. Work up for infectious disease, end-organ damage, and malignancy with flow cytometry and cytogenetics from blood, bone marrow and lymph node biopsy were negative. Mepolizumab 100 mg injected subcutaneously was given, leading to progressive decline in AEC to 3,370 cells/microliter after 14 days. Fevers, fatigue, and lymphadenopathy resolved. Monthly mepolizumab and close monitoring is planned. <h3>Discussion</h3> HES is a heterogenous group of disorders; of paramount concern is development of malignancy and end-organ damage due to eosinophilic infiltration of tissues. Although effective for hypereosinophilia, long-term treatment with corticosteroids is associated with significant adverse events and may cause diagnostic uncertainty when monitoring pre-malignant conditions. While mepolizumab is approved for children ≥6 years of age for the treatment of asthma, it is not approved for HES in this age group. This case highlights that mepolizumab is an effective steroid-sparing therapy in young children with hypereosinophilia that allows continued monitoring for malignancy without masking or delaying diagnosis from corticosteroid use.

EGPA: A DIAGNOSTIC DILEMMA

<h3>Introduction</h3> Eosinophilic granulomatosis with polyangiitis (EGPA) is a diagnostically difficult disorder due to multisystem involvement, and dual categorization with hypereosinophilic syndromes and systemic vasculitides. The early allergic phase may present in isolation for years prior to eosinophilic organ infiltration and vasculitis, highlighting the importance of consistent screening and multidisciplinary treatment in preventing complications. <h3>Case Description</h3> A 40-year-old male with allergic rhinitis, chronic rhinosinusitis with nasal polyps, and severe persistent asthma presented with peripheral eosinophilia (maximum 2950/μL) and uncontrolled asthma. Workup of secondary causes of hypereosinophilia was unrevealing. Sinus CT revealed extensive mucosal thickening with near complete opacification and lung CT showed bilateral lung ground-glass opacities admixed with consolidative opacities. Patient underwent endoscopic sinus surgery and bronchoscopy with biopsies failing to show signs of granulomata/vasculitis or eosinophilic infiltration. Evaluation of pertinent biomarkers and echocardiogram were also unrevealing. Despite this, given the concerning constellation of symptoms and a positive rheumatoid factor, EGPA remained on the differential with possibility of biopsy sampling error and seronegative ANCA vasculitis. Patient was treated with prolonged steroid taper followed by benralizumab for uncontrolled severe eosinophilic asthma with only temporary relief followed by mepolizumab, the first FDA biologic agent approved for EGPA. <h3>Discussion</h3> This patient presents with multiple features concerning for EGPA. Even without a current pathologic diagnosis, EGPA presents in phases and remains high on our differential. It is crucial to continue monitoring for end organ involvement and new systemic symptoms. New biologic agents present a promising therapy resulting in increased remission and reduced glucocorticoid use.

CML-216 Hypereosinophilia Syndrome With FIP1L1-PDGFRA Transcript Revealed by Cardiac Involvement

Hypereosinophilic syndrome (HES) is defined by eosinophilia greater than 1.5 G/L persisting for more than 6 months and associated with specific visceral damage (cardiac, neurological, pulmonary, etc.), after elimination of "classic" causes of hypereosinophilia. A myeloproliferative variant of HES is associated with the fusion of the FIP1L1 and PGDFRα genes, resulting in the constitutive activation of a receptor with tyrosine kinase activity. We report a case revealed unexpectedly by cardiac involvement (a mitral valve disease). A 25-year-old man with no particular history, allergies, or cardiovascular risk factors was hospitalized in the cardiology department for sudden-onset precordialgia associated with low-grade fever. The clinical examination: a general state preserved asthenic, nocturnal fever with precordialgia, and stage IV splenomegaly. ECG: unremarkable; heart echo: a thickened mitral valve with moderate mitral leakage, with rupture of the chords giving moderate grade II mitral insufficiency. Three blood cultures taken at the time of the fever peak came back sterile. FNS: anemia reduced to 9 g/dL normochromic normocytic aregenerative, activated thrombocytopenia to 124 G/L, hyperleukocytosis to 65,000/mm3, including 81% of eosinophilic polynuclear cells (52,650 elements/mm3) without myelemia. Myelogram: a very rich smear with eosinophilic hyperplasia at all stages of maturation. A thoraco-abdominopelvic CT scan showed heterogeneous splenomegaly with parenchymal involvement in centro-lobular ground glass, predominantly apical with areas of geographical somatic vertebral bone condensation staged in the dorsolumbar and pelvis. A corticosteroid test was negative, and a molecular cytogenetic study revealed the FIP1L1-PDGFRA fusion transcript in 88% of cells with a rearrangement of the locus at 4q12. The patient was put on imatinib 100 mg/day for 15 days then 200 mg/day with prophylactic anticoagulation. The evolution was favorable with a normalization of the FNS after 20 days. After 6 months of treatment, a FISH was requested, having objectified the complete disappearance of the cytogenetic anomaly. Chronic eosinophilic leukemia with FIP1L1-PDGFRA can be serious and fatal in the event of diagnostic delay and the nature of the affected organ. Patients with clinical manifestations consistent with HES should be investigated for evidence of clonality of hematopoiesis and a search for a T-lymphocyte population for treatment decisions.

S3593 Eosinophilic Gastritis in Idiopathic Hypereosinophilic Syndrome: A Case Report

Introduction: Idiopathic hypereosinophilic syndrome (IHES) is a group of myeloproliferative disorders causing multi-organ dysfunction with unknown etiology. We report a case of IHES in a patient presenting with gastric wall thickening, multiple organ damage including acute coronary syndrome, encephalopathy, and multiple cortical infarcts. Case Description/Methods: A 47-year-old male patient with past medical history significant for type 2 diabetes mellitus and hypertension presented with nausea, vomiting, abdominal pain, and food intolerance for 7 days. He also complained of intermittent, substernal chest pain for 1-2 days at presentation. His labs were significant for elevated troponin of serum creatinine of 2.85mg/dL and significant leukocytosis (32.80 10^3/cmm). Absolute eosinophilic count was elevated at 14.70 10^3/cmm. Echocardiogram showed hypokinetic mid inferior and inferolateral walls. CT chest/abdomen angiogram was done for concerns of dissection. It showed diffuse gastric wall thickening with upper abdominal retroperitoneal lymphadenopathy and extensive retroperitoneal fat stranding. He was started on antiplatelet agent and heparin drip. Ischemic workup was deferred as troponin plateaued and patient had new-onset altered mental status. MRI brain showed numerous punctate cortical and subcortical foci of restricted diffusion consistent with acute watershed distribution infarcts. In view of possible need for dual anti-platelet therapy and the high concern for gastric malignancy on CT that required tissue biopsy, gastroenterology was consulted for esophagogastroduodenoscopy (EGD). It did not show any gastric mass but diffuse gastritis. Biopsy showed mild chronic gastritis and a focal area showing increased eosinophilic infiltration with eosinophilic cryptitis (Figure). An extensive workup for eosinophilia including infectious etiology returned negative. No secondary causes of hypereosinophilia were identified. Patient was started on 1mg/kg of prednisone with normalization of eosinophils to 0 within 24 hours. Steroids were tapered and patient improved clinically with resolution of altered mental status, abdominal pain, and chest pain. Follow-up EGD has been scheduled to re-evaluate eosinophilic deposits. Discussion: The stomach biopsy showing eosinophilia was the key to diagnosis. Resolution of peripheral eosinophilia with steroids confirms the diagnosis in the absence of a secondary cause. A repeat EGD with biopsy is scheduled to look for histopathological resolution.Figure 1.: Gastric mucosa with increased eosinophilic infiltration within the lamina propria and focal glandular involvement with eosinophils.

Mechanisms and Neuroimaging Patterns of Hypereosinophilia-Related Ischemic Stroke: A Narrative Review through Three Cases.

Background: Hypereosinophilic syndromes (HES) are a group of relatively rare disorders in which neurological manifestations, including ischemic stroke, are common. The hypothesized pathophysiological mechanisms are hypercoagulability, cardioembolism (mainly mediated by myocardial involvement) and damage to the endothelium. A variable ischemic pattern has been described, including an association of territorial and border zone ischemic stroke. Methods: Three patients who presented to our department with acute stroke were selected aiming to show these three different mechanisms inferred from the stroke pattern on brain Magnetic Resonance Imaging (MRI) and to simultaneously illustrate the three main causes of HES. Results and Discussion: The first patient is a 55-year-old man with an abrupt onset of aphasia due to an acute ischemic stroke involving the left parietal lobule and the angular gyrus; recent lab test had shown hypereosinophilia. An extensive workup excluded primary and secondary causes of hypereosinophilia so a diagnosis of idiopathic hypereosinophilia was done and he was treated with high doses of steroids. The second patient had severe hypereosinophilia and developed multiple small, scattered ischemic lesions, mainly in border zone zones. The history of severe asthma and recurrent sinusitis supported the diagnosis of EGPA (Eosinophilic Granulomatosis with Polyangiitis); considering the severe clinical conditions and the presumptive role of hypereosinophilia in determining her symptoms, steroid treatment was promptly started, with good clinical response. The third patient also presented with multiple metachronous ischemic lesions, both in cortical and border zone distribution and marked eosinophilia; the diagnostic work-up found an ovarian cancer. She was treated with steroids and then underwent surgery and adjuvant chemotherapy. Conclusions: HES should be considered in stroke etiological evaluation, although it is a rare disorder, and border zones pattern without large artery steno-occlusion on neuroimaging may help to raise the suspicion in the neurovascular diagnostic pathway. A thorough research of the sources of hypereosinophilia should be performed to select the appropriate therapy.

Hematological hypereosinophilia

Hematological disorders are the third cause of hypereosinophilia, after allergic and parasitic disease. The objective of our study is to show the epidemiological, clinical, biological and therapeutic characteristics of hematological hypereosinophilia. This is a retrospective study over a 4-year period (March 2017-March 2021) concerning 14 patients with hematological hypereosinophilia. Fourteen patients were included (9 women and 5 men). The median age at diagnosis was 55 years. Hematological hypereosinophilia was mainly of clonal etiology. Clinical manifestations were either specific to hypereosinophilia, such as organ damage, or related to the etiology of hypereosinophilia, such as hepato-splenomegaly and lymphadenopathy. Moderate and severe forms were the most commonly reported. Several other quantitative and qualitative abnormalities of the blood picture were reported. Identification of the FIP1L1-PDGFRA fusion gene by molecular biology (RT-PCR) was positive in two patients. Imatinib was the main treatment for clonal forms. Hematological hypereosinophilia is a rare and complex pathology. Our study has confirmed this epidemiological, clinical, biological and therapeutic heterogeneity and has enabled us to realize the contribution of molecular biology in the diagnosis and the treatment of hypereosinophilia.

Diagnosis and Management of Pediatric Hypereosinophilic Syndrome

Hypereosinophilic syndrome (HES) is a diverse group of disorders characterized by peripheral blood eosinophilia of 1.5× 109/L (1,500/μL) or greater with evidence of end-organ damage attributable to eosinophilia and no other cause of the end-organ damage. The HES is rare, especially in children. This review aims to provide best practices in diagnosis and treatment of HES in children, including how to differentiate between primary and secondary causes of hypereosinophilia; how to distinguish the differences in clinical presentation, treatment, and prognosis of HES in children and adults; and how to identify key steps in the evaluation and management of HES in children.

EOSINOPHILS LEAD THE WAY

TOPIC: Lung Pathology TYPE: Medical Student/Resident Case Reports INTRODUCTION: Hypereosinophilic Syndrome (HES) is a rare condition characterized by sustained eosinophil counts greater than 1.5x103/uL with pathologic confirmation of tissue hypereosinophilia (HE). It usually affects multiple organs in the absence of clonal or other secondary causes of eosinophilia. The most common organs affected are the lungs, skin, heart, gastrointestinal tract, and brain. CASE PRESENTATION: This is an 81-year-old male patient with history of alcohol abuse, hypertension, and atrial fibrillation, who presented with diffuse skin itching and burning sensation for three days after working with polyvinyl chloride (PVC) tubing material. He referred having associated generalized weakness, anorexia, and dry cough. Labs were remarkable for having eosinophilia of 17x10^3/uL, mild transaminitis (SGPT:54 U/L, SGOT:45 U/L), elevated high sensitive troponins of 41-43 without delta and worsening renal function with serum creatinine increasing from 0.9 to 1.9 mg/dL. Immunoglobulin E was found to be elevated in 774.8, however Strongyloides IgG antibody and Schistosoma antibody were negative, ruling out endemic parasite involvement. Chest CT scan without contrast revealed moderate centrilobular emphysema, mild areas of ground glass opacities and tree-in-bud opacities bilaterally, for which it was decided to undergo bronchoscopy examination to exclude other etiologies, including malignancy or pneumoconiosis. This procedure revealed no lesions or masses, with bronchoalveolar lavage reporting no malignant cells, as well as negative acid-fast bacilli or fungal organisms. To rule out myelodysplastic syndrome a bone marrow biopsy was performed revealing hypercellular marrow with 48 percent of eosinophils, however flow cytometry showed no clonal cells or blasts, as well as negative BCL/ABL and PDGFR alpha. These findings were consistent with Idiopathic Hypereosinophilic Syndrome, for which he was started on prednisone 40 mg PO daily. DISCUSSION: HE can be confirmed by bone marrow biopsy of more than 20 percent of eosinophils. Most of these patients tolerate and respond well to glucocorticoid therapy, however in refractory cases the tyrosine kinase inhibitor imatinib has shown to improve the patient's outcome. CONCLUSIONS: It is essential to rule out secondary causes of hypereosinophilia, which may be seen in parasitic infections, pneumoconiosis, or malignancy, to prevent delay in diagnosis and prompt adequate therapy. REFERENCE #1: Roufosse, F.E., et al. Hypereosinophilic syndromes. Orphanet J Rare Dis 2, 37 (2007) DISCLOSURES: No relevant relationships by Christina Arraut-Hernandez, source=Web Response No relevant relationships by Jose Gutierrez-Nunez, source=Web Response No relevant relationships by Francisco Tirado-Polo, source=Web Response

Evaluation of Etiological Factors Causing Hypereosinophilia in Children

Objective: Patients with persistent eosinophilia may have many conditions ranging from relatively benign diseases such as parasitic serious infections to life-threatening serious diseases. We aimed to determine the etiological causes of hypereosinophilia in children. Material and Methods: Patients under 18 years of age who had complete blood counts in Ankara Child Health and Diseases Hematology Oncology Training and Research Hospital’s pediatric clinics between January 2013-January 2016 were retrospectively analyzed. Hypereosinophilia was defined as having at least two peripheral blood absolute eosinophil counts greater than or equal to 1500/mm3.The results of the examinations and diagnoses when the patients were detected with hypereosinophilia were recorded from the hospital records. Results: Three hundred and forty patients who underwent complete blood count were found to have hypereosinophilia. Seventy patients whose file records could not be accessed were excluded from the study. Two-hundred seventy patients (56% male) with a median age of 5 (IQR:1-12) years were included in our study. When the diagnoses of patients were examined, 48 (17.8%) had allergic diseases, 21 (7.8%) had immunodeficiency, 14 (5.2%) had parasitic disease. 15 (5.5%) had tumor, 4 (1.5%) had leukemia, 2 (0.7%) had hypereosinophilic syndrome, 2 (0.7%) had adrenal insufficiency and 2 (0.7%) had burn. Ninety-nine (36.7%) patients were found to use medication for any disease (acute or chronic). As a result of the examinations performed in 63 (23.3%) patients, it was found that there was no reason to explain hypereosinophilia. Conclusion: The number of eosinophils may increase in many conditions. The cause of increase in eosinophil may not always be found. Further studies are needed on the long-term prognosis of these patients.

Evaluation and Differential Diagnosis of Hypereosinophilia in Rheumatology Practice

Background: There has been no investigation so far on the prevalence or causes of hypereosinophilia during rheumatic diseases. Objectives: The study aimed to identify the prevalence and causes of hypereosinophilia among the patients followed in a rheumatology department. Methods: The patients aged 18 years or over followed in our rheumatology department between January 2010 and December 2019 who had at least one AEC ≥1,500/µL measurement in their peripheral blood count were identified retrospectively. Results: Over the 10 years, a total of 130,769 peripheral blood counts were performed, of which 3.9% showed eosinophilia and 0.065% showed hypereosinophilia. Hypereosinophilia was identified in 85 patients. The underlying rheumatic disease was determined in 89.4% (n = 76) of patients. Of these, the most frequent one was rheumatoid arthritis at a ratio of 40.8%, followed by eosinophilic granulomatosis with polyangiitis (EGPA) at a ratio of 10.5%. Hypereosinophilia was in primary form in 3.5% of the patients, whereas secondary to another condition in 91.8% (n = 78) of the cases and idiopathic in 4.7% (n = 4) of patients. The most common cause of secondary hypereosinophilia was drug induced, as detected in 61.2%, followed by allergic conditions in 11.5% and EGPA in 9.4%. In 15.2% (n = 13) of the cases, hypereosinophilia was associated with an underlying rheumatic disease. In the cases with drug-induced hypereosinophilia, most often (in 28.8%) methotrexate was the offending agent. Conclusions: Rheumatologists should be cognizant that hypereosinophilia concurrent to rheumatic diseases is usually not due to the underlying rheumatic disease, except for the conventional eosinophil-related rheumatic diseases.

S2513 Giant Cell Hepatitis Due to Drug-Induced Autoimmune Hepatitis from Dupilumab

INTRODUCTION: Giant cell hepatitis (GCH) is a pathologic diagnosis characterized by liver inflammation and large multinucleated hepatocytes. GCH is a common pathologic entity in infants but is exceedingly rare in adults. It is typically in response to drugs, autoimmune hepatitis (AIH), viruses and malignancy. We present a case of drug-induced autoimmune hepatitis causing giant cell transformation. CASE DESCRIPTION/METHODS: A 24-year-old male with eosinophilic asthma, chronic eosinophilia, primary sclerosing cholangitis (PSC) and Crohn’s disease presented with right upper quadrant pain, jaundice, anorexia, lymphadenopathy and weight loss. Labs on admission were AST 973 (u/L), ALT 801 (u/L), AP 225 (u/L), total bilirubin 16.6 (mg/dL), direct bilirubin 11.2 (mg/dL), INR 2.4, absolute eosinophil count 20.4 (k/uL). Extensive serologic work up of acute liver injury was unrevealing with the exception of a total IgG of 5291 (mg/dL). An MRI abdomen demonstrated hepatomegaly, non-specific hepatitis and findings consistent with his known PSC. Workup for infectious, autoimmune and malignant causes of hypereosinophilia was negative. Three months prior to admission, he was started on dupilumab for his eosinophilic asthma. A liver biopsy was pursued. H&E Staining (Figure 1) noted prominent giant cell hepatocellular transformation and hepatocyte ballooning degeneration. There were plasma cell, lymphocyte and eosinophil portal infiltrates present. Trichrome staining (Figure 2) showed fibrosis in a periportal and patchy sinusoidal pattern. The pathologic analysis was most consistent with giant cell hepatitis. His clinical and pathologic diagnosis was consistent with GCH due to drug-induced AIH from dupilumab. Management included discontinuation of dupilumab and IV methylprednisolone which was transitioned to a prolonged prednisone taper at discharge. After 6 months, his liver function tests have nearly normalized. DISCUSSION: GCH is a common pathologic entity in infants but is rare in adults. Fewer than 100 reported adult cases are present in the literature. AIH followed by drug-induced and viral hepatitis are most frequently causative of GCH. Our patient’s negative serologic workup, biopsy findings, and timing of dupilumab initiation to acute hepatitis makes drug-induced autoimmune hepatitis the most likely etiology. There have been no previous reports that dupilumab has been implicated in drug-induced liver injury, drug-induced AIH or has been responsible for the pathologic diagnosis of Giant Cell Hepatitis.Figure 1.: Liver biopsy (H&E stained slide, 200x): This portal tract demonstrates a mixed inflammatory infiltrate composed of lymphocytes, plasma cells, and eosinophils without vasculitis or ductulitis. The portal tract is surrounded by the prominent multinucleated, syncytial giant hepatocytes and ballooning degeneration.Figure 2.: Liver biopsy (Massons's Trichrome stain, 200x): The trichrome staining demonstrates increased periportal fibrosis and patchy perisinusoidal fibrosis.

Hypereosinophilic syndrome—a rare adverse event of anti-cytokine treatment in rheumatoid arthritis resolved after Janus kinase inhibitor therapy

Eosinophilia is uncommon in early rheumatoid arthritis (RA). The most frequent causes of hypereosinophilia during RA treatment are atopic eczema, allergy, helminth infection, haematological malignancy and drug-associated complications. The pathogenesis of this abnormality associated with anti-cytokine therapy is still unknown. We report the case of a young woman with RA and eosinophilia accompanied by systemic symptoms such as dyspnoea, fluid retention and eosinophilic vasculitis. An interesting observation was the persistence of eosinophilia during treatment with various biologics and its normalization after switching to the Janus kinase inhibitor baricitinib.

A case of hypereosinophilic syndrome with eosinophilic myocarditis secondary to nabumetone

Introduction: Hypereosinophilic syndromes are a group of disorders defined by an absolute eosinophil count greater than 1.5 × 109/L that leads to eosinophil-mediated end-organ damage. Cardiac involvement can range from asymptomatic inflammation of the myocardium to endomyocardial fibrosis and irreversible constrictive cardiomyopathy. Case Report: We present the case of a patient who presented with confusion and was found to have an absolute eosinophil count of 8.08 × 109/L as well as clinical findings consistent with eosinophilic myocarditis. It was determined that her clinical presentation was due to a new medication she had taken, nabumetone. Other causes of hypereosinophilia were ruled out. She improved with two days of pulse dose methylprednisolone and subsequent prednisone taper with complete resolution of her cardiomyopathy and normalization of her absolute eosinophil count. Conclusion: While there are no guidelines available for the treatment of eosinophilic myocarditis, corticosteroids should be considered in patients with evidence of cardiomyopathy in the setting of hypereosinophilia. Hypereosinophilic syndrome is an uncommonly recognized adverse event of non-steroidal anti-inflammatory drug (NSAID) therapy.

P681 Surprise imaging findings in an asymptomatic patient with an ECG suggestive of apical hypertrophic cardiomyopathy

Abstract We present the case of a 55-year old woman with an unremarkable past medical history, allergic to eggs and cinnamon and without any clinical complaints, who presented for a routine ECG prior to a dental implant procedure. The ECG revealed signs of left ventricular (LV) hypertrophy with deep negative T waves in V2-V6 (Figure) suggesting apical hypertrophic cardiomyopathy. Her physical exam was unremarkable and a transthoracic echocardiography (TTE) was ordered. The TTE revealed normal LV dimensions, a normal global systolic function of both ventricles, but most remarkably, an isoechoic mass that occupied the whole apex and one third of the LV cavity (Figure), with a maximum thickness of 22 mm and a 2 mm hyperechogenic lining towards the LV, all these findings being suggestive of Loeffler endocarditis. The routine laboratory tests showed (apart from a slightly increased LDL-cholesterol and normal BNP values) hypereosinophilia: more than 10% of the white blood count. Chest X-Ray and the abdominal scan showed no signs of pulmonary or hepatic infiltration. Cardiac magnetic resonance imaging was scheduled, but the patient has claustrophobia and was unable to perform the exam. The aetiological workup included the investigation of allergic, hematologic, as well as parasitic causes of the hypereosinophilic syndrome. Consequently, serological tests for Coxiella, Chlamydia, Echinococcus and Toxocara were all performed. The IgG antibodies for Toxocara canii were found in a very high level, indicating a chronic parasitic infection as a possible cause of the hypereosinophilic syndrome. The hematologic exams were all within normal limits. The endomyocardial biopsy, the gold standard for diagnosis could not be performed for technical reasons. The first step in the management of hypereosinophilia (HE) is stopping exposure to the trigger, as well as specific treatment- albendazole. The patient received oral anticoagulant treatment in order to prevent thromboembolic complications, which are frequently reported in this clinical setting. Loeffler’s endocarditis is usually a late cardiac manifestation of the HE syndrome. This is a rare and surprising case of an incidental imaging diagnosis in a totally asymptomatic patient after a routine ECG that was suggestive of hypertrophic cardiomyopathy. The challenge consisted in finding the cause of HE in order to attempt an aetiological treatment. Although the allergic and parasitic causes were most likely, considering the patient’s history, a hematologic malignancy had to be excluded. HE associated with toxocariasis rarely causes cardiac manifestations, but it should not be excluded when the patient has a history of canine exposure. The most fearsome complication in this case is the embolization of the eosinophilic mass, but the prompt management and routine follow-up allow the prevention of a thromboembolic event. Abstract P681 Figure. ECG and TTE apical views