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 Table of Contents  
CASE REPORT
Year : 2017  |  Volume : 5  |  Issue : 2  |  Page : 77-81

Hypereosinophilic syndrome mimicking acute coronary syndrome


1 Department of Medicine, Pt. B.D. Sharma University of Health Sciences, Rohtak, Haryana, India
2 Department of Pathology, Pt. B.D. Sharma University of Health Sciences, Rohtak, Haryana, India

Date of Web Publication20-Jun-2017

Correspondence Address:
Deepak Jain
Department of Medicine, Pt. B.D. Sharma University of Health Sciences, Rohtak - 124 001, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/heartindia.heartindia_5_17

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  Abstract 

Hypereosinophilic syndrome (HES) is a heterogeneous group of disorders with peripheral blood hypereosinophilia and eosinophil-mediated organ involvement. It may be primary, secondary, or idiopathic. In very rare cases, HES can be familial occurring as an autosomal dominant disorder. Cardiac involvement usually presents as heart failure, intracardiac thrombus, arrhythmias, and rarely as acute coronary syndrome (ACS) and is a major cause of morbidity and mortality. Cardiac magnetic resonance imaging has emerged as a diagnostic modality in diagnosis of eosinophilic endomyocardial disease. We report a case of a young male with familial HES presenting as ACS and discuss diagnostic and therapeutic clinical management.

Keywords: Acute coronary syndrome, heart failure, hypereosinophilic syndrome, myocarditis


How to cite this article:
Chhabra P, Jain D, Aggarwal H K, Mor S, Jain P. Hypereosinophilic syndrome mimicking acute coronary syndrome. Heart India 2017;5:77-81

How to cite this URL:
Chhabra P, Jain D, Aggarwal H K, Mor S, Jain P. Hypereosinophilic syndrome mimicking acute coronary syndrome. Heart India [serial online] 2017 [cited 2020 Sep 25];5:77-81. Available from: http://www.heartindia.net/text.asp?2017/5/2/77/208555


  Introduction Top


Hypereosinophilic syndrome (HES) is defined as peripheral blood hypereosinophilia (blood eosinophils >1.5 × 109/l) with eosinophil-mediated organ dysfunction or damage after exclusion of all possible causes. Familial HES is as an autosomal dominant disorder characterized by marked eosinophilia and progression to organ damage in some, but not all family members with a genetic mutation. HES can be primary, secondary, or idiopathic. Cardiac involvement is a major cause of morbidity and mortality and affects about 50% of patients.[1] Clinical manifestations include signs and symptoms of heart failure, intracardiac thrombus, arrhythmias, and less frequently, pericarditis and myocardial ischemia.[2] The outcome is variable and depends on the extent and progression of endomyocardial fibrosis, with an estimated 5-year mortality of around 30%. HES presenting as acute coronary syndrome (ACS) is very rarely reported in literature.


  Case Report Top


Eighteen years male nonsmoker, nonalcoholic presented to the emergency department with complaints of chest pain, which was typical retrosternal in location, radiating to left arm and associated with sweating. There was no history of shortness of breath, orthopnea, and pedal edema. He did not have a prior history of similar episode of chest pain, stroke, ischemic heart disease, asthma, hypertension, and diabetes mellitus. Patient was hemodynamically stable with blood pressure of 110/70 mmHg and pulse rate of 58/min regular. General physical examination was unremarkable. Cardiovascular and respiratory system examination was normal. Electrocardiogram (ECG) showed deep symmetrical T-wave inversion in inferolateral leads [Figure 1]. Creatine phosphokinase-MB (CPK-MB) was raised with a value of 110 U/L (normal range 0–25 U/L) and Troponin T was also elevated with a value of 2.15 ng/ml (normal range 0.00–0.07 ng/ml). Patient was managed as non-ST elevation myocardial infarction and started on antiplatelet drugs.
Figure 1: Electrocardiogram showing deep symmetrical T-wave inversion in inferolateral leads

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On investigations, peripheral blood film examination showed hemoglobin of 12.5 g/dl, total leukocyte count 44,000/cumm with polymorphs 30%, lymphocytes 12%, monocytes 3%, eosinophils 55%, with absolute eosinophil count (AEC) of 24,200/cumm, and absolute platelet count of 3 lac/cumm, with no atypical cells. Subsequent examination of peripheral blood film also revealed AEC more than 20,000/cumm. Blood sugar, serum lipids, prothrombin time index (PTI)/international normalized ratio, and renal and liver functions were normal. Antinuclear antibodies, cytoplasmic antineutrophil cytoplasmic antibodies (ANCA), and perinuclear ANCA were negative and total IgE was in the normal range with value of 80 IU/ml. Stool and urine complete examinations were normal. Bone marrow biopsy (BMB) revealed hypercellular marrow for age with marked prominence of eosinophils and eosinophilic precursors consisting 60% of all nucleated cells, with no atypical cells noted [Figure 2]. Findings of BMB ruled out any primary clonal cause of HES. FIP1L1-PDGFRA mutation by fluorescence in situ hybridization technique was negative. Chest X-ray and ultrasound abdomen were normal. Transthoracic echocardiography showed apical akinesia with hypokinetic posterior interventricular septum and left ventricular wall and ejection fraction of 40% with Grade 1 diastolic dysfunction. Computed tomography coronary angiography was normal with calcium score of zero [Figure 3]. Cardiac magnetic resonance imaging (MRI) showed thinned out a large area in the lateral wall of left ventricle, i.e., a full thickness infarct of 3 cm length in lateral wall of left ventricle which was further progressing into subendocardium. There was no evidence of any intracardiac thrombus. Cardiac MRI findings were consistent with an endomyofibrosis pattern (with extensive areas of subendocardial hyperintensity) which was highly suggestive of eosinophilic endomyocarditis [Figure 4].
Figure 2: Bone marrow biopsy showing hypercellular marrow with marked prominence of eosinophils and eosinophilic precursors

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Figure 3: Normal computed tomography coronary angiograph

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Figure 4: Cardiac magnetic resonance imaging findings consistent with an endomyofibrosis pattern

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Patient's father, his only sibling (brother), and his paternal uncle were found to have AEC of more than 6000/cumm on repeated occasions. AEC of his mother was normal. However, their ECG and cardiac echo were normal, and there was no other organ involvement, thus having an asymptomatic idiopathic HES. The clinical findings, family history, and investigations lead on to final diagnosis of familial HES with eosinophilic endomyocarditis presenting as ACS. Genetic studies were planned to make a definite confirmation of familial hypereosinophilia, thus benefiting patient and his family but could not be done because of nonavailability in our institution and financial constraints.

Patient was started on oral steroids and anti-ischemic treatment. Subsequently, his eosinophilic count has settled and he got revealed of his symptoms and discharged in a stable condition. He is presently on regular follow-up with his eosinophil counts in normal range.


  Discussion Top


HES is a heterogeneous group of disorders characterized by hypereosinophilia (AEC >1.5 × 109/l) and organ involvement of varying intensity. It includes all clinical presentations comprising serum hypereosinophilia with organ damage as a direct outcome of eosinophilic infiltration.

In 1975, Chusid et al. established three diagnostic criteria for HES, i.e., a persistent eosinophilia of 1500 eosinophils/cumm for >6 months, with no evidence of allergic, parasitic, or any other known causes of eosinophilia and manifestations of organ involvement.[3] The new definition includes symptom-free patients at the time of diagnosis with identified etiologies and also does not require a previous -month period of hypereosinophilia.[4] In primary (or neoplastic) HES, hypereosinophilia occurs due to underlying stem cell, myeloid or eosinophilic neoplasm, and is monoclonal. Diagnosis requires morphological, cytogenic, or molecular evidence of a myeloid neoplasm. In secondary HES, hypereosinophilia is due to stimulation by increased levels of eosinophilopoetic cytokinesis and is polyclonal. Parasitic infections, drugs, allergic disorders, and certain solid tumors are the various etiologies of secondary HES. In idiopathic HES, the underlying cause of HES remains unknown despite carrying out a thorough investigative workup and excluding out all primary and secondary causes.

Cardiac involvement in HES often occurs in the myeloproliferative forms.[5] Cardiovascular involvement in HES occurs in around 50% of cases. Cardiac involvement has three different pathological stages: the necrotic, thrombotic, and fibrotic stage. The first is an acute necrotic stage due to infiltration of eosinophils in the myocardium. Eosinophils have a longer survival time in cardiac tissue, and their degranulation is responsible for causing damage to the myocardium. Eosinophil-derived neurotoxin, major basic protein, cationic protein, and reactive oxygen species are various toxins released by the eosinophils. These toxins may damage endothelial cells and myocytes, leading to necrosis and thrombosis and finally resulting in endomyocardial fibrosis. There may be valvular involvement in the form of mitral and tricuspid regurgitation due to papillary muscle dysfunction and severe inflammatory changes in the endomyocardium.[6] The intermediate thrombotic phase is characterized by mural thrombi and thrombus formation along the damaged endocardium. The left ventricle is more affected, ventricular apex being the most common site. The third stage is the fibrotic stage, in which the granulation tissue progresses to hyaline fibrosis. This end stage is similar to that in other hypereosinophilic diseases affecting the heart (such as tropical endomyocardial fibrosis in tropical parasitic infections), proving the eosinophilia itself rather than the underlying etiology is responsible for the damage. Finally, restrictive cardiomyopathy occurs due to decreased compliance of left ventricle as result of mural fibrosis. Patients usually remain asymptomatic in early stages and often present in later stages, after developing restrictive or dilated cardiomyopathy. The initial presentation of eosinophilic myocarditis is nonspecific, and dyspnea is the most presenting symptom. Chest pain, cough, and palpitations can also be some uncommon presenting complaints. Cardiac involvement most commonly manifests as heart failure, intracardiac thrombus, arrhythmias, and pericarditis or very rarely as myocardial ischemia.

T-wave inversions and ST-T wave abnormalities are a frequent electrocardiographic manifestation, suggestive of an ACS, probably due to endomyocardial fibrosis and inflammation. Cardiac bio-enzymes such as troponins and CPK MB increase in the acute necrotic stage. A study showed that patients with biopsy-proven eosinophilic endomyocardial infiltration and normal echocardiography had elevated troponin T levels which are normalized after treatment with steroids. This suggests that troponin T can be a sensitive marker for early cardiac damage and can thus help in guiding treatment.[7] Echocardiography usually reveals regional areas of hypokinesia or akinesia and restrictive left ventricular filling pattern in the fibrotic stage. Coronary artery disease must be excluded by a coronary angiogram. Cardiac MRI has an emerging important role in the noninvasive diagnosis of cardiac involvement in HES.[8] Hyperintense myocardial area on T2-weighted images is suggestive of increased free water content due to myocardial edema and/or necrosis. Delayed subendocardial enhancement following gadolinium imaging is typically seen revealing myocardial inflammation and fibrosis, with high sensitivity in all stages of endomyocardial damage. However, endomyocardial biopsy remains the gold standard for diagnosing eosinophil myocardial disease. However, endomyocardial biopsy has limitations in terms of poor sensitivity (about 50%) because of sampling error due to segmental inflammatory infiltration and variability in the interpretation of biopsy results. However, diagnostic yield of endomyocardial biopsy can be increased by cardiac MRI-guided biopsy.

Management of HES includes immunosuppressive therapy for the underlying eosinophilia and conventional therapy for cardiac failure if present. Corticosteroid therapy should be initiated as early as possible because any delay increases the risk of significant restrictive heart failure. Prednisolone started at a dose of 1 mg/kg/day has shown favorable outcomes with a resolution of eosinophilia and improvement of symptoms.[9] There is no evidence for the use of anticoagulation therapy for prophylaxis of thrombotic complications. There is no absolute correlation between AEC and eosinophil-mediated tissue damage. Interleukin-5 (IL-5) antagonist mepolizumab is recommended in patients with lymphocytic variant of HES. Tyrosine kinase inhibitor imatinib is used for HES patients of chronic eosinophilic leukemia having FIP1L1-PDGFRA mutation.[10] Novel therapies including alemtuzumab, a human monoclonal antibody directed against CD52 on eosinophils, have been reviewed recently. Although some patients successfully underwent allogeneic stem cell transplantation, its role is not well established in HES.

Familial eosinophilia is an autosomal dominant disorder characterized by peripheral hypereosinophilia of unidentifiable cause with or without organ involvement. Genomic studies have provided evidence for linkage on chromosome 5q31-q33. This region contains the cytokine gene cluster, which includes three genes, namely, those for IL-3, IL-5, and granulocyte/macrophage colony-stimulating factor whose products play important roles in the development and proliferation of eosinophils. Patients with familial HES usually remain asymptomatic. In the present case, the patient presented with chest pain initially suspected to be having an ACS. On investigations, he had persistent hypereosinophilia and was finally diagnosed as idiopathic HES with eosinophilic endomyocarditis presenting as an ACS. Patient was also suspected to have familial HES because of his brother, father, and paternal uncle although asymptomatic had hypereosinophilia but conformation requires genetic studies which are not available in our institute. To conclude, in a young patient presenting with a classical ACS without any risk factors, a thorough investigative workup for all possible causes of ACS must be done including basic investigations such as complete hemogram which also carry importance and thus are essential.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Kleinfeldt T, Nienaber CA, Kische S, Akin I, Turan RG, Körber T, et al. Cardiac manifestation of the hypereosinophilic syndrome: New insights. Clin Res Cardiol 2010;99:419-27.  Back to cited text no. 1
    
2.
ten Oever J, Theunissen LJ, Tick LW, Verbunt RJ. Cardiac involvement in hypereosinophilic syndrome. Neth J Med 2011;69:240-4.  Back to cited text no. 2
    
3.
Chusid MJ, Dale DC, West BC, Wolff SM. The hypereosinophilic syndrome: Analysis of fourteen cases with review of the literature. Medicine (Baltimore) 1975;54:1-27.  Back to cited text no. 3
    
4.
Valent P, Klion AD, Horny HP, Roufosse F, Gotlib J, Weller PF, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. J Allergy Clin Immunol 2012;130:607-12.e9.  Back to cited text no. 4
    
5.
Ogbogu PU, Rosing DR, Horne MK 3rd. Cardiovascular manifestations of hypereosinophilic syndromes. Immunol Allergy Clin North Am 2007;27:457-75.  Back to cited text no. 5
    
6.
Aggarwal HK, Jain D, Kaverappa V, Jain P, Kumar A, Yadav S. Idiopathic hypereosinophilic syndrome presenting as severe Loeffler's endocarditis. Arq Bras Cardiol 2013;100:e43-6.  Back to cited text no. 6
    
7.
Sato Y, Taniguchi R, Yamada T. Measurements of serum concentrations of cardiac troponin T in patients with hypereosinophilic syndrome: A sensitive non-invasive marker of cardiac disease. Intern Med 2000;39:350.  Back to cited text no. 7
    
8.
Debl K, Djavidani B, Buchner S, Poschenrieder F, Heinicke N, Feuerbach S, et al. Time course of eosinophilic myocarditis visualized by CMR. J Cardiovasc Magn Reson 2008;10:21.  Back to cited text no. 8
    
9.
Klion AD, Bochner BS, Gleich GJ, Nutman TB, Rothenberg ME, Simon HU, et al. Approaches to the treatment of hypereosinophilic syndromes: A workshop summary report. J Allergy Clin Immunol 2006;117:1292-302.  Back to cited text no. 9
    
10.
Pardanani A, Brockman SR, Paternoster SF, Flynn HC, Ketterling RP, Lasho TL, et al. FIP1L1-PDGFRA fusion: Prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia. Blood 2004;104:3038-45.  Back to cited text no. 10
    


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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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