Pediatric Hematology and Oncology, 31:375–379, 2014Copyright C© Informa Healthcare USA, Inc.ISSN: 0888-0018 print / 1521-0669 onlineDOI: 10.3109/08880018.2013.806619

LETTER

Loeffler Endocarditis in a Pediatric Patient

Anastasia Keivanidou,1 Andreas Giannopoulos,1

Theodotis Papageorgiou,2 Emmanouil Hatzipantelis,2 Zoi Pana,2

and Fani Athanasiadou2

1Pediatric Cardiology Clinic, 2nd Pediatric Department, Ahepa University Hospital, AristotleUniversity of Thessaloniki, Thessaloniki, Greece; 2Pediatric Hematology-Oncology Clinic,2nd Pediatric Department, Ahepa University Hospital, Aristotle University of Thessaloniki,Thessaloniki, Greece

Loefler endocarditis is a potential fatal adverse event of hypereosinophilic syndrome. We report acase of a 5-year-old girl diagnosed with peripheral hypereosinophilia refractory to corticosteroidtherapy who developed eosinophilia-related endocarditis. Echocardiography revealed infiltrationof the left ventricular free wall and the posterior mitral leaflet causing moderate mitral regurgi-tation. Genetic tests failed to recognize FIPiLi-PDGRFA genotype; however imatinib, a tyrosine ki-nase inhibitor was initiated. After a 4-week period of treatment there was a complete resolutionof eosinophilia and a complete recovery of cardiac manifestation. This case highlights the intro-duction of imatinib for the treatment of hypereosinophilic syndrome refractory to corticosteroidtherapy even in the absence of FIPiLi-PDGRFA genotype in pediatric patients.

Keywords children, corticosteroid treatment, genotype, hypereosinophilic syndrome, imatinib,loefler syndrome

INTRODUCTION

Hypereosinophilic syndrome (HES) was first described in 1968 by Hardy and Ander-son and was defined later in 1975 by Chusid as (i) persistent eosinophilia of 1500eosinophils/mm3 for longer than 6 months, (ii) exclusion of secondary eosinophilia,such as parasitic infection, drugs, connective tissue disorders, vasculitis, malignan-cies, or allergies, and (iii) eosinophilia-related organ involvement [1–2]. Cardiac man-ifestation is found in more than 50% of the patients and is responsible for the unfavor-able adverse events [3]. Infiltration of the myocardium by eosinophilic cells, followingendocardium thickening, is known as “Loeffler’s endocarditis” and may lead to restric-tive cardiomyopathy [4,5]. We report the case of a 5-year-old girl diagnosed with HESwho developed Loeffler endocarditis and the diagnostic and therapeutic options.

Case PresentationA 5-year-old girl with no significant past medical history was referred from her dis-trict hospital to our department with a history of 48 h of cough and peripheral

Received 31 March 2013; accepted 15 May 2013; published online 2013.Address correspondence to Anastasia Keivanidou. Pediatric Cardiology Clinic, 2nd PediatricDepartment, Ahepa University Hospital, Aristotle University of Thessaloniki, 1 Kyriakidi Street,54636 Thessaloniki, Greece. Email: keivanidou@yahoo.com

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blood eosinophilia. On physical examination she was hemodynamically stable, tem-perature was 36.8◦C and O2 Saturation was 88%. Wheezing and mild tachycardiawas noted on examination of respiratory and cardiovascular systems. During exam-ination of the abdomen, hepatomegaly of 2 cm and splenomegaly of 2 cm bellowcostal margin was also of noted. Laboratory tests revealed white blood cell count152,000 cells/mL with 80% eosinophils (absolute eosinophil count 121,600 cell/mL),hemoglobin 11.4 g/dL, hematocrit 33.6%, MCV 85.7 fl, MCH 29.1 pg, platelets 285,000mm3, glucose 87 mg/dL, and CRP 2.2 mg/dL. Bone marrow biopsy was rich in cellswith increased myelopoiesis and eosinophilia. Genetic tests were unable to identifythe presence of FIPiLi-PDGRFA-fusion gene that encodes the fusion protein with ty-rosine kinase activity [6]. All causes of secondary eosinophilia were excluded and nomyeloproliferative disorder was found. Twelve-lead ECG was normal and transtho-rasic echocardiogram showed no signs of myocardial involvement. She commencedon corticosteroids, oral prednisolone 35 mg/24 h in three divided doses, immediatelyafter the diagnosis of HES was made. Two months later eosinophilia was still presentand by that time transthorasic echocardiography showed infiltration of left ventricularfree wall and mitral valve posterior leaflet, causing moderate insufficiency. Diameterof the left ventricle and systolic function were preserved. No thrombus was identified(Figures 1 and 2). 12-lead ECG showed T wave inversions in III, avF, V4-V6. Becauseof the persistent eosinophilia and the cardiac involvement corticosteroids were dis-continued and imatinib, a tyrosine kinase inhibitor, was initiated in a dosage 400 mgb.i.d. In four weeks of time, eosinophilia was reduced and left ventricle infiltration wasresolved. Fibrosis did not develop and only mild mitral valve insufficiency was left.Twelve-lead ECG also returned to normal. After 4 months of follow-up, eosinophiliawas resolved and echocardiography showed only mild mitral insufficiency. No addi-tional medication (ACE inhibitors or beta-blocker) or coagulation was given.

FIGURE 1 Long axis view of the left ventricle showing the eosinophilic infiltration of the left ventric-ular lateral wall and the posterior mitral valve leaflet. Anterior mitral valve leaflet appears normal.

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Loeffler Endocarditis

FIGURE 2 Four chamber apical view showing the eosinophilic infiltration of the left ventricularlateral wall. No thrombus was identified.

DISCUSSION

Loefler endocarditis is the condition at which heart is being affected by eosinophilicinfiltration, causing thrombi, and fibrosis. It was first described by Loefler in 1936in cardiac autopsy of two patients who died after two decades of leukocytosis andeosinophilia. Findings showed fibrosis of the myocardium but not the valves [4].

Cardiac manifestation of HES include eosinophilic infiltration of the myocardium,mural thrombi, and thrombus formation and endocardiac fibrosis [3,7]. Eosinophilicinfiltration of the myocardium represents the first stage of the disease with a durationthat ranges from a few days to 3 months and is considered to be asymptomatic [7].Mural thrombi and thrombus formation is initiated by a damaged endocardium andaffects more often the apices [3,7,8]. At this stage, which lasts about 10 months, normalmyocardium is replaced by the organized thrombus. This is followed by the third stageat which the damaged myocardium becomes thickened and fibrotic [5,7].

Cardiac involvement in HES is expected in 50% of the patients and includes en-docardiac fibrosis with mural thrombi formation affecting the apices of both ventri-cles [9]. Mural fibrosis results in reduction of the compliance of left ventricle leadingprogressively to restrictive cardiomyopathy. Mitral valve pupillary muscles and cor-dae tendinae may also be affected and cause mitral regurgitation. In more advancedcases, myocardial damage may affect conduction system and provoke arrhythmias.Embolization of district organs can happen in approximately 25% [2,8].

Electrocardiographic findings are seen in about one-third of patients with Loeflerendocarditis. T-wave alterations are most frequent observed due to subendocardiacinjury after fibrosis and inflammation. Premature ventricular beats and signs of leftventricular hypertrophy are also seen [10].

Echocardiography reveals endomyocardial thickening due to eosinophilic infil-tration. Posterior mitral leaflet can also be affected restricting its motion. Thrombi

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formation is another, rather unfavorable feature occupying the apices of bothventricles. Pericardial effusion can also be seen [2,8, 10, 11].

Although corticosteroids are the gold standard therapy of all types of HES,imatinib—a novel tyrosine kinase inhibitor—has recently been introduced as a thera-peutic option in children with FIPiLi-PDGRFA genotype and in adults without FIPiLi-PDGRFA genotype [9, 12]. The present case demonstrates some unusual features ofHES, as corticosteroid therapy had no beneficial effect and imatinib had a positiveresponse although our patent was FIPiLi-PDGRFA genotype negative. Our findingsdemonstrate that even patients without the FIPiLi-PDGRFA genotype may possiblybenefit from imatinib; although the response rate could be relatively slow. From theextensive review of the literature only few cases of pediatric hypereosinophilia havebeen described and FIPiLi-PDGRFA genotype was recognized in even fewer. Imatinidwas proposed as a therapeutic option in those children with FIPiLi-PDGRFA genotypeand in adults without FIPiLi-PDGRFA genotype. To the best of our knowledge, this isthe first time that imatinib was introduced to the management of hyperoesinophilicsyndrome in a pediatric patient with negative FIPiLi-PDGRFA genotype. However, theduration of the therapy, the possibility of relapse and the long-term heart effects stillremain to be carefully assessed.

CONCLUSION

In this case, we describe the management of hyperoesinophilic syndrome in a pedi-atric patient with negative FIPiLi-PDGRFA genotype. Corticosteroids failed to resolveeosinophilia and imatinib—a novel tyrosine kinase inhibitor—introduced as a thera-peutic option. The results were encouraging, since eosinophils returned to normal andno cardiac dysfunction remained. We believe that this case is unique, since this is thefirst time that imatinib has been used to the management of hyperoesinophilic syn-drome in a pediatric patient with negative FIPiLi-PDGRFA genotype. We trust that ourcase will add to the management of these patients, though further experience must begained.

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for thecontent and writing of the paper.

REFERENCES

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with review of the literature. Medicine (Baltimore). 1975 ;54(1):1–27.[3] Weller PF, Bubley GJ. The idiopathic hypereosinophilic syndrome. Blood. 1994;83(10):2759–2779.[4] Loffler W. Endocarditis parietalis fibroplastica mit Bluteosinophilie. Schweiz Med Wochenschr.

1936;65:817–820.[5] Tai PC, Ackerman SJ, Spry CJ, et al. Deposits of eosinophil granule proteins in cardiac tissues of pa-

tients with eosinophilic endomyocardial disease. Lancet. 1987;1(8534):643–647.[6] Cools J, DeAngelo DJ, Gotlib J, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1

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[7] Brockington IF, Olsen EG. Eosinophilia and endomyocardial fibrosis. Postgrad Med J.1972;48(566):740–741.

[8] Ogbogu PU, Rosing DR, Horne MK 3rd. Cardiovascular manifestations of hypereosinophilic syn-dromes. Immunol Allergy Clin North Am. 2007;27(3):457–475.

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[9] ten Oever J, Theunissen LJ, Tick LW, Verbunt RJ. Cardiac involvement in hypereosinophilic syn-drome. Neth J Med. 2011;69(5):240–244.

[10] Parrillo JE, Borer JS, Henry WL, et al. The cardiovascular manifestations of the hypereosinophilic syn-drome. Prospective study of 26 patients, with review of the literature Am J Med. 1979;67(4):572–582.

[11] Dedieu N, Giardini A, Khambadkone S, Marek J. Eosinophilic heart disease in a paediatric patient.Eur J Echocardiogr. 2011;12(1):E3.

[12] Kleinfeldt T, Nienaber CA, Kische S, et al. Cardiac manifestation of the hypereosinophilic syndrome:new insights. Clin Res Cardiol. 2010;99(7):419–427.

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