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Loeffler Endocarditis: Background, Pathophysiology, Frequency
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Loeffler Endocarditis
Author: Sohail A Hassan, MD; Chief Editor: Richard A Lange, MD, MBA more...
Updated: Feb 17, 2015
Background
Loeffler endocarditis and endomyocardial fibrosis are restrictive cardiomyopathies,
defined as diseases of the heart muscle that result in impaired ventricular filling with
normal or decreased diastolic volume of either or both ventricles. Systolic function
and wall thickness may remain normal, especially early in the disease, as reported by
Richardson and associates.[1, 2] Both conditions are associated with eosinophilia.
The associations among eosinophilia, active carditis, and multiorgan involvement
were first described by Loeffler in 1936.[3] Pathologic specimens in Loeffler
endocarditis show eosinophilic myocarditis, a tendency toward endomyocardial
fibrosis and clinical manifestations of thromboembolism, and acute heart failure.
Eosinophilic states that may occur in association with Loeffler endocarditis include
hypereosinophilic syndrome, eosinophilic leukemia, carcinoma, lymphoma, drug
reactions or parasites, as reported in multiple case series.
Although eosinophilic endocardial disease has been well described, myocardial and
vascular damage due to eosinophilic infiltration and degranulation is rarely diagnosed
during life, as reported by Oakley et al and others.[4] Herzog et al and Tonnesen et al
have proposed that the reason for this situation may be the rapidly fatal evolution of
most cases of eosinophilic arteritis and myocarditis.[5, 6] These conditions are usually
diagnosed based on postmortem examination and nonspecificity of clinical
manifestations, as reported by Kim et al, Isaka et al, and Seshadri et al.[7, 8, 9]
Pathophysiologically, the fibrotic stage of Loeffler endocarditis is very similar to the
disease entity described as endomyocardial fibrosis, which is indolent in comparison
to Loeffler endocarditis. The tropical form of endomyocardial fibrosis is associated
with eosinophilia, a common finding in Loeffler endocarditis.
Pathophysiology
Endomyocardial damage in Loeffler endocarditis is well known and described in a
study by Solley and associates.[10] Myocardial involvement is less well known and has
been considered a manifestation of an acute necrotic stage of eosinophilic
endomyocardial disease, as reported by Olsen and colleagues.[11] More recently,
cases of isolated eosinophilic myocarditis have been reported without signs of
endomyocardial involvement, with or without vasculitis.
Additionally, idiopathic eosinophilic endomyocarditis, in the absence of peripheral
eosinophilia, has been reported by Priglinger et al.[12]
Morphologic abnormalities of eosinophils have been noted in patients with Loeffler
endocarditis, suggesting that these eosinophils were mature or stimulated. The
intracytoplasmic granular content of activated eosinophils is thought to be responsible
for the toxic damage to the heart, as reported by Tai and associates.[13] Spry et al
reported eosinophilic degranulation of basic proteins causing myocardial damage in
tissue cultures in vitro.[14] Gliech et al reported a dose-dependent cytotoxic effect of
the eosinophilic granular proteins, inhibiting multiple enzyme systems.[15]
The cationic eosinophilic proteins bind to the anionic endothelial protein,
thrombomodulin. This complex impairs anticoagulant activities, leading to enhanced
endocardial thrombus formation, as reported by Slungaard and colleagues.[16]
Toxins released by the eosinophils include eosinophil-derived neurotoxin, cationic
protein, major basic protein, reactive oxygen species, and arachidonic acid
derivatives. As described by Cunningham et al, these toxins may cause endothelial
and myocyte damage, resulting in thrombosis, fibrosis, and infarction.[17]
The intensity and timing of the active carditis is related closely to the severity of the
circulating eosinophilia. Some have suggested that, particularly in the tropics, patients
who present with later fibrotic stages of endomyocardial disease may have had either
transient earlier bouts of moderate eosinophilia with spontaneous resolution, or only
moderate levels of eosinophilia leading to a low-grade endomyocarditis with gradual
progressive fibrosis, as reported by Olsen et al.[11]
Molecular pathophysiology
Cools et al reported a landmark finding by treating patients with hypereosinophilic
syndrome (HES) with imatinib, a tyrosine kinase inhibitor.[18] Among the findings were
the following:
The gene defect is localized to an interstitial chromosomal deletion on
chromosome band 4q12, resulting in fusion of the Fip1-like1 ( FIP1L1) gene
to the platelet-derived growth factor gene alpha ( PDGFRA). The protein
product of this gene is a tyrosine kinase enzyme that transforms the
hematopoietic stem cells. This FIP1L1-PDGFRA fusion gene defect was
identified in 9 of 16 patients treated with imatinib.
This study also highlights the importance of reclassifying HES as a
myeloproliferative disorder of a possible single clone based on genotyping, as
the FIP1L1-PDGFRA gene rearrangement is a clonal abnormality.
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Treatment with imatinib caused rapid regression of eosinophilic proliferation
and endomyocardiopathy in subsequent cases reported by Vandenberghe et
al and Rotoli et al. [19, 20]
The following list summarizes the initial clinical presentations of eosinophilic
endomyocardial disease in relation to the predominant pathologic stage of the
disease as reported by Alderman et al in the Textbook of Cardiovascular
Medicine.[21] Death is usually related to multiorgan dysfunction in the presence of
congestive heart failure.
The initial clinical presentation and stages of eosinophilic endomyocardial disease are
descreibed below.[21]
Necrotic stage (early stage)
Hypereosinophilia with systemic illness (20-30%) is associated with the following
signs/symptoms:
Fever
Sweating
Chest pain (as described by Bestetti et al [22] )
Lymphadenopathy
Splenomegaly
Acute carditis (20-50%) is associated with the following signs/symptoms:
Anorexia
Weight loss
Cough
Pulmonary infiltrates
Skin and retinal lesion
Atrioventricular valve (AV) valve regurgitation
Biventricular failure
Polymorphic ventricular tachycardia [23]
Thrombotic stage
Thrombotic emboli (10-20%) are associated with the following signs/symptoms:
Cerebral, splenic, renal, and coronary infarction
Splinter hemorrhages
Fibrotic stage (late stage)
Restrictive myopathy (10%) are associated with the following signs/symptoms:
AV valvular regurgitation
Right and left heart failure
The image shows dense fibrosis of ventricle in a postmortem dissected heart.
Myocardial as well as valvular involvement with Loffler endocarditis. This image shows dense
fibrosis of ventricle in a postmortem dissected heart.
Frequency
United States
The condition is rare and is seen mostly in immigrants from Africa, Asia, and South
America.
International
Loeffler endocarditis is primarily confined to the rain forest (tropical and temperate)
belts of Africa, Asia, and South America.
Mortality/Morbidity
The literature reports a 35-50% 2-year mortality rate in patients with advanced
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myocardial fibrosis. Substantially better survival rates may be seen in less
symptomatic patients who have milder forms of the disease. As noted, this rate may
reflect underdiagnosis of clinically inapparent disease, as for other types of
cardiomyopathy.
Prognosis
The overall prognosis of patients with Loeffler endocarditis is poor and depends on
the location of involvement in the heart.
The disease is usually slow in onset, with progression to increasing degrees of right
and left heart failure.
Sudden death and syncope are not as common as in other causes of restrictive
cardiomyopathy
Race
The condition has a predilection for African and African American populations, notably
the Rwanda tribe in Uganda, and for people of low socioeconomic status. Whether
this is due to genetic factors or the epidemiology of underlying environmental factors
is not known.
Sex
Loeffler endocarditis has a predilection for males. However, endomyocardial fibrosis,
which has similar clinical manifestations, is found equally frequently in both sexes.
Age
The reported age range is 4-70 years. Loeffler endocarditis particularly affects young
males, as does its close counterpart, endomyocardial fibrosis, which is more
common in children and young adults.
Clinical Presentation
Contributor Information and Disclosures
Author
Sohail A Hassan, MD Cardiologist and Cardiac Electrophysiologist, Eastside Cardiovascular Medicine; Director or
Electrophysiology at St John Macomb Hospital; Assistant Professor of Medicine, Wayne State University School of
Medicine
Sohail A Hassan, MD is a member of the following medical societies: American College of Cardiology, American
College of Physicians, American Heart Association, Michigan State Medical Society, Heart Rhythm Society
Disclosure: Received honoraria from Medtronic, for speaking and teaching; Received honoraria from Zoll for
speaking and teaching; Received honoraria from Boeringer Ingelheim for speaking and teaching; Received
honoraria from St Jude''''''''s Medical for speaking and teaching; Received honoraria from Boston Scientific
corporation for speaking and teaching; Received honoraria from Biotronik for speaking and teaching; Received
honoraria from Sanofi Aventis for speaking and teaching.
Coauthor(s)
Henry Kim, MD, MPH Fellowship Director, Department of Cardiology, Henry Ford Hospital
Henry Kim, MD, MPH is a member of the following medical societies: American Medical Association
Disclosure: Nothing to disclose.
Fatima Ansari University of Michigan
Disclosure: Nothing to disclose.
Specialty Editor Board
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College
of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Marschall S Runge, MD, PhD Charles and Anne Sanders Distinguished Professor of Medicine, Chairman,
Department of Medicine, Vice Dean for Clinical Affairs, University of North Carolina at Chapel Hill School of
Medicine
Marschall S Runge, MD, PhD is a member of the following medical societies: American Physiological Society,
American Society for Clinical Investigation, American Society for Investigative Pathology, Association of American
Physicians, Texas Medical Association, Southern Society for Clinical Investigation, American Federation for Clinical
Research, Association of Professors of Medicine, Association of Professors of Cardiology, American Association
for the Advancement of Science, American College of Cardiology, American College of Physicians-American
Society of Internal Medicine, American Federation for Medical Research, American Heart Association
Disclosure: Received honoraria from Pfizer for speaking and teaching; Received honoraria from Merck for speaking
and teaching; Received consulting fee from Orthoclinica Diagnostica for consulting.
Chief Editor
Richard A Lange, MD, MBA President, Texas Tech University Health Sciences Center, Dean, Paul L Foster
School of Medicine
Richard A Lange, MD, MBA is a member of the following medical societies: Alpha Omega Alpha, American College
of Cardiology, American Heart Association, Association of Subspecialty Professors
Disclosure: Nothing to disclose.
Acknowledgements
Viqar Maria, MD Resident Physician, Department of Internal Medicine, St John Hospital and Medical Center
Viqar Maria, MD is a member of the following medical societies: American College of Physicians
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Disclosure: Nothing to disclose.
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