Transcript Q Fever Endocarditis: An Unusual Presentation

Q Fever Endocarditis: An Unusual Presentation
Martin Espinosa Ginic¹, MD, Allen T. Griffin,² MD, and Raul Nakamatsu,²,3 MD
Department of Medicine, Division of Cardiovascular Medicine¹ and Division of Infectious Diseases², Robley Rex VAMC3
ABSTRACT
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Objectives: Endocarditis due to C. burnetii is distinguished by negative blood cultures in standard
bacteriologic media as well as small or even absent vegetations on echocardiography. In this case report, we
present a distinctly unusual case of Q fever endocarditis marked by large vegetations and associated
paravalvular abscess.
Case Report: The patient is a 50-year-old male with history of diabetes mellitus, nephropathy with nephrotic
syndrome, diastolic heart dysfunction, coronary artery disease, and severe aortic stenosis with aortic valve
replacement who presented with gradually worsening shortness of air, weight loss, fatigue, severe headaches,
night sweats, and an episode of fever. Diagnostic studies revealed no immediate source of fever, but clinical
evidence of congestive heart failure was present. Echocardiography revealed a large 1.7 cm highly mobile
vegetation on the ventricular side of the bioprosthetic aortic valve with an associated paravalvular abscess.
MRI of the brain revealed multiple embolic lesions. All blood cultures off antibiotics were persistently negative.
Serologies for potential causes of culture-negative endocarditis were procured and revealed titers of C. burnetii
of 1:2048 (phase I IgG) consistent with the diagnosis of Q fever endocarditis. The patient was initiated on
doxycycline and hydroxychloroquine, had aortic valvular replacement, and recovered uneventfully with later
decline associated with medication non-compliance.
Conclusions: This patient presented with culture-negative endocarditis later found to be related to C. burnetii,
the agent of Q fever. Quite distinct from most cases of endovascular infection due to this organism, this
patient not only had a distinctly large vegetation with embolic phenomenon to the brain, but also had
paravalvular spread. This case illustrates that Q fever should be considered in the differential diagnosis of all
cases of culture negative endocarditis regardless of vegetation size.
DISCUSSION
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INTRODUCTION
Coxiella burnetii (C. burnetii), the agent of Q fever, typically presents as a self-limiting illness resembling
influenza with or without an accompanying pneumonia or hepatitis. Less commonly, Q fever becomes a
chronic illness manifested by endovascular involvement in those with predisposing cardiac lesions or
prostheses. While C. burnetii is an uncommon etiology of endocarditis in the United States, the cardiac
valvular lesions often differ fundamentally from those of most bacteria, and the pathogen cannot be isolated in
standard media. These distinctions offer clues to the pathogen’s presence for clinicians less familiar with this
illness. In the following case presentation, we elucidate an instance of Q fever endocarditis acquired in the
United States that is marked by unusual cardiac manifestations.
CASE PRESENTATION
A 50-year-old Caucasian male presented with three weeks of shortness of breath, headaches, and generalized
swelling. He noted associated night sweats, malaise, weight loss, and one episode of fever to 101°F.
The patient’s past medical history included diabetes mellitus complicated by nephropathy with nephrotic
syndrome, coronary artery disease, and severe aortic stenosis with bioprosthetic aortic valve replacement and
coronary artery bypass grafting one year prior to presentation. He resided in a suburban area of Kentucky and
had never traveled outside the United States. However, he reported working on a dairy farm until 2002.
Upon hospital presentation, physical exam revealed a chronically ill appearing thin male with anasarca and
signs of muscle wasting. Vital signs were: blood pressure, 188/104mmHg; pulse, 80 beats per minute;
respiratory rate, 22 breaths per minute; temperature, 96.2F; and O2 saturation, 97% on room air. Cardiac
auscultation revealed a loud midsystolic murmur heard best in the left parasternal area on expiration. Lung
auscultation revealed bibasilar crackles. Chest roentgenogram showed mild pulmonary edema.
Transthoracic echocardiogram (TTE) revealed a highly mobile 1.7 x 0.9 cm vegetation located on the
ventricular side of the aortic valve extending to the base of the anterior MV leaflet that protruded into the LV
outflow tract during systole (Figure 1). Later, transesophageal echo (TEE) confirmed the vegetation attached
at the junction of the prosthetic aortic valve ring to the anterior mitral valve leaflet, all consistent with
endocarditis. In addition, a 0.5cm thick echogenic layer along the posterior aspect of the aortic root consistent
with paravalvular abscess was noted (Figure 1). Left Ventricular Ejection Fraction (LVEF) was 51%. ECG
showed normal sinus rhythm with no signs of acute ischemia or conduction abnormalities.
Appropriate diuretic therapy was given with improvement of the heart failure symptoms. Antibiotics were not
begun initially given the patient’s stability, subacute course, and unknown etiology of endocarditis. All blood
cultures were negative.
Due to negative blood cultures, further diagnostic tests were pursued for fastidious organisms (Table 2).
Serologic studies for causes of culture-negative endocarditis were negative with the exception of a phase I
immunoglobulin G (IgG) against C. burnetii at 1:2048 consistent with the diagnosis of Q fever endocarditis.
Subsequently, the patient was begun on oral doxycycline and hydroxychloroquine. He later developed mild
dysarthria and vertigo, and embolic posterior circulation strokes where confirmed by MRI (Figure 2). The
patient was taken to cardiac surgery emergently where he had replacement of his bioprosthetic aortic valve
with a mechanical prosthesis, and debridement with reconstruction of the aortic root. He recovered
uneventfully; repeat phase I titers before hospital discharged declined to 1:1024. Unfortunately, the patient was
erratically compliant with his medications and months later developed progressive paravalvular aortic
regurgitation with significant dehiscence of the prosthetic valve and consequent heart failure that led to his
death. The valvular dehiscence was thought to be related to recurrence of infection.
Figure 1. Echocardiography: A) Trasthoracic parasternal long axis view during isovolumetric contraction revealing large vegetation
extending to the anterior leaflet of the mitral valve. B) Trasthoracic parasternal long axis view during end systole with partial occlusion of the
left ventricular outflow tract by large vegetation. C) Apical four chamber view with vegetation attached at the junction of aortic valve ring to
base of anterior mitral valve. D) Transeshophageal short axis view at the aortic valve level revealing periprosthetic aortic rood abscess.
RV: Right ventricle, LV: Left ventricle, RA: Right atrium, LA: Left atrium, AV: Aortic Valve.
Table 1. Laboratory results upon admission
Parameter
Value
White blood cell count (cells/mm3)
7,700
Hemoglobin (g/dl)
8.8
Platelets (cells/mm³)
179,000
ESR (mm/hour)
68
Sodium (mmol/L)
138
Potassium (mmol/L)
4.9
Bicarbonate (mmol/L)
27
Chloride (mmol/L)
109
Blood urea nitrogen (mg/dl)
29
Creatinine (mg/dl)
1.6
Glucose (mg/dl)
131
Calcium (mg/dl)
7.7
Alkaline phosphatase (U/L)
194
AST (U/L)
39
ALT (U/L)
40
Total bilirubin (mg/dl)
0.1
Albumin (g/dl)
1.7
Total protein (g/dl)
4.7
C-reactive protein (mg/L)
9.3
Epidemiology of Coxiella burnetii:
Q fever has traditionally been associated with rural areas and livestock where aerosolization of organisms,
particularly from birth products, or consumption of unpasteurized milk has resulted in illness. However,
exposure need not be rural, as C. burnetii is capable of traveling great distances to cause infection. Pets,
particularly felines, have also been shown to transmit the pathogen through aerosolization from birth
products.
As many as 2.9 % of the United States population has serologic evidence of past infection; however,
consistently no more than 20-160 cases are reported to the Centers for Disease Control and Prevention
yearly. The preponderance of instances are from rural, midwestern states.
Given its hardiness in nature, ability to traverse great distances and result in infection, and extreme
infectiousness, C. burnetti is a feared agent of bioterrorism.
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Q fever, originally described in 1937 by E.H. Derrick in Queensland, Australia, as a pathologic entity in
slaughterhouse workers, is caused by C. burnetii, a small, strictly intracellular, Gram-negative bacterium of
the Coxiellaceae family.
Clinical Presentation:
Q fever manifestations can be divided into acute and chronic. Acute infection is more common and marked
by hepatitis (40%), pneumonia and hepatitis (20%), pneumonia alone (17%), or fever alone (17%).
Exceptionally unusual presentations include meningoencephalitis (1%), meningitis (1%), myocarditis (0.7%),
pericarditis, osteomyelitis, and uveitis or optic neuritis. Chronic infection is more common in the elderly or
those with impaired immunity, with endocarditis being by far the most frequent presentation (60-70%),
followed by rare infections of the arteries, bones, and liver. In Q fever endocarditis, prosthetic heart valves or
an underlying valvular disorder is invariably present (88% of cases). Common complaints of chronic Q fever
are headache, fevers, chills, night sweats, and muscle pain. Signs of heart failure are typical as are embolic
events. Vegetations are characteristically small or absent; abscess formation is scarcely reported. Despite
appropriate care, mortality rates may be as high as 24%.
Diagnosis:
Serology, by microimmunofluorescence, is currently the preferred means of diagnosis. The optimal titer for
diagnosis of acute Q fever has been shown to be ≥1:200 for IgG and ≥1:50 for IgM (phase II) while ≥1:800 for
IgG (phase I) has been found to be optimal for chronic Q fever.
Treatment:
For endocarditis, combination therapy is superior to monotherapy, and the majority of patients require
surgery, particularly if paravalvular extension is present. Doxycycline in combination with hydroxychloroquine
is recommended. A minimum of three years of therapy has been suggested although the addition of
hydroxychloroquine may allow the duration to be shortened. Titers should be followed for a period of five
years to help ensure no recurrence transpires off treatment.
CONCLUSIONS
The current case illustrates the indolent course of Q fever endocarditis with its invariably negative cultures in
a feeble patient with preexisting valvulopathy. In contrast to the vast majority of Q fever cases, however, the
patient not only had a large aortic valve vegetation, but he also had a distinctly uncharacteristic paravalvular
abscess that mandated surgery. The current case emphasizes the need to be cognizant of the diagnosis in
all cases of culture-negative endocarditis, including those with atypical cardiac manifestations.
Figure 2: Axial T2-Flair MRI image revealing multiple areas of
abnormally restricted diffusion in the posterior circulation territory,
largest in the left cerebellar hemisphere. Findings are consistent
with tromboembolic stroke lesions.
ESR: Erythrocyte Sedimentation Rate; AST: Aspartate Aminotransferase;
ALT: Alanine Aminotransferase.
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Table 2. Results of diagnostic assays to ascertain the etiology of culture-negative endocatditis
Assay
Value
Bartonella henselae and quintana IFA
<1:64
Coxiella burnetii phase I titers
1:2048
Legionella pneumophila IFA
<1:64 (IgG)
Legionella pneumophila urinary antigen
Not detectable
Chlamydia pneumoniae serology
IgM and IgG negative
Mycoplasma pneumoniae serology
IgM and IgG negative
Brucella species serologya
IgM and IgG negative
Histoplasma capsulatum urinary antigen
Not detectable
Fungal isolator cultures
No growth
aIncludes
serology for Brucella melitensis, abortus, canis, and suis; IFA indicates indirect fluorescent antibody; IgM, immunoglobulin M; IgG, immunoglobulin G.
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