- Email: [email protected]
Coxiella burnetii infection of left atrial thrombus mimicking an atrial myxoma
International Journal of Infectious Diseases 14S (2010) e319–e321
Contents lists available at ScienceDirect
International Journal of Infectious Diseases journal homepage: www.elsevier.com/locate/ijid
Case Report
Coxiella burnetii infection of left atrial thrombus mimicking an atrial myxoma Mario Ferna´ndez-Ruiz a,b,*, Francisco Lo´pez-Medrano b, Fe´lix Alonso-Navas a, Jose´ Marı´a Aguado b a b
Department of Internal Medicine, University Hospital ‘‘12 de Octubre’’, Avda. Co´rdoba, s/n, 28041 Madrid, Spain Infectious Diseases Unit, University Hospital ‘‘12 de Octubre’’, Madrid, Spain
A R T I C L E I N F O
S U M M A R Y
Article history: Received 2 September 2009 Received in revised form 9 December 2009 Accepted 26 February 2010
Infection of intracardiac thrombi is extremely unusual. Coxiella burnetii is a well-recognized etiologic agent of negative-blood culture endocarditis and vascular graft infection. Herein we describe the first reported case, to our knowledge, of C. burnetii infection of a large left-sided intracardiac thrombus that was initially misdiagnosed as an atrial myxoma. Diagnosis was confirmed by direct immunofluorescence assay, electron microscopy, and C. burnetii-specific polymerase chain reaction analysis performed on tissue sections of the thrombus. ß 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Corresponding Editor: William Cameron, Ottawa, Canada Keywords: Atrial myxoma Coxiella burnetii Infected intracardiac thrombus Left atrial mass Polymerase chain reaction analysis Q fever
1. Introduction Nowadays the demonstration of large left atrial thrombi is an infrequent event, as there has been a tendency towards a reduced incidence of native valve disease and the use of anticoagulant therapy has become more widespread in clinical practice. In this setting, infected intracardiac thrombi represent a very rare condition, usually reported in the ventricular chamber.1–4 The etiologic agents most frequently involved in such cases are Gramnegative bacilli1,2 (Escherichia coli, Klebsiella pneumoniae, or Salmonella species) and Staphylococcus aureus.4 Only occasional examples of infection of a left atrial thrombus may be found in the literature.5–7 The most frequent clinical presentation of chronic Q fever, caused by Coxiella burnetii, is negative-blood culture endocarditis, although infections of aneurysms and vascular grafts have also been described.8,9 To the best of our knowledge no previous case of C. burnetii infection of a left atrial thrombus has been reported to date. 2. Case report A previously healthy 62-year-old male presented to our clinic with persistent daily fever of 7-month duration associated with
* Corresponding author. Tel.: +34 91 763 99 59; fax: +34 91 763 99 59. E-mail address: [email protected] (M. Ferna´ndez-Ruiz).
marked asthenia, hyporexia, and a 10-kg weight loss over that period of time. He was a current smoker and had no previous history of valvular heart disease. At admission, his blood pressure was 130/70 mmHg and pulse rate 105/min. Physical examination revealed an 8-cm tender hepatomegaly and a 5-cm firm splenomegaly, with no abnormal findings on heart auscultation. Initial laboratory investigations showed hemoglobin 12 g/dl, white cell count 10.8 109/l (65% neutrophils), platelets 183 109/l, alkaline phosphatase 197 IU/l (normal, 40– 130), lactic dehydrogenase 310 IU/l (normal, 90–230), erythrocyte sedimentation rate (ESR) 54 mm/h, and a positive serologic test for hepatitis C virus (HCV). The remaining diagnostic studies, including repeated blood and urine cultures, determination of serum tumor markers, and serologic tests for Brucella, Leishmania and Salmonella spp, Treponema (rapid plasma reagin and passive hemagglutination), human immunodeficiency virus, and other hepatotropic viruses, were either within the normal range or negative. A chest X-ray was normal; transthoracic echocardiography (TTE) was not available at first presentation. Abdominal ultrasound confirmed the presence of a homogeneous hepatosplenomegaly with no signs of portal hypertension. A laparoscopy-guided liver biopsy was compatible with the diagnosis of persistent chronic hepatitis. The Mantoux test (5 IU purified protein derivative) was positive at 11 mm, with repeated sputum samples negative for acid-fast bacilli (AFB). A bone marrow biopsy provided no further information, and there was no evidence of monoclonal component in serum or urine. In view of
1201-9712/$36.00 – see front matter ß 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijid.2010.02.2259
[(Figure_1)TD$IG]
e320
M. Ferna´ndez-Ruiz et al. / International Journal of Infectious Diseases 14S (2010) e319–e321
Figure 1. Pathological specimen of the giant thrombus (approximately 8 8 cm in size) resected from the left atrial chamber.
his stable clinical condition, the patient was discharged with careful ambulatory follow-up. However, and because of the continuous nature of the symptoms, he was readmitted to our centre 6 months later. Laboratory tests revealed a sharp rise in the ESR (110 mm/h) and in the serum creatinine (from normal values to 274 mmol/l), with microscopic hematuria and proteinuria (2000 mg/day). A percutaneous renal biopsy was performed, showing mesangial matrix expansion and extracapillary glomerular proliferation with focal crescent formation. Repeat cryoglobulin determination was negative. In order to rule out the suspected diagnosis of extranodal lymphoproliferative disease, the patient underwent an open splenectomy. Histological and microbiological examination of the specimen revealed epithelioid granulomas with areas of central necrosis, with no evidence of AFB by Ziehl–Neelsen staining method; a tissue culture in Lo¨wenstein–Jensen medium was also negative. In the course of the postoperative period, the patient developed progressive symptoms of congestive heart failure. Auscultation revealed the appearance of an apical grade IV/VI systolic murmur that had not been present on initial examination 6 months prior. The TTE showed normal atrial and ventricular dimensions with a large (approximately 9 cm2), hyperechogenic, mobile mass attached to the atrial septum that prolapsed during systolic phase into the left ventricle; cardiac valves were normal. The presumptive diagnosis of left atrial myxoma was made and surgical excision of the mass was performed through a transatrial approach. Intraoperative findings demonstrated a soft gelatinous mass, measuring 8 8 cm (Figure 1), histological analysis of which was consistent with an organized thrombus with abundant neutrophils and fibrin; Giemsa stain showed focally abundant microorganisms highly suggestive of C. burnetii. A direct immu[(Figure_2)TD$IG]
Figure 2. Electron microscope image of the left atrial thrombus showing multiple oval-shaped intracellular microorganisms compatible with Coxiella burnetii.
nofluorescence assay on a paraffin-embedded thrombus section with monoclonal antibodies to C. burnetii was also clearly positive. Finally, electron microscopic examination demonstrated the presence of numerous oval-shaped intracellular microorganisms equally compatible with C. burnetii (Figure 2). A strongly positive polymerase chain reaction (PCR) assay was performed on a tissue sample from the thrombus using primers of the H fragment (879 bp) of the QpH1 plasmid, as previously described by Mallavia et al.10 The QpH1 H fragment constitutes a region that is shared by all C. burnetii plasmids, and homologous sequences have also been found in the plasmidless strains of this microorganism. In addition, the diagnosis was confirmed by serologic tests, showing C. burnetii phase I antibody titer (immunoglobulin G (IgG)) 2560 and phase II antibody titer (IgG) 1280; complement fixation was also positive at a titer of 1:4096. In view of these results, antibiotic therapy with oral doxycycline (200 mg twice daily) was started. In the subsequent weeks the patient’s general condition showed a marked clinical improvement, with progressive resolution of fever and asthenia and progressive improvement of ESR (36 mm/h) and serum creatinine (114.9 mmol/l). Doxycycline was maintained for a total of 12 months. Five years later the patient remains asymptomatic with no recurrence of fever or signs of congestive heart failure; serologic tests for C. burnetii have become negative. 3. Discussion The differential diagnosis of an atrial mass may be quite broad and often involves such entities as primary intracardiac neoplasms (mainly myxoma), vegetations, thrombi, or intracardiac cysts. TTE and transesophageal echocardiography (TEE) remain the noninvasive diagnostic procedures of choice in order to characterize the location, appearance, site of attachment, and mobility of the mass.11 Shrestha et al. have demonstrated the high specificity (98.8%) and acceptable sensitivity (58.8%) of two-dimensional TTE in the diagnosis of left atrial thrombi.12 However, differentiation between the diagnoses (myxoma and thrombus) can often be difficult and is frequently only possible during surgery, as shown in the present case and other previous reports.11,13,14 Unfortunately, TEE was not available for our patient at the time of clinical evaluation. Infection of an intracardiac thrombus constitutes a rare condition in the literature, frequently associated with an aneurysm complicating transmural wall left ventricular myocardial infarction.1,4 Gram-negative bacilli, mainly Enterobacteriaceae, are the microorganisms most commonly responsible for this infection, reflecting the well-known high tropism of Salmonella spp for abnormal endothelial surfaces.1,15 Additional cases caused by methicillin-resistant S. aureus have been reported in patients undergoing hemodialysis who have developed a right atrial thrombus associated with indwelling central venous catheters.16 To our knowledge, this is the first case to be reported in the literature of C. burnetii infection of an intracardiac thrombus (PubMed search using the terms ‘Coxiella burnetii’ or ‘Q fever’, ‘infection’ and ‘intracardiac thrombus’). The main feature of Q fever probably resides in its clinical polymorphism. Negative-blood culture infective endocarditis is one of its most common manifestations, found in up to 70% of cases, although the real incidence may be underestimated.17 C. burnetii infection of thoracic or abdominal aortic aneurysms and synthetic vascular grafts constitutes another serious but frequently unrecognized complication, usually diagnosed by serologic methods.8,9 Our patient had had no previous environmental exposure to C. burnetii. However, 10–40% of affected subjects may have had no evident contact with animal reservoirs, particularly in endemic areas such as central and northern Spain.17 Chronic infection by C. burnetii is a well-recognized cause of
M. Ferna´ndez-Ruiz et al. / International Journal of Infectious Diseases 14S (2010) e319–e321
granulomatous hepatitis and, more rarely, glomerulonephritis, as demonstrated in the case reported herein.17,18 However, the potential implication of HCV infection in the etiopathogenesis of this latter condition must also be considered. Serologic testing remains the reference technique for Q fever diagnosis. Culture methods for C. burnetii are not routinely performed in view of the extreme infectivity of the microorganism and its potential use for bioterrorism purposes.9,17 PCR-based methods have been successfully applied to the detection of C. burnetii from various tissue samples, such as native or prosthetic heart valves, aortic vascular grafts, and synovial specimens.8,19 We believe that our case illustrates an original example of the application of this diagnostic method, particularly in the presence of an uncommon clinical picture of chronic Q fever. On the other hand, the potential risk of a false-positive PCR result on the thrombus sample associated with C. burnetii DNA contamination was reasonably ruled out in view of the compatible serologic, direct immunofluorescence, and electron microscopy findings. In summary, we report the first published case of C. burnetii infection of an atrial thrombus in a patient with prolonged fever and granulomatous hepatitis as the main clinical manifestations, and emphasize the value of PCR-based methods in the diagnosis of such an uncommon condition. Acknowledgements We thank to Dr Louis P. Mallavia, from Washington State University (Pullman, WA), Dr Miguel A´ngel Martı´nez Gonza´lez, from University Hospital ‘‘12 de Octubre’’ (Madrid, Spain), and Dr Francisco Soriano, from Fundacio´n Jime´nez Dı´az-Capio (Madrid, Spain), for their kind technical assistance in PCR analysis, electron microscopy examination, and direct immunofluorescence assay, respectively. No funds were received to support this work. Conflict of interest: No conflict of interest to declare. References 1. Schofield PM, Rahman AN, Ellis ME, Dunbar EM, Bray CL, Brooks N. Infection of cardiac mural thrombus associated with left ventricular aneurysm. Eur Heart J 1986;7:1077–82.
e321
2. Cheung A, Choi A. Infection of mural thrombus: a case report and literature review. J Intern Med 1990;227:281–3. 3. Senior R, Raftery EB. Infection of left ventricular thrombus in a patient with silent myocardial infarction: a unique complication. Eur Heart J 1993;14: 997–8. 4. Ruiz-Baile´n M, Ramos-Cuadra JA, Arago´n-Extremera VM, Rucabado-Aguilar L. Septic shock secondary to infection of a left ventricular thrombus. Interact Cardiovasc Thorac Surg 2009;9:706–8. 5. Segura J, Anguita M, Vivancos R, Franco M, Romo E, Sua´rez de Lezo J, et al. [Listeria monocytogenes endocarditis in a patient with mitral prosthesis, left auricular thrombus and adenocarcinoma of the colon]. Rev Esp Cardiol 1992;45:483–5. 6. Okayama H, Kawasaki S, Takagaki Y, Kawada H, Sumimoto T, Hirayama T. Infection of left atrial thrombus associated with mitral stenosis: a case report. Chest 2000;117:1201–3. 7. Dedeilias P, Roussakis A, Koletsis EN, Zervakis D, Hountis P, Prokakis C, et al. Left atrial giant thrombus infected by Escherichia coli. Case report. J Cardiothorac Surg 2008;3:18. 8. Fournier PE, Casalta JP, Piquet P, Tournigand P, Branchereau A, Raoult D. Coxiella burnetii infection of aneurysms or vascular grafts: report of seven cases and review. Clin Infect Dis 1998;26:116–21. 9. Sessa C, Vokrri L, Porcu P, Maurin M, Stahl JP, Magne JL. Abdominal aortic aneurysm and Coxiella burnetii infection: report of three cases and review of the literature. J Vasc Surg 2005;42:153–8. 10. Mallavia LP, Whiting LL, Minnick MF, Heinzen R, Reschke D, Foreman M, et al. Strategy for detection and differentiation of Coxiella burnetii strains using the polymerase chain reaction. Ann N Y Acad Sci 1990;590:572–81. 11. Dhawan S, Tak T. Left atrial mass: thrombus mimicking myxoma. Echocardiography 2004;21:621–3. 12. Shrestha NK, Moreno FL, Narciso FV, Torres L, Calleja HB. Two-dimensional echocardiographic diagnosis of left-atrial thrombus in rheumatic heart disease. A clinicopathologic study Circulation 1983;67:341–7. 13. Leventhal LJ, Borofsky MA, Bergey PD, Schumacher Jr HR. Antiphospholipid antibody syndrome with right atrial thrombosis mimicking an atrial myxoma. Am J Med 1989;87:111–3. 14. Mahdhaoui A, Bouraoui H, Amine MM, Mokni M, Besma T, Hajri SE, et al. The transesophageal echocardiographic diagnosis of left atrial myxoma simulating a left atrial thrombus in the setting of mitral stenosis. Echocardiography 2004;21:333–6. 15. Ferna´ndez Guerrero ML, Aguado JM, Arribas A, Lumbreras C, de Gorgolas M. The spectrum of cardiovascular infections due to Salmonella enterica: a review of clinical features and factors determining outcome. Medicine (Baltimore) 2004;83:123–38. 16. Roguin A, Reisner SA. Right atrial mass related to indwelling central venous catheters in patients undergoing dialysis. Eur J Echocardiogr 2000;1:222–3. 17. Hartzell JD, Wood-Morris RN, Martinez LJ, Trotta RF. Q fever: epidemiology, diagnosis, and treatment. Mayo Clin Proc 2008;83:574–9. 18. Perez-Fontan M, Huarte E, Tellez A, Rodriguez-Carmona A, Picazo ML, MartinezAra J. Glomerular nephropathy associated with chronic Q fever. Am J Kidney Dis 1988;11:298–306. 19. Landais C, Fenollar F, Constantin A, Cazorla C, Guilyardi C, Lepidi H, et al. Q fever osteoarticular infection: four new cases and a review of the literature. Eur J Clin Microbiol Infect Dis 2007;26:341–7.
Contents lists available at ScienceDirect
International Journal of Infectious Diseases journal homepage: www.elsevier.com/locate/ijid
Case Report
Coxiella burnetii infection of left atrial thrombus mimicking an atrial myxoma Mario Ferna´ndez-Ruiz a,b,*, Francisco Lo´pez-Medrano b, Fe´lix Alonso-Navas a, Jose´ Marı´a Aguado b a b
Department of Internal Medicine, University Hospital ‘‘12 de Octubre’’, Avda. Co´rdoba, s/n, 28041 Madrid, Spain Infectious Diseases Unit, University Hospital ‘‘12 de Octubre’’, Madrid, Spain
A R T I C L E I N F O
S U M M A R Y
Article history: Received 2 September 2009 Received in revised form 9 December 2009 Accepted 26 February 2010
Infection of intracardiac thrombi is extremely unusual. Coxiella burnetii is a well-recognized etiologic agent of negative-blood culture endocarditis and vascular graft infection. Herein we describe the first reported case, to our knowledge, of C. burnetii infection of a large left-sided intracardiac thrombus that was initially misdiagnosed as an atrial myxoma. Diagnosis was confirmed by direct immunofluorescence assay, electron microscopy, and C. burnetii-specific polymerase chain reaction analysis performed on tissue sections of the thrombus. ß 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Corresponding Editor: William Cameron, Ottawa, Canada Keywords: Atrial myxoma Coxiella burnetii Infected intracardiac thrombus Left atrial mass Polymerase chain reaction analysis Q fever
1. Introduction Nowadays the demonstration of large left atrial thrombi is an infrequent event, as there has been a tendency towards a reduced incidence of native valve disease and the use of anticoagulant therapy has become more widespread in clinical practice. In this setting, infected intracardiac thrombi represent a very rare condition, usually reported in the ventricular chamber.1–4 The etiologic agents most frequently involved in such cases are Gramnegative bacilli1,2 (Escherichia coli, Klebsiella pneumoniae, or Salmonella species) and Staphylococcus aureus.4 Only occasional examples of infection of a left atrial thrombus may be found in the literature.5–7 The most frequent clinical presentation of chronic Q fever, caused by Coxiella burnetii, is negative-blood culture endocarditis, although infections of aneurysms and vascular grafts have also been described.8,9 To the best of our knowledge no previous case of C. burnetii infection of a left atrial thrombus has been reported to date. 2. Case report A previously healthy 62-year-old male presented to our clinic with persistent daily fever of 7-month duration associated with
* Corresponding author. Tel.: +34 91 763 99 59; fax: +34 91 763 99 59. E-mail address: [email protected] (M. Ferna´ndez-Ruiz).
marked asthenia, hyporexia, and a 10-kg weight loss over that period of time. He was a current smoker and had no previous history of valvular heart disease. At admission, his blood pressure was 130/70 mmHg and pulse rate 105/min. Physical examination revealed an 8-cm tender hepatomegaly and a 5-cm firm splenomegaly, with no abnormal findings on heart auscultation. Initial laboratory investigations showed hemoglobin 12 g/dl, white cell count 10.8 109/l (65% neutrophils), platelets 183 109/l, alkaline phosphatase 197 IU/l (normal, 40– 130), lactic dehydrogenase 310 IU/l (normal, 90–230), erythrocyte sedimentation rate (ESR) 54 mm/h, and a positive serologic test for hepatitis C virus (HCV). The remaining diagnostic studies, including repeated blood and urine cultures, determination of serum tumor markers, and serologic tests for Brucella, Leishmania and Salmonella spp, Treponema (rapid plasma reagin and passive hemagglutination), human immunodeficiency virus, and other hepatotropic viruses, were either within the normal range or negative. A chest X-ray was normal; transthoracic echocardiography (TTE) was not available at first presentation. Abdominal ultrasound confirmed the presence of a homogeneous hepatosplenomegaly with no signs of portal hypertension. A laparoscopy-guided liver biopsy was compatible with the diagnosis of persistent chronic hepatitis. The Mantoux test (5 IU purified protein derivative) was positive at 11 mm, with repeated sputum samples negative for acid-fast bacilli (AFB). A bone marrow biopsy provided no further information, and there was no evidence of monoclonal component in serum or urine. In view of
1201-9712/$36.00 – see front matter ß 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijid.2010.02.2259
[(Figure_1)TD$IG]
e320
M. Ferna´ndez-Ruiz et al. / International Journal of Infectious Diseases 14S (2010) e319–e321
Figure 1. Pathological specimen of the giant thrombus (approximately 8 8 cm in size) resected from the left atrial chamber.
his stable clinical condition, the patient was discharged with careful ambulatory follow-up. However, and because of the continuous nature of the symptoms, he was readmitted to our centre 6 months later. Laboratory tests revealed a sharp rise in the ESR (110 mm/h) and in the serum creatinine (from normal values to 274 mmol/l), with microscopic hematuria and proteinuria (2000 mg/day). A percutaneous renal biopsy was performed, showing mesangial matrix expansion and extracapillary glomerular proliferation with focal crescent formation. Repeat cryoglobulin determination was negative. In order to rule out the suspected diagnosis of extranodal lymphoproliferative disease, the patient underwent an open splenectomy. Histological and microbiological examination of the specimen revealed epithelioid granulomas with areas of central necrosis, with no evidence of AFB by Ziehl–Neelsen staining method; a tissue culture in Lo¨wenstein–Jensen medium was also negative. In the course of the postoperative period, the patient developed progressive symptoms of congestive heart failure. Auscultation revealed the appearance of an apical grade IV/VI systolic murmur that had not been present on initial examination 6 months prior. The TTE showed normal atrial and ventricular dimensions with a large (approximately 9 cm2), hyperechogenic, mobile mass attached to the atrial septum that prolapsed during systolic phase into the left ventricle; cardiac valves were normal. The presumptive diagnosis of left atrial myxoma was made and surgical excision of the mass was performed through a transatrial approach. Intraoperative findings demonstrated a soft gelatinous mass, measuring 8 8 cm (Figure 1), histological analysis of which was consistent with an organized thrombus with abundant neutrophils and fibrin; Giemsa stain showed focally abundant microorganisms highly suggestive of C. burnetii. A direct immu[(Figure_2)TD$IG]
Figure 2. Electron microscope image of the left atrial thrombus showing multiple oval-shaped intracellular microorganisms compatible with Coxiella burnetii.
nofluorescence assay on a paraffin-embedded thrombus section with monoclonal antibodies to C. burnetii was also clearly positive. Finally, electron microscopic examination demonstrated the presence of numerous oval-shaped intracellular microorganisms equally compatible with C. burnetii (Figure 2). A strongly positive polymerase chain reaction (PCR) assay was performed on a tissue sample from the thrombus using primers of the H fragment (879 bp) of the QpH1 plasmid, as previously described by Mallavia et al.10 The QpH1 H fragment constitutes a region that is shared by all C. burnetii plasmids, and homologous sequences have also been found in the plasmidless strains of this microorganism. In addition, the diagnosis was confirmed by serologic tests, showing C. burnetii phase I antibody titer (immunoglobulin G (IgG)) 2560 and phase II antibody titer (IgG) 1280; complement fixation was also positive at a titer of 1:4096. In view of these results, antibiotic therapy with oral doxycycline (200 mg twice daily) was started. In the subsequent weeks the patient’s general condition showed a marked clinical improvement, with progressive resolution of fever and asthenia and progressive improvement of ESR (36 mm/h) and serum creatinine (114.9 mmol/l). Doxycycline was maintained for a total of 12 months. Five years later the patient remains asymptomatic with no recurrence of fever or signs of congestive heart failure; serologic tests for C. burnetii have become negative. 3. Discussion The differential diagnosis of an atrial mass may be quite broad and often involves such entities as primary intracardiac neoplasms (mainly myxoma), vegetations, thrombi, or intracardiac cysts. TTE and transesophageal echocardiography (TEE) remain the noninvasive diagnostic procedures of choice in order to characterize the location, appearance, site of attachment, and mobility of the mass.11 Shrestha et al. have demonstrated the high specificity (98.8%) and acceptable sensitivity (58.8%) of two-dimensional TTE in the diagnosis of left atrial thrombi.12 However, differentiation between the diagnoses (myxoma and thrombus) can often be difficult and is frequently only possible during surgery, as shown in the present case and other previous reports.11,13,14 Unfortunately, TEE was not available for our patient at the time of clinical evaluation. Infection of an intracardiac thrombus constitutes a rare condition in the literature, frequently associated with an aneurysm complicating transmural wall left ventricular myocardial infarction.1,4 Gram-negative bacilli, mainly Enterobacteriaceae, are the microorganisms most commonly responsible for this infection, reflecting the well-known high tropism of Salmonella spp for abnormal endothelial surfaces.1,15 Additional cases caused by methicillin-resistant S. aureus have been reported in patients undergoing hemodialysis who have developed a right atrial thrombus associated with indwelling central venous catheters.16 To our knowledge, this is the first case to be reported in the literature of C. burnetii infection of an intracardiac thrombus (PubMed search using the terms ‘Coxiella burnetii’ or ‘Q fever’, ‘infection’ and ‘intracardiac thrombus’). The main feature of Q fever probably resides in its clinical polymorphism. Negative-blood culture infective endocarditis is one of its most common manifestations, found in up to 70% of cases, although the real incidence may be underestimated.17 C. burnetii infection of thoracic or abdominal aortic aneurysms and synthetic vascular grafts constitutes another serious but frequently unrecognized complication, usually diagnosed by serologic methods.8,9 Our patient had had no previous environmental exposure to C. burnetii. However, 10–40% of affected subjects may have had no evident contact with animal reservoirs, particularly in endemic areas such as central and northern Spain.17 Chronic infection by C. burnetii is a well-recognized cause of
M. Ferna´ndez-Ruiz et al. / International Journal of Infectious Diseases 14S (2010) e319–e321
granulomatous hepatitis and, more rarely, glomerulonephritis, as demonstrated in the case reported herein.17,18 However, the potential implication of HCV infection in the etiopathogenesis of this latter condition must also be considered. Serologic testing remains the reference technique for Q fever diagnosis. Culture methods for C. burnetii are not routinely performed in view of the extreme infectivity of the microorganism and its potential use for bioterrorism purposes.9,17 PCR-based methods have been successfully applied to the detection of C. burnetii from various tissue samples, such as native or prosthetic heart valves, aortic vascular grafts, and synovial specimens.8,19 We believe that our case illustrates an original example of the application of this diagnostic method, particularly in the presence of an uncommon clinical picture of chronic Q fever. On the other hand, the potential risk of a false-positive PCR result on the thrombus sample associated with C. burnetii DNA contamination was reasonably ruled out in view of the compatible serologic, direct immunofluorescence, and electron microscopy findings. In summary, we report the first published case of C. burnetii infection of an atrial thrombus in a patient with prolonged fever and granulomatous hepatitis as the main clinical manifestations, and emphasize the value of PCR-based methods in the diagnosis of such an uncommon condition. Acknowledgements We thank to Dr Louis P. Mallavia, from Washington State University (Pullman, WA), Dr Miguel A´ngel Martı´nez Gonza´lez, from University Hospital ‘‘12 de Octubre’’ (Madrid, Spain), and Dr Francisco Soriano, from Fundacio´n Jime´nez Dı´az-Capio (Madrid, Spain), for their kind technical assistance in PCR analysis, electron microscopy examination, and direct immunofluorescence assay, respectively. No funds were received to support this work. Conflict of interest: No conflict of interest to declare. References 1. Schofield PM, Rahman AN, Ellis ME, Dunbar EM, Bray CL, Brooks N. Infection of cardiac mural thrombus associated with left ventricular aneurysm. Eur Heart J 1986;7:1077–82.
e321
2. Cheung A, Choi A. Infection of mural thrombus: a case report and literature review. J Intern Med 1990;227:281–3. 3. Senior R, Raftery EB. Infection of left ventricular thrombus in a patient with silent myocardial infarction: a unique complication. Eur Heart J 1993;14: 997–8. 4. Ruiz-Baile´n M, Ramos-Cuadra JA, Arago´n-Extremera VM, Rucabado-Aguilar L. Septic shock secondary to infection of a left ventricular thrombus. Interact Cardiovasc Thorac Surg 2009;9:706–8. 5. Segura J, Anguita M, Vivancos R, Franco M, Romo E, Sua´rez de Lezo J, et al. [Listeria monocytogenes endocarditis in a patient with mitral prosthesis, left auricular thrombus and adenocarcinoma of the colon]. Rev Esp Cardiol 1992;45:483–5. 6. Okayama H, Kawasaki S, Takagaki Y, Kawada H, Sumimoto T, Hirayama T. Infection of left atrial thrombus associated with mitral stenosis: a case report. Chest 2000;117:1201–3. 7. Dedeilias P, Roussakis A, Koletsis EN, Zervakis D, Hountis P, Prokakis C, et al. Left atrial giant thrombus infected by Escherichia coli. Case report. J Cardiothorac Surg 2008;3:18. 8. Fournier PE, Casalta JP, Piquet P, Tournigand P, Branchereau A, Raoult D. Coxiella burnetii infection of aneurysms or vascular grafts: report of seven cases and review. Clin Infect Dis 1998;26:116–21. 9. Sessa C, Vokrri L, Porcu P, Maurin M, Stahl JP, Magne JL. Abdominal aortic aneurysm and Coxiella burnetii infection: report of three cases and review of the literature. J Vasc Surg 2005;42:153–8. 10. Mallavia LP, Whiting LL, Minnick MF, Heinzen R, Reschke D, Foreman M, et al. Strategy for detection and differentiation of Coxiella burnetii strains using the polymerase chain reaction. Ann N Y Acad Sci 1990;590:572–81. 11. Dhawan S, Tak T. Left atrial mass: thrombus mimicking myxoma. Echocardiography 2004;21:621–3. 12. Shrestha NK, Moreno FL, Narciso FV, Torres L, Calleja HB. Two-dimensional echocardiographic diagnosis of left-atrial thrombus in rheumatic heart disease. A clinicopathologic study Circulation 1983;67:341–7. 13. Leventhal LJ, Borofsky MA, Bergey PD, Schumacher Jr HR. Antiphospholipid antibody syndrome with right atrial thrombosis mimicking an atrial myxoma. Am J Med 1989;87:111–3. 14. Mahdhaoui A, Bouraoui H, Amine MM, Mokni M, Besma T, Hajri SE, et al. The transesophageal echocardiographic diagnosis of left atrial myxoma simulating a left atrial thrombus in the setting of mitral stenosis. Echocardiography 2004;21:333–6. 15. Ferna´ndez Guerrero ML, Aguado JM, Arribas A, Lumbreras C, de Gorgolas M. The spectrum of cardiovascular infections due to Salmonella enterica: a review of clinical features and factors determining outcome. Medicine (Baltimore) 2004;83:123–38. 16. Roguin A, Reisner SA. Right atrial mass related to indwelling central venous catheters in patients undergoing dialysis. Eur J Echocardiogr 2000;1:222–3. 17. Hartzell JD, Wood-Morris RN, Martinez LJ, Trotta RF. Q fever: epidemiology, diagnosis, and treatment. Mayo Clin Proc 2008;83:574–9. 18. Perez-Fontan M, Huarte E, Tellez A, Rodriguez-Carmona A, Picazo ML, MartinezAra J. Glomerular nephropathy associated with chronic Q fever. Am J Kidney Dis 1988;11:298–306. 19. Landais C, Fenollar F, Constantin A, Cazorla C, Guilyardi C, Lepidi H, et al. Q fever osteoarticular infection: four new cases and a review of the literature. Eur J Clin Microbiol Infect Dis 2007;26:341–7.