IMAGES IN RADIOLOGY Robert G. Stern, MD, Section Editor
Bright Spots: Q Fever Prosthetic Valve Endocarditis Burke A. Cunha, MD,b,d Laura A. Wolfe, DO,c Arthur Gran, MD,b Vijayapraveena Paruchuri, MD,a George Gubernikoff, MDa a
Division of Cardiology and bDivision of Infectious Disease, cDepartment of Medicine, Winthrop-University Hospital, Mineola, and dState University of New York School of Medicine, Stony Brook, NY.
PRESENTATION Positron emission tomography (PET) serendipitously uncovered the culprit when a 59-year-old woman presented with fever of unknown origin. Her past medical history was remarkable for Hodgkin’s lymphoma, which had been treated with radiation and chemotherapy. Radiotherapy caused restrictive cardiomyopathy, and subsequently, mitral valve and aortic valve regurgitation became so severe that she underwent mechanical valve replacement for both valves.
ASSESSMENT Physical examination revealed bilateral diffuse basilar lung crackles, and a systolic murmur (II/IV) was heard at the base. The patient had a temperature of 99.2 F (37.3 C), a pulse rate of 88 beats/minute, a respiratory rate of 14 breaths/min, and a blood pressure of 128/58 mm Hg. Importantly, she did not have hepatosplenomegaly, splinter hemorrhages, Osler’s nodes, Janeway lesions, Roth spots, or subconjunctival or palatal petechiae. Results from laboratory tests included a white blood cell count of 16.3 x103 cells/ mm3, a hemoglobin of 12.8 g/dL, and a platelet count of 354,000 per mm3 (normal, 160,000-392,000 per mm3). Her C-reactive protein was 60.15 mg/L (normal, < 39 mg/L), and her erythrocyte sedimentation rate was 64 mm/h. Additional test results included alkaline phosphatase, 134 IU/L (normal, 25-100 IU/L), aspartate aminotransferase, 65 IU/L (normal, 13-39 IU/L), and alanine aminotransferase, 72 IU/L (normal, 4-36 IU/L). A chest radiograph showed a small nodule in the right lung. This triggered concern for malignancy, given the Funding: None. Conflict of Interest: None. Authorship: LAW and VP provided the cardiac case information. GG provided the cardiac imaging. AG provided the literature search and BAC wrote and edited the article. Requests for reprints should be addressed to Burke A. Cunha, MD, Chief, Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501. E-mail address: [email protected] 0002-9343/$ -see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjmed.2013.08.011
patient’s lymphoma history. Computed tomography (CT) of the lungs then disclosed the nodule in the right lower lobe, along with a second nodule in the right upper lobe. Further investigation was carried out with a PET/CT scan. While no metabolic activity was present in the pulmonary nodules, hypermetabolic activity was prominent in the area of the mechanical aortic valve (Figure). With lung malignancy ruled out, the PET scan suggested possible prosthetic valve endocarditis. Transthoracic and transesophageal echocardiography were performed, but no vegetations or valvular abnormalities were seen. Blood cultures were negative, and a workup for culture-negative endocarditis was performed.
DIAGNOSIS Fever of unknown origin may be defined as a fever higher than 101 F (38.3 C) that persists for 1 month or more and remains undiagnosed after a focused inpatient/outpatient workup.1 In adults, fever of unknown origin is due mainly to malignancy, infection, or rheumatic/inflammatory disorders. Malignancies are most often responsible, but infectious etiologies remain important.1,2 Although endocarditis is a diagnostic consideration in those with fever, heart murmur, and cardiac vegetation, Q fever endocarditis can be especially challenging to diagnose.2-5 First reported by Derrick in 1937, Q fever is a zoonosis caused by Coxiella burnetii. It presents acutely as an atypical pneumonia or chronically as culture-negative endocarditis. Chronic Q fever is a common cause of infectious culture-negative endocarditis, and it usually involves the mitral or aortic valve.5,6 Patients with native heart valves damaged by rheumatic or degenerative disease are particularly susceptible to C. burnetii, but the organism also has a predilection for vascular grafts or prostheses.7,8-11 Thus, among patients with fever of unknown origin, chronic Q fever is in the differential diagnosis of infectious culture-negative endocarditis, especially in patients with a history of known exposure to infected animals, such as parturient cats, or ingestion of unpasteurized dairy products.2-4
1058
The American Journal of Medicine, Vol 126, No 12, December 2013 unknown origin. The patient rapidly became afebrile on a regimen of oral doxycycline. Her elevated erythrocyte sedimentation rate and C. burnetii phase I titers decreased gradually until her prosthetic valve endocarditis was cured without aortic valve replacement.18,19
References Figure Positron emission tomography showed hypermetabolic activity in the area of the patient’s mechanical aortic valve (arrow).
The diagnosis of Q fever is difficult and is based on serology, since C. burnetii vegetations are very small or not visible on transthoracic or transesophageal echocardiography.5-7,12,13 Highly elevated C. burnetii phase I titers (> 1:800) are diagnostic.9 Recently, the diagnosis of C. burnetii vascular graft infection has been suggested by PET scans.14-16 Patients are often afebrile with few, if any, localizing signs.7,12 Q fever endocarditis should be suspected in patients with culture-negative aortic aneurysm or vascular graft infections, as well as in patients with preexisting valvular disease who develop a new paravalvular leak.8-11,13,17 Fever of unknown origin combined with negative blood cultures and otherwise unexplained splenomegaly should suggest Q fever in the differential diagnosis.7,9 For our patient, a neoplastic etiology was the main diagnostic concern during the investigation into the cause of her fever of unknown origin. Because the nodules seen on radiography and CT were thought to be malignant, a PET scan was obtained. But the nodules showed no increase in metabolic activity, an indication that they were not malignant. At the same time, hypermetabolic activity was seen in the area of the mechanical prosthetic aortic valve. Although transthoracic and transesophageal echocardiography showed no vegetations, the presumptive diagnosis of her fever of unknown origin was infectious culture-negative prosthetic valve endocarditis. A workup for infectious causes of culture-negative endocarditis was done, and included titers for Bartonella species, Brucella species, Legionella species, Mycoplasma species, Tropheryma whipplei, and C. burnetii. Titers for Brucella, Bartonella, and Legionella species were negative. However, the C. burnetii (Q fever) phase 1 titer was > 1:800 and the phase 2 titer was >1:150, confirming that Q fever aortic prosthetic valve endocarditis caused the patient’s fever of unknown origin.
MANAGEMENT To the best of our knowledge this is the first reported case where PET/CT scanning suggested possible Q fever aortic valve prosthetic valve endocarditis as the source of fever of
1. Murray HW, ed. FUO: Fever of Undetermined Origin. Mount Kisco, NY: Futura Publishing; 1983:27-48. 2. Cunha BA. Fever of unknown origin. In: Gorbach SL, Bartlett JB, Blacklow NR, eds. Infectious Diseases in Medicine and Surgery. 3rd ed. Phildelphia, PA: WB Saunders Company; 2004:1568-1577. 3. Petersdorf RG, Beeson PB. Fever of unexplained origin: report on 100 cases. Medicine (Baltimore). 1961;40:1-30. 4. Cunha BA. Fever of unknown origin in malignancies. In: Cunha BA, ed. Fever of Unknown Origin. New York: Informa Healthcare USA; 2007:27-34. 5. Houpikian P, Raoult D. Blood culture-negative endocarditis in a reference center: etiologic diagnosis of 348 cases. Medicine (Baltimore). 2005;84:162-173. 6. Scott JW, Baddour LM, Tleyjeh IM, Moustafa S, Sun YG, Mookadam F. Q fever endocarditis: the Mayo Clinic experience. Am J Med Sci. 2008;336:53-57. 7. Mazokopakis EE, Karefilakis CM, Starakis IK. Q fever endocarditis. Infect Disord Drug Targets. 2010;10:27-31. 8. Pagano D, Allen SM, Bonser RS. Homograft aortic valve and root replacement for severe destructive native or prosthetic endocarditis. Eur J Cardiothorac Surg. 1984;8:173-176. 9. Khavkin T. Coxiella burnetii infection in prosthetic devices. Rev Infect Dis. 1989;11:835. 10. Raoult D, Abbara S, Jassal DS, Kradin RL. Case records of the Massachusetts General Hospital. Case 5-2007. A 53-year-old man with a prosthetic aortic valve and recent onset of fatigue, dyspnea, weight loss and sweats. N Engl J Med. 2007;356:715-725. 11. Mesana TG, Collart F, Caus T, Salamand A. Q fever endocarditis: a surgical view and a word of caution. J Thorac Cardiovasc Surg. 2003;125:217-218. 12. Million M, Thuny F, Richet H, Raoult D. Long-term outcome of Q fever endocarditis: a 26-year personal survey. Lancet Infect Dis. 2010;10:527-535. 13. Alshukairi AN, Morshed MG, Reiner NE. Q fever presenting as recurrent, culture-negative endocarditis with aortic prosthetic valve failure: a case report and review of the literature. Can J Infect Dis Med Microbiol. 2006;17:341-344. 14. Merhej V, Cammilleri S, Piquet P, Casalta JP, Raoult D. Relevance of the positron emission tomography in the diagnosis of vascular graft infection with Coxiella burnetii. Comp Immunol Microbiol Infect Dis. 2012;35:45-49. 15. Blockmans D, Knockaert D, Maes A, et al. Clinical value of [(18)F] fluorodeoxyglucose positron emission tomography for patients with fever of unknown origin. Clin Infect Dis. 2001;32:191-196. 16. Nazar AH, Naswa N, Sharma P, et al. Spectrum of 18F-FDG PET/CT findings in patients presenting with fever of unknown origin. AJR Am J Roentgenol. 2012;199:175-185. 17. Fernández-Guerrero ML, Muelas JM, Aguado JM, et al. Q fever endocarditis on porcine bioprosthetic valves. Clinicopathologic features and microbiologic findings in three patients treated with doxycycline, cotrimoxazole, and valve replacement. Ann Intern Med. 1988;108:209-213. 18. Krol A, Kogan V, Cunha BA. Q fever bioprosthetic aortic valve endocarditis (PVE) successfully treated with doxycycline monotherapy. Heart Lung. 2008;37:157-160. 19. Lecaillet A, Mallet MN, Raoult D, Rolain JM. Therapeutic impact of the correlation of doxycycline serum concentrations and the decline of phase I antibodies in Q fever endocarditis. J Antimicrob Chemother. 2009;63:771-774.
Bright Spots: Q Fever Prosthetic Valve Endocarditis Burke A. Cunha, MD,b,d Laura A. Wolfe, DO,c Arthur Gran, MD,b Vijayapraveena Paruchuri, MD,a George Gubernikoff, MDa a
Division of Cardiology and bDivision of Infectious Disease, cDepartment of Medicine, Winthrop-University Hospital, Mineola, and dState University of New York School of Medicine, Stony Brook, NY.
PRESENTATION Positron emission tomography (PET) serendipitously uncovered the culprit when a 59-year-old woman presented with fever of unknown origin. Her past medical history was remarkable for Hodgkin’s lymphoma, which had been treated with radiation and chemotherapy. Radiotherapy caused restrictive cardiomyopathy, and subsequently, mitral valve and aortic valve regurgitation became so severe that she underwent mechanical valve replacement for both valves.
ASSESSMENT Physical examination revealed bilateral diffuse basilar lung crackles, and a systolic murmur (II/IV) was heard at the base. The patient had a temperature of 99.2 F (37.3 C), a pulse rate of 88 beats/minute, a respiratory rate of 14 breaths/min, and a blood pressure of 128/58 mm Hg. Importantly, she did not have hepatosplenomegaly, splinter hemorrhages, Osler’s nodes, Janeway lesions, Roth spots, or subconjunctival or palatal petechiae. Results from laboratory tests included a white blood cell count of 16.3 x103 cells/ mm3, a hemoglobin of 12.8 g/dL, and a platelet count of 354,000 per mm3 (normal, 160,000-392,000 per mm3). Her C-reactive protein was 60.15 mg/L (normal, < 39 mg/L), and her erythrocyte sedimentation rate was 64 mm/h. Additional test results included alkaline phosphatase, 134 IU/L (normal, 25-100 IU/L), aspartate aminotransferase, 65 IU/L (normal, 13-39 IU/L), and alanine aminotransferase, 72 IU/L (normal, 4-36 IU/L). A chest radiograph showed a small nodule in the right lung. This triggered concern for malignancy, given the Funding: None. Conflict of Interest: None. Authorship: LAW and VP provided the cardiac case information. GG provided the cardiac imaging. AG provided the literature search and BAC wrote and edited the article. Requests for reprints should be addressed to Burke A. Cunha, MD, Chief, Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501. E-mail address: [email protected] 0002-9343/$ -see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjmed.2013.08.011
patient’s lymphoma history. Computed tomography (CT) of the lungs then disclosed the nodule in the right lower lobe, along with a second nodule in the right upper lobe. Further investigation was carried out with a PET/CT scan. While no metabolic activity was present in the pulmonary nodules, hypermetabolic activity was prominent in the area of the mechanical aortic valve (Figure). With lung malignancy ruled out, the PET scan suggested possible prosthetic valve endocarditis. Transthoracic and transesophageal echocardiography were performed, but no vegetations or valvular abnormalities were seen. Blood cultures were negative, and a workup for culture-negative endocarditis was performed.
DIAGNOSIS Fever of unknown origin may be defined as a fever higher than 101 F (38.3 C) that persists for 1 month or more and remains undiagnosed after a focused inpatient/outpatient workup.1 In adults, fever of unknown origin is due mainly to malignancy, infection, or rheumatic/inflammatory disorders. Malignancies are most often responsible, but infectious etiologies remain important.1,2 Although endocarditis is a diagnostic consideration in those with fever, heart murmur, and cardiac vegetation, Q fever endocarditis can be especially challenging to diagnose.2-5 First reported by Derrick in 1937, Q fever is a zoonosis caused by Coxiella burnetii. It presents acutely as an atypical pneumonia or chronically as culture-negative endocarditis. Chronic Q fever is a common cause of infectious culture-negative endocarditis, and it usually involves the mitral or aortic valve.5,6 Patients with native heart valves damaged by rheumatic or degenerative disease are particularly susceptible to C. burnetii, but the organism also has a predilection for vascular grafts or prostheses.7,8-11 Thus, among patients with fever of unknown origin, chronic Q fever is in the differential diagnosis of infectious culture-negative endocarditis, especially in patients with a history of known exposure to infected animals, such as parturient cats, or ingestion of unpasteurized dairy products.2-4
1058
The American Journal of Medicine, Vol 126, No 12, December 2013 unknown origin. The patient rapidly became afebrile on a regimen of oral doxycycline. Her elevated erythrocyte sedimentation rate and C. burnetii phase I titers decreased gradually until her prosthetic valve endocarditis was cured without aortic valve replacement.18,19
References Figure Positron emission tomography showed hypermetabolic activity in the area of the patient’s mechanical aortic valve (arrow).
The diagnosis of Q fever is difficult and is based on serology, since C. burnetii vegetations are very small or not visible on transthoracic or transesophageal echocardiography.5-7,12,13 Highly elevated C. burnetii phase I titers (> 1:800) are diagnostic.9 Recently, the diagnosis of C. burnetii vascular graft infection has been suggested by PET scans.14-16 Patients are often afebrile with few, if any, localizing signs.7,12 Q fever endocarditis should be suspected in patients with culture-negative aortic aneurysm or vascular graft infections, as well as in patients with preexisting valvular disease who develop a new paravalvular leak.8-11,13,17 Fever of unknown origin combined with negative blood cultures and otherwise unexplained splenomegaly should suggest Q fever in the differential diagnosis.7,9 For our patient, a neoplastic etiology was the main diagnostic concern during the investigation into the cause of her fever of unknown origin. Because the nodules seen on radiography and CT were thought to be malignant, a PET scan was obtained. But the nodules showed no increase in metabolic activity, an indication that they were not malignant. At the same time, hypermetabolic activity was seen in the area of the mechanical prosthetic aortic valve. Although transthoracic and transesophageal echocardiography showed no vegetations, the presumptive diagnosis of her fever of unknown origin was infectious culture-negative prosthetic valve endocarditis. A workup for infectious causes of culture-negative endocarditis was done, and included titers for Bartonella species, Brucella species, Legionella species, Mycoplasma species, Tropheryma whipplei, and C. burnetii. Titers for Brucella, Bartonella, and Legionella species were negative. However, the C. burnetii (Q fever) phase 1 titer was > 1:800 and the phase 2 titer was >1:150, confirming that Q fever aortic prosthetic valve endocarditis caused the patient’s fever of unknown origin.
MANAGEMENT To the best of our knowledge this is the first reported case where PET/CT scanning suggested possible Q fever aortic valve prosthetic valve endocarditis as the source of fever of
1. Murray HW, ed. FUO: Fever of Undetermined Origin. Mount Kisco, NY: Futura Publishing; 1983:27-48. 2. Cunha BA. Fever of unknown origin. In: Gorbach SL, Bartlett JB, Blacklow NR, eds. Infectious Diseases in Medicine and Surgery. 3rd ed. Phildelphia, PA: WB Saunders Company; 2004:1568-1577. 3. Petersdorf RG, Beeson PB. Fever of unexplained origin: report on 100 cases. Medicine (Baltimore). 1961;40:1-30. 4. Cunha BA. Fever of unknown origin in malignancies. In: Cunha BA, ed. Fever of Unknown Origin. New York: Informa Healthcare USA; 2007:27-34. 5. Houpikian P, Raoult D. Blood culture-negative endocarditis in a reference center: etiologic diagnosis of 348 cases. Medicine (Baltimore). 2005;84:162-173. 6. Scott JW, Baddour LM, Tleyjeh IM, Moustafa S, Sun YG, Mookadam F. Q fever endocarditis: the Mayo Clinic experience. Am J Med Sci. 2008;336:53-57. 7. Mazokopakis EE, Karefilakis CM, Starakis IK. Q fever endocarditis. Infect Disord Drug Targets. 2010;10:27-31. 8. Pagano D, Allen SM, Bonser RS. Homograft aortic valve and root replacement for severe destructive native or prosthetic endocarditis. Eur J Cardiothorac Surg. 1984;8:173-176. 9. Khavkin T. Coxiella burnetii infection in prosthetic devices. Rev Infect Dis. 1989;11:835. 10. Raoult D, Abbara S, Jassal DS, Kradin RL. Case records of the Massachusetts General Hospital. Case 5-2007. A 53-year-old man with a prosthetic aortic valve and recent onset of fatigue, dyspnea, weight loss and sweats. N Engl J Med. 2007;356:715-725. 11. Mesana TG, Collart F, Caus T, Salamand A. Q fever endocarditis: a surgical view and a word of caution. J Thorac Cardiovasc Surg. 2003;125:217-218. 12. Million M, Thuny F, Richet H, Raoult D. Long-term outcome of Q fever endocarditis: a 26-year personal survey. Lancet Infect Dis. 2010;10:527-535. 13. Alshukairi AN, Morshed MG, Reiner NE. Q fever presenting as recurrent, culture-negative endocarditis with aortic prosthetic valve failure: a case report and review of the literature. Can J Infect Dis Med Microbiol. 2006;17:341-344. 14. Merhej V, Cammilleri S, Piquet P, Casalta JP, Raoult D. Relevance of the positron emission tomography in the diagnosis of vascular graft infection with Coxiella burnetii. Comp Immunol Microbiol Infect Dis. 2012;35:45-49. 15. Blockmans D, Knockaert D, Maes A, et al. Clinical value of [(18)F] fluorodeoxyglucose positron emission tomography for patients with fever of unknown origin. Clin Infect Dis. 2001;32:191-196. 16. Nazar AH, Naswa N, Sharma P, et al. Spectrum of 18F-FDG PET/CT findings in patients presenting with fever of unknown origin. AJR Am J Roentgenol. 2012;199:175-185. 17. Fernández-Guerrero ML, Muelas JM, Aguado JM, et al. Q fever endocarditis on porcine bioprosthetic valves. Clinicopathologic features and microbiologic findings in three patients treated with doxycycline, cotrimoxazole, and valve replacement. Ann Intern Med. 1988;108:209-213. 18. Krol A, Kogan V, Cunha BA. Q fever bioprosthetic aortic valve endocarditis (PVE) successfully treated with doxycycline monotherapy. Heart Lung. 2008;37:157-160. 19. Lecaillet A, Mallet MN, Raoult D, Rolain JM. Therapeutic impact of the correlation of doxycycline serum concentrations and the decline of phase I antibodies in Q fever endocarditis. J Antimicrob Chemother. 2009;63:771-774.
