Accepted Manuscript Sinus Bradycardia: Can We Blame Ehrlichiosis? Poojita Shivamurthy, M.B.B.S. Saqib Ali Gowani, M.D. Rahul Mutneja, M.B.B.S. Sparsha Kukunoor, M.B.B.B. Mamta Shah, M.B.B.S. Russell Stein, M.D. PII:
S0002-9343(14)00794-3
DOI:
10.1016/j.amjmed.2014.09.002
Reference:
AJM 12674
To appear in:
The American Journal of Medicine
Received Date: 25 July 2014 Revised Date:
28 August 2014
Accepted Date: 2 September 2014
Please cite this article as: Shivamurthy P, Gowani SA, Mutneja R, Kukunoor S, Shah M, Stein R, Sinus Bradycardia: Can We Blame Ehrlichiosis?, The American Journal of Medicine (2014), doi: 10.1016/ j.amjmed.2014.09.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title: Sinus Bradycardia: Can We Blame Ehrlichiosis?
Poojita Shivamurthy M.B.B.S.1; Saqib Ali Gowani M.D.2; Rahul Mutneja M.B.B.S.1; Sparsha Kukunoor M.B.B.B.,1 Mamta Shah M.B.B.S.1; Russell Stein M.D.3 1
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Department of Medicine 263 Farmington Avenue University of Connecticut Health Center Farmington, CT 06030 USA
2
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Heart Failure Fellow Saint Francis Hospital and Medical Center 114 Woodland Street,Hartford,CT-06105 USA Cardiologist Hartford Hospital University of Connecticut Health Center Hartford, CT 06102 USA
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Corresponding Author: Poojita Shivamurthy M.B.B.S. Department of Medicine 263 Farmington Avenue University of Connecticut Health Center Farmington, CT 06030, USA Phone number: +1 860-471-5712 E-mail: [email protected]
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Funding source: None
Conflict of interest: None All authors had access to the data and a role in writing the manuscript.
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Article type: Clinical Communications to the Editor Key words: Ehrlichiosis, relative bradycardia, anaplasmosis, tick-borne, morulae. Running head: Severe sinus bradycardia in ehrlichiosis.
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To the Editor Introduction:
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Relative bradycardia is defined as lack of physiological increase in heart rate by ten beats per minute for each degree increase in temperature beyond 102⁰F.1 Several gram negative intracellular organisms, viral infections and tick-borne illnesses are associated with relative bradycardia (Table 1)1. This may be of diagnostic significance in right clinical setting.
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Case Report:
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Discussion:
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A 54-year-old female presented with five days of high-grade fever associated with rigors, fatigue, and diffuse headache. She denied tick bites and recent outdoor activities. She had fever of 103⁰F and heart rateof 85 beats per minute indicating relative bradycardia. Blood pressure was 80/51 mm Hg. Laboratory data revealed pancytopenia (white blood cells of 2,300 /mm3, platelets of 50,000/mm3 and hemoglobin of 10.8 g/dL) with transaminitis (aspartate transaminase of 138 U/L and alanine transaminase of 122 U/L). Three liters of normal saline improved systolic blood pressure to 90 mmHg but heart rate had dropped to 50 beats per minute. Electrocardiogram revealed sinus bradycardia (Figure 1). While being resuscitated, heart rate worsened to 30 beats per minute with a temperature of 101.50F again indicating pulse-temperature deficit. As patient experienced lightheadedness, dopamine was begun to maintain heart rate above 60beats per minute. Bradycardia recurred with attempts to wean dopamine. Peripheral smear showed a granulocytic left shift with intracytoplasmic morulae consistent with ehrlichiosis. Lyme titers were negative. Doxycycline was begun immediately. Fever and bradycardia resolved in 48 hours. Cardiac markers were normal. An echocardiogram showed normal ejection fraction without wall motion abnormalities.
Ehrlichiosis is a steadily rising tick borne infection endemic in northeastern United States. Human granulocytic anaplasmosis is a form of ehrlichiosis caused by Anaplasma phagocytophilum, transmitted by the Ixodes tick2. Patients present with fever and malaise 5-21 days after an infected tick bite, which they may not recall. Leukopenia, thrombocytopenia and elevated transaminases can be present. Fatality is less than 1% with HGA with 17% of hospitalized patients requiring intensive care.2Delay in treatment leads to complications including toxic shock syndrome, acute respiratory distress syndrome, and myocarditis.2 A few case series of Ehrlichia canis infection linked with relative bradycardia have been reported.3,4 There have been case reports of conduction abnormalities associated with myocarditis5,6. One case of
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anaplasmosis with biopsy proven inflammatory cell infiltration of sinus node and bundle branch system was reported.5 There was no evidence to suggest myocarditis or involvement of conduction system of heart that could explain our patient’s bradycardia. Conclusion:
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In endemic regions, human granulocytic anaplasmosis should be considered in patients with fever and relative bradycardia. Doxycycline should be promptly initiated while diagnostic tests are awaited. Coinfection with babesiosis, Lyme disease and Rocky Mountain spotted fever should also be considered, as there is significant overlapping of symptoms, geographical distributions and sharing of vectors.
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References:
1. Cunha BA. The diagnostic significance of relative bradycardia in infectious disease.ClinMicrobiol Infect. 2000;6(12):633-634.
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2. Thomas RJ, Dumler JS, Carlyon JA. Current management of human granulocytic anaplasmosis, human monocytic ehrlichiosis and ehrlichiaewingii ehrlichiosis.Expert Rev Anti Infect Ther. 2009;7(6):709-722. 3. Fishbein DB, Sawyer LA, Holland CJ, et al. Unexplained febrile illnesses after exposure to ticks. infection with an ehrlichia? JAMA. 1987;257(22):3100-3104. 4. Conrad ME. Ehrlichia canis: A tick-borne rickettsial-like infection in humans living in the southeastern united states. Am J Med Sci. 1989;297(1):35-37.
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5. Jahangir A, Kolbert C, Edwards W, Mitchell P, Dumler JS, Persing DH. Fatal pancarditis associated with human granulocytic ehrlichiosis in a 44-year-old man. Clin Infect Dis. 1998;27(6):1424-1427.
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6. Nayak SU, Simon GL. Myocarditis after trimethoprim/sulfamethoxazole treatment for ehrlichiosis. Emerg Infect Dis. 2013;19(12):1975-1977.
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Legends: Figure 1: ECG-sinus bradycardia at 42 bpm. Table 1: Organisms associated with relative bradycardia.
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Table 1: Organisms associated with relative bradycardia Bacterial infections: Listeria, Legionella, Salmonella typhi, Orientiatsutsugamushi, Malaria, Leptospira, Q fever, Chlamydia pneumoniae.
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Tickborne infections: Babesia, Rocky Mountain Spotted Fever, Lyme disease. Viral infections: Dengue virus, ECHO virus, Yellow fever virus, Crimean Congo hemorrhagic virus
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S0002-9343(14)00794-3
DOI:
10.1016/j.amjmed.2014.09.002
Reference:
AJM 12674
To appear in:
The American Journal of Medicine
Received Date: 25 July 2014 Revised Date:
28 August 2014
Accepted Date: 2 September 2014
Please cite this article as: Shivamurthy P, Gowani SA, Mutneja R, Kukunoor S, Shah M, Stein R, Sinus Bradycardia: Can We Blame Ehrlichiosis?, The American Journal of Medicine (2014), doi: 10.1016/ j.amjmed.2014.09.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title: Sinus Bradycardia: Can We Blame Ehrlichiosis?
Poojita Shivamurthy M.B.B.S.1; Saqib Ali Gowani M.D.2; Rahul Mutneja M.B.B.S.1; Sparsha Kukunoor M.B.B.B.,1 Mamta Shah M.B.B.S.1; Russell Stein M.D.3 1
RI PT
Department of Medicine 263 Farmington Avenue University of Connecticut Health Center Farmington, CT 06030 USA
2
SC
Heart Failure Fellow Saint Francis Hospital and Medical Center 114 Woodland Street,Hartford,CT-06105 USA Cardiologist Hartford Hospital University of Connecticut Health Center Hartford, CT 06102 USA
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Corresponding Author: Poojita Shivamurthy M.B.B.S. Department of Medicine 263 Farmington Avenue University of Connecticut Health Center Farmington, CT 06030, USA Phone number: +1 860-471-5712 E-mail: [email protected]
M AN U
3
EP
Funding source: None
Conflict of interest: None All authors had access to the data and a role in writing the manuscript.
AC C
Article type: Clinical Communications to the Editor Key words: Ehrlichiosis, relative bradycardia, anaplasmosis, tick-borne, morulae. Running head: Severe sinus bradycardia in ehrlichiosis.
ACCEPTED MANUSCRIPT
RI PT
To the Editor Introduction:
SC
Relative bradycardia is defined as lack of physiological increase in heart rate by ten beats per minute for each degree increase in temperature beyond 102⁰F.1 Several gram negative intracellular organisms, viral infections and tick-borne illnesses are associated with relative bradycardia (Table 1)1. This may be of diagnostic significance in right clinical setting.
M AN U
Case Report:
AC C
Discussion:
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TE D
A 54-year-old female presented with five days of high-grade fever associated with rigors, fatigue, and diffuse headache. She denied tick bites and recent outdoor activities. She had fever of 103⁰F and heart rateof 85 beats per minute indicating relative bradycardia. Blood pressure was 80/51 mm Hg. Laboratory data revealed pancytopenia (white blood cells of 2,300 /mm3, platelets of 50,000/mm3 and hemoglobin of 10.8 g/dL) with transaminitis (aspartate transaminase of 138 U/L and alanine transaminase of 122 U/L). Three liters of normal saline improved systolic blood pressure to 90 mmHg but heart rate had dropped to 50 beats per minute. Electrocardiogram revealed sinus bradycardia (Figure 1). While being resuscitated, heart rate worsened to 30 beats per minute with a temperature of 101.50F again indicating pulse-temperature deficit. As patient experienced lightheadedness, dopamine was begun to maintain heart rate above 60beats per minute. Bradycardia recurred with attempts to wean dopamine. Peripheral smear showed a granulocytic left shift with intracytoplasmic morulae consistent with ehrlichiosis. Lyme titers were negative. Doxycycline was begun immediately. Fever and bradycardia resolved in 48 hours. Cardiac markers were normal. An echocardiogram showed normal ejection fraction without wall motion abnormalities.
Ehrlichiosis is a steadily rising tick borne infection endemic in northeastern United States. Human granulocytic anaplasmosis is a form of ehrlichiosis caused by Anaplasma phagocytophilum, transmitted by the Ixodes tick2. Patients present with fever and malaise 5-21 days after an infected tick bite, which they may not recall. Leukopenia, thrombocytopenia and elevated transaminases can be present. Fatality is less than 1% with HGA with 17% of hospitalized patients requiring intensive care.2Delay in treatment leads to complications including toxic shock syndrome, acute respiratory distress syndrome, and myocarditis.2 A few case series of Ehrlichia canis infection linked with relative bradycardia have been reported.3,4 There have been case reports of conduction abnormalities associated with myocarditis5,6. One case of
ACCEPTED MANUSCRIPT
anaplasmosis with biopsy proven inflammatory cell infiltration of sinus node and bundle branch system was reported.5 There was no evidence to suggest myocarditis or involvement of conduction system of heart that could explain our patient’s bradycardia. Conclusion:
RI PT
In endemic regions, human granulocytic anaplasmosis should be considered in patients with fever and relative bradycardia. Doxycycline should be promptly initiated while diagnostic tests are awaited. Coinfection with babesiosis, Lyme disease and Rocky Mountain spotted fever should also be considered, as there is significant overlapping of symptoms, geographical distributions and sharing of vectors.
SC
References:
1. Cunha BA. The diagnostic significance of relative bradycardia in infectious disease.ClinMicrobiol Infect. 2000;6(12):633-634.
M AN U
2. Thomas RJ, Dumler JS, Carlyon JA. Current management of human granulocytic anaplasmosis, human monocytic ehrlichiosis and ehrlichiaewingii ehrlichiosis.Expert Rev Anti Infect Ther. 2009;7(6):709-722. 3. Fishbein DB, Sawyer LA, Holland CJ, et al. Unexplained febrile illnesses after exposure to ticks. infection with an ehrlichia? JAMA. 1987;257(22):3100-3104. 4. Conrad ME. Ehrlichia canis: A tick-borne rickettsial-like infection in humans living in the southeastern united states. Am J Med Sci. 1989;297(1):35-37.
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5. Jahangir A, Kolbert C, Edwards W, Mitchell P, Dumler JS, Persing DH. Fatal pancarditis associated with human granulocytic ehrlichiosis in a 44-year-old man. Clin Infect Dis. 1998;27(6):1424-1427.
EP
6. Nayak SU, Simon GL. Myocarditis after trimethoprim/sulfamethoxazole treatment for ehrlichiosis. Emerg Infect Dis. 2013;19(12):1975-1977.
AC C
Legends: Figure 1: ECG-sinus bradycardia at 42 bpm. Table 1: Organisms associated with relative bradycardia.
ACCEPTED MANUSCRIPT
Table 1: Organisms associated with relative bradycardia Bacterial infections: Listeria, Legionella, Salmonella typhi, Orientiatsutsugamushi, Malaria, Leptospira, Q fever, Chlamydia pneumoniae.
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Tickborne infections: Babesia, Rocky Mountain Spotted Fever, Lyme disease. Viral infections: Dengue virus, ECHO virus, Yellow fever virus, Crimean Congo hemorrhagic virus
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