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Smallpox Vaccination-associated Myopericarditis is More Common with the Newest Smallpox Vaccine
The Journal of Emergency Medicine, Vol. 46, No. 3, pp. e85–e87, 2014 Published by Elsevier Inc. Printed in the USA 0736-4679/$ - see front matter
Letters to the Editor , SMALLPOX VACCINATION-ASSOCIATED MYOPERICARDITIS IS MORE COMMON WITH THE NEWEST SMALLPOX VACCINE
and the decision was made to administer tenecteplase 35 mg intravenously in consultation with the cardiologist. No cardiac catheterization suite is present in the deployed theater of operations. Within 20 min of administration of thrombolytic, his pain resolved, and his ECG showed resolution of his ST-segment elevation in the inferior leads and the ST depressions in his anterior leads. He was admitted to the intensive care unit, and he remained stable and without pain, dysrhythmias, or return of ST elevation. His troponin I level peaked at 13.3 ng/mL. He was flown back to Germany within 48 h. Subsequent coronary angiography revealed normal coronary arteries, but echocardiography demonstrated decreased contractility of a focal segment of his inferior wall 3 days after his initial presentation. He was determined to have developed a smallpox vaccine-related myopericarditis, but no biopsy was performed to confirm the diagnosis. Drs. Taylor and Eckart provided an excellent review of the diagnosis and management of this uncommon disorder, but given recent changes in the smallpox vaccine manufacturing for the American military, we wanted to comment on the increased rate of myopericarditis as a supplement to their discussion. The World Health Organization (WHO) successfully eradicated smallpox from human reservoirs in the 1980s due to an aggressive, world-wide vaccination program. The vaccination for the US military ended in 1990 (2,3). However, many adverse reactions were noted from smallpox vaccinations (Table 1). Cardiac complications have occasionally been reported in the literature, but few fatalities are reported (4). Although there has been strong evidence to link the smallpox vaccine to myopericarditis, there have not been enough data to support a causal link between the vaccines and dilatated cardiomyopathy or ischemic heart disease (5). Due to the renewed threat of bioterrorism, the risk of using smallpox as a weapon of mass destruction led the U.S. military to resume mandatory smallpox vaccinations of its personnel in 2002. By June 2004, 667,980 people were vaccinated in the US. Of those vaccinated, 82 cases of myopericarditis were reported within 30 days of vaccination, with most presenting 7–12 days after vaccination (5). This is a case rate of 12 per 100,000 vaccinations (5,6). The background rate of myopericarditis in
, To the Editor: We read the article by Dr. Taylor and Dr. Eckart regarding smallpox vaccination-mediated myocarditis with great interest (1). During a recent deployment to Afghanistan, we had a similar case of smallpox vaccine-mediated myopericarditis that presented as an acute ST-segment elevation myocardial infarction (MI) on electrocardiogram (ECG). A 27-year-old man presented to our military emergency department in Afghanistan complaining of acute onset of crushing substernal chest pain and dyspnea. His symptoms had occurred intermittently for the past 3 days but became persistent and severe 30 min prior to arrival. Of note, he had arrived in Afghanistan from the United States (US) 1 week prior. He denied cough, fever, vomiting, or radiation of pain, and the pain was not positional in nature. He had not experienced any prior history of similar symptoms. His past medical history was significant only for a smallpox immunization he received 2 weeks prior to presentation. His physical examination demonstrated an anxious and sweating Caucasian male with unremarkable vital signs. He had a normal cardiac and pulmonary examination without a friction rub. The remainder of his evaluation was normal except for a small lesion on his left deltoid consistent with a smallpox immunization in the proper stage of healing 2 weeks after inoculation. His initial ECG showed 2-mm ST-segment elevation in the inferior leads (II, III, aVF) with reciprocal ST depression in V1 and slight depression in V2 (Figure 1). He was given 325 mg of aspirin and three doses of sublingual nitroglycerin without any relief. He subsequently was given intravenous fentanyl with a slight decrease in pain. His troponin I results showed an elevated level: 5.5 ng/mL. Bedside cardiac ultrasound demonstrated a grossly normal heart without a pericardial effusion, Disclaimer: The views expressed in this article are those of the author(s) and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government. e85
e86
Letters to the Editor
Figure 1. Electrocardiogram on arrival showing ST-segment elevation in the inferior leads (II, III, aVF) and slight elevations in V3–V6 with reciprocal ST depression in V1 and V2.
nonvaccinated persons was 2.2 per 100,000 during 2002 over a 30-day observation period and a rate of only 2.1 per 100,000 in previously vaccinated individuals (7). Whereas the cases of dermatological and neurological adverse effects have remained at historically low levels, case rates of myopericarditis have increased significantly in the past decade. This may be due to improved imaging modalities and new laboratory studies (8). In addition, the numbers of subjects vaccinated have increased significantly since the cited period, with over 1.1 million U.S. military members being vaccinated as of September 2006 (8). Due to a shortage of the previous smallpox vaccine (DryvaxÔ, Wyeth Laboratories, Inc., Collegeville, PA), the U.S. government contracted with Acambis, Inc. (Cambridge, MA) to develop and manufacture a new vaccine. ACAM2000Ô replaced Dryvax for all smallpox Table 1. Reported Complications of Smallpox Vaccine Dermatologic
Neurologic Cardiac
Autoinoculation Eczema Erythema multiforme major Generalized vaccinia Encephalitis Myelitis Myocarditis Pericarditis
vaccinations in 2008. As noted, the adverse reaction case rate of myopericarditis for the old vaccine was 12 cases per 100,000 doses. ACAM200, during phase III trials, by testing all subjects with serial electrocardiogram (ECG) and cardiac troponins, had a myopericarditis case rate of 573 per 100,000 doses in vaccine-naı¨ve patients – a 40-fold increase from the old vaccine (8). Many of these patients with positive ECGs and laboratory markers were asymptomatic, and clinical significance of these asymptomatic cases of myocarditis is currently unknown. Our case report and subsequent evaluation of the literature, in conjunction with the work done by Drs. Taylor and Eckart, has two relevant conclusions for practicing emergency physicians. First, myopericarditis associated with the smallpox vaccine is a rare but recognized complication that is increasing with both the routine vaccination of military members and the new vaccine ACAM2000. Second, in an austere military environment, or other areas where acute MI cannot be definitively ruled out, it is reasonable to treat myopericarditis as an acute MI until proven otherwise, up to and including thrombolytic therapy. Smallpox vaccine-related myopericarditis, although rare, must be considered in any patient who presents with chest pain within 30 days of smallpox immunization.
The Journal of Emergency Medicine
David I. Bruner, MD, FAAEM Naval Medical Center Portsmouth Virginia Bradley S. Butler, MD, FACEP University of Arizona College of Medicine Maricopa Medical Center Phoenix, Arizona http://dx.doi.org/10.1016/j.jemermed.2013.06.001
REFERENCES 1. Taylor CL, Eckart RE. Chest pain, ST elevation, positive cardiac enzymes in an austere environment: differentiating smallpox vaccination-mediated myocarditis and acute coronary syndrome in Operation Iraqi Freedom. J Emerg Med 2012;42:267–70.
e87 2. Martin DB. The cause of death in smallpox: an examination of the pathology record. Mil Med 2002;167:546–51. 3. World Health Organization. The global eradication of smallpox: Final report of the global commission for the certification of smallpox eradication. History of International Public Health, No. 4. Geneva, Switzerland: World Health Organization; 1980. 4. Cassimatis DC, Atwood JE, Engler RM, et al. Smallpox vaccination and myopericarditis: a clinical review. J Am Coll Cardiol 2004;43: 1503–10. 5. Neff J, Modlin J, Birkhead GS, et al. Monitoring the safety of a smallpox vaccination program in the United States: report of the Joint Smallpox Vaccine Safety Working Group of the Advisory Committee on Immunization Practices and the Armed Forces Epidemiological Board. Clin Infect Dis 2008;46:S258–70. 6. Centers for Disease Control and Prevention (CDC). Update: cardiacrelated events during the civilian smallpox vaccination programd United States, 2003. MMMR Morb Mortal Wkly Rep 2003;52:492–6. 7. Arness MK, Eckart RE, Love SS, et al. Myopericarditis following smallpox vaccination. Am J Epidemiol 2004;160:642–51. 8. Nalca A, Zumbrun EE. ACAM2000: the new smallpox vaccine for United States Strategic National Stockpile. Drug Des Devel Ther 2010;4:71–9.
Letters to the Editor , SMALLPOX VACCINATION-ASSOCIATED MYOPERICARDITIS IS MORE COMMON WITH THE NEWEST SMALLPOX VACCINE
and the decision was made to administer tenecteplase 35 mg intravenously in consultation with the cardiologist. No cardiac catheterization suite is present in the deployed theater of operations. Within 20 min of administration of thrombolytic, his pain resolved, and his ECG showed resolution of his ST-segment elevation in the inferior leads and the ST depressions in his anterior leads. He was admitted to the intensive care unit, and he remained stable and without pain, dysrhythmias, or return of ST elevation. His troponin I level peaked at 13.3 ng/mL. He was flown back to Germany within 48 h. Subsequent coronary angiography revealed normal coronary arteries, but echocardiography demonstrated decreased contractility of a focal segment of his inferior wall 3 days after his initial presentation. He was determined to have developed a smallpox vaccine-related myopericarditis, but no biopsy was performed to confirm the diagnosis. Drs. Taylor and Eckart provided an excellent review of the diagnosis and management of this uncommon disorder, but given recent changes in the smallpox vaccine manufacturing for the American military, we wanted to comment on the increased rate of myopericarditis as a supplement to their discussion. The World Health Organization (WHO) successfully eradicated smallpox from human reservoirs in the 1980s due to an aggressive, world-wide vaccination program. The vaccination for the US military ended in 1990 (2,3). However, many adverse reactions were noted from smallpox vaccinations (Table 1). Cardiac complications have occasionally been reported in the literature, but few fatalities are reported (4). Although there has been strong evidence to link the smallpox vaccine to myopericarditis, there have not been enough data to support a causal link between the vaccines and dilatated cardiomyopathy or ischemic heart disease (5). Due to the renewed threat of bioterrorism, the risk of using smallpox as a weapon of mass destruction led the U.S. military to resume mandatory smallpox vaccinations of its personnel in 2002. By June 2004, 667,980 people were vaccinated in the US. Of those vaccinated, 82 cases of myopericarditis were reported within 30 days of vaccination, with most presenting 7–12 days after vaccination (5). This is a case rate of 12 per 100,000 vaccinations (5,6). The background rate of myopericarditis in
, To the Editor: We read the article by Dr. Taylor and Dr. Eckart regarding smallpox vaccination-mediated myocarditis with great interest (1). During a recent deployment to Afghanistan, we had a similar case of smallpox vaccine-mediated myopericarditis that presented as an acute ST-segment elevation myocardial infarction (MI) on electrocardiogram (ECG). A 27-year-old man presented to our military emergency department in Afghanistan complaining of acute onset of crushing substernal chest pain and dyspnea. His symptoms had occurred intermittently for the past 3 days but became persistent and severe 30 min prior to arrival. Of note, he had arrived in Afghanistan from the United States (US) 1 week prior. He denied cough, fever, vomiting, or radiation of pain, and the pain was not positional in nature. He had not experienced any prior history of similar symptoms. His past medical history was significant only for a smallpox immunization he received 2 weeks prior to presentation. His physical examination demonstrated an anxious and sweating Caucasian male with unremarkable vital signs. He had a normal cardiac and pulmonary examination without a friction rub. The remainder of his evaluation was normal except for a small lesion on his left deltoid consistent with a smallpox immunization in the proper stage of healing 2 weeks after inoculation. His initial ECG showed 2-mm ST-segment elevation in the inferior leads (II, III, aVF) with reciprocal ST depression in V1 and slight depression in V2 (Figure 1). He was given 325 mg of aspirin and three doses of sublingual nitroglycerin without any relief. He subsequently was given intravenous fentanyl with a slight decrease in pain. His troponin I results showed an elevated level: 5.5 ng/mL. Bedside cardiac ultrasound demonstrated a grossly normal heart without a pericardial effusion, Disclaimer: The views expressed in this article are those of the author(s) and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government. e85
e86
Letters to the Editor
Figure 1. Electrocardiogram on arrival showing ST-segment elevation in the inferior leads (II, III, aVF) and slight elevations in V3–V6 with reciprocal ST depression in V1 and V2.
nonvaccinated persons was 2.2 per 100,000 during 2002 over a 30-day observation period and a rate of only 2.1 per 100,000 in previously vaccinated individuals (7). Whereas the cases of dermatological and neurological adverse effects have remained at historically low levels, case rates of myopericarditis have increased significantly in the past decade. This may be due to improved imaging modalities and new laboratory studies (8). In addition, the numbers of subjects vaccinated have increased significantly since the cited period, with over 1.1 million U.S. military members being vaccinated as of September 2006 (8). Due to a shortage of the previous smallpox vaccine (DryvaxÔ, Wyeth Laboratories, Inc., Collegeville, PA), the U.S. government contracted with Acambis, Inc. (Cambridge, MA) to develop and manufacture a new vaccine. ACAM2000Ô replaced Dryvax for all smallpox Table 1. Reported Complications of Smallpox Vaccine Dermatologic
Neurologic Cardiac
Autoinoculation Eczema Erythema multiforme major Generalized vaccinia Encephalitis Myelitis Myocarditis Pericarditis
vaccinations in 2008. As noted, the adverse reaction case rate of myopericarditis for the old vaccine was 12 cases per 100,000 doses. ACAM200, during phase III trials, by testing all subjects with serial electrocardiogram (ECG) and cardiac troponins, had a myopericarditis case rate of 573 per 100,000 doses in vaccine-naı¨ve patients – a 40-fold increase from the old vaccine (8). Many of these patients with positive ECGs and laboratory markers were asymptomatic, and clinical significance of these asymptomatic cases of myocarditis is currently unknown. Our case report and subsequent evaluation of the literature, in conjunction with the work done by Drs. Taylor and Eckart, has two relevant conclusions for practicing emergency physicians. First, myopericarditis associated with the smallpox vaccine is a rare but recognized complication that is increasing with both the routine vaccination of military members and the new vaccine ACAM2000. Second, in an austere military environment, or other areas where acute MI cannot be definitively ruled out, it is reasonable to treat myopericarditis as an acute MI until proven otherwise, up to and including thrombolytic therapy. Smallpox vaccine-related myopericarditis, although rare, must be considered in any patient who presents with chest pain within 30 days of smallpox immunization.
The Journal of Emergency Medicine
David I. Bruner, MD, FAAEM Naval Medical Center Portsmouth Virginia Bradley S. Butler, MD, FACEP University of Arizona College of Medicine Maricopa Medical Center Phoenix, Arizona http://dx.doi.org/10.1016/j.jemermed.2013.06.001
REFERENCES 1. Taylor CL, Eckart RE. Chest pain, ST elevation, positive cardiac enzymes in an austere environment: differentiating smallpox vaccination-mediated myocarditis and acute coronary syndrome in Operation Iraqi Freedom. J Emerg Med 2012;42:267–70.
e87 2. Martin DB. The cause of death in smallpox: an examination of the pathology record. Mil Med 2002;167:546–51. 3. World Health Organization. The global eradication of smallpox: Final report of the global commission for the certification of smallpox eradication. History of International Public Health, No. 4. Geneva, Switzerland: World Health Organization; 1980. 4. Cassimatis DC, Atwood JE, Engler RM, et al. Smallpox vaccination and myopericarditis: a clinical review. J Am Coll Cardiol 2004;43: 1503–10. 5. Neff J, Modlin J, Birkhead GS, et al. Monitoring the safety of a smallpox vaccination program in the United States: report of the Joint Smallpox Vaccine Safety Working Group of the Advisory Committee on Immunization Practices and the Armed Forces Epidemiological Board. Clin Infect Dis 2008;46:S258–70. 6. Centers for Disease Control and Prevention (CDC). Update: cardiacrelated events during the civilian smallpox vaccination programd United States, 2003. MMMR Morb Mortal Wkly Rep 2003;52:492–6. 7. Arness MK, Eckart RE, Love SS, et al. Myopericarditis following smallpox vaccination. Am J Epidemiol 2004;160:642–51. 8. Nalca A, Zumbrun EE. ACAM2000: the new smallpox vaccine for United States Strategic National Stockpile. Drug Des Devel Ther 2010;4:71–9.