- Email: [email protected]
Late Recurrence of Rheumatic Fever
CASE-LETTER
Late Recurrence of Rheumatic Fever
A
59-year-old man with a history of systolic heart failure (HF) was admitted to another hospital in March 2015, with severe dyspnea on exertion for 1 week. He was found to be in decompensated HF, treated with intravenous diuretics and transferred to a quaternary care hospital for evaluation for advanced HF therapies. He was born in 1955 in the Dominican Republic and had multiple febrile illnesses in childhood and decreased exercise tolerance as a young adult. At the age of 19, he immigrated to the United States at which time he was diagnosed with rheumatic heart disease (RHD). He underwent aortic valve replacement with a Bjork–Shiley valve at the age of 21. He was never treated with antibiotic prophylaxis for rheumatic fever (RF). In 2012, he underwent redo sternotomy with suture repair of a periprosthetic aortic valve leak. At that time, he underwent placement of a single lead implantable cardioverter defibrillator for severely depressed left ventricular systolic function, with subsequent upgrade to a biventricular implantable cardioverter defibrillator and ablation of the atrioventricular node for atrial fibrillation. On presentation to the quaternary care hospital, further questioning revealed an 1-week history of mild sore throat, severe and persistent migratory joint pains, which was initially localized to the left hip and left ankle, and a diffuse, erythematous rash on the extremities that had resolved before admission. He was febrile at 101.6°F, and physical exam was significant for volume overload and tenderness over the left hip at the greater trochanter. Radiographs of the left hip showed evidence of arthritis. There was no significant abnormality in xrays of the left ankle. An echocardiogram revealed mildly thickened mitral valve leaflets with diastolic doming of the anterior leaflet, and a calcified and immobile posterior leaflet suggesting a rheumatic etiology. There was mild mitral stenosis and mild mitral regurgitation. A mechanical aortic valve was in place, and the left ventricular ejection fraction was 40%. Laboratory studies revealed sterile blood cultures drawn on days 2 to 6 of hospital stay, elevated erythrocyte sedimentation rate of 107 mm/hr (normal , 10), elevated C reactive protein of 14.3 mg/dL (normal , 0.8), and a negative rapid streptococcal antigen detection test on throat swab. The patient’s throat culture was positive for light growth of group A streptococcus (GAS). Antistreptolysin O antibody titers were elevated to 1,300 IU/mL (normal , 117 IU/mL). On day 2 of hospitalization, he developed left knee pain and was noted to have an effusion. Arthrocentesis did not show any evidence of infection, and synovial fluid cultures were sterile. Based on clinical and laboratory findings, he was diagnosed with acute RF. He was treated with a single dose of intramuscular benzathine penicillin G 1.2 million units. He was additionally started on choline magnesium trisalicylate 1g 3 times daily for anti-inflammatory effect. He had rapid improvement of his joint pain, improvement of HF symptoms and resolution of fevers. For this reason, his HF symptoms were attributed to carditis from RF, and evaluation for advanced therapies for HF was put on hold. He was discharged after 7 days of hospitalization with follow-up with his primary care physician and cardiologist, with plans to initiate oral penicillin prophylaxis in 4 weeks of time.
342
Recurrences of RF in adults have been reported between 2 and 30 years after the index episode.1 In the last 20 years, reports of recurrent RF in the medical literature have been few and far between, and none have been reported from the United States. There are estimated 15 million cases of RHD worldwide and leading to 233,000 annual deaths. Although RHD remains a major cause of morbidity and mortality globally, the overall incidence of acute RF is decreasing, and it is rarely encountered by physicians in the United States. From 1970 to 2009, in the United States, the prevalence of acute RF was reported to be up to 40 cases/100,000 persons, whereas in some developing countries, it was reported to be over 100 cases/100,000 persons.2 This case highlights the importance of continued attention to RF in the United States in patients with previous episodes of the disease. RF is an immune response to GAS pharyngitis. Streptococcal skin infections have not been implicated in RF. At least one third of cases of acute RF result from clinically unrecognized GAS infections.3 The basis of the diagnosis of RF remains the Jones criteria (Table 1), which was initially published in 1944, with successive revisions, most recently in 2015, that have progressively increased its specificity and decreased its sensitivity.4,5 Until 1992, the Jones criteria represented consensus guidelines; the 2015 revision was the first to classify recommendations by the Classification of Recommendations and Level of Evidence categories. Additionally, the 2015 guidelines reflect a major change in paradigm for the diagnosis of RF, with the incorporation of echocardiographic parameters for the diagnosis of carditis. This change was based on over 25 studies showing the utility of echocardiography with Doppler in the diagnosis of subclinical carditis. In the 2015 revision, a diagnosis of recurrent RF may be made with 2 major, 1 major and 2 minor, or 3 minor criteria alone in the setting of preceding GAS pharyngitis. However, this revision did not address the echocardiographic diagnosis of carditis in the context of recurrent RF in the presence of chronic RHD.5 In this patient, 2 major and 3 minor Jones criteria were satisfied (clinical carditis, polyarthritis, fever and elevated acute phase reactants) in the presence of positive throat cultures and elevated streptococcal antibody titers. Prolongation of the PR interval was not assessed in the setting of atrial fibrillation. Primary prevention of RF is accomplished by identification and treatment of GAS pharyngitis. Penicillin remains the cornerstone of treatment for GAS pharyngitis, with 100% of GAS demonstrating in vitro susceptibility to all beta-lactam agents. Current guidelines from the American Heart Association recommend the following regimens for the treatment of GAS pharyngitis for primary prevention of acute RF: oral penicillin V at a dose of 500 mg 2 to 3 times daily for 10 days, amoxicillin 50 mg/kg once daily for 10 days or intramuscular benzathine penicillin G 1.2 million units once. Patients with penicillin allergy may be treated with narrow spectrum cephalosporins, clindamycin, azithromycin or clarithromycin.3 Antimicrobial treatment for acute RF mirrors that for GAS pharyngitis, regardless of the presence of pharyngitis at the time of diagnosis of acute RF. HF management, with attention to valvular heart disease, is necessary in patients with carditis. Aspirin remains the mainstay of anti-inflammatory therapy in practice. The evidence for the efficacy of antiinflammatory medications in acute RF is antiquated, and data on the efficacy of recently developed anti-inflammatory medications are necessary.6 In this patient, choline magnesium trisalicylate was chosen for anti-inflammatory effect. This has a decreased effect on platelet inhibition in comparison with
The American Journal of the Medical Sciences
Volume 350, Number 4, October 2015
Case-Letter
TABLE 1. Guidelines for the diagnosis of acute RF (Jones criteria): a comparison of the 1992 and 2015 criteria 1992 Criteria 2015 Criteria Diagnosis
2 major, or 1 major and 2 minor
Major criteria
Carditis Polyarthritis Chorea Erythema marginatum Subcutaneous nodules Arthralgia Fevers Elevated acute phase reactants Prolonged PR interval
Minor criteria
Initial: 2 major, or 1 major and 2 minor Recurrence: 2 major or 1 major and 2 minor or 3 minor Carditis (clinical and/or subclinical diagnosed by echocardiography) Polyarthritis (monoarthritis or polyarthralgia in moderate, high-risk populations) Chorea Erythema marginatum Subcutaneous nodules Polyarthralgia (monoarthralgia in moderate, high-risk populations) Fevers Elevated acute phase reactants Prolonged PR interval
Evidence of preceding group A streptococcal pharyngitis is required to apply these criteria: elevated or rising streptococcal antibodies, a positive throat culture for GAS or a positive group A streptococcal carbohydrate antigen test in a child with a high pretest probability of streptococcal pharyngitis.4,5
acetylated salicylates. As this patient required long-term anticoagulation for his mechanical aortic valve, this medication was chosen to reduce his excess bleeding risk. Secondary prevention of RF is the long-term use of antibiotic therapy in patients with a previous episode of acute RF to prevent recurrence. Recurrent episodes of RF may cause worsening of the severity of RHD. The 2009 American Heart Association Guidelines on Rheumatic Fever Treatment and Prevention recommendations for secondary prevention are either 250 mg of oral penicillin V twice daily or 1.2 million units of intramuscular penicillin G every 4 weeks, the latter of which is the most efficacious regimen.3,7 Most failures of prophylaxis occur due to noncompliance, therefore, individual patient factors should be considered when deciding between oral and intramuscular injection regimens.3 There is a potential for bleeding from intramuscular injections in the setting of long-term anticoagulation, which many patients receive as a result of valve prostheses for RHD. The appropriate duration of secondary prophylaxis with antimicrobials depends on a patient’s individual risk of recurrence, which increases with multiple previous episodes of recurrences and decreases as the interval lengthens since the last recurrence. For patients with persistent valvular disease, prophylaxis is recommended by the American Heart Association for 10 years after the last episode of acute RF or until 40 years of age (whichever is longer), with potentially lifelong prophylaxis for high-risk patients. Prophylaxis should continue even after valve surgery, including prosthetic valve replacement.3 Those in close contact with children, health care workers, military personnel, economically disadvantaged populations and those living in crowded or unsanitary conditions are all at increased risk of recurrence of RF because they are at higher risk of acquiring GAS upper respiratory tract infections. In addition, all family members of affected patients should be screened and treated for streptococcal infections when symptomatic to prevent reinfection of the patient with GAS.3 Appropriate antibiotic prophylaxis in this patient may have prevented a recurrence of RF. In summary, this case illustrates the continued presence of acute RF in the United States, and the need for its recognition by internists and cardiologists, when it presents as HF. Antibiotic therapy and prophylaxis for this disease is effective, low cost and often prevents progression of the disease. For this reason, it is particularly important to apply the clinical and
Copyright Ó 2015 by the Southern Society for Clinical Investigation.
laboratory tests that encompass the Jones criteria to make this diagnosis and prevent the morbidity and mortality associated with untreated RF.
Loheetha Ragupathi, MD Justin Herman, MD Paul Mather, MD Jefferson Heart Institute, Thomas Jefferson University Hospital Philadelphia, PA E-mail: [email protected] The authors have no financial or other conflicts of interest to disclose. REFERENCES 1. Wee AS, Goodwin JF. Acute rheumatic fever and carditis in older adults. Lancet 1966;2:239–42. 2. Seckeler MD, Hoke TR. The worldwide epidemiology of acute rheumatic fever and rheumatic heart disease. Clin Epidemiol 2011; 3:67–84. 3. Gerber MA, Baltimore RS, Eaton CB, et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation 2009;119:1541–51. 4. Guidelines for the diagnosis of rheumatic fever. Jones Criteria, 1992 update. Special Writing Group of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young of the American Heart Association. JAMA 1992; 268:2069–73. 5. Gewitz MH, Baltimore RS, Tani LY, et al. Revision of the jones criteria for the diagnosis of acute rheumatic Fever in the era of Doppler echocardiography: a scientific statement from the american heart association. Circulation 2015;131:1806–18. 6. Cilliers A, Manyemba J, Adler AJ, et al. Anti-inflammatory treatment for carditis in acute rheumatic fever. Cochrane Database Syst Rev 2012; 6:CD003176. 7. Manyemba J, Mayosi BM. Penicillin for secondary prevention of rheumatic fever. Cochrane Database Syst Rev. 2002;(3):CD002227.
343
Late Recurrence of Rheumatic Fever
A
59-year-old man with a history of systolic heart failure (HF) was admitted to another hospital in March 2015, with severe dyspnea on exertion for 1 week. He was found to be in decompensated HF, treated with intravenous diuretics and transferred to a quaternary care hospital for evaluation for advanced HF therapies. He was born in 1955 in the Dominican Republic and had multiple febrile illnesses in childhood and decreased exercise tolerance as a young adult. At the age of 19, he immigrated to the United States at which time he was diagnosed with rheumatic heart disease (RHD). He underwent aortic valve replacement with a Bjork–Shiley valve at the age of 21. He was never treated with antibiotic prophylaxis for rheumatic fever (RF). In 2012, he underwent redo sternotomy with suture repair of a periprosthetic aortic valve leak. At that time, he underwent placement of a single lead implantable cardioverter defibrillator for severely depressed left ventricular systolic function, with subsequent upgrade to a biventricular implantable cardioverter defibrillator and ablation of the atrioventricular node for atrial fibrillation. On presentation to the quaternary care hospital, further questioning revealed an 1-week history of mild sore throat, severe and persistent migratory joint pains, which was initially localized to the left hip and left ankle, and a diffuse, erythematous rash on the extremities that had resolved before admission. He was febrile at 101.6°F, and physical exam was significant for volume overload and tenderness over the left hip at the greater trochanter. Radiographs of the left hip showed evidence of arthritis. There was no significant abnormality in xrays of the left ankle. An echocardiogram revealed mildly thickened mitral valve leaflets with diastolic doming of the anterior leaflet, and a calcified and immobile posterior leaflet suggesting a rheumatic etiology. There was mild mitral stenosis and mild mitral regurgitation. A mechanical aortic valve was in place, and the left ventricular ejection fraction was 40%. Laboratory studies revealed sterile blood cultures drawn on days 2 to 6 of hospital stay, elevated erythrocyte sedimentation rate of 107 mm/hr (normal , 10), elevated C reactive protein of 14.3 mg/dL (normal , 0.8), and a negative rapid streptococcal antigen detection test on throat swab. The patient’s throat culture was positive for light growth of group A streptococcus (GAS). Antistreptolysin O antibody titers were elevated to 1,300 IU/mL (normal , 117 IU/mL). On day 2 of hospitalization, he developed left knee pain and was noted to have an effusion. Arthrocentesis did not show any evidence of infection, and synovial fluid cultures were sterile. Based on clinical and laboratory findings, he was diagnosed with acute RF. He was treated with a single dose of intramuscular benzathine penicillin G 1.2 million units. He was additionally started on choline magnesium trisalicylate 1g 3 times daily for anti-inflammatory effect. He had rapid improvement of his joint pain, improvement of HF symptoms and resolution of fevers. For this reason, his HF symptoms were attributed to carditis from RF, and evaluation for advanced therapies for HF was put on hold. He was discharged after 7 days of hospitalization with follow-up with his primary care physician and cardiologist, with plans to initiate oral penicillin prophylaxis in 4 weeks of time.
342
Recurrences of RF in adults have been reported between 2 and 30 years after the index episode.1 In the last 20 years, reports of recurrent RF in the medical literature have been few and far between, and none have been reported from the United States. There are estimated 15 million cases of RHD worldwide and leading to 233,000 annual deaths. Although RHD remains a major cause of morbidity and mortality globally, the overall incidence of acute RF is decreasing, and it is rarely encountered by physicians in the United States. From 1970 to 2009, in the United States, the prevalence of acute RF was reported to be up to 40 cases/100,000 persons, whereas in some developing countries, it was reported to be over 100 cases/100,000 persons.2 This case highlights the importance of continued attention to RF in the United States in patients with previous episodes of the disease. RF is an immune response to GAS pharyngitis. Streptococcal skin infections have not been implicated in RF. At least one third of cases of acute RF result from clinically unrecognized GAS infections.3 The basis of the diagnosis of RF remains the Jones criteria (Table 1), which was initially published in 1944, with successive revisions, most recently in 2015, that have progressively increased its specificity and decreased its sensitivity.4,5 Until 1992, the Jones criteria represented consensus guidelines; the 2015 revision was the first to classify recommendations by the Classification of Recommendations and Level of Evidence categories. Additionally, the 2015 guidelines reflect a major change in paradigm for the diagnosis of RF, with the incorporation of echocardiographic parameters for the diagnosis of carditis. This change was based on over 25 studies showing the utility of echocardiography with Doppler in the diagnosis of subclinical carditis. In the 2015 revision, a diagnosis of recurrent RF may be made with 2 major, 1 major and 2 minor, or 3 minor criteria alone in the setting of preceding GAS pharyngitis. However, this revision did not address the echocardiographic diagnosis of carditis in the context of recurrent RF in the presence of chronic RHD.5 In this patient, 2 major and 3 minor Jones criteria were satisfied (clinical carditis, polyarthritis, fever and elevated acute phase reactants) in the presence of positive throat cultures and elevated streptococcal antibody titers. Prolongation of the PR interval was not assessed in the setting of atrial fibrillation. Primary prevention of RF is accomplished by identification and treatment of GAS pharyngitis. Penicillin remains the cornerstone of treatment for GAS pharyngitis, with 100% of GAS demonstrating in vitro susceptibility to all beta-lactam agents. Current guidelines from the American Heart Association recommend the following regimens for the treatment of GAS pharyngitis for primary prevention of acute RF: oral penicillin V at a dose of 500 mg 2 to 3 times daily for 10 days, amoxicillin 50 mg/kg once daily for 10 days or intramuscular benzathine penicillin G 1.2 million units once. Patients with penicillin allergy may be treated with narrow spectrum cephalosporins, clindamycin, azithromycin or clarithromycin.3 Antimicrobial treatment for acute RF mirrors that for GAS pharyngitis, regardless of the presence of pharyngitis at the time of diagnosis of acute RF. HF management, with attention to valvular heart disease, is necessary in patients with carditis. Aspirin remains the mainstay of anti-inflammatory therapy in practice. The evidence for the efficacy of antiinflammatory medications in acute RF is antiquated, and data on the efficacy of recently developed anti-inflammatory medications are necessary.6 In this patient, choline magnesium trisalicylate was chosen for anti-inflammatory effect. This has a decreased effect on platelet inhibition in comparison with
The American Journal of the Medical Sciences
Volume 350, Number 4, October 2015
Case-Letter
TABLE 1. Guidelines for the diagnosis of acute RF (Jones criteria): a comparison of the 1992 and 2015 criteria 1992 Criteria 2015 Criteria Diagnosis
2 major, or 1 major and 2 minor
Major criteria
Carditis Polyarthritis Chorea Erythema marginatum Subcutaneous nodules Arthralgia Fevers Elevated acute phase reactants Prolonged PR interval
Minor criteria
Initial: 2 major, or 1 major and 2 minor Recurrence: 2 major or 1 major and 2 minor or 3 minor Carditis (clinical and/or subclinical diagnosed by echocardiography) Polyarthritis (monoarthritis or polyarthralgia in moderate, high-risk populations) Chorea Erythema marginatum Subcutaneous nodules Polyarthralgia (monoarthralgia in moderate, high-risk populations) Fevers Elevated acute phase reactants Prolonged PR interval
Evidence of preceding group A streptococcal pharyngitis is required to apply these criteria: elevated or rising streptococcal antibodies, a positive throat culture for GAS or a positive group A streptococcal carbohydrate antigen test in a child with a high pretest probability of streptococcal pharyngitis.4,5
acetylated salicylates. As this patient required long-term anticoagulation for his mechanical aortic valve, this medication was chosen to reduce his excess bleeding risk. Secondary prevention of RF is the long-term use of antibiotic therapy in patients with a previous episode of acute RF to prevent recurrence. Recurrent episodes of RF may cause worsening of the severity of RHD. The 2009 American Heart Association Guidelines on Rheumatic Fever Treatment and Prevention recommendations for secondary prevention are either 250 mg of oral penicillin V twice daily or 1.2 million units of intramuscular penicillin G every 4 weeks, the latter of which is the most efficacious regimen.3,7 Most failures of prophylaxis occur due to noncompliance, therefore, individual patient factors should be considered when deciding between oral and intramuscular injection regimens.3 There is a potential for bleeding from intramuscular injections in the setting of long-term anticoagulation, which many patients receive as a result of valve prostheses for RHD. The appropriate duration of secondary prophylaxis with antimicrobials depends on a patient’s individual risk of recurrence, which increases with multiple previous episodes of recurrences and decreases as the interval lengthens since the last recurrence. For patients with persistent valvular disease, prophylaxis is recommended by the American Heart Association for 10 years after the last episode of acute RF or until 40 years of age (whichever is longer), with potentially lifelong prophylaxis for high-risk patients. Prophylaxis should continue even after valve surgery, including prosthetic valve replacement.3 Those in close contact with children, health care workers, military personnel, economically disadvantaged populations and those living in crowded or unsanitary conditions are all at increased risk of recurrence of RF because they are at higher risk of acquiring GAS upper respiratory tract infections. In addition, all family members of affected patients should be screened and treated for streptococcal infections when symptomatic to prevent reinfection of the patient with GAS.3 Appropriate antibiotic prophylaxis in this patient may have prevented a recurrence of RF. In summary, this case illustrates the continued presence of acute RF in the United States, and the need for its recognition by internists and cardiologists, when it presents as HF. Antibiotic therapy and prophylaxis for this disease is effective, low cost and often prevents progression of the disease. For this reason, it is particularly important to apply the clinical and
Copyright Ó 2015 by the Southern Society for Clinical Investigation.
laboratory tests that encompass the Jones criteria to make this diagnosis and prevent the morbidity and mortality associated with untreated RF.
Loheetha Ragupathi, MD Justin Herman, MD Paul Mather, MD Jefferson Heart Institute, Thomas Jefferson University Hospital Philadelphia, PA E-mail: [email protected] The authors have no financial or other conflicts of interest to disclose. REFERENCES 1. Wee AS, Goodwin JF. Acute rheumatic fever and carditis in older adults. Lancet 1966;2:239–42. 2. Seckeler MD, Hoke TR. The worldwide epidemiology of acute rheumatic fever and rheumatic heart disease. Clin Epidemiol 2011; 3:67–84. 3. Gerber MA, Baltimore RS, Eaton CB, et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation 2009;119:1541–51. 4. Guidelines for the diagnosis of rheumatic fever. Jones Criteria, 1992 update. Special Writing Group of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young of the American Heart Association. JAMA 1992; 268:2069–73. 5. Gewitz MH, Baltimore RS, Tani LY, et al. Revision of the jones criteria for the diagnosis of acute rheumatic Fever in the era of Doppler echocardiography: a scientific statement from the american heart association. Circulation 2015;131:1806–18. 6. Cilliers A, Manyemba J, Adler AJ, et al. Anti-inflammatory treatment for carditis in acute rheumatic fever. Cochrane Database Syst Rev 2012; 6:CD003176. 7. Manyemba J, Mayosi BM. Penicillin for secondary prevention of rheumatic fever. Cochrane Database Syst Rev. 2002;(3):CD002227.
343