Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Diagnosis of rheumatic fever: Beyond Jones criteria molecular diagnosis of streptococcal infection is being debated in the literature. In this review all the issues pertaining to the diagnosis of rheumatic fever beyond Jones’ criteria are presented. Diagnosis of rheumatic fever: Beyond Jones criteria streptococcal infection is enough for the diagnosis of recurrence. Practically, the two most important physical findings that confirm the diagnosis of recurrence are pericardial rub and subcutaneous nodules. However, these manifestations are extremely uncommon. ■ Diagnosis of recurrence of rheumatic fever Primary episode of RF S Ramakrishnan, MD, DM Associate Professor, Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India Abstract Rheumatic fever (RF) and rheumatic heart disease (RHD) is still prevalent in many parts of the world. Jones’ criteria to diagnose RF are extremely useful, yet there are some important limitations. Modified Jones criteria cannot be used for the diagnosis of recurrences of rheumatic fever for which the WHO criteria may be better. Whether echocardiography should be routinely used for the diagnosis of RF is debated in the literature. Studies have shown that the prevalence of subclinical carditis in acute RF is high, but in the absence of long term follow-up data the outcome remains undefined. Echocardiograpic criteria should be part of Jones’ criteria at least for areas with a higher prevalence of RF and RHD. Further, inclusion of monoarthritis, polyarthalgia and better definition of fever and biochemical markers is suggested by some national guidelines on rheumatic fever. More outcome based studies are needed to evaluate changes in the diagnostic criteria for rheumatic fever. Key Words Rheumatic fever ● Echocardiography ● Diagnosis ● Jones criteria ● ■ Introduction Rheumatic heart disease continues unabated in many parts of the globe. Classical rheumatic fever presenting with polyarthritis, chorea or advanced heart failure is still encountered in many parts of India.1 Rheumatic fever remains one of the diseases whose diagnosis was based on a set of validated criteria for more than half a century. In fact, the first set of diagnostic criteria, the Jones’ criteria were introduced in 1944.2 Since then, the criteria have undergone major changes. The last set of modified criteria by the American Heart Association (AHA) was published 3 in 1992. The importance of a preceding streptococcal infection has been emphasized in subsequent revisions of the Jones’ criteria, and has been designated as an essential criterion. The diagnosis of a recent group A streptococcal infection may be made using a positive throat culture, rapid streptococcal antigen test, elevated or raising streptococcal antibody test. The major manifestations included in modified Jones’ criteria include carditis, polyarthritis, chorea, erythema marginatum and subcutaneous nodules. The minor manifestations include fever, arthralgia, elevated acute phase reactants – erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and prolonged PR interval on the electrocardiogram. Acute rheumatic fever is diagnosed if two major, or one major with two minor criteria are fulfilled with an evidence of recent streptococcal infection.3 Jones’ criteria are extremely useful in the diagnosis of rheumatic fever, yet there are some important limitations. Modified Jones’ criteria cannot be used for the diagnosis of recurrences of rheumatic fever. Whether the use of echocardiography significantly aids the diagnosis of rheumatic fever is an important practical issue. Further, need to modify the criteria to include monoarthritis, polyarthalgia, fever (>37.5oC), biochemical markers and Received: 12-08-12; Revised: 30-08-12; Accepted: 04-09-12 Disclosures: This article has not received any funding and has no vested commercial interest Acknowledgements: None 262 J. Preventive Cardiology Vol. 2 ■ No. 2 ■ November 2012 ■ The majority of rheumatic fever cases are concentrated in developing countries, where recurrences are common. In fact, in the tertiary care centres the majority of active rheumatic fever patients are due to recurrence of disease. Recurrence of rheumatic fever may be diagnosed using the 2002–2003 WHO criteria (Table 1) for the diagnosis of 4 rheumatic fever and rheumatic heart disease. Table 1: 2002–2003 WHO criteria for the diagnosis of rheumatic fever4 • Two major or one major and two minor manifestations plus evidence of a preceding group A streptococcal infection Recurrent attack of RF in a patient without established rheumatic heart disease • Two major or one major and two minor manifestations plus evidence of a preceding group A streptococcal infection Major manifestations Recurrent attack of RF in a patient with established rheumatic heart disease Carditis Polyarthritis • Chorea Two minor manifestations plus evidence of a preceding group A streptococcal infection Erythema marginatum Rheumatic chorea Subcutaneous nodules Minor manifestations • Clinical: Fever, polyarthralgia Laboratory: Elevated acute phase reactants (erythrocyte sedimentation rate or leukocyte count), electrocardiogram: prolonged P-R interval Supporting evidence of a preceding streptococcal infection within the last 45 days — Elevated or rising antistreptolysin-O or other streptococcal antibody Positive throat culture Rapid antigen test for group A streptococci Recent scarlet fever Recurrent attack of rheumatic fever in a patient without established rheumatic heart disease is diagnosed, if they satisfy two major or one major and two minor criteria along with an evidence of a preceding group A streptococcal infection. It is similar to the criteria for diagnosing a first attack. Recurrent attack of rheumatic fever in a patient with established rheumatic heart disease can be made, if they fulfil 2 minor manifestations plus an evidence of a preceding group A streptococcal infection. Thus, in someone with an established rheumatic heart disease, arthralgia, fever and evidence of preceding group A J. Preventive Cardiology Vol. 2 ■ No. 2 ■ November 2012 ■ Other major manifestations or evidence of Insidious onset rheumatic carditis; group A streptococcal infection not required ■ Echocardiography in the diagnosis of rheumatic fever Valvulitis is the most important manifestation of acute carditis in rheumatic fever and echocardiography is best suited to confirm, and to assess the severity of valvular involvement in rheumatic fever. Echocardiography gives excellent details of the structural abnormalities, and the Doppler allows the evaluation of functional abnormalities. Yet, echocardiography has not been included as a criterion 5 in the diagnosis of rheumatic fever. A significant number of patients with suspected acute rheumatic carditis have no clinical murmurs but have documented valve disease and regurgitation on echocardiography. The reported prevalence of subclinical carditis in rheumatic fever ranges from 0–53%.5 A meta-analysis6 of nearly 20 studies that included 1700 rheumatic fever patients reported a weighted pooled prevalence of subclinical carditis of 16.8% (95% confidence interval [CI] 11.9-21.6). With the application of the World Health Organization echocardiographic criteria, the prevalence of subclinical carditis increased to 18.1% (95% CI 11.1-25.2).6 The prevalence of persistence or deterioration of subclinical 263 Diagnosis of rheumatic fever: Beyond Jones criteria molecular diagnosis of streptococcal infection is being debated in the literature. In this review all the issues pertaining to the diagnosis of rheumatic fever beyond Jones’ criteria are presented. Diagnosis of rheumatic fever: Beyond Jones criteria streptococcal infection is enough for the diagnosis of recurrence. Practically, the two most important physical findings that confirm the diagnosis of recurrence are pericardial rub and subcutaneous nodules. However, these manifestations are extremely uncommon. ■ Diagnosis of recurrence of rheumatic fever Primary episode of RF S Ramakrishnan, MD, DM Associate Professor, Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India Abstract Rheumatic fever (RF) and rheumatic heart disease (RHD) is still prevalent in many parts of the world. Jones’ criteria to diagnose RF are extremely useful, yet there are some important limitations. Modified Jones criteria cannot be used for the diagnosis of recurrences of rheumatic fever for which the WHO criteria may be better. Whether echocardiography should be routinely used for the diagnosis of RF is debated in the literature. Studies have shown that the prevalence of subclinical carditis in acute RF is high, but in the absence of long term follow-up data the outcome remains undefined. Echocardiograpic criteria should be part of Jones’ criteria at least for areas with a higher prevalence of RF and RHD. Further, inclusion of monoarthritis, polyarthalgia and better definition of fever and biochemical markers is suggested by some national guidelines on rheumatic fever. More outcome based studies are needed to evaluate changes in the diagnostic criteria for rheumatic fever. Key Words Rheumatic fever ● Echocardiography ● Diagnosis ● Jones criteria ● ■ Introduction Rheumatic heart disease continues unabated in many parts of the globe. Classical rheumatic fever presenting with polyarthritis, chorea or advanced heart failure is still encountered in many parts of India.1 Rheumatic fever remains one of the diseases whose diagnosis was based on a set of validated criteria for more than half a century. In fact, the first set of diagnostic criteria, the Jones’ criteria were introduced in 1944.2 Since then, the criteria have undergone major changes. The last set of modified criteria by the American Heart Association (AHA) was published 3 in 1992. The importance of a preceding streptococcal infection has been emphasized in subsequent revisions of the Jones’ criteria, and has been designated as an essential criterion. The diagnosis of a recent group A streptococcal infection may be made using a positive throat culture, rapid streptococcal antigen test, elevated or raising streptococcal antibody test. The major manifestations included in modified Jones’ criteria include carditis, polyarthritis, chorea, erythema marginatum and subcutaneous nodules. The minor manifestations include fever, arthralgia, elevated acute phase reactants – erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and prolonged PR interval on the electrocardiogram. Acute rheumatic fever is diagnosed if two major, or one major with two minor criteria are fulfilled with an evidence of recent streptococcal infection.3 Jones’ criteria are extremely useful in the diagnosis of rheumatic fever, yet there are some important limitations. Modified Jones’ criteria cannot be used for the diagnosis of recurrences of rheumatic fever. Whether the use of echocardiography significantly aids the diagnosis of rheumatic fever is an important practical issue. Further, need to modify the criteria to include monoarthritis, polyarthalgia, fever (>37.5oC), biochemical markers and Received: 12-08-12; Revised: 30-08-12; Accepted: 04-09-12 Disclosures: This article has not received any funding and has no vested commercial interest Acknowledgements: None 262 J. Preventive Cardiology Vol. 2 ■ No. 2 ■ November 2012 ■ The majority of rheumatic fever cases are concentrated in developing countries, where recurrences are common. In fact, in the tertiary care centres the majority of active rheumatic fever patients are due to recurrence of disease. Recurrence of rheumatic fever may be diagnosed using the 2002–2003 WHO criteria (Table 1) for the diagnosis of 4 rheumatic fever and rheumatic heart disease. Table 1: 2002–2003 WHO criteria for the diagnosis of rheumatic fever4 • Two major or one major and two minor manifestations plus evidence of a preceding group A streptococcal infection Recurrent attack of RF in a patient without established rheumatic heart disease • Two major or one major and two minor manifestations plus evidence of a preceding group A streptococcal infection Major manifestations Recurrent attack of RF in a patient with established rheumatic heart disease Carditis Polyarthritis • Chorea Two minor manifestations plus evidence of a preceding group A streptococcal infection Erythema marginatum Rheumatic chorea Subcutaneous nodules Minor manifestations • Clinical: Fever, polyarthralgia Laboratory: Elevated acute phase reactants (erythrocyte sedimentation rate or leukocyte count), electrocardiogram: prolonged P-R interval Supporting evidence of a preceding streptococcal infection within the last 45 days — Elevated or rising antistreptolysin-O or other streptococcal antibody Positive throat culture Rapid antigen test for group A streptococci Recent scarlet fever Recurrent attack of rheumatic fever in a patient without established rheumatic heart disease is diagnosed, if they satisfy two major or one major and two minor criteria along with an evidence of a preceding group A streptococcal infection. It is similar to the criteria for diagnosing a first attack. Recurrent attack of rheumatic fever in a patient with established rheumatic heart disease can be made, if they fulfil 2 minor manifestations plus an evidence of a preceding group A streptococcal infection. Thus, in someone with an established rheumatic heart disease, arthralgia, fever and evidence of preceding group A J. Preventive Cardiology Vol. 2 ■ No. 2 ■ November 2012 ■ Other major manifestations or evidence of Insidious onset rheumatic carditis; group A streptococcal infection not required ■ Echocardiography in the diagnosis of rheumatic fever Valvulitis is the most important manifestation of acute carditis in rheumatic fever and echocardiography is best suited to confirm, and to assess the severity of valvular involvement in rheumatic fever. Echocardiography gives excellent details of the structural abnormalities, and the Doppler allows the evaluation of functional abnormalities. Yet, echocardiography has not been included as a criterion 5 in the diagnosis of rheumatic fever. A significant number of patients with suspected acute rheumatic carditis have no clinical murmurs but have documented valve disease and regurgitation on echocardiography. The reported prevalence of subclinical carditis in rheumatic fever ranges from 0–53%.5 A meta-analysis6 of nearly 20 studies that included 1700 rheumatic fever patients reported a weighted pooled prevalence of subclinical carditis of 16.8% (95% confidence interval [CI] 11.9-21.6). With the application of the World Health Organization echocardiographic criteria, the prevalence of subclinical carditis increased to 18.1% (95% CI 11.1-25.2).6 The prevalence of persistence or deterioration of subclinical 263 Ramakrishnan S carditis at 3–23 months after diagnosis is 44.7% (95% CI 6 19.3-70.2). The echocardiographic changes during an episode of rheumatic fever are summarized (Table 2). Pathological regurgitation is better defined by the recent World Heart 7 Federation (WHF) guidelines. For echocardiography to be included as a diagnostic criterion, three things are necessary.5 1. The incidence of subclinical carditis should be significant 2. The outcome of subclinical carditis should not be benign 3. Treatment or prophylaxis should alter the outcome; even though subclinical carditis has been shown to be relatively frequent, the natural history and outcome is not well established Table 2: Echocardiographic features of rheumatic carditis (modified from ref. no. 5) Valvular regurgitation Pathological MR (all four Doppler criteria must be met)7 1. Seen in 2 views 2. In at least one view jet length 2 cm 3. Peak velocity ³ 3 m/sec 4. Pan-systolic jet in at least one envelope Pathological AR (all four Doppler criteria must be met)7 1. Seen in 2 views 2. In at least one view jet length ³ 1 cm 3. Peak velocity ³ 3 m/sec 4. Pan-diastolic jet in at least one envelope Leaflet 1. Prolapse 2. Coaptation failure 3. Thickening (> 4 mm) 4. Reduced mobility 5. Nodules Annular dilatation Chordal elongation/rupture Increased echogenicity of subvalvular apparatus Pericardial effusion Ventricular dilatation and dysfunction (almost always with significant regurgitation) 264 Echocardiography is more sensitive and accurate in identifying valvular involvement in acute rheumatic fever. Clinical skills are declining among the physicians. Echocardiographic population screening studies have confirmed that even moderate regurgitations are, at times, not audible.8 During an episode of acute rheumatic fever, murmurs may be missed even by experienced clinicians because of associated tachycardia. In the acute phase, even moderate mitral or aortic regurgitation may not be clinically audible because of hemodynamic reasons. A few studies have suggested that subclinical carditis as a major Jones’ criterion influences the diagnosis of acute rheumatic fever in 11–16% of patients only.9,10 Echocardiography is essential and useful in ruling out infective endocarditis in patients of established rheumatic heart disease. Those who oppose the inclusion of echocardiography as a criterion for the diagnosis of rheumatic fever argue that diagnosis of subclinical carditis does not alter the treatment, prognosis or long term follow-up strategy. Since, most of the patients with subclinical carditis are likely to be asymptomatic or mildly symptomatic; they need not be treated with steroids. The long term outcome of subclinical carditis is not known. However, studies of earlier era studying the long term follow-up have most likely included patients with subclinical carditis in the nocarditis group, which is shown to have a relatively better prognosis. 11 Physiological regurgitation and regurgitation due to fever and anemia are more common. With the routine use of echocardiography such patients may be wrongly labelled as rheumatic fever. Over-diagnosis will result in the individual receiving penicillin injections unnecessarily, every 3 weekly, for a minimum of 10 years. The availability of echocardiography is limited in areas where rheumatic fever is highly prevalent. For all these reasons, it is still argued that echocardiography should not be included as a 5,12 criterion for the diagnosis of rheumatic carditis. However, subclinical carditis patients need secondary prophylaxis. According to the major guidelines, the duration of prophylaxis is determined by the presence or 13 absence of carditis. Hence, it may be wiser to perform an echocardiography for the presence or absence of carditis before stopping prophylaxis in countries with limited resources.5 For diagnosing subclinical carditis by echocardiography, abnormal morphology in the valve along with a functional abnormality should be shown and the regurgitation should be inaudible. The pathological changes due to rheumatic fever in the valve apparatus may include leaflet prolapse, coaptation failure, thickening of the leaflets, reduced mobility and nodules. Functional abnormality commonly J. Preventive Cardiology Vol. 2 ■ No. 2 ■ November 2012 ■ Diagnosis of rheumatic fever: Beyond Jones criteria ■ Investigations as criteria includes mitral and/or aortic regurgitation. 14 The most recent rheumatic fever Australian and New 15 Zealand guidelines have accepted echocardiographic subclinical carditis as a major criterion among the high prevalence regions. They have recommended that all patients with suspected or definite RF should undergo echocardiography to identify evidence of carditis and assess the severity of carditis. With hand held and mobile forms of echocardiography, it may be made available in remote areas of the world. Population based studies in India suggest an unacceptably high prevalence of rheumatic heart disease of 20.4/1000 in asymptomatic school children screened with echocardiography.8 The only way to reduce the burden is to identify cases correctly and to institute secondary prophylaxis, which becomes mandatory. Hence, in India we need to incorporate subclinical carditis as a major criterion as any other region with high prevalence of rheumatic fever, where the consequences of under diagnosis is greater than overdiagnosis. ■ Other clinical variables as criteria It is increasingly being recognized that polyarthralgia and monoarthritis are common in patients with acute rheumatic fever, especially during recurrences. A few small studies from India have suggested that there was no difference between patients presenting with polyarthritis or polyarthralgia.16 However, inclusion of polyarthralgia as a major criterion will reduce the specificity of the criteria. In a study of aboriginal Australian population, among 216 patients with possible rheumatic fever 35% had monoarthritis and 13% would have satisfied the criteria for 17 diagnosis if monoarthritis were a major criterion. More importantly half of them developed rheumatic heart disease later. Monoarthritis may be more important in the diagnosis of a recurrent episode and its use to diagnose a first episode will make the criteria nonspecific. Further, a few studies have shown that nearly one forth of patients have atypical joint manifestations and nearly half of them 18 have evidence of clinical carditis. Aseptic monoarthritis with history of NSAID use, after exclusion of other potential causes, has been accepted as a major criterion and polyarthralgia as a minor criterion by recent guidelines.14,15 Definition of fever for the diagnosis of rheumatic fever has also been modified. Recent Australian guidelines14 have included fever as a minor manifestation based on a reliable history (in the absence of documented temperature), if antiinflammatory medication has already been administered apart from documented fever with a oral, tympanic or rectal temperature greater than 38°C on admission. J. Preventive Cardiology Vol. 2 ■ No. 2 ■ November 2012 ■ For acute phase reactants, an elevated serum CRP level of 14 ³ 30 mg/L or ESR of ³ 30 mm/h is required. Evidence of recent streptococcal infection is essential for the diagnosis of rheumatic fever. Antistreptolysin-O (ASO) titre is most widely used. The antideoxyribonuclease B (anti-DNase B) titres improve specificity. The reference range for these antibody titres is shown to vary with age and background 4,14 rate of streptococcal infections. Previous data suggest that a rise in the ASO titre occurs in 75–80% of untreated GAS pharyngeal infections, and that the addition of antiDNase B titre increases the sensitivity of testing to up to 19 96%. The serum ASO titre usually rises within 1–2 weeks, and reaches a maximum at about 3–6 weeks after infection, while the serum anti-DNase B titre can take up to 6–8 weeks to reach a maximum.20 ASO titre starts to fall in 6–8 weeks, and the anti-DNase B titre in 3 months after infection.21 In the absence of re-infection, the ASO titre usually approaches pre-infection levels after 6–12 months, whereas the anti-DNase B titre tends to remain elevated for a longer period.21 Since, there is a significant and variable latent period from infection to clinical manifestation, patients are likely to present at a variable time after the initial infection. Hence, a serial ASO testing is not recommended for the initial diagnosis. Serial testing could be important in the follow-up of patients treated with aspirin/steroid. If the initial titre is below the upper limit of normal for age, testing may be repeated 10–14 days later.14 The upper limit of normal of ASO is considered as 240 Todd units in adults and 320 Todd units in children over 22 5-years of age. However, normal reference values are likely to vary among various geographical locations and there are no recent studies from India. Other national guidelines have suggested age specific cut-off for ASO and Anti-DNAase, 14,15 which may have the same fallacy. A positive rapid antigen test or throat culture is insufficient, as up to 50% of those with a positive throat culture could be carriers.15 Conclusion ■ To conclude, the prevalence of subclinical carditis in acute rheumatic fever is high, but in the absence of long term follow-up data the outcome remains undefined. Echocardiograpic criteria should be part of Jones’ criteria at least for areas with a higher prevalence of rheumatic fever and rheumatic heart disease. Similarly, variation in joint involvement like polyarthralgia or monoarthritis should be included. More outcome based studies are needed to evaluate such changes to diagnostic criteria for rheumatic fever. 265 Ramakrishnan S carditis at 3–23 months after diagnosis is 44.7% (95% CI 6 19.3-70.2). The echocardiographic changes during an episode of rheumatic fever are summarized (Table 2). Pathological regurgitation is better defined by the recent World Heart 7 Federation (WHF) guidelines. For echocardiography to be included as a diagnostic criterion, three things are necessary.5 1. The incidence of subclinical carditis should be significant 2. The outcome of subclinical carditis should not be benign 3. Treatment or prophylaxis should alter the outcome; even though subclinical carditis has been shown to be relatively frequent, the natural history and outcome is not well established Table 2: Echocardiographic features of rheumatic carditis (modified from ref. no. 5) Valvular regurgitation Pathological MR (all four Doppler criteria must be met)7 1. Seen in 2 views 2. In at least one view jet length 2 cm 3. Peak velocity ³ 3 m/sec 4. Pan-systolic jet in at least one envelope Pathological AR (all four Doppler criteria must be met)7 1. Seen in 2 views 2. In at least one view jet length ³ 1 cm 3. Peak velocity ³ 3 m/sec 4. Pan-diastolic jet in at least one envelope Leaflet 1. Prolapse 2. Coaptation failure 3. Thickening (> 4 mm) 4. Reduced mobility 5. Nodules Annular dilatation Chordal elongation/rupture Increased echogenicity of subvalvular apparatus Pericardial effusion Ventricular dilatation and dysfunction (almost always with significant regurgitation) 264 Echocardiography is more sensitive and accurate in identifying valvular involvement in acute rheumatic fever. Clinical skills are declining among the physicians. Echocardiographic population screening studies have confirmed that even moderate regurgitations are, at times, not audible.8 During an episode of acute rheumatic fever, murmurs may be missed even by experienced clinicians because of associated tachycardia. In the acute phase, even moderate mitral or aortic regurgitation may not be clinically audible because of hemodynamic reasons. A few studies have suggested that subclinical carditis as a major Jones’ criterion influences the diagnosis of acute rheumatic fever in 11–16% of patients only.9,10 Echocardiography is essential and useful in ruling out infective endocarditis in patients of established rheumatic heart disease. Those who oppose the inclusion of echocardiography as a criterion for the diagnosis of rheumatic fever argue that diagnosis of subclinical carditis does not alter the treatment, prognosis or long term follow-up strategy. Since, most of the patients with subclinical carditis are likely to be asymptomatic or mildly symptomatic; they need not be treated with steroids. The long term outcome of subclinical carditis is not known. However, studies of earlier era studying the long term follow-up have most likely included patients with subclinical carditis in the nocarditis group, which is shown to have a relatively better prognosis. 11 Physiological regurgitation and regurgitation due to fever and anemia are more common. With the routine use of echocardiography such patients may be wrongly labelled as rheumatic fever. Over-diagnosis will result in the individual receiving penicillin injections unnecessarily, every 3 weekly, for a minimum of 10 years. The availability of echocardiography is limited in areas where rheumatic fever is highly prevalent. For all these reasons, it is still argued that echocardiography should not be included as a 5,12 criterion for the diagnosis of rheumatic carditis. However, subclinical carditis patients need secondary prophylaxis. According to the major guidelines, the duration of prophylaxis is determined by the presence or 13 absence of carditis. Hence, it may be wiser to perform an echocardiography for the presence or absence of carditis before stopping prophylaxis in countries with limited resources.5 For diagnosing subclinical carditis by echocardiography, abnormal morphology in the valve along with a functional abnormality should be shown and the regurgitation should be inaudible. The pathological changes due to rheumatic fever in the valve apparatus may include leaflet prolapse, coaptation failure, thickening of the leaflets, reduced mobility and nodules. Functional abnormality commonly J. Preventive Cardiology Vol. 2 ■ No. 2 ■ November 2012 ■ Diagnosis of rheumatic fever: Beyond Jones criteria ■ Investigations as criteria includes mitral and/or aortic regurgitation. 14 The most recent rheumatic fever Australian and New 15 Zealand guidelines have accepted echocardiographic subclinical carditis as a major criterion among the high prevalence regions. They have recommended that all patients with suspected or definite RF should undergo echocardiography to identify evidence of carditis and assess the severity of carditis. With hand held and mobile forms of echocardiography, it may be made available in remote areas of the world. Population based studies in India suggest an unacceptably high prevalence of rheumatic heart disease of 20.4/1000 in asymptomatic school children screened with echocardiography.8 The only way to reduce the burden is to identify cases correctly and to institute secondary prophylaxis, which becomes mandatory. Hence, in India we need to incorporate subclinical carditis as a major criterion as any other region with high prevalence of rheumatic fever, where the consequences of under diagnosis is greater than overdiagnosis. ■ Other clinical variables as criteria It is increasingly being recognized that polyarthralgia and monoarthritis are common in patients with acute rheumatic fever, especially during recurrences. A few small studies from India have suggested that there was no difference between patients presenting with polyarthritis or polyarthralgia.16 However, inclusion of polyarthralgia as a major criterion will reduce the specificity of the criteria. In a study of aboriginal Australian population, among 216 patients with possible rheumatic fever 35% had monoarthritis and 13% would have satisfied the criteria for 17 diagnosis if monoarthritis were a major criterion. More importantly half of them developed rheumatic heart disease later. Monoarthritis may be more important in the diagnosis of a recurrent episode and its use to diagnose a first episode will make the criteria nonspecific. Further, a few studies have shown that nearly one forth of patients have atypical joint manifestations and nearly half of them 18 have evidence of clinical carditis. Aseptic monoarthritis with history of NSAID use, after exclusion of other potential causes, has been accepted as a major criterion and polyarthralgia as a minor criterion by recent guidelines.14,15 Definition of fever for the diagnosis of rheumatic fever has also been modified. Recent Australian guidelines14 have included fever as a minor manifestation based on a reliable history (in the absence of documented temperature), if antiinflammatory medication has already been administered apart from documented fever with a oral, tympanic or rectal temperature greater than 38°C on admission. J. Preventive Cardiology Vol. 2 ■ No. 2 ■ November 2012 ■ For acute phase reactants, an elevated serum CRP level of 14 ³ 30 mg/L or ESR of ³ 30 mm/h is required. Evidence of recent streptococcal infection is essential for the diagnosis of rheumatic fever. Antistreptolysin-O (ASO) titre is most widely used. The antideoxyribonuclease B (anti-DNase B) titres improve specificity. The reference range for these antibody titres is shown to vary with age and background 4,14 rate of streptococcal infections. Previous data suggest that a rise in the ASO titre occurs in 75–80% of untreated GAS pharyngeal infections, and that the addition of antiDNase B titre increases the sensitivity of testing to up to 19 96%. The serum ASO titre usually rises within 1–2 weeks, and reaches a maximum at about 3–6 weeks after infection, while the serum anti-DNase B titre can take up to 6–8 weeks to reach a maximum.20 ASO titre starts to fall in 6–8 weeks, and the anti-DNase B titre in 3 months after infection.21 In the absence of re-infection, the ASO titre usually approaches pre-infection levels after 6–12 months, whereas the anti-DNase B titre tends to remain elevated for a longer period.21 Since, there is a significant and variable latent period from infection to clinical manifestation, patients are likely to present at a variable time after the initial infection. Hence, a serial ASO testing is not recommended for the initial diagnosis. Serial testing could be important in the follow-up of patients treated with aspirin/steroid. If the initial titre is below the upper limit of normal for age, testing may be repeated 10–14 days later.14 The upper limit of normal of ASO is considered as 240 Todd units in adults and 320 Todd units in children over 22 5-years of age. However, normal reference values are likely to vary among various geographical locations and there are no recent studies from India. Other national guidelines have suggested age specific cut-off for ASO and Anti-DNAase, 14,15 which may have the same fallacy. A positive rapid antigen test or throat culture is insufficient, as up to 50% of those with a positive throat culture could be carriers.15 Conclusion ■ To conclude, the prevalence of subclinical carditis in acute rheumatic fever is high, but in the absence of long term follow-up data the outcome remains undefined. Echocardiograpic criteria should be part of Jones’ criteria at least for areas with a higher prevalence of rheumatic fever and rheumatic heart disease. Similarly, variation in joint involvement like polyarthralgia or monoarthritis should be included. More outcome based studies are needed to evaluate such changes to diagnostic criteria for rheumatic fever. 265 Ramakrishnan S ■ References 1. Ramakrishnan S, Kothari SS, Juneja R, Bhargava B, Saxena A, Bahl VK. Prevalence of rheumatic heart disease: has it declined in India? Natl Med J India 2009;22(2):72–4. 2. Jones T. Diagnosis of rheumatic fever. JAMA 1944;126:481–484. 3. Special Writing Group of the Committee on Rheumatic Fever E and Kawasaki Disease of the Council on Cardiovascular Disease in the Young of the American Heart Association, Guidelines for the diagnosis of rheumatic fever. Jones Criteria, 1992 update. JAMA 1992;268(15):2069–73. 4. WHO Expert Consultation on Rheumatic Fever and Rheumatic Heart Disease (2001: Geneva, Switzerland). Rheumatic fever and rheumatic heart disease: Report of a WHO Expert Consultation. WHO Technical Report Series, vol. 923. Geneva: World Health Organization; 2004. 5. Ramakrishnan S. Echocardiography in acute rheumatic fever. Ann Pediatr Cardiol 2009;2(1):61–4. 6. Tubridy-Clark M, Carapetis JR. Subclinical carditis in rheumatic fever: A systematic review. Int J Cardiol 2007;119:54–8. 7. Reményi B, Wilson N, Steer A, Ferreira B, Kado J, Kumar K, et al. World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease—an evidence-based guideline. Nat Rev Cardiol 2012;9(5):297–309. 8. Saxena A, Ramakrishnan S, Roy A, Seth S, Krishnan A, Misra P, et al. Prevalence and outcome of subclinical rheumatic heart disease in India: the RHEUMATIC (Rheumatic Heart Echo Utilisation and Monitoring Actuarial Trends in Indian Children) study. Heart 2011;97(24):2018–22. 9. Vijayalakshmi IB, Vishnuprabhu RO, Chitra N, Rajasri R, Anuradha TV. The efficacy of echocardiographic criterions for the diagnosis of carditis in acute rheumatic fever. Cardiol Young 2008;18:586–92. 10. Wilson NJ, Morreau J, Voss L, Stewart J, Lennon D. The influence of subclinical carditis on the diagnosis of acute rheumatic fever. Heart Lung Circ 2005;14:S1117. 11. Brand A, Dollberg S, Keren A. The prevalence of valvular regurgitation in children with structurally normal hearts: A color Doppler echocardiographic study. Am Heart J 1992;123:177–80. 12. Saxena A. Diagnosis of rheumatic fever: Current status of Jones criteria and role of echocardiography. Indian J Pediatr 2000;67:S11–4. 13. Gerber MA, Baltimore RS, Eaton CB, Gewitz M, Rowley AH, Shulman ST, 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. 14. RHD Australia (ARF/RHD writing group), National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand. Australian guideline for prevention, diagnosis and management of acute rheumatic fever and rheumatic heart disease (2nd edition) 2012. 15. Atatoa-Carr P, Lennon D, Wilson N. New Zealand Rheumatic Fever Guidelines Writing Group. Rheumatic fever diagnosis, management, and secondary prevention: A New Zealand guideline. N Z Med J 2008;121:59–69. 16. Cherian G. Acute rheumatic fever—the Jones criteria: a review and a case for polyarthralgia. J Assoc Physicians India. 1979;27(5):453–7. 17. Carapetis JR, Currie BJ. Rheumatic fever in a high incidence population: the importance of monoarthritis and low grade fever. Arch Dis Child 2001;85(3):223–7. 18. Nair PM, Philip E, Bahuleyan CG, Thomas M, Shanmugham JS, Suguna Bai NS. The first attack of acute rheumatic fever in childhood—clinical and laboratory profile. Indian Pediatr 1990;27:241–46. 19. Markowitz M, Gordis L. Rheumatic fever, in Major problems in clinical pediatrics, vol 2, A. Schaffer, Editor. 1972, WB Saunders: Philadelphia. 20. Kaplan E, Ferrieri P, Wannamaker LW. Comparison of the antibody response to streptococcal cellular and extracellular antigens in acute pharyngitis. J Paediatr 1974. 84(1): p. 21–28. 21. McCarty M. The antibody response to streptococcal infections, in Streptococcal infections, M. McCarty, Editor. 1954, Columbia University Press: New York. p. 130–142. 22. Burdash NM, Teti G, Hund P. Streptococcal antibody tests in rheumatic fever. Ann Clin Lab Sci. 1986;16(2):163–70. Address for correspondence Dr. S. Ramakrishnan: Email: [email protected] Prevention of rheumatic fever and rheumatic heart disease I B Vijayalakshmi, MD, DM Professor of Pediatric Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, India ■ Introduction Abstract It is estimated that 15.6 million people are affected worldwide by acute rheumatic fever (ARF) and 3 lakhs out of 5 lakhs individuals that acquire ARF every year go on to develop rheumatic heart disease (RHD). ARF follows 0.3–3% of cases of group A beta-hemolytic streptococcal (GABHS) pharyngitis. As many as 39% of persons with ARF may develop varying degrees of pancarditis associated with valve insufficiency, heart failure and even death. 3 million have chronic heart failure requiring repeated hospitalization. There are estimated 330,000 deaths annually and many survivors are left with disabilities. According to World Health Organization bulletin of 1981, more than 50% of ARF/RHD detected in surveys and health check-up camps are unaware of their disease and more than 70% do not receive secondary prophylaxis regularly. It is important to know the currently accepted and effective methods of prevention and RF control program and other important preventive strategies. Although, strategies for preventing RHD are proven, simple, cheap and cost effective, unfortunately they are not adequately implemented. The timely echocardiography can detect clinical carditis, and subclinical carditis more precisely and accurately. Echocardiography, a modern facility when used as diagnostic criteria can prevent both over diagnosis and under diagnosis. Primodial, primary, secondary preventions are very important. The Mobile Heart Care units with diagnostic kit and mobile echocardiography machine can bring more patients into the net of secondary prophylaxis. The proper implementation of RHD control programs depends on dedicated coordinator working with the missionary zeal. Key Words Subclinical carditis ● ● Echocardiographic criteria ● RF control program Acute Rheumatic fever (ARF) and rheumatic heart disease (RHD) were widely prevalent throughout the world at the beginning of the second half of the twentieth century. However, during the ensuing decades the disease’s major impact has been centred in developing countries like India, which constitute a majority of the world’s population. As with so many other health problems, these are countries which can least afford the economic and social costs for the management of ARF and RHD. Particularly frustrating has been the fact that ARF and RHD are theoretically preventable. In patients who develop ARF, therapy is directed toward eliminating the group A streptococcal pharyngitis (GABHS) if still present, suppressing inflammation from the autoimmune response and providing supportive treatment for congestive heart failure in patients with RHD. If GABHS infections of the upper respiratory tract are prevented or are effectively treated, neither initial nor recurrent attacks of rheumatic fever occur and that is the goal of prevention. The medical and public health issues are further complicated by the fact that group A streptococcal infections are universally endemic. As there is no available vaccine for group A infections, prevention measures remain dependent upon accurate clinical diagnosis and appropriate antibiotic treatment of GABHS infections. Rheumatic fever prevention programmes utilizing recommended clinical and laboratory techniques for diagnosis and antibiotic treatment of GABHS infections are cost-effective. It is important to know the currently accepted and effective methods of prevention of ARF and role of WHF, WHO and Vaccine in ARF control programme. Received: 21-05-12; Revised: 25-06-12; Accepted: 09-07-12 Disclosures: This article has not received any funding and has no vested commercial interest Acknowledgements: None 266 J. Preventive Cardiology Vol. 2 ■ No. 2 ■ November 2012 ■ J. Preventive Cardiology Vol. 2 ■ No. 2 ■ November 2012 ■ 267