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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
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Endocarditis, and Kawasaki Disease Committee of the Council on
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the Interdisciplinary Council on Quality of Care and Outcomes
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14. RHD Australia (ARF/RHD writing group), National Heart
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management of acute rheumatic fever and rheumatic heart
disease (2nd edition) 2012.
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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
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