2. 2
ARF
Immunologically mediated inflammatory
response
Delayed sequel to GABH Strept. throat
infection
Genetically susceptible individuals
Developed world - dramatic decline in
incidence
Developing world – still a major problem –
20 million new cases/year
Introduction
3. 3
ARF - Aetiopathogenesis
Definite aetiology ??
Antigenic mimicry between streptococcal M-protein
epitopes & human tissues (heart valves, myosin,
synovium & basal ganglia)
Autoimmunity in genetically susceptible individuals
Constant association with HLA class II antigens (HLA
B5)
Age – 5 -18 yrs
Incidence:
Developed world - 0.05/1000 population
Developing world - 24/ 1000 population
4. 4
Making the diagnosis of
streptococcal pharyngitis
Streptococcal pharyngitis (Group A beta-
hemolytic pharyngitis)
Only 10-15% incidence in adults with
pharyngitis
But a 40% incidence in children with
pharyngitis
5. 5
Making the diagnosis of streptococcal
pharyngitis
Scoring system for risk of strep pharyngitis:
1. Temperature > 37.8 degrees C
2. Tonsillar exudate
3. Anterior cervical lymphadenopathy
Three factors present = 40-50% risk of strep
pharyngitis
Only two factors present = 15% risk
Consider increased risk for known exposure or
community outbreak
6. 6
Making the diagnosis of
streptococcal pharyngitis
Clinical diagnosis
Fever and sore throat are always present
Rarely seen are rhinitis, conjunctivitis,
bronchitis, laryngitis or diarrhea
Must have pharyngeal edema or exudate
Must have cervical lymphadenopathy
7. 7
Diagnosis of ARF
No “gold standard”
No specific clinical/lab. test to establish
diagnosis
Diagnosis based on revised (updated)
Jones criteria
1944 T. Duckett Jones
Final revision 1992 – by committee on
Rheumatic Fever, Endocarditis, Kawasaki
Disease of the AHA
8. 8
Updated Jones Criteria:
(need 2 major or 1 major and 2 minor criteria AND
evidence of infection):
Major manifestations
Carditis Erythema marginatum
Polyarthritis Subcutaneous nodules
Chorea
Minor manifestations
Clinical findings: arthalgia and fever
Lab findings: ↑ESR, ↑C-reactive protein, ↑acute-phase
reactants, prolonged PR interval
Supporting evidence of antecedent streptococcal infection
Positive throat culture or rapid streptococcal antigen test
Elevated or rising streptococcal antibody titers
Exception :
Chorea
Indolent carditis
13. 13
Clinical findings in ARF
Carditis
may have an insidious or subclinical onset:
40-50% incidence with first attack of ARF
More common in younger children
Decreased risk with increasing degree of polyarthritis
Is frequently a pancarditis, may be asymptomatic.
Usually appears in the first 3 weeks of an ARF attack.
Suggested by presence of :
Pericarditis, cardiomegaly, CHF, new heart murmur(s)
Less specific findings:
ECG changes: PR interval (>0.04), P wave contour change,
inverted T waves
Resting tachycardia – even during sleep
Arrythmias
14. 14
Carditis
Onset of new heart murmur(s):
Mitral regurgitation/insufficiency – high pitched
blowing holosystolic apical murmur, grade 2 or
higher that radiates to axilla
Aortic regurgitation – high pitched decrescendo
murmur at aortic area
Mitral stenosis and aortic stenosis are classic
findings of chronic rheumatic heart disease.
25% go on to develop mitral stenosis
40% will develop mitral insufficiency
15. 15
Polyarthritis
Classically is a migratory polyarthritis:
Affects large joints sequentially (knees, elbows, ankles and
wrists usually) with multiple joints involved at the same
time.
Diagnosis based on joint pain along with heat, swelling,
redness and tenderness.
May have arthralgias –-- pain without associated findings.
Adolescent children are more likely to have only
one arthritic joint
50% have 6 or more joints involved (↑arthritis =
↓carditis).
Usually lasts < 4 weeks without residual damage
16. 16
Erythema Marginatum
The rash specific for ARF.
10% incidence
Described as a macular or raised erythematous
rash in rings or crescent shapes with clear
centers.
Nonpruritic and nonpainful
Lesions come and go in minutes to hours.
May occur intermittently for weeks to months
Primarily seen on trunk and proximal extremities.
17. 17
Subcutaneous Nodules
10% incidence in ARF
More likely to be present with carditis
Are only present for days to a couple of
weeks
May be recurrent however
Description:
Firm, painless, < 2cm nodules found over bony
prominences or tendons
Common on elbows, knees, wrists, ankles and Achilles
tendon
Usually one to a few dozen nodules
Indistinguishable from rheumatoid nodules
There is no treatment
18. 18
Sydenham’s Chorea
Involuntary movements of the hands, face
and feet:
5-15% incidence
May also involve muscular weakness and emotional
lability
Often there is a long latent period between
antecedent streptococcal pharyngitis and the
onset of chorea.
Movements are suppressible with sedation
Females affected more often than males
Attacks often last for several months
19. 19
Laboratory Findings
No definitive tests
1. If there is no recent documented
streptococcal pharyngitis, then you need to
check a rapid streptococcal antigen test
following by throat culture if antigen test negative
2. Acute phase reactants : ESR, CRP,
3. Serum titer of antistreptococcal antibodies
(ASO)
80% will have a positive titer within 2 mths of ARF
onset
20. 20
Treatment
Prevention of initial attack of RF (primary
prevention)
eradication of streptococci
Anti inflammatory treatment
aspirin, steroids
Prevention of recurrence (secondary
prevention)
antibiotic prophylaxis
21. 21
Treatment of ARF with Medications:
1. Antibiotics – Benzathine penicillin G
(aka bicillin LA) 1.2 million units IM for
positive throat culture to prevent
spread of ARF-causing streptococcal
strain.
Alternatives:Alternatives:
Penicillin V 250mg BID po for 10days
Erythromycin 250mg QID x 10day for penicillin
allergic patients
22. 22
Treatment of ARF with Medications:
2. Salicylates – for fever and joint
pain/swelling
100mg/kg/d of aspirin for children
Should see prompt response in joints
Treat arthralgias with analgesics
NSAIDs ok for aspirin allergic/intolerant but not
studied.
23. 23
Treatment of ARF with Medications:
3. Corticosteroids – use when salicylates
fail and whenever carditis is present.
No proof of cardiac damage prevention.
2mg/kg mg oral prednisone
2-3 week course with taper for arthritis and
fever.
Up to 6 week course with 2 week taper for
carditis.
Continue aspirin for one month after
stopping steroid
24. 24
Treatment of Carditis/Heart Failure
All carditis patients receive
corticosteroids.
Strict bed rest for at least 4 weeks
Conventional therapies are used to treat
specific symptoms such as heart failure.
25. 25
Treatment of Sydenham’s Chorea
Mainstay of treatment is:
Quiet environment (symptoms disappear
during sleep and are are less frequent with
less environmental stimulation).
Sedation:
Benzodiazepines
Haloperidol for more severe cases
26. 26
Prevention of ARF recurrences:
High risk for ARF recurrence with repeat
episodes of streptococcal pharyngitis.
Recurrences ↓with ↑age and with the number
of years since last attack
Recurrences are more common in those with
a history of ARF carditis and in children.
Children have a 20% risk of recurrence
in 1st
five years.
27. 27
Prevention of ARF recurrences
Need continuous antibiotic prophylaxis
for at least 5 years or until patient at
least into their early 20s
Primary recommendation:
Benzathine penicillin G (Bicillin LA) – IM every
4 weeks
May give every 3 weeks for those at highest
risk
Alternative: Sulfadiazine 500mg QD for < 27#,
1000mg QD for > 27#
Erythromycin 250mg BID for PCN allergic
28. 28
Endocarditis Prophylaxis
Patients with residual rheumatic
valvular disease also need
endocarditis prophylaxis
Use a different antibiotic than that
used for ARF recurrence prevention
29. 29
Prognosis
Initial mortality rate is 1-2%
Persistent carditis = poorer prognosis
30% mortality within 10 years for children
80% of children affected with ARF live to
adulthood
Adults – 2/3 are affected with rheumatic valvular
disease after 10 years
30. 30
Questions needing answer…..
Should we treat all sore throat with antibiotics to
prevent rheumatic fever ?
What is the best anti inflammatory drug in
carditis to prevent RHD?
Aspirin? Steroid?
What is the best mode of administration of
penicillin in secondary prophylaxis?
Should we use echocardiographic finding as a
major/minor criterion in diagnosis of carditis in
ARF ?
31. 31
Antibiotics for sore throat ?
Del Mar CB, Glasziou PP, Spinks AB. Antibiotics
for sore throat. The Cochrane Database of
Systematic Reviews 2010, Issue 2. Art. No.:
CD000023
Objectives: To assess the benefits of antibiotics in the
management of sore throat
Search of the literature from 1945 to 2003
Selection: Trials of antibiotic against control with
either suppurative complications & non-suppurative
complications of sore throat
Twenty-six studies
32. 32
Results & Conclusion:
Antibiotics confer relative benefits in the
treatment of sore throat. However, the absolute
benefits are modest
Protecting sore throat sufferers against
suppurative and non-suppurative complications
in modern Western society can be achieved only
by treating with antibiotics many who will
derive no benefit
In emerging economies where rates of acute
rheumatic fever are high, the number needed
to treat may be much lower
33. 33
Anti-inflammatory treatment for
carditis in ARF
Cilliers AM, Manyemba J, Saloojee H. Anti-
inflammatory treatment for carditis in acute
rheumatic fever. The Cochrane Database of
Systematic Reviews 2009, Issue 2. Art. No.:
CD003176
Objectives: To assess the effects of anti-inflammatory
agents (aspirin, corticosteroids & immunoglobulin) for
preventing or reducing further heart valve damage in
patients with ARF
Literature search from1966 to 2005
Eight RCT
34. 34
Results & Conclusion:
No significant difference in the risk of cardiac disease
at one year between the corticosteroid-treated and
aspirin-treated groups (relative risk 0.87, 95% confidence interval
0.66 to 1.15)
Use of prednisone (relative risk 1.78, 95% CI 0.98 to 3.34) or
intravenous immunoglobulins (relative risk 0.87, 95% CI 0.55 to
1.39) when compared to placebo did not reduce the risk
of developing heart valve lesions at one year
CONCLUSION: No benefit in using corticosteroids or
intravenous immunoglobulin to reduce the risk of
heart valve lesions in patients with ARF
35. 35
Penicillin for secondary
prevention of ARF
Manyemba J, Mayosi BM. Penicillin for
secondary prevention of rheumatic fever. The
Cochrane Database of Systematic Reviews
2000, Issue 3. Art. No.: CD002227
Objectives: To assess the effects of penicillin
compared to placebo and the effects of different
penicillin regimens and formulations for preventing
strept.infection and rheumatic fever recurrence
Nine studies
36. 36
Four trials (n=1098) compared IM with oral penicillin
and all showed that IM penicillin reduced RF
recurrence and Strept. throat infections
compared to oral penicillin
One trial (n= 249) showed 3-weekly IM penicillin inj.
reduced strept. throat infections (RR 0.67, 95% CI 0.48
to 0.92) compared to 4-weekly dose
Conclusions:
IM penicillin more effective than oral penicillin in
preventing RF recurrence and strept. throat infections
Two-weekly or 3-weekly injections appeared to be
more effective than 4-weekly injections
Results & Conclusion:
37. 37
Should Echocardiography used as a
criterion in diagnosing rheumatic
carditis?
Ferrieri P et al. Proceedings of the Jones Criteria
workshop. AHA scientific statement. Circulation
2002;106:2521-2523
Echocardiography should only be used as an
adjunctive technique to confirm clinical findings and to
evaluate chamber sizes, ventricular function & valvar
morphology
It should not be used as a major/minor criterion for
establishing the diagnosis of carditis of ARF in the
absence of clinical findings