Teaching presentation on Rheumatic fever, including etiology, clinical features, diagnosis and treatment. Evidence based approach in management.

1. Dr.Sid Kaithakkoden MD
MBBS,DCH,DNB,MD,MRCPCH,FCPS
alavisaid@aol.com

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

9. 9

10. 10
Rheumatic Aortic Valve

11. 11
Erythema marginatum

12. 12

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

38. 38