This document provides an overview of acute rheumatic fever presented by Dr. Renesha Islam. Some key points: - Acute rheumatic fever is an immune response to Group A streptococcus infection that causes inflammation of the heart, joints, brain and skin. It often damages the heart valves long term. - Major symptoms include migratory polyarthritis in joints (75% of cases), carditis (50-60% of cases, involving the heart valves, myocardium and pericardium), Sydenham's chorea (10-15% of cases), erythema marginatum and subcutaneous nodules (rare). - Diagnosis is based on the revised Jones criteria

1. Presenter:
DR. RENESHA ISLAM
RESIDENT (PHASE-A)
PAEDIATRIC HEMATOLOGY
& ONCOLOGY
WELCOME TO SEMINAR ON
ACUTE RHEUMATIC FEVER
PRESENTED BY
DR. RENESHA ISLAM
Resident-Phase A
(PAEDIATRIC HEMATOLOGY
& ONCOLOGY)

2. ACUTE
RHEUMATIC FEVER
• Acute rheumatic fever is a post infectious
immune response to group A streptococcus
(GAS) that results in a diffuse inflammatory
disease involving the joints and heart and less
frequently the brain, skin and subcutaneous
tissue.
• It has a tendency to recur.

3. • Rheumatic fever causes chronic progressive
damage to the heart and its valves.
• But it is the most preventable disease of all
CVS diseases.
• It is so named because of its similarity in
presentation to Rheumatism.

4. Etiology
 Group A beta hemolytic streptococci
(GABS)
 Serotypes (M types 1,3,5,6,18,29) are
more frequently isolated.

5. EPIDEMIOLOGY
• The incidence of ARF in some developing
countries exceeds 50 per 1,00,000 children.
• World wide , rheumatic heart disease remains
the most common form of acquired heart
disease in all age groups .

6. Epidemiology ( Cont…)
• Incidence peaks in 5-15 yrs. age group.
• More male patients of RF than female.
• Females are more vulnerable to develop congestive
heart failure than male.
• Most of the patient belongs to the low
socioeconomic group.
• Higher incidence of streptococcal sore throat
observed during winter.

7. EPIDEMIOLOGY
• In the USA at the beginning of the 20th century
annual incidence was 100-200/1,00,000 population.
• By the early 1980s the annual incidence was
decreased as low as 0.5/1,00,000 population.
• This Sharp decline in the incidence of ARF has been
observed in other industrialized countries as well.

8. Several theories of the pathogenesis of acute rheumtic
fever have been proposed.
Main two are:
a. IMMUNOLOGIC THEORY
b. CYTOTOXICITY THEORY
PATHOGENESIS

9. IMMUNOLOGIC THEORY
• It has been suggested that patients of
rheumatic fever produce antibodies against
streptococcal cell wall and cell membrane
proteins .
• The streptococcal antigen and human
myocardium appear to be identical
antigenically.

10. IMMUNOLOGIC THEORY
• Most important antigenic proteins of GAS in external
layer of cell wall are M ( M1 , M5 , M6 & M9 ) T, & R
proteins.
The following antigens of streptococci cross react to
connective tissue antigens :
• Streptococcal M protein cross react to cardiac myosin
• Streptococcal membrane antigen cross reactive with
myocardial smooth muscle sarcolemma.
• Hyaluronate capsule of streptococcus cross-reactive
with heart valve glycoprotein.

11. IMMUNOLOGIC THEORY
• Other antigenic Components – Cell wall group A
carbohydrate, Capsular hyaluronate, protoplast
membrane.
• Immunogenic cross reactivity occurs between
streptococcal components ( M protein , cell wall group
A carbohydrate etc ) and tissues of heart , joints and
brain .

13. IMMUNOLOGIC THEORY Cont.
Steps or sequence in pathogenesis :
Streptococcus pyogenes-sore throat pharyngitis
Antigen of S. Pyogenes
Immune response (B cell or humoral) in 2-4 weeks.
Antistreptococcal antibodies against the antigens.
Antibodies react with cross-reactive antigens of conncetive
tissue (heart, joints)
Systemic inflammation of connective tissue.

14. CYTOTOXICITY THEORY
• The cytotoxicity theory suggests that a GAS toxin
may be involved in the pathogenesis of acute
rheumatic fever and rheumatic heart disease.
• GAS produces several enzymes that are cytotoxic to
mammalian cardiac cells , such as streptolysin O.
• one of the major problems with the cytotoxicity
hypothesis is its inability to explain the latent period
between GAS pharyngitis and the onset of acute
rheumatic fever.

15. PATHOLOGY
 Microscopically-Focal inflammatory
nodule known as Aschoff body which is
pathognomonic of rheumatic fever.
The nodule is formed by fibrinoid
necrosis of collagen surrounded by
lymphocytes, macrophage & occasional
plasma cells. It may be found in all 3
layers of heart, joints & subcutaneous
tissue.
 Macroscopically-Most obvious in the
heart valves & the pericardium. The
valve cusps become thickened by
oedema & by the infiltration of
capillaries.

16. PATHOLOGY Cont.
These are common on the mitral or aortic valve cusp
& seldom affect the tricuspid or pulmonary valves.
When the pericardium is involved it becomes
thickened, may contain a fibrinous straw coloured
effusion.

17. Clinical Manifestations
As because no clinical or laboratory finding is
pathognomic for acute rheumatic fever,
T. Duckett Jones in 1944 proposed guidelines to aid in
dignosis and to limit over diagnosis.
The Jones criteria , as revised in 2015 by AHA
are for the diagnosis of the initial attack of ARF &
recurrent attacks.

18. Guidelines for the diagnosis of initial attack of Rheumatic fever (Jones
Criteria, Updated 2015)
Major
Manifestations
Minor
Manifestations
Supporting Evidence of
antecedent GAS infection.
-Carditis
-Polyarthritis
-Erythema
marginatum
-Subcutaneous
nodules
-Chorea
Clinical features:
- Arthralgia
- Fever
Laboratory features:
●Elevated acute phase
reactants
- ESR
- CRP
●Prolonged P-R
interval
- positive throat swab culture
or
- Rapid Streptococcal antigen test
or
- Elevated or increasing streptococcal
antibody titer .
The presence of 2 major or of 1 major and 2 minor manifestations
indicates a high probability of ARF if supported by evidence of
preceding GAS infection_ INITIAL ATTACK.

19. RECURRENT ATTACK –
2 major or 1 major & 2 minor or 3 minor
menifestations (the latter 1 only in the moderate/
high risk population plus evidence of recent GAS
infection.

20. Exceptions:
• There are 3 circumstances in which the
diagnosis of ARF can be made without strict
adherence to the Jones criteria :
1.Chorea
2.Indolent carditis
3.Recurrences of acute RF,
may or may not fulfill Jones criteria.

21. Migratory Polyarthritis
- Most common feature:
present in 75% cases.
- Typically involves larger Joints. (Knees, ankles,
elbows, wrists) Involvement of spine, hips and small
joints of the feet and hand are uncommon.
- Joints are generally hot, red, swollen and exquisitely
tender, even the friction of bedclothes is
uncomfortable. Pain is more marked than swelling.

22. Migratory Polyarthritis (continued) ……
- characteristically migratory in nature.
- A dramatic response to salicylates (aspirin) is
characteristic.
- typically not deforming. If left untreated the
joint swelling disappear spontaneously in 3-4
weeks time leaving no permanent deformities of
joints.

23. • There is often an inverse relationship
between :
the severity of arthritis
and
the severity of cardiac involvement .

24. Carditis
-Most serious manifestation
- Present in 50-60% cases.
- Characteristic pancarditis
(involves all the 3 layers of heart . i.e.
endocardium, myocardium, pericardium)

25. Carditis (continued) ……
- Endocardits (valvulitis) : is a universal
finding in rheumatic Carditis.
where as the presence of pericarditis or
myocarditis is variable.
- Murmurs present due to valvular
involvement.

26. Carditis (continued) ……
Mitral regurgitation is characterized by a high-
pitched apical holosystolic murmur radiating to
the axilla. There may be associated with an
apical mid-diastolic murmur of relative mitral
stenosis. Aortic insufficiency is characterized by
a high-pitched decrescendo diastolic murmur at
the upper left sternal border.

27. Carditis (continued) ……
• Valvular insufficiency is characteristic of both acute
& convalescent stages of ARF whereas valvular
stenosis usually appears several years or even
decades after the acute illness.
• Most cases consist of either isolated mitral valvular
disease or combined aortic and mitral valvular
disease. Isolated aortic or right-sided valvular
involvement is uncommon.
• Serious and long-term illness is related entirely to
valvular heart disease as a consequence of a single
attack or recurrent attacks of acute rheumatic fever.
-

28. Carditis (continued) ……
Myocarditis:
- Present with tachycardia( which is
disproportionate to the degree of fever & is
present during sleep), conduction defect,
cardiomegaly. Gallop rhythm is common
physical findings.
Pericarditis:
- Present with (chest pain ,Pericardial rub &
effusion)

29. Sydenham’s Chorea
- Occurs in 10-15% cases.
-Usually presents as an Isolated, frequently
subtle , neurologic behavior disorder.
- there is involuntary, purposeless,
nonrepeatative movements of the limbs , face
and trunk.
.

30. -Clinical maneuvers to elicit features of chorea include :
1. Milk maid’s grip. (Irregular contractions of the muscles
of the hands while squeezing the examiner's finger).
2. Spooning and pronation of hands when arms extended.
3. Wormian darting movements of tongue upon
protrusion.
4. Deterioration of hand writing. (to evaluate fine motor
movement)

31. - Exacerbated by stress disappeared with sleep.
- Associated features : Emotional liability ,
incoordination , poor school performance ,
uncontrollable movements and facial grimacing.

32. Erythema Marginatum

33. Erythema Marginatum

34. Erythema Marginatum:
- It is rare , occurs in < 3% of patient
but highly characteristic for ARF .
- Erythematous, non-pruritic ,serpiginous , macular
lesion with pale centres.
-It occurs primarily on the trunk and extremities,
but not on the face.
-It can be accentuated by warming the skin .

35. Subcutaneous Nodule

36. Subcutaneous Nodules:
-these are rare (≤ 1% of patients)
- Firm, non tender, freely movable nodules . Approx. 1
cm in diameter.
-present along extensor surfaces of tendons near bony
prominences.
- There is a correlation between the presence of these
nodules and carditis or significant RHD.

37. OTHER MANIFESTATIONS
• Fever: remittent in nature,
>102⁰ F
• Arthralgia.

38. Differential Diagnoses
Arthritis Carditis Chorea
Rheumatoid
Arthritis
 Reactive arthritis
Serum Sickness
 Sickle cell
disease
 Malignancy
 SLE
 V. Myocarditis
V. Pericarditis
Infective
endocarditis
Kawasaki disease
Congenital Heart
Disease
Mitral valve
prolapse
Innocent murmur
Huntington
chorea
Wilson disease
SLE
Cerebral palsy
Tics

39. Investigations
 Evidence of recent group A streptococcal infection-
• Throat swab culture
• Streptococcal antibodies titre
Antistreptolysin O (ASO)
Anti deoxyribonuclease (Anti DNase B)
Antihyaluronidase (AH).
 If only single antibody is measured (ASO titer) only 80-85% of
patients have an elevated titer.
 However , 95- 100 % have an elevation, if 3 different antibodies
are measured.

40. Investigations contd…
 Evidence of the systemic inflammation-
»  WBC
» ESR - raised, CRP – raised.
 Evidence of Cardiac involvement-
• Chest X-ray - Cardiomegaly, Pulmonary
congestion.
• ECG- prolonged P-R interval, tachycardia,
T-wave inversion in pericarditis.
• Echocardiography - Can provide a more accurate
diagnosis than auscultation.

41. Treatment of Rheumatic fever :-
A) Counselling, General measures & bed rest.
B) Treatment of group A streptococcal
infection.
C) Anti-inflammatory therapy.
D) Management of special condition- if
present e.g. - Heart failure, Chorea etc.

42. A) General measures & bed rest:
Table: Guide for bed rest & ambulation in pt with ARF
Diet- Normal but salt & water restriction (if heart failure)
Cardiac status Bed rest Gradual
ambulation
No carditis 2 wk 2 wks
Carditis, no cardiomegaly 4 wks 4 wks
Carditis with cardiomegaly 6 wks 6 wks
Carditis, heart failure Strict bed rest for as long as heart
failure is present & gradual
ambulation for 3 month

43.  It is preferable to ensure adequate rest till the
following clinical & laboratory criteria are met:
1) Normal body temperature.
2) Disappearance of joint symptoms and signs.
3) Absence of tachycardia at rest specially during sleep.
4) Disappearance of signs of heart failure.
5) Return of heart size to normal in chest x-ray
6) Return of ESR to less than 25 mm in 1st hour
7) C-Reactive protein becomes negative.
8) PR interval in ECG returns to normal or stabilized if it
was prolonged.
9) Disappearance of subcutaneous nodule, if any.

44. B) Treatment of streptococcal
infection-
 Inj.Benzathine penicillin G - If wt>30 kg 1.2
million U , wt ≤ 30 kg, 6 lac U given as single
I/M dose.
or
 Oral penicillin 250 mg 4 times daily for 10 days
or
If patient allergic to penicillin ,
 Erythromycin - 40 mg/kg/day - 4 times daily -
for 10 days.

45. C) Anti-inflammatory drugs:
Recommended Anti-inflammatory agents for ARF:
Arthralgia: Analgesics only (paracetamol can be
used)
Arthritis only and/or carditis without cardiomegaly
or CHF:
Aspirin 50-70 mg/kg/day in 4divided doses PO for 3-5
days, followed by 50 mg/kg/day in 4 divided doses PO for
3 wk and half that dose for another 2-4 wk.

46. Anti-inflammatory drugs (contd…….
 Carditis and cardiomegally or CHF
Should be treated with corticosteroids.
Dose of prednisolone- 2 mg/kg/day in 4 divided
doses for 2-3 wk followed by half the dose for 2-3 wk
and then tapering of the dose by 5 mg/24 hr every 2-
3 days.
When prednisone is being tapered, aspirin should be
started at 50 mg/kg/day in 4 divided doses for 6 wk
to prevent rebound of inflammation.

47. Treatment of special condition (if present)
Treatment of Sydenham’s chorea:
 Phenobarbitone - 16-32 mg every 6-8 hourly PO.
If phenobarbitone is ineffective ,
 Haloperidol - 0.01-0.03 mg/kg/day 12 hourly PO.
 Chlorpromazine - 0.5mg/kg every 4-6 hourly PO.
Erythema marginatum and subcutaneous nodules has
no specific treatment.

48. Complications:
• Arthritis and Chorea of ARF resolve completely.
• Long term sequele of ARF usually limited to the
heart -
 Rheumatic valvular heart disease.
 Infective endocarditis.

49. Rheumatic valvular lesions
Valves involved % of cases
Mitral valve alone 50
Mitral and aortic valves 40
Mitral, aortic and tricuspid 5
aortic valve alone 2
All other combinations 3

50. Prevention
There are two components for prevention of RHD.
Improvement of socioeconomic
1. General measure Avoidance of overcrowding
Health education.
Primary prophylaxis
2. Drug prophylaxis
Secondary prophylaxis

51. Prevention:
• Primary Prophylaxis : refers to antibiotic
treatment of the Strep. URTI to prevent an initial
attack of RF (before the 9th day of symptoms of
acute GAS Pharyngitis is highly effective.)
• However, approximately 30% of patients with acute
rheumatic fever do not recall a preceding episode of
pharyngitis and did not seek therapy.

52. Prevention (contd…)
Secondary Prophylaxis:refers to the prevention of
colonization or infection of URT with GAS in individual who have
already had a previous attack of ARF.

53. Secondary prevention (contd…)
 Duration of prophylaxis:
• RF without carditis - 5 yr or until 21 yr of age ,
(whichever is longer)
• RF with Carditis without residual heart disease -
10 yr or until 21 yr of age (whichever is longer)
• RF with carditis with valvular heart disease - 10
yr or until 40yr of age (whichever is longer),
sometimes life long prophylaxis

54. Prognosis:
Prognosis of ARF depend on the-
1. Clinical manifestation present at the time of
initial episode.
2. Severity of the initial episode.
3. The presence of recurrences.
• Approximately 70% of the pt with carditis during
the initial episode of ARF recover with no
residual heart disease.
• The more severe the initial cardiac
involvement, the greater the risk for residual
heart disease.

55. Prognosis (contd…)
• Pt. without carditis during the initial attack are
unlikely to have carditis with recurrences.
• Pt. with Carditis during the initial episode are
likely to have carditis with recurrences.
• The risk of permanent heart damage increases
with each recurrences.