ACUTE RHEUMATIC FEVER

2. Acute rheumatic fever (ARF) is a multisystem
disease resulting from an autoimmune
reaction to infection with group A
streptococcus.

4.  ARF is mainly a disease of children aged 5 - 14
years
The prevalence of RHD, peaks between 25 and
40 years.
 There is no clear gender association for ARF
 RHD more commonly affects females,
twice as frequently as males.

5.  Organism Factors
 ARF is exclusively caused by infection of
the upper respiratory tract with group A
streptococci .
 Classically, certain M-serotypes (types 1, 3, 5,
6, 14, 18, 19, 24, 27, and 29) in high-incidence
regions

6.  Familial clustering of cases and concordance in
monozygotic twins—particularly for chorea—
confirm that susceptibility to ARF is an inherited
characteristic.
 (HLA) class II alleles appear to be strongly
associated with susceptibility.
 High levels of circulating mannose-binding lectin
and polymorphisms of transforming growth
factor 1 gene.


9.  Because of the similarity btw hyaluronic acid
in GAS capsule and in the connective tissue of
the joints, Ab produced against GAS capsule
will start to attack the joints and causes
arthritis.
 M-protein in GAS cell wall and the
myocardium are similar, thus Ab produced
against GAS cell wall will attack heart and will
cause carditis and so forth.
 Similarly Ab against NAG in GAS will affect

10.  When a susceptible host encounters a group A
streptococcus, an autoimmune reaction results, which
leads to damage to human tissues as a result of cross-
reactivity between epitopes on the organism and the host
Cross-reactive epitopes are present in the streptococcal M
protein and the N-acetylglucosamine of group A
streptococcal carbohydrate and are immunologically
similar to molecules in human myosin, tropomyosin,
keratin, actin, laminin, vimentin, and N-
acetylglucosamine. It is currently thought that the initial
damage is due to cross-reactive antibodies attaching at
the cardiac valve endothelium, allowing the entry of
primed CD4+ T cells, leading to subsequent T cell-
mediated inflammation.

11.  There is a latent period of 3 weeks (1–5
weeks) between the streptococcal infection
and the appearance of the clinical features of
ARF.
 The exceptions are chorea and indolent
carditis, which may follow prolonged latent
periods lasting up to 6 months.

12.  The most common clinical presentation of
ARF is polyarthritis and fever.
 Polyarthritis is present in 60–75% of cases
and carditis in 50–60%.
 The prevalence of chorea in ARF varies <2%
to 30%.
 Erythema marginatum and subcutaneous
nodules are now rare, being found in <5% of
case

13.  Up to 60% of patients with ARF progress to RHD.
 The endocardium, pericardium, or myocardium may
be affected.
 Valvular damage is the hallmark of rheumatic carditis.
 The mitral valve is almost always affected,
sometimes together with the aortic valve; isolated
aortic valve involvement is rare.
 Early valvular damage leads to regurgitation.

14.  Therefore the characteristic manifestation of
carditis in previously unaffected individuals is
MR, sometimes accompanied by AR .
 First-degree AV block
 Softening of the first heart sound

15.  The typical arthritis is migratory, moving from
one joint to another over a period of hours. ARF
almost always affects the large joints—most
commonly the knees, ankles, hips, and elbows—
and is asymmetric.
 Aseptic monoarthritis
 The joint manifestations are highly responsive to
salicylates and other nonsteroidal anti-
inflammatory drugs (NSAIDs).

16.  Follows a prolonged latent period after
group A streptococcal infection, and is found
mainly in females.
 The choreiform movements affect
particularly the head and the upper limbs .
 Chorea eventually resolves completely
usually within 6 weeks

17.  The classic rash of ARF is erythema
marginatum
 Pink macules that clear centrally, leaving a
serpiginous, spreading edge. The rash is
evanescent, appearing and disappearing
before the examiner's eyes. It occurs usually
on the trunk, sometimes on the limbs, but
almost never on the face.

19.  Subcutaneous nodules occur as painless, small
(0.5–2 cm), mobile lumps beneath the skin
overlying bony prominences, particularly of
the hands, feet, elbows, occiput, and
occasionally the vertebrae.
 They are a delayed manifestation, appearing
3 weeks after the onset of disease, and are
commonly associated with carditis.

21.  Fever occurs in most cases of ARF, although
rarely in cases of pure chorea.
 Elevated acute-phase reactants are also
present in most cases. ,C-reactive protein
(CRP) and erythrocyte sedimentation rate
(ESR) are often dramatically elevated.
Occasionally the peripheral leukocyte count
is mildly elevated.

22.  anti-streptolysin O (ASO) and anti-DNase B
(ADB) titers.

23.  Post-streptococcal reactive arthritis (PSRA) is
(1) small-joint involvement that is often
symmetric;
 (2) a short latent period following
streptococcal infection (usually <1 week);
 (3) occasional causation by nongroup A
-hemolytic streptococcal infection;
 (4) slower responsiveness to salicylates;
 (5) the absence of other features of ARF,
particularly carditis.

24.  Pediatric autoimmune neuropsychiatric
disorders associated with streptococcal infection
(PANDAS) is a term that links a range of tic
disorders and obsessive-compulsive symptoms
with group A streptococcal infections. People
with PANDAS are said not to be at risk of
carditis, unlike patients with Sydenham's
chorea. The diagnoses of PANDAS and PSRA
should rarely be made in populations with a high
incidence of ARF.

25. MAJOR CRITERIA
1. Carditis
2. Arthritis
3. Subcutaneous nodules
4. Erythema marginatum
5. Chorea

26. CLINICAL
1. Fever
2. Arthralgia
3. Previous h/o rheumatic fever
LABORATORY
1. Acute phase reactants
2. PR prolongation

27. Evidence of recent streptococcal infection
evidenced by
1. Increase in ASO
2. Positive throat culture for streptococcal
infection
3. Recent history of scarlet fever
4. Rapid antigen test for group A streptococcus

28.  2 major / 1 major and 2 minor in the
presence of essential criteria.

29. DIAGNOSTIC CATEOGORIES CRITERIA
Primary episode of rheumatic fever Two major or one major and two minor
manifestations plus evidence of preceding
group A streptococcal infection
Recurrent attack of rheumatic fever in a
patient without established rheumatic heart
disease
Two major or one major and two minor
manifestations plus evidence of preceding
group A streptococcal infection
Recurrent attack of rheumatic fever in a
patient with established rheumatic heart
disease
Two minor manifestations plus evidence of
preceding group A streptococcal infectionc
Rheumatic chorea Insidious onset rheumatic
carditis
Other major manifestations or evidence of
group A streptococcal infection not required

30. Chronic valve lesions of rheumatic heart
disease (patients presenting for the first
time with pure mitral stenosis or mixed
mitral valve disease and/or aortic valve
disease)
Do not require any other criteria to be
diagnosed as having rheumatic heart
disease

31. 
Recommended for all cases
 White blood cell count
 Erythrocyte sedimentation rate
 C-reactive protein
 Blood cultures if febrile
 Electrocardiogram
 Chest x-ray if clinical or echocardiographic evidence of carditis
 Echocardiogram (consider repeating after 1 month if negative)
 Throat swab (preferably before giving antibiotics)–culture for
group A streptococcus
 Anti-streptococcal serology: both anti-streptolysin O and anti-
DNase B titres, if available (repeat 10–14 days later if 1st test not
confirmatory)

32.  Tests for alternative diagnoses, depending on
clinical features
 Repeated blood cultures if possible
endocarditis
 Joint aspirate (microscopy and culture) for
possible septic arthritis
 Copper, ceruloplasmin, anti-nuclear antibody,
drug screen for choreiform movements
 Serology and auto-immune markers for
arboviral, auto-immune or reactive arthritis

33.  Penicillin is the drug of choice and can be
given orally [as phenoxymethyl penicillin, 500
mg (250 mg for children< 27 kg) PO twice
daily, or amoxicillin 50 mg/kg (max 1 g) daily,
for 10 days] or as a single dose of 1.2 million
units (600,000 units for children 27 kg) IM
benzathine penicillin G.

34.  Aspirin is the drug of choice. An initial dose of 80–100
mg/kg per day in children (4–8 g/d in adults) in 4–5
divided doses is often needed for the first few days up
to 2 weeks.
 When the acute symptoms are substantially resolved,
the dose can be reduced to 60–70 mg/kg per day for a
further 2–4 weeks.
 Naproxen at a dose of 10–20 mg/kg per day has been
reported to lead to good symptomatic response.

35. Cases of severe carditis (causing heart failure)
with glucocorticoids in the belief that they
may reduce the acute inflammation and
result in more rapid resolution of failure.
Prednisone or prednisolone are recommended
at doses of 1–2 mg/kg per day (maximum, 80
mg). Glucocorticoids are often only required
for a few days or up to a maximum of 3 weeks

36.  Carbamazepine
 Sodium valproate
 Intravenous Immunoglobulin (Ivig)

37.  Primary Prevention
 Avoid overcrowded housing.

38.  Mainstay of primary prevention for ARF
remains primary prophylaxis (i.e., the timely
and complete treatment of group A
streptococcal sore throat with antibiotics

39.  Oral penicillin V (250 mg) can be given twice-
daily

40.  Benzathine penicillin G (1.2 million units, or
600,000 units if <27 kg) delivered every 4
weeks.
 Erythromycin (250 mg) twice daily.

41. Category of Patient Duration of Prophylaxis
Rheumatic fever without carditis For 5 years after the last attack or 21 years of a
(whichever is longer
Rheumatic fever with carditis but no residual
valvular disease
For 10 years after the last attack, or 21 years o
age (whichever is longer
Rheumatic fever with persistent valvular disease,
evident clinically or on echocardiography
For 10 years after the last attack, or 40 years o
age (whichever is longer). Sometimes lifelong
prophylaxis