An acute illness caused by an autoimmune response to infection with group A Streptococcus, leading to a range of possible symptoms and signs affecting any or all of heart, joints, brain, skin and subcutaneous tissues

1. Acute Rheumatic Fever
- Dr. Akif A.B

2. DEFINITION
 Acute rheumatic fever
 An acute illness caused by an autoimmune response to infection
with group A Streptococcus, leading to a range of possible
symptoms and signs affecting any or all of heart, joints, brain,
skin and subcutaneous tissues
 Rheumatic carditis
 Active inflammation of the heart tissues, most importantly the
mitral and/or the aortic valves, caused by acute rheumatic fever.
Rheumatic carditis can lead to chronic damage that remains after
the acute inflammatory episode has resolved
 Rheumatic heart disease
 The persistent damage to heart valves resulting in mitral and/or
aortic regurgitation, or in long-standing cases stenosis, that
remains as a result of acute rheumatic fever with rheumatic
carditis. Complications of rheumatic heart disease include heart
failure, embolic stroke, endocarditis and atrial fibrillation.

3. EPIDEMIOLOGY
 More than 2.4 million children have rheumatic
heart disease worldwide; 94% of these are in
developing countries
 Worldwide there are over 330,000 new cases of
acute rheumatic fever each year
 Overall, it is estimated that there are over 25
million people affected by rheumatic heart
disease leading to 345,000 deaths per year

4. Epidemiology of
Rheumatic Fever in India

5.  The burden of RF/RHD has been estimated and
reported since 1960s from hospital-based,
population-based [Table 2], and school-based
survey studies, using different case definitions
and screening methods.
 There are no survey studies estimating the
burden of RF/RHD based on national- and state
representative sample using uniform screening
method at the different timeline to evaluate the
trends of the burden of RF/RHD in India

6. HOSPITAL BASED STUDIES

7. HOSPITAL BASED STUDIES
 Hospital admission data show a decline in admission rates of RF/RHD overtime
period. RF/RHD accounted for 30%e50% of total admissions until the early
1980s, and it declined to 5% -26% in the late 1990s
 Whether the declining trends in admission rate truly reflects the decreasing
incidence is much to be debated
 Inadequacy of hospital statistics, varied hospital admission policies, and a large
number of corporate hospitals coming up can cause significant bias in hospital-
based data
 The emergence of an epidemic of coronary artery disease (CAD) and lack of
interest among cardiologists in RHD has further compounded the problem
 The only useful forgone conclusion can be derived from hospital statistics if the
data are derived from the same hospital over a different time period
 A study from territory care center in Orissa showed no change in admission rate
over a decade and the admission rate of 50% in 2013

8. Population-based survey
studies
 Data from population-based surveys are likely to
give us reliable estimates of the prevalence of
RF/RHD
 There are no data available about the prevalence
of RF/RHD based on active surveillance studies
in a representative sample of the country or the
state
 The available data are based on estimation
performed in cities or rural areas of certain
regions of the states in different points of time
using either clinical screening method alone or
confirmed by echocardiography

10. SCHOOL BASED SURVEYS

11. Survey studies with clinical
screening method (period 1960s to
1990s)
 The estimation of prevalence of RF/RHD among
school children performed in the period from
1970s until 1990s was based on clinical
screening method alone
 Thus, reported figures of prevalence have the
limitation of sensitivity and specificity of the cases
reported

13. Survey studies with clinical screening
confirmed by echocardiography (period
1990s to 2000)
 The epidemiological studies with clinical
screening followed by confirmation of suspected
cases with echocardiography using Doppler-
based World Health Organization criteria in urban
and rural school children in different regions of
the country from early 90s to early 2000s
reported prevalence ranging from 1.3/1000 to
6.4/1000
 The reported variation in the prevalence of
RF/RHD may be an indication of a varied burden
of RF/RHD across different regions, urban, rural
areas, and/or temporal trends apart from
methodological-related factors

16. ESTIMATED BURDEN OF
DISEASE
 From available data from RHD studies, the estimated
average prevalence is 0.5/1000 children in age group
of 5-15 years
 There are expected to be more than 3.6 million
patients of RHD estimated from 2011 census
 Almost 44,000 patients are added every year, and
expected mortality is 1.5%-3.3% per year
 These figures still may be the underestimation of
disease as no data are available from large populous,
underdeveloped states such Bihar, Jharkhand, and so
on

17.  Low Risk
 Children aged 5–14 years living in a community with
an incidence of RF of <2/100,000/year or
 Any age where the prevalence of chronic rheumatic
carditis is one or more/1000 per year are
considered low risk
 High Risk
 Children living in areas with an incidence of two or
more/100,000/year in children aged 5–14 years
 Prevalence of chronic rheumatic carditis more than
one/1000/year at any age are considered at a
moderate to high risk of developing the disease

20. RISK FACTORS

21. AGE
 The incidence of initial cases of ARF is highest in
children aged 5–14 years, although first episodes
do occur in younger children, with reported cases
of ARF in those as young as 2–3 years old
 Initial episodes can also occur in older
adolescents and adults, although cases in people
>30 years of age are rare
 By contrast, recurrent episodes often affect
slightly older children, adolescents and young
adults but are rarely observed beyond the age of
35–40 years

22. AGE
 RHD is a chronic disease caused by accumulated
heart valve damage from a single severe or, more
commonly, multiple recurrent ARF episodes
 This means that, although RHD occurs in
children, its prevalence peaks in adulthood,
usually between the ages of 25 years and 45
years

23. SEX
 ARF is equally common in males and females
 RHD occurs more commonly in females, with
a relative risk of 1.6 to 2.0 compared with
males
 In addition, these sex differences might be
stronger in adolescents and adults than in
children

24.  The reasons for this association are not clear, but
intrinsic factors such as greater autoimmune
susceptibility, as observed in systemic lupus
erythematosus
 Extrinsic factors such as greater exposure to GAS
infection in women than in men as a result of
closer involvement in child-rearing might explain
this difference
 In addition, women and girls might experience
reduced access to primary and secondary ARF
prophylaxis compared with men and boys, and
this could also contribute to differences in RHD
rates between females and males

25. Environmental factors
 Poverty and economic disadvantage
 Household overcrowding is perhaps the best
described risk factor and reduced
overcrowding has been cited as one of the
most important factors underlying the decline
in ARF incidence in wealthy countries during
the twentieth century

26. ORGANISM FACTORS
 ARF is exclusively caused by infection of the
upper respiratory tract with group A streptococci
 Although classically, certain M-serotypes
(particularly types 1, 3, 5, 6, 14, 18, 19, 24, 27,
and 29) were associated with ARF, in high-
incidence regions, it is now thought that any
strain of group A streptococcus has the potential
to cause ARF
 The potential role of skin infection and of groups
C and G streptococci is currently being
investigated

27. HOST FACTORS
 Approximately 3–6% of any population may be
susceptible to ARF
 44% concordance in monozygotic twins compared to
12% in dizygotic twins
 Some human leukocyte antigen (HLA) class II alleles,
particularly HLA-DR7 and HLA-DR4, appear to be
associated with susceptibility
 Whereas other class II alleles have been associated
with protection (HLA-DR5, HLA-DR6, HLA-DR51,
HLA-DR52, and HLA-DQ)

28. IMMUNE RESPONSE
 Most widely accepted theory of rheumatic fever
pathogenesis is based on the concept of
molecular mimicry, whereby an immune response
targeted at streptococcal antigens (mainly
thought to be on the M protein and the N-
acetylglucosamine of group A streptococcal
carbohydrate) also recognizes human tissues
 An alternative hypothesis proposes that the initial
damage is due to streptococcal invasion of
epithelial surfaces, with binding of M protein to
type IV collagen allowing it to become
immunogenic, but not through the mechanism of
molecular mimicry.

29. Pathogenesis
 After GAS infection of the pharynx, neutrophils,
macrophages and dendritic cells phagocytose
bacteria and present antigen to T cells
 Both B and T cells respond to the GAS infection,
initially by antibody production (IgM and IgG) and
subsequently through T cell activation (mainly CD4+
cells)
 In susceptible individuals, the host response against
GAS will trigger autoimmune reactions against host
tissues mediated by both Streptococcus spp.-specific
antibodies and T cells through a process called
molecular mimicry

31. PATHOLOGY

36. CLINICAL FEATURES

37.  There is a latent period of ~3 weeks (1–5 weeks)
between the precipitating group A 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
 Although many patients report a prior sore throat,
the preceding group A streptococcal infection is
commonly subclinical; in these cases, it can only
be confirmed using streptococcal antibody testing

38.  The most common clinical features are
polyarthritis (present in 60–75% of cases) and
carditis (50–60%)
 The prevalence of chorea in ARF varies
substantially between populations, ranging from
<2 to 30%
 Erythema marginatum and subcutaneous nodules
are now rare, being found in <5% of cases

39. HEART INVOLVEMENT
 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.
 Damage to the pulmonary or tricuspid valves is
usually secondary to increased pulmonary pressures
resulting from left-sided valvular disease.

40. Valve involvement Prevalance
Isolated MS 25%
Combined MS and MR 40%
MS + Aortic Valve 35%
MS + Tricuspid valve
involvement
6%

41.  Early valvular damage leads to regurgitation.
 Over ensuing years, usually as a result of recurrent
episodes,leaflet thickening, scarring, calcification, and
valvular stenosis may develop
 Therefore, the characteristic manifestation of
carditis in previously unaffected individuals is mitral
regurgitation, sometimes accompanied by aortic
regurgitation
 Myocardial inflammation may affect electrical
conduction pathways, leading to P-R interval
prolongation (first-degree atrioventricular block or
rarely higher level block)

42. JOINT INVOLVEMENT
 Joint involvement is seen in 70% of patients
 The joint pain is typically described as “migratory,”
which refers to the sequential involvement of
joints, with inflammation resolving in one joint and
then beginning in another joint
 In some cases the joint involvement may be
additive rather than migratory, with simultaneous
involvement of several joints

43.  The affected joint may be inflamed for only a few days to 1 week before
the inflammation subsides
 The polyarthritis is severe for approximately 1 week in two thirds of
patients and may last another 1 to 2weeks in the remainder before it
resolves completely
 If joint swelling persists after 4 weeks, it becomes necessary to
consider other conditions, such as juvenile idiopathic arthritis or
systemic lupus erythematosus (SLE)
 At the onset of the illness the joint involvement is asymmetric and
usually affects the lower limbs initially before spreading to the upper
limbs
 Monoarthritis has been reported in 17% to 25% of patients
 The large joints such as the knees, ankles, elbows, and wrists are most
frequently involved

44. Jaccoud arthritis or
arthropathy
 chronic post–rheumatic fever arthropathy is a rare
manifestation of rheumatic fever characterized by
deformities of the fingers and toes
 There is ulnar deviation of the fingers, especially the fourth
and fifth fingers, flexion of the metacarpophalangeal joints,
and hyperextension of the proximal interphalangeal joints
(i.e., swan neck deformity)
 The hand is usually painless, and there are no signs of
inflammation
 The deformities are usually correctible but may become
fixed in the later stages
 There are no true erosions on radiography, and the
rheumatoid factor is usually negative

45. CHOREA
 Sydenham’s chorea commonly occurs in the absence of other
manifestations
 Prolonged latent period after group A streptococcal infection, and
is found mainly in females
 The choreiform movements affect particularly the head (causing
characteristic darting movements of the tongue) and the upper
limbs
 They may be generalized or
restricted to one side of the body
(hemi-chorea)
 Lasts from 6weeks to 6 months

46. ERYTHEMA MARGINATUM
 It begins as 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

47. SUBCUTANEOUS NODULES
 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 2–3
weeks after the onset of disease, last for just a
few days up to 3 weeks, and are commonly
associated with carditis

49.  Fever occurs in most cases of ARF, although
rarely in cases of pure chorea
 Although high-grade fever (=39°C) is the rule,
lower grade temperature elevations are not
uncommon
 Elevated acute-phase reactants are also present
in most cases

50. DIAGNOSIS

52. EVOLUTION OF JONES
CRITERIA

54. Erythema marginatum was elevated to a major status, and evidence of
preceding beta-hemolytic
Streptococcal infection was accorded minor status
Minor criteria (abdominal and precordial pain, epistaxis, pulmonary findings
and anemia) were
Dropped
The most prominent difference, however, was the downgrading of arthralgia and
previous rheumatic fever or rheumatic heart disease to a minor status

55. REVISED JONES CRITERIA-
1965
 Distinguishing feature of this revision as the
necessity of demon strating evidence of recent
streptocoecal infection.
 This followed the recognition of the
streptococcal etiology of rheumatic fever, and of
the fact that streptococcal antibodies could be
demonstrated in the great majority of patients
with rheumatic fever

61. EVIDENCE OF A PRECEDING
GROUP A
STREPTOCOCCAL INFECTION
 With the exception of chorea and low-grade
carditis, both of which may become manifest
many months later, evidence of a preceding
group A streptococcal infection is essential in
making the diagnosis of ARF
 Because most cases do not have a positive throat
swab culture or rapid antigen test, serologic
evidence is usually needed
 The most common serologic tests are the anti-
streptolysin O (ASO) and anti-DNase B (ADB)

62.  The antistreptolysin O test is usually obtained
first, and if it is not elevated, an
antideoxyribonuclease B test may be performed
 Antistreptolysin O titers begin to rise
approximately 1 week and peak 3 to 6 weeks
after the infection
 Antideoxyribonuclease B titers begin to rise 1 to 2
weeks and peak 6 to 8 weeks after the infection

64. Raised antistreptolysin O level
(ASO)
 Rheumatic fever
 Glomerulonephritis
 Endocarditis.
 Scarlet fever
 Titres >200IU (160 Todd Units)

65. TREATMENT

66.  The aim of treatment of a proven attack of
rheumatic fever is:
 To suppress the inflammatory response and thus
minimize the effects of inflammation on the heart
and joints
 To eradicate the GAS from the pharynx
 To provide symptomatic relief
 To commence secondary prophylaxis

67. Unconfirmed diagnosis,
presenting with monoarthritis
 If acute rheumatic fever is suspected, admission
to the hospital for observation and further
investigation is indicated
 Salicylate therapy is usually withheld pending
confirmation of the diagnosis, and simple
analgesics such as paracetamol or codeine are
recommended in the interim
 Salicylates are withheld to facilitate diagnosis;
they reduce arthritic pain but do not affect the
long-term outcome of the disease

68. Confirmed acute rheumatic
fever
 The outcome of rheumatic valvular lesions has not been
shown to be affected by the administration of penicillin
during an episode of acute rheumatic fever
 However, penicillin is recommended by the authors to
ensure eradication of streptococci in the throat whether
there has been a positive throat culture or not
 The choice is either oral phenoxymethylpenicillin (penicillin
V) for 10 days or a single injection of benzathine
benzylpenicillin
 As penicillin is the first-line choice for secondary
prophylaxis it is recommended that a patient with reported
penicillin allergy be investigated carefully

69. ANTIBIOTICS
 Even though throat swabs taken during the acute attack of
rheumatic fever are rarely positive for GAS, it is advisable for
patients to receive
 Thereafter, secondary prophylaxis should be commenced All
patients with ARF should receive antibiotics sufficient to treat the
precipitating group A streptococcal infection
 Penicillin is the drug of choice
Antibiotics Dose Duration
Benzathine
penicillin G
1.2 million units
(600,000 units for
children ≤27 kg)
Single dose I.M
Amoxicillin 50 mg/kg
(maximum, 1 g)
10days
Phenoxymethyl
penicillin
(Penicillin V)
500 mg [250 mg
for children ≤27
kg] PO twice
daily
10days

70. CARDITIS
 Most patients with mild or moderate carditis without cardiac failure do
not require any therapy
 A subset of patients with carditis who develop cardiac failure do require
treatment:
 Bed rest with ambulation as tolerated
 Medical management of heart failure; first-line therapy is diuretics, and
ACE inhibitors may be added in severe heart failure or where aortic
regurgitation is present
 Despite the absence of high-quality evidence to support the use of
glucocorticoid therapy for patients with carditis and severe heart failure,
there is consensus among clinicians treating rheumatic fever that the
use of glucocorticoids can speed recovery
 Two meta-analyses have failed to show any benefit of glucocorticoids
over placebo, although contributing studies were old and generally of
low quality
 There is no evidence that salicylates or intravenous immunoglobulin
(IVIG) improve the outcome from carditis in rheumatic fever and we do

71. BED REST
 The longstanding recommendation of bed rest
would appear to be appropriate mainly to lessen
joint pain
 The duration of bed rest should be individually
determined, but ambulation can usually be
started once the fever has subsided and acute-
phase reactants are returning to normal
 Strenuous exertion should be avoided, especially
for those with carditis

72. SALICYLATES AND NSAIDs
 These may be used for the treatment of arthritis, arthralgia, and fever,
once the diagnosis is confirmed
 They are of no proven value in the treatment of carditis or chorea
 Aspirin is the drug of choice, delivered at a dose of 50–60 mg/kg per
day, up to a maximum of 80–100 mg/kg per day (4–8 g/d in adults) in 4–
5 divided doses
 Fever, joint manifestations, and elevated acute phase reactants
sometimes recur up to 3 weeks after the medication is discontinued
 This does not indicate a recurrence and can be managed by
recommencing salicylates for a brief period
 Naproxen at a dose of 10–20 mg/kg per day is a suitable alternative to
aspirin and has the advantage of twice-daily dosing

73. CHOREA MANAGEMENT
 Medications to control the abnormal movements do not
alter the duration or outcome of chorea
 Milder cases can usually be managed by providing a calm
environment
 In patients with severe chorea, carbamazepine or sodium
valproate is preferred to haloperidol
 A response may not be seen for 1–2 weeks, and
medication should be continued for 1–2 weeks after
symptoms subside
 There is recent evidence that corticosteroids are effective
and lead to more rapid symptom reduction in chorea

74. PROGNOSIS
 Untreated, ARF lasts on average 12 weeks
 With treatment, patients are usually discharged
from hospital within 1–2 weeks
 Inflammatory markers should be monitored every
1–2 weeks until they have normalized (usually
within 4–6 weeks), and an echocardiogram
should be performed after 1 month to determine if
there has been progression of carditis

75. PRIMARY PROPHYLAXIS
 The mainstay of primary prevention for ARF
remains primary prophylaxis (i.e., the timely and
complete treatment of group A streptococcal sore
throat with antibiotics)
 If commenced within 9 days of sore throat onset,
a course of penicillin (as outlined above for
treatment of ARF) will prevent almost all cases of
ARF

77.  ARF can recur as a result of subsequent GAS
infections and each recurrence can worsen RHD
 Thus, the priority in disease management is to
prevent ARF recurrences using long-term
penicillin treatment, which is known as secondary
prophylaxis

78. SECONDARY PROPHYLAXIS
 The best antibiotic for secondary prophylaxis is benzathine
penicillin G (1.2 million units, or 600,000 units if ≤27 kg)
delivered every 4 weeks
 It can be given every 3 weeks, or even every 2 weeks, to
persons considered to be at particularly high risk, although
in settings where good compliance with an every-4-week
dosing schedule can be achieved, more frequent dosing is
rarely needed
 Oral penicillin V (250 mg) can be given twice daily instead
but is less effective than benzathine penicillin G
 Penicillin-allergic patients can receive erythromycin (250
mg) twice daily.

80. AHA Recommendations

81. WHO Criteria