This document provides information on acute rheumatic fever (RF), including its causes, presentation, diagnosis, treatment, and prognosis. RF is an autoimmune disease that occurs after a streptococcal throat infection in genetically susceptible individuals. It commonly affects children ages 5-15 and can involve the heart, joints, brain, and skin. Diagnosis requires supporting evidence of a recent streptococcal infection via antibody testing. Treatment involves anti-inflammatory drugs like aspirin and corticosteroids. Recurrences increase the risk of rheumatic heart disease, so long-term antibiotic prophylaxis is important. The prognosis depends on initial severity and recurrences, with carditis carrying the greatest risk of permanent heart damage.

1. ACUTE RHEUMATIC FEVER
DR.HASHMI.S

2.  Rheumatic fever (RF) is an autoimmune, multiorgan
inflammatory disease that occurs as a result of group A β-
hemolytic streptococcal infection in genetically susceptible
individuals
 Prevalence of acute rheumatic fever and rheumatic heart
disease (RHD) in Indian population varies from 0.5 /1000 to
11/1000 in various studies.
 The disease actually has it’s roots in childhood (5-15 yr)
 Latent period of 1‐3weeks

3.  About 50% of children with ARF will suffer from RHD
 Sex–Both sex Equally Affected
 Not all serotypes of GAS can cause rheumatic fever.
 When some GAS strains (e.g., M type 4) caused acute
pharyngitis in a very susceptible rheumatic population, there
were no recurrences of RF.
 Certain serotypes of GAS (M types 1, 3, 5, 6, 18, 29) are
more frequently isolated from patients with acute RF than are
other serotypes.

4.  Predisposing Factor s–
 – 1.Low Socioeconomic status
 – 2.Over crowding
 – 3.Poor Medical Care

5. PATHOLOGIC LESIONS
 Fibrinoid degeneration of connective tissue,
 inflammatory edema
 inflammatory cell infiltration & proliferation of specific cells
• ASHCOFF NODULES,
• Pancarditis in the heart
• Arthritis in the joints
• Ashcoff nodules in the subcutaneous tissue
• Basal gangliar lesions resulting in chorea

6. PATHOGENESIS
 1.Cytotoxicity theory: Enzymes like streptolysin O cause tissue
damage
 2.Immune-mediated pathogenesis:
 The antigenicity of several GAS cellular and extracellular
epitopes and their immuno- logic cross reactivity with cardiac
antigenic epitopes also lends support to the hypothesis of
molecular mimicry – e.g., Common epitopes are shared between
certain GAS components (e.g., M protein, cell membrane, group
A cell wall carbohydrate, capsular hyaluronate) and specific
mammalian tissues (e.g., heart valve, sarcolemma, brain, joint)

8. certain rheumatogenic M proteins (M1, M5, M6, and M19)
share epitopes with human myocardial proteins such as
tropomyosin and myosin.
 3. Binding of an M protein N-terminus domain to a region of
collagen type IV leads to an antibody response to the
collagen, resulting in ground substance inflammation
especially in subendothelial areas like cardiac valves and
myocardium.

11. THE MODIFICATIONS INTRODUCED IN 2015
IN THE JONES CRITERIA ARE AS FOLLOWS:
 In the major criteria:
 Low risk population: clinical and/or subclinical
carditis. AHA recommends that all the patients with
suspected RF undergo Doppler echocardiographic
examination, even if no clinical signs of carditis are
present . In doubtful cases it is recommended that
echocardiography is repeated.
 Medium and high risk population: also clinical and/or
subclinical carditis and arthritis – monoarthritis or
polyarthritis, possibly also with polyarthralgia

12.  In the minor criteria:
 Low risk population: the parameters of inflammation
and the level of fever were defined precisely.
 Medium and high risk population: monoarthralgia,
also with defined parameters of inflammation and the
level of fever.

16.  Involvement of the spine, small joints of the hands and feet,
or hips is uncommon.
 Rheumatic joints are classically hot, red, swollen, and
exquisitely tender, with even the friction of bedclothes being
uncomfortable.
 severely inflamed joint can become normal within 1-3 days
without treatment, even as 1 or more other large joints
become involved.
 Severe arthritis can persist for several weeks in untreated
patients.

17.  Monoarticular arthritis is unusual unless antiinflammatory
therapy is initiated prematurely, aborting the progression of the
migratory polyarthritis
 If a child with fever and arthritis is suspected to have acute RF,
it is better to withhold salicylates and observe for migratory
progression.
 A dramatic response to even low doses of salicylates is another
characteristic feature of the arthritis, and the absence of such a
response should suggest an alternative diagnosis.

18.  Synovial fluid in acute RF usually has 10,000-100,000 white
blood cells/μL with a predominance of neutrophils, protein
level of approximately 4 g/dL, normal glucose level, and
forms a good mucin clot.
 Frequently, arthritis is the earliest manifestation of acute RF
and may correlate temporally with peak antistreptococcal
antibody titers.
 There is often an inverse relationship between the severity of
arthritis and the severity of cardiac involvement.

19.  In Moderate/High-Risk populations only, monoarthritis in the
absence of prior inflammatory therapies, or even
polyarthralgia without frank objective signs of arthritis, can
fulfill this major criterion.
 Before polyarthralgia should be considered a major
criterion in the Moderate/High-Risk population, other
potential causes should be excluded.

24. A major change in the 2015 revision
of the Jones Criteria :acceptance of
• subclinical carditis (defined as without a murmur of
valvulitis but with echocardiographic evidence of valvulitis)
• clinical carditis (with a valvulitis murmur) as fulfilling the
major criterion of carditis in all populations.

25. • Echocardiographic
(Doppler) criteria:
THE
ECHOCARDIOGRAPHIC
CRITERIA DEVELOPED
BY AHA IN 2012 ARE AS
FOLLOWS

26. Pathological
mitral
regurgitation
– 4 criteria
(all must be
met)
Visible at
least in 2
projections.
Regurgitation jet
length >/=2 cm
atleast in one
projection
Regurgitation
peak velocity > 3
m/s.
Regurgitation
pansystolic.

27. Pathological
aortic
regurgitation – 4
criteria (all must
be met):
Visible at
least in 2
projections.
Regurgitation
jet length ≥ 1
cm at least in 1
projection.
Regurgitation
peak velocity
> 3 m/s.
Regurgitation
pandiastolic.

28. ECHOCARDIOGRAPHIC
MORPHOLOGICAL CRITERIA

29. Acute mitral
valve
involvement
Dilatation of
mitral
annulus.
Elongation
of chordae
tendineae.
Rupture of
chorda
tendinea with
acute mitral
regurgitation.
Prolapse of
anterior
(less often
posterior)
leaflet.
Nodular
lesions on
leaflets.

30. chronic
mitral valve
involvement
Thickening of
leaflets.
Thickening of
chordae
tendinea, with
their fusion.
Limited
mobility of
leaflets.
Calcifications.

31. ACUTE AND
CHRONIC
AORTIC VALVE
INVOLVEMENT:
Symmetrical
or focal
thickening of
leaflets.
Disturbed
leaflet
coaptation
(leaflet closing
during systole).
Limited
mobility of
leaflets.
Prolapse of
leaflets

32.  most serious manifestations of acute RF: Carditis and resultant
chronic rheumatic heart disease and account for essentially all
the associated morbidity and mortality.
 Rheumatic carditis is characterized by pancarditis
 Endocarditis (valvulitis) is a universal finding in rheumatic
carditis, whereas the presence of pericarditis or myocarditis is
variable.
 Myocarditis and/or pericarditis without clinical evidence of
endocarditis almost never is rheumatic carditis; alternate
etiologies (especially viral) need to be sought.

33.  Most rheumatic heart disease is isolated mitral valvular
disease or combined aortic and mitral valvular disease.
 Isolated aortic or right-sided valvular involvement is quite
uncommon.
 Serious and long-term illness is related entirely to the severity
of valvular heart disease as a consequence of a single attack or
recurrent attacks of acute RF.

34. mitral and/or aortic valvular stenosis usually
appears years or even decades after the acute
illness.
Valvular insufficiency is characteristic of
both acute and convalescent stages of acute
RF

35.  Developing countries:acute RF often younger age, mitral
stenosis and aortic stenosis may develop sooner after acute RF
than in developed countries and can occur in young children.
 Echocardiographic findings include pericardial effusion,
decreased ventricular contractility, and aortic and/or mitral
regurgitation.

36.  Mitral regurgitation high-pitched apical holosystolic
murmur radiating to the axilla.
 Significant MR, this + apical mid-diastolic murmur of
relative mitral stenosis.
 Aortic insufficiency  high-pitched decrescendo diastolic
murmur at the left sternal border.
 Carditis occurs in approximately 50–60% of all cases of acute
RF.

37.  Recurrent attacks of acute RF in patients who had
carditis with their initial attack are associated with high
rates of carditis with increasing severity of cardiac
disease.
 The major consequence of acute rheumatic carditis is
chronic, progressive valvular disease, particularly
valvular stenosis, which can require valve replacement.

38. CHOREA

39. CHOREA
Emotional
lability
Incoordination
poor school
performance
uncontrollable
movements
facial
grimacing
all exacerbated by stress and disappearing with sleep.

40. Chorea occasionally is unilateral
(hemichorea).
Onset can be insidious, with symptoms being
present for several months before recognition.
Diagnosis :clinical findings +
supportive evidence of GAS
antibodies
rarely if ever leads to permanent neurologic
sequelae.

42. • Non tender
• Late manifestation
•Occur around 6 weeks after onset of
RF

43. RECENT GROUP A STREPTOCOCCUS INFECTION
 An absolute requirement for the diagnosis of acute RF is
supporting evidence of a recent GAS infection.
 Acute RF typically develops 10-21 days after an acute episode of
GAS pharyngitis  clinical findings of pharyngitis are no longer
present and only 10–20% of patients still harbor GAS in the
throat.
 One third of patients with acute RF have no history of an
antecedent pharyngitis.
 Therefore, evidence of an antecedent GAS infection is usually
based on elevated or rising serum antistreptococcal antibody
titers.

44.  Slide agglutination test (Streptozyme) : detect antibodies
against 5 different GAS antigens.
 If only a single antibody is measured (usually anti–
streptolysin O) only 80–85% of patients with acute
RF have an elevated titer;
 95– 100% have an elevation if 3 different antibodies (anti–
streptolysin O, anti– DNase B, antihyaluronidase) are
measured.
Advantage Disadvantage
Rapid Lees standardised
Simple to perform Less reproducible
Widely available

45.  Therefore, when acute RF is suspected clinically, multiple
antibody tests should be performed.
 Except for chorea, the clinical findings of acute RF generally
coincide with peak antistreptococcal antibody responses.
 Most patients with chorea have elevation of antibodies to at
least 1 GAS antigen.

50. ARTHRITIS/CARDITIS
 Anti inflammatory agents (e.g., salicylates, corticosteroids)
should be withheld if arthralgia or atypical arthritis is the only
clinical manifestation of presumed acute RF.
 Premature treatment with one of these agents may interfere
with the development of the characteristic migratory
polyarthritis and thus obscure the diagnosis of acute RF.
 Acetaminophen  pain and fever.

51. TYPICAL
MIGRATORY
POLYARTHRITIS
CARDITIS WITHOUT
CARDIOMEGALY OR
CONGESTIVE
HEART FAILURE

52. ASPIRIN
50-70 mg/kg/day in 4 divided
doses (PO) for 3-5 days,
50 mg/kg/day in 4 divided doses
PO x 2-3 wk
half that dose for another 2-4
wk.

53. CORTICOSTEROIDS carditis and more than
minimal cardiomegaly
and/or congestive heart
failure

54. When prednisone is being tapered, start aspirin 50 mg/kg/day in
4 divided doses for 6 wk to prevent rebound of inflammation.
tapering of the dose by 5 mg/24 hr every 2-3 days.
1mg/kg/day for 2-3 wk
2 mg/kg/day in 4 divided doses for 2-3 wk,

55.  Supportive therapies for moderate to severe carditis : digoxin,
fluid and salt restriction, diuretics,and oxygen.
 The cardiac toxicity of digoxin is enhanced with myocarditis.
 Termination of the antiinflammatory therapy may be followed
by the reappearance of clinical manifestations or of elevation
in ESR and CRP (rebound).
 It may be prudent to increase salicylates or corticosteroids
until near normalization of inflammatory markers is achieved.

56. DOES VALVE SURGERY HAVE A ROLE?
 Occasionally, costly open heart surgery may be the only option
to manage severe heart valve lesions that occur in patients with
rheumatic heart disease.
 The timing of valve surgery is significant because the presence
of active rheumatic carditis at the time of surgery is an important
predictor of valve failure and the need for reoperation.
 Several studies have shown that valvular regurgitation and not
myocarditis is the cause of heart failure in patients with active
rheumatic carditis.

57.  Although aggressive medical therapy may provide temporary
improvement, surgical treatment of severe valve lesions in
patients with acute carditis and heart failure may be a lifesaving
measure.
 Valve replacement under these circumstances may be the
preferred surgical option.
 Repair of a damaged valve is the procedure of choice overall
because it avoids the risk of many of the complications of
prosthetic valves, including thromboemboli, bleeding, and
teratogenic events associated with warfarin administration, and
also the poor durability of bioprosthetic valves in younger
patients.
 All patients undergoing surgery require secondary prophylaxis.

58. SYDENHAM CHOREA
Anti
inflammatory
agents are usually
not indicated.
Sedatives early
in the course of
chorea;
phenobarbital
(16-32 mg every 6-8 hr PO)
If phenobarbital is ineffective,
haloperidol (0.01-0.03 mg/kg/24 hr divided
twice daily PO)
chlorpromazine (0.5 mg/kg every 4-6 hr PO)
should be initiated.
Some patients
may benefit from
a few-week
course of
corticosteroids

59. PROGNOSIS
 The prognosis for patients with acute rheumatic fever depends
on the clinical manifestations present at the initial episode, the
severity of the initial episode, and the presence of recurrences.
 Approximately 50–70% of patients with carditis during the
initial episode of acute RF recover with no residual heart
disease; the more severe the initial cardiac involvement, the
greater the risk for residual heart disease.
 Patients without carditis during the initial episode are less
likely to have carditis with recurrent attacks, but there is a
stepwise increase in cardiac involvement as the number of
episodes increases

60.  In contrast, patients with carditis during the initial episode
are very likely to have carditis with recurrences, and the risk
for permanent heart damage increases with each recurrence.
 Patients who have had acute RF are susceptible to recurrent
attacks following reinfection of the upper respiratory tract
with GAS, with approximately 50% risk with each GAS
pharyngitis.
 Therefore, these patients require long-term continuous
chemoprophylaxis.
 Before antibiotic prophylaxis was available, 75% of patients
who had an initial episode of acute RF had 1 or more
recurrences in their lifetime.

61.  These recurrences were a major source of morbidity and
mortality.
 The risk of recurrence is highest in the 1st 5 yr after the initial
episode and decreases with time.
 Approximately 20% of patients who present with “pure”
chorea who are not given secondary prophylaxis develop
rheumatic heart disease within 20 yr.
 Therefore, patients with chorea, even in the absence of other
manifestations of RF, require long-term antibiotic prophylaxis

62. PREVENTION

63. PRIMARY
 Appropriate antibiotic therapy instituted before the 9th day of
symptoms of acute GAS pharyngitis is highly effective in
preventing first attacks of acute RF.
 However, approximately 30% of patients with acute RF do
not recall a preceding episode of pharyngitis and did not seek
therapy.

64. SECONDARY

65. RF;No
carditis
5 - 10 yrs from last
episodeOR till 21 years of
age(whichever is longer)
RF; Carditis
–no residual
RHD
10 yrs from last episode or till 25
yrs(whichever is longer)
RF
Carditis;RHD
10 yrs from last episode or till 40 yrs age
(whichever is longer)
Gerber MA, Baltimore RS, Eaton CB, et al: Prevention of rheumatic fever and diagnosis
and treatment of acute streptococcal pharyngitis
Secondary Prophylaxis–How Long to give ?

66.  In certain highrisk patients, and in certain areas of the world
where the incidence of rheumatic fever is particularly high, use
of benzathine penicillin G every 3 wk may be necessary
because serum concentrations of penicillin may decrease to
marginally effective levels after 3 wk.
 In In the United States, administration of benzathine
penicillin G every 3 wk is recommended only for those who
have recurrent acute RF despite adherence to a 4 wk regimen.

67. NEWER MODES OF TREATMENT
 IVIG
 Valproate for chorea
 Anti-cytokine adjuvants

68.  IVIG did not alter the natural history of ARF, with no
detectable difference in the clinical, laboratory, or
echocardiographic parameters of the disease process during
the subsequent 12 months.
 Recent work has indicated that intravenous immunoglobulin
(IVIG) may be of benefit in immune-mediated cardiac
disorders.
 This is seen particularly in Kawasaki disease, in which the use
of high-dose IVIG markedly reduces the prevalence of
coronary artery abnormalities.
 Intravenous Immunoglobulin in Acute Rheumatic Fever A Randomized Controlled Trial L. M. Voss
, N. J. Wilson , J. M. Neutze , R. M. L. Whitlock , R. V. Ameratunga , L. M. Cairns , and D. R. Lennon
Originally published23 Jan 2001https://doi.org/10.1161/01.CIR.103.3.401Circulation. 2001;103:401–406

69.  Plasma concentrations of inflammatory cytokines (IL-1
alpha, IL-1 beta, IL-6, IL-8 and TNF alpha) were determined
by ELISA in 27 patients with acute rheumatic fever (RF), 12
with only arthritis (RFA) and 15 with rheumatic heart disease
(RHD), before, during and after treatment.
 These findings suggest that inflammatory cytokines, as TNF
alpha, IL-8 and IL-6, may play a pathogenic role in rheumatic
fever.

70.  The occurrence of numerous M protein serotypes that are
rheumatogenic has complicated the development of vaccines, and
research is ongoing.
 Vaccines such as the 26 valent type specific one are already in phase II
human trials, and the C region M protein peptide vaccine, which is
almost ready for trials in humans, may offer some hope for protection
against streptococcal pharyngitis in the future.
 A more recent study in animals showed that giving antisurface bound
C5a peptidase serum by the intranasal route protected mice against
streptococcal infection.
 Its use in humans may prevent colonisation and infection of the human
pharynx, thereby eliminating potential reservoirs that maintain
endemic disease