Faculty of Medicine

University of Brawijaya
Rheumatic fever is an inflammatory disease
that appears as a delayed nonsuppurative
sequel to group A streptococcal infection of
the pharynx.
It affects the heart, joints, central nervous
system, skin, and subcutaneous tissues with
varying frequency
Clinical manifestation of RF
migratory polyarthritis
Fever
carditis
Sydenham's chorea,
subcutaneous nodules,
erythema marginatum.

Rheumatic fever is a clinical syndrome for which no specific
diagnostic test exists.
No symptom, sign, or laboratory test result is
pathognomonic, although several combinations of them
are diagnostic.
Its importance relates to involvement of
the heart, which, though rarely fatal
during the acute stage, may lead to
rheumatic valvular disease, a chronic
and progressive condition that causes
cardiac disability or death many years
after the initial event.
Antecedent infection of the upper
respiratory tract with group A
streptococcus is necessary for the
development of rheumatic fever.
This etiologic relation has been clearly
established by clinical, immunologic, and
epidemiologic studies.

Cutaneous streptococcal infection may lead
to acute glomerulonephritis but has never
been demonstrated to cause acute rheumatic
fever (ARF).
















At least one third of patients deny previous
sore throat, and cultures of the pharynx are
often negative for group A streptococci at the
onset of ARF.
An antibody response to streptococcal
extracellular products can be demonstrated
in almost all cases, and the attack rate of ARF
is strongly correlated with the magnitude of
the antibody response.

ARF is a major health problem in the
developing countries of Asia, Africa, Middle
East, and Latin America.
A World Health Organization survey
conducted between 1986 and 1990 estimated
the prevalence of ARF and chronic rheumatic
heart disease per 1000 schoolchildren to be
12.6 in Zambia, 10.2 in Sudan, and 7.9 in
Bolivia.


Hospital statistics from many
developing countries reveal that 10 to 35
percent of all cardiac admissions are for
ARF and rheumatic heart disease.
Most common among children in the 5
to 15 year age group.


No clear-cut sex predilection, although there
is a female preponderance in rheumatic
mitral stenosis and in Sydenham's chorea
occurring after puberty.
The attack rate of ARF following untreated
exudative tonsillitis varies, depending upon
the epidemiologic circumstances and the
rheumatogenic potential of prevalent
streptococcal strains.
The twentieth century witnessed a dramatic decline
in the incidence of ARF and rheumatic heart disease
in industrialized nations.

The reasons for this decline are unclear, but they
most likely relate to improved living standards
(including decreases in household crowding),
efficacy of antimicrobials in treatment of acute
streptococcal pharyngitis and prevention of
recurrent rheumatic attacks, and changes in the
rheumatogenicity of prevalent streptococcal strains.
13. Bisno AL. Group A streptococcal infections and acute rheumatic fever. N Engl J Med 1991;325:783793.
The exact mechanism by which group A streptococcus
causes ARF remains unexplained.
Possibilities include
(1) toxic effects of streptococcal products, particularly
streptolysins S or O, which are capable of inducing
tissue injury;
(2) a serum sicknesslike reaction; and
(3) autoimmune phenomena induced by similarity or
identity of certain streptococcal antigens to a wide
variety of human tissue antigens.
Although no mechanism has been unequivocally proven,
autoimmunity, or, more precisely, molecular mimicry,
appears to be most likely.
Even in severe epidemics of exudative
pharyngitis, ARF affects only a small
proportion of infected persons.
This fact, coupled with the known familial
aggregation of ARF cases, has long suggested
the possibility of a genetic predisposition
to rheumatic attacks.
ARF is characterized by exudative and proliferative
inflammatory lesions of the connective tissue, most
notably of the heart, joints, and subcutaneous
tissue.
When carditis ensues, all layers of the heart are
involved.
Pericarditis is common, and fibrinous pericarditis is
occasionally present.
The pericardial inflammation usually resolves over
time with no clinically significant sequelae
Endocardial involvement is responsible
for chronic rheumatic valvulitis.
Small fibrinous, verrucous vegetations, 1
to 2 mm in diameter, are seen on the
atrial surface at sites of valve coaptation
and on the chordae tendineae.
Healing of the valvulitis leads to
granulation and fibrosis of the leaflets and
fusion of the chordae.
Valvular stenosis or incompetence may
result.
The mitral valve is involved most
frequently, followed by the aortic valve.
ARF may involve different organ systems
such as heart, joints, skin, and central
nervous system.
The clinical picture depends upon the
systems involved, and the manifestations
may appear singly or in various combinations
General
High fever, lassitude, prostration, tachycardia
Cardiac
Cardiomegaly, congestive heart failure,
Acute pericarditis, pericardial effusion
Apical pansystolic murmur (mitral regurgitation)
Apical mid-diastolic murmur (Carey Coombs)
Basal diastolic (aortic regurgitation)


Dermatologic
Subcutaneous nodules
Erythema marginatum
Rheumatologic
Arthralgia
Migratory polyarthritis
Neurologic
Sydenham's chorea

The latent period from the onset of
streptococcal sore throat to the onset of
initial and recurrent attacks of ARF varies
between 1 and 5 weeks with a median of 19
days.
The mode of onset is quite variable. An
abrupt onset with fever and toxicity is
common in patients in whom acute
polyarthritis is the presenting complaint.
Carditis is the only manifestation of ARF
that has the potential to cause long-term
disability and death.
Severe valvular regurgitation may precipitate
intractable heart failure and may be fatal
during the acute phase of the disease.
Fortunately, this complication is quite rare.
Carditis usually appears within the first 3
weeks of the illness.
The cardiac involvement is frequently mild or
even asymptomatic, but occasionally the
course can be fulminant.
In most patients with acute rheumatic fever,
cardiac enzymes, such as troponin I, are
normal or only minimally elevated.

The diagnosis of carditis requires the
presence of one of the following four
manifestations:
(1) organic cardiac murmurs not
previously present,
(2) cardiomegaly,
(3) pericarditis, and
(4) congestive heart failure.
Arthritis is the most frequent major
manifestation of ARF.
Involvement of larger joints such as knees,
ankles, elbows, and wrists is more common.
Several joints are involved in quick
succession, and each for a brief period,
resulting in the typical picture of migratory
polyarthritis accompanied by signs and
symptoms of an acute febrile illness.
These nodules are seen in only 1 to 21 percent
of patients with ARF.
They are most often associated with carditis
and rarely appear as an isolated manifes-
tation of ARF.
They are round, firm, painless, freely movable
subcutaneous lesions varying in size from 0.5
to 2.0 cm.
This rash is usually found on the trunk and
proximal parts of the extremities, with the
face being spared.
It begins as an erythematous macule or
papule that extends outward while skin in the
center returns to normal.
Lesions may merge and form serpiginous
patterns.

They blanch on pressure, are never pruritic or
indurated, and are not influenced by anti-
inflammatory therapy.

The onset may be insidious or even
subclinical when mild carditis is the initial
manifestation.
Most attacks begin with polyarthritis, and
occasionally this may be preceded by
abdominal pain and fleeting signs of
peritoneal inflammation, which may be
misdiagnosed as acute appendicitis.

This neurologic disorder often occurs in
isolation, either unaccompanied by other
major manifestations of ARF or after a latent
period of several months, at a time when all
other manifestations of ARF have subsided.
It is characterized by rapid, purposeless,
involuntary movements, most noticeable in
the extremities and face.

The arms and legs flail about in erratic, jerky,
uncoordinated movements.
The speech is usually slurred and jerky.
The involuntary movements disappear during
sleep and may be suppressed by sedation.
The patient is unable to sustain a tetanic
muscular contraction.
Emotional lability is characteristic of
Sydenham's chorea and may often precede
other neurologic manifestations
Minor manifestations of ARF include
fever, arthralgia, and laboratory
evidences of inflammation.
Fever usually ranges from 38.4 to
40C (101.12F to 104) and rarely
lasts for more than 3 to 4 weeks.

Arthralgia is pain in one or more joints
without objective evidence for
inflammation.
When diagnosing ARF using the Jones
criteria, arthralgia should not be
considered a minor manifestation when
arthritis is present

Abdominal pain in ARF is the result of
peritoneal inflammation and may be
confused with acute appendicitis or
sickle cell crisis.
Because it occurs at the onset of the
illness, other manifestations of ARF may
not yet be present.

Epistaxis has been reported as a
manifestation of ARF, but it is not clear to
what extent it may be attributable to the
large doses of aspirin administered for
treatment of the disease.
Tachycardia may be out of proportion to
fever and persists during sleep.

A mild-to-moderate normochromic normocytic
anemia and leukocytosis with an increased
proportion of polymorphonuclear leukocytes are
common.
Elevated serum levels of C-reactive protein and an
increased erythrocyte sedimentation rate are
almost always present, indicating the presence of
acute inflammation.
An exception is "pure" chorea that may appear after
these markers of inflammation have returned to
normal.

Persistent sinus tachycardia that does not
resolve during sleep is common in the
presence of carditis.
Sinus bradycardia and sinus arrhythmia may
be present in some patients and can be
abolished by the administration of atropine.
Prolongation of the PR interval is a common
abnormality.
High probability of ARF:
Evidence of a preceding group A
streptococcal infection
Two major criteria
One major criteria plus two minor
criteria
rheumatoid arthritis,
juvenile rheumatoid arthritis,
systemic lupus erythematosus,
serum sickness, sickle cell crisis or cardiopathy,
rubella arthritis,
septic arthritis (especially gonococcal arthritis in
adolescent patients),
Lyme disease,
infective endocarditis,
viral myocarditis, and
early stages of Henoch-Schnlein purpura
systemic lupus erythematosus,
neoplasms involving the basal ganglia,
legionnaires' disease,
hypoparathyroidism,
antiphospholipid syndrome,
Wilson's disease, and
Huntington's disease.
Chorea is also seen occasionally in women taking
oral contraceptives and during pregnancy ("chorea
gravidarum").
Antibiotics neither modify the course of the
disease nor prevent the development of
rheumatic carditis
a course of antibiotics to eradicate group A
streptococci remaining in the pharynx and
tonsils is usually given
Penicillin G benzathine (1.2 million U
intramuscularly as a single injection) is the
treatment of choice for patients who are not allergic
to penicillin.
Erythromycin is prescribed for the penicillin-allergic
patient.
An oral cephalosporin is an acceptable alternative if
the penicillin allergy is not of the immediate type.
Following this, continuous prophylactic therapy is
given to prevent streptococcal pharyngitis
Anti inflammatory agents are given to
suppress the autoimmune response
Aspirin is effective . Aspirin is very effective in
reducing fever, toxicity, and inflammation of
the joints. It is given as tolerated in a dosage of
90 to 100 mg/kg per day in children and 6 to 8
g/day in adults in divided doses, every 4 h.
Corticosteroids are used if carditis is present
Corticosteroids are used in patients with
carditis manifested by heart failure and in
patients who do not tolerate aspirin or whose
symptoms do not respond well to this drug.

Prednisone 40 to 60 mg/day in divided doses
is given for 2 to 3 weeks, and the dosage is
gradually reduced over the following 3 weeks
Congestive heart failure is managed in the
conventional manner.
Digoxin should be used cautiously in the
presence of myocarditis.
After the acute attack subsides, the level of
physical activity is determined by the cardiac
status.
Patients without residual cardiac disease do
not require restriction of physical activity
Manifestations of chronic rheumatic heart
disease include MR and aortic regurgitation
or stenosis, congestive heart failure, and
atrial fibrillation.
The ultimate cardiac prognosis of an
individual ARF episode is rather directly
related to the severity of cardiac involvement
during the acute phase, provided that the
patient is protected from recurrent attack

The risk of developing ARF following a
symptomatic or asymptomatic streptococcal
infection is much higher in patients who have
experienced a previous attack than it is in
those who are nonrheumatic.
Recurrence rate following immunologically
confirmed streptococcal upper respiratory
infection has been as high as 16 percent.
It is therefore crucial that ARF
patients be protected optimally
from streptococcal infections.
This is accomplished by continuous
antimicrobial prophylaxis