RHEUMATIC
FEVER
“It licks the joints, but bites the heart”.
(French Physician Ernst-Charles Lasegue 1884)
BEN WAKA
CHIEF CONSULTANT
UMB/19-A/189
FACILITATOR; DR. JULIANA
OBJECTIVES
• Definition
• Epidemiology & etiology
• Pathogenesis & pathophysiology
• Clinical presentation
• Diagnostic evaluation
• Treatment
• Prognosis
DEFINITION
• Acute rheumatic fever (ARF) is an inflammatory disease resulting from an
autoimmune reaction to infection with group A streptococci.
• It affects the heart, joints, central nervous system and subcutaneous tissue.
cardiac valvular damage [rheumatic heart disease (RHD)], may persist after
the other features have disappeared
• Following the initial pharyngitis, a latent period of two to three weeks
occurs before the first signs or symptoms of ARF appear
• The disease presents with various manifestations that may include
arthritis, carditis, chorea, subcutaneous nodules, and erythema
marginatum.
EPIDEMIOLOGY
• Acute rheumatic fever (ARF) usually affects children (most commonly
between 5 and 15 years) or young adults,
• It was recently estimated that among indigenous groups and developing
nations between 15 to 19 million people are affected by RHD, with
approximately one-quarter of a million deaths occurring each year.
• it remains endemic in parts of Asia, Africa and South America, with an annual
incidence in some countries of more than 100 per 100 000;
• It is the most common cause of acquired heart disease in childhood and
adolescence.
• Risk factors include: overcrowding, poverty, age, nutrition and genetic
susceptibility.
ETIOLOGY
• Epidemiologic studies suggest an individual propensity to develop rheumatic fever,
a nonsuppurative complication of group A streptococcal infection of the upper
respiratory tract must occur, which occurs most commonly in children 5 to 15 years
of age.
• Streptococcus pyogenes (b-hemolytic group A streptococci) cause both superficial
infections (e.g. pharyngitis, impetigo) and invasive diseases.
• Rheumatic fever occurs in 3% of patients who carry an infecting strain for more
than 3 weeks after convalescence, whereas persons carrying the organism for less
than 3 weeks have an incidence of only 0.3%.
• Patients with streptococcal infections and a history of previous rheumatic fever
have a 5 to 50% greater incidence of rheumatic fever than do patients with no prior
history of the disease; this tendency declines with age.
• Environmental factors (latitude, altitude, humidity), nutrition, crowding, and age
appear to influence the incidence of rheumatic fever, probably because the same
factors influence the incidence of streptococcal infection.
PATHOGENESIS
• A streptococcal pharyngeal infection is required, and genetic susceptibility may be
present.
• 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
• Following the initial pharyngitis, a latent period of two to three weeks occurs
before the first signs or symptoms of ARF appear
• The ability of group A streptococcus to cause disease is highly dependent on M
protein, which in the non immune host mediates an anti-phagocytic effect by
inhibiting the alternative pathway of complement activation.
• Acquired immunity to GAS infection is based on the development of opsonic
antibodies directed against the antiphagocytic epitopes of M protein.
• Epitopes present in the cell wall, cell membrane, and the A, B, and C repeat regions
of the streptococcal M protein are immunologically similar to molecules in human
myosin, tropomyosin, keratin, actin, laminin, vimentin, and N-acetylglucosamine.
• This molecular mimicry is the basis for the autoimmune response that leads to ARF.
• It has been hypothesized that human molecules—particularly epitopes in cardiac
myosin—result in T cell sensitization. These T cells are then recalled following
subsequent exposure to group A streptococci bearing immunologically similar
epitopes.
• The pathognomonic lesion of rheumatic fever is the Aschoff body, an inflammatory
lesion associated with swelling and fragmentation of collagen fibers and alterations
in the staining characteristics of connective tissue.
• Endocarditis produces a verrucous valvitis that may heal with fibrous thickening
and adhesions of valve commissures and chordae tendineae, resulting in variable
degrees of valve stenosis and insufficiency.
• The mitral and aortic valves are affected most commonly, the
tricuspid less frequently, and the pulmonary valve rarely.
• Pathologic changes in the joints consist of exudation with
edema of synovial membranes, focal necrosis in the joint
capsule, edema and inflammation in periarticular tissue, and
joint effusion.
• Subcutaneous nodules seen during the acute phase of the
disease resemble Aschoff bodies and are granulomas with
localized areas of fibrinoid swelling of collagen and
perivascular infiltration with large cells, pale nuclei, and
prominent nucleoli.
CLINICAL FEATURES
• Pharyngitis usually occurs two to four weeks before the onset of ARF symptoms.
• The clinical illness is self-limited, but damage to the valves may be chronic and progressive,
resulting in cardiac decompensation and death.
• Acute rheumatic fever occurs most frequently in children from four to nine years of age.
• The onset of the disease usually is characterized by an acute febrile illness that may manifest
itself in one of several ways:
1. Migratory arthritis predominantly involving the large joints
2. Carditis and valvulitis
3. Central nervous system involvement (e.g. Sydenham chorea)
4. Rash
5. Some combination of the above
• Arthritis:
• In the classic, untreated case, the arthritis of rheumatic fever affects several joints in quick
succession, each for a short time
• The knees, ankles, elbows, and wrists are affected most commonly, with the leg joints typically
being involved first.
• The onset of arthritis in different joints usually overlaps, giving the appearance that the
disease "migrates" from joint to joint.
• Thus, the terms "migrating" or "migratory" often are used to describe the polyarthritis of
rheumatic fever.
• Joint involvement is more common and more severe in teenagers and young adults than in
children.
• Arthritis usually is the earliest symptomatic manifestation of ARF, although asymptomatic
carditis may come first.
• Typically, inflammation is present in six to 16 joints, and each joint is inflamed for no more
than one week
• Carditis
• : Rheumatic fever produces a pancarditis affecting the pericardium, epicardium, myocardium,
and endocardium.
• Cardiac manifestations may be subtle and include a variety of signs or symptoms: Mild to
moderate chest discomfort, pleuritic chest pain, or a pericardial friction rub are indications of
pericarditis.
• Physical examination may reveal new or changing murmurs.
• Mitral regurgitation is the most common finding.
• The combination of severe valvular damage and myocardial dysfunction from myocarditis can
lead to heart failure
• Chorea:
• Sydenham chorea (SC), also known as St. Vitus dance, St. Johannis' chorea, chorea minor, and
rheumatic chorea is a neurologic disorder consisting of abrupt, purposeless, nonrhythmic
involuntary movements, muscular weakness, and emotional disturbances
• The movements commonly are more marked on one side, are occasionally unilateral
(hemichorea), and cease during sleep.
• Muscle weakness is best revealed by asking the patient to squeeze the examiner's hands; the
pressure of the patient's grip increases and decreases continuously and capriciously, a
phenomenon known as relapsing grip or "milking sign."
• Emotional changes manifest themselves in outbursts of inappropriate behavior, including
crying and restlessness.
• In rare cases, the psychologic manifestations may be severe and may result in transient
psychosis.
• Neurologic examination fails to reveal sensory losses or involvement of the pyramidal tract.
• Diffuse hypotonia may be present
• Subcutaneous nodules:
• These skin lesions in ARF have many identifying characteristics
• The nodules are firm and painless.
• The overlying skin is not inflamed and usually can be moved over the nodules.
• The diameter varies from a few millimeters to one or two centimeters.
• The nodules most commonly are located over a bony surface or prominence or near tendons.
• The number of nodules varies from a single lesion to a few dozen and averages three or four;
when numerous, the nodules usually are symmetric.
• Nodules are present for one or more weeks, rarely for more than a month.
• They are smaller and more short-lived than the nodules of rheumatoid arthritis.
• Furthermore, although the elbows are involved most frequently in both diseases, rheumatic
fever nodules are more common on the olecranon, whereas rheumatoid nodules usually are
found 3 to 4 cm distally.
• Rheumatic subcutaneous nodules generally appear only after the first weeks of illness and
usually only in patients with carditis.
• In contemporary outbreaks of ARF, nodules have been the least common manifestation,
appearing in no more than 5 percent of patients
• Erythema marginatum:
• Erythema marginatum is an evanescent, non-pruritic rash, pink or faintly red, usually affecting
the trunk and sometimes the proximal parts or the limbs, but not the face
• Because the margin of the lesion usually is continuous, making a ring, it also is known as
"erythema annulare"
• Individual lesions may appear, disappear, and even reappear in a matter of hours.
• A hot bath or shower may make them more evident or may even reveal them for the first
time.
• Erythema marginatum usually occurs early in the disease.
• It often persists or recurs when all other manifestations of disease have disappeared.
DIAGNOSIS
Diagnosis is usually guided by Jones Criteria that was recently adopted by the
WHO
JONES CRITERIA
• If supported by evidence of a preceding group A streptococcal infection, the presence of two
major manifestations or of one major and two minor manifestations is indicative of a high
probability of acute rheumatic fever
• Major manifestations: The five major manifestations are:
1. Carditis
2. Polyarthritis
3. Chorea
4. Erythema marginatum
5. Subcutaneous nodules
• Minor manifestations: The four minor manifestations are:
• Clinical findings
1. Arthralgia
2. Fever
• Laboratory findings
1. Elevated acute phase reactants (erythrocyte sedimentation rate, C-reactive
protein)
2. Prolonged PR interval
• Evidence of preceding streptococcal infection: Any one of the following is considered
adequate evidence of infection.
• Positive throat culture for group A beta-hemolytic streptococci or positive rapid
streptococcal antigen test
• Elevated or rising streptococcal antibody titer, most often antistreptolysin O
• Exceptions: The 1992 guidelines noted three settings in which the diagnosis of acute
rheumatic fever could be made without strict adherence to the Jones criteria
• In each setting, the diagnosis is presumptive until other causes have been excluded.
• Chorea as the only manifestation
• Indolent carditis as the only manifestation in patients who come to medical attention
months after the acute infection
• Recurrent rheumatic fever in patients with a history of rheumatic fever or rheumatic
heart disease
DIAGNOSIS
• Tests
DIFFERENTIAL DIAGNOSIS
• SLE
• Bacterial endocarditis
• Sickle cell anemia
• Infective endocarditis
• Kawasaki disease
• Gonococcal arthritis
• Juvenile rheumatoid arthritis
• Lyme disease
• Reactive arthritis
• Septic arthritis
• Bacterial sepsis
TREATMENT
• The major goals in the treatment of acute rheumatic fever are:
1. Primary prevention (Eradication of streptococci)
2. Anti inflammatory treatment (aspirin, steroids)
3. Supportive management and management of complications
4. Secondary prevention (prevention of recurrent attacks)
• There is no therapy that slows progression of valvular damage in patients with ARF.
• Duration of prophylaxis: The duration of prophylaxis is not well defined, and depends
upon the number of previous attacks, the time lapsed since the last attack, the risk of
exposure to streptococcal infections, the age of the patient, and the presence or absence of
cardiac involvement
• Most physicians believe that prophylaxis should continue at least until the patient is a young
adult (18 to 20 years), which usually is 10 years from an acute attack with no recurrence
• WHO guidelines: The World Health Organization (WHO) published guidelines for
secondary prevention of ARF in 2001
• The WHO recommendations for the duration of secondary prophylaxis are:
1. Patients without proven carditis — At least five years of antibiotic prophylaxis
following diagnosis of ARF or until age 18
2. Patients with mild mitral regurgitation — At least ten years of prophylaxis or
until age 25
3. Patients with severe valve disease and/or after valve surgery — Life-long
prophylaxis
• In my opinion, individuals with documented evidence of rheumatic heart disease should be
on continuous prophylaxis indefinitely because rheumatic fever can recur as late as the fifth
or sixth decade of life.
• Regardless of whether or not prophylaxis is continued, there should always be a low threshold
to test and treat acute episodes of group A streptococcal pharyngitis.
REFERENCE
• Harrisons Principles of Internal Medicine 17th Edition
• Davidson’s Principles and Practice of Internal Medicine 20th
Edition
• Nelson’s Textbook of Pediatrics
• Kirii Notes
THE END
