++
Acute rheumatic fever is a nonsuppurative sequela of pharyngeal
infection with group A streptococcus. Target organs of the inflammatory
process include the heart, joints, central nervous system, and subcutaneous
tissues. Cardiac involvement may be lifelong and is the most important
consequence of this disease.
++
Acute rheumatic fever (ARF) occurs most often in the winter and
spring seasons, and most commonly in children ages 5 to 15. Much
less commonly, it has been reported in the preschool age group. Familial
susceptibility to ARF may be related to the presence of specific human
leukocyte antigens or other genetic markers.9-11 Asian/Pacific
Islander children have recently been identified as a group with
a possibly increased genetic susceptibility.12 Patients
with ARF have a high likelihood of developing it again when reinfected
with group A streptococcus; this tendency declines with age and
with increased time since the last episode. Environmental factors
such as nutrition, crowding, and age all appear to influence the
incidence of acute rheumatic fever, probably because the same factors
influence the incidence of streptococcal pharyngitis.
++
Antigenic differences among group A streptococcus serotypes are
related to the bacteria’s M protein, found within its cell
wall. Recent data demonstrated a shift in prevalence of many of
the “rheumatogenic” M types13-15 to “nonrheumatogenic” M
types causing streptococcal pharyngitis in the United States over
the past 40 years that parallels the decrease in the incidence of
acute rheumatic fever over this period.13 Most
recent reports of clusters of acute rheumatic fever have come from
the Salt Lake City, Utah, area or military barrack settings.14,15
++
Organ damage that occurs during acute rheumatic fever (ARF) is
immune-mediated. The time interval of 10 days to 3 weeks between streptococcal
pharyngitis and ARF is consistent with a cellular and humoral immune
response. Cross-reactivity of streptococcal antigens and human cardiac,
synovial, and brain antigens also supports an immune mechanism of
ARF.
++
Pathologic changes are found throughout the body in connective
tissue and around small blood vessels. The pathognomonic lesion
of rheumatic fever is the Aschoff body, a painless nodular lesion
consisting of fibrinoid changes in connective tissue and a collection of
lymphocytes, plasma cells, and histiocytes. Within the heart, the
endocardium and myocardium are most often affected. The pericardium
may also be involved as a result of the inflammatory process within
the myocardium or a manifestation of serositis. Active valvulitis
results in variable degrees of valve insufficiency, with chronic
changes possibly leading to valvular stenosis. 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. These
changes are completely reversible. Subcutaneous nodules seen during the
acute phase of the disease histologically resemble Aschoff bodies. “Rheumatic
pneumonia” consists of exudative and inflammatory changes
without Aschoff bodies. Pathologic changes in patients with chorea
are not consistent, and little postmortem information is available
because patients with active chorea rarely die.
+++
Clinical Features
and Diagnosis
++
Many of the clinical manifestations of acute rheumatic fever
occur in infectious, inflammatory, and other collagen vascular disorders.
Diagnostic consideration of a patient presenting with a combination
of cardiac, joint, and dermatologic abnormalities may include rheumatoid
arthritis, systemic lupus erythematosus, Kawasaki disease, rubella,
parvovirus, infective endocarditis, or inflammatory bowel disease.
++
Diagnosis criteria of rheumatic fever, known as the “Jones
criteria”, require that an individual have either two major
criteria, or on major criterion plus two minor criteria along with evidence
of streptococcal infection. Exceptions are chorea or indolent carditis,
which each may by themselves indicate rheumatic fever. The five
major criteria include:
++
1. Migratory polyarthritis
2. Carditis
3. Subcutaneous nodules
4. Erythema marginatum
5. Syndenham’s chorea
++
++
1. Fever
2. Arthralgia
3. Increased erythrocyte sedimentation rate or C-reactive protein
4. Leukocytosis
5. Electrocardiogram changes showing features of heart block
6. Evidence of Streptococcal infection such as elevated Antistreptolysin
O or DNAase
7. Previous episode of rheumatic fever
++
Classic acute rheumatic fever presents with acute migratory
polyarthritis associated with fever. The joints are red,
hot, swollen, exquisitely tender, and painful if moved. In general the
larger joints of the extremities are affected, but arthritis rarely
may occur in the spine and other joints such as the temporomandibular and
sternoclavicular joints; arthritis of fingers and toes is more common
in older than younger patients. Usually, pain and effusion subside in
one joint as another becomes involved, but several joints may be
involved simultaneously. Polyarthritis is the most common of the major
criteria and lasts less than 4 to 6 weeks, even if untreated. Characteristic
is a dramatic response to salicylates.
++
Rheumatic carditis may be asymptomatic. Carditis
may affect the endocardium (valves), myocardium, or pericardium. Endocarditis manifested
by pathologic murmurs is the hallmark of carditis of acute rheumatic
fever. The most frequent murmur is an apical systolic murmur of mitral
regurgitation. With severe mitral regurgitation, the third heart
sound may be followed or replaced by a low-pitched mid-diastolic rumble.
The early diastolic murmur of aortic regurgitation is the second
most common murmur in acute rheumatic fever and generally occurs
only in patients who also have mitral regurgitation. Patients without
audible murmurs may have subclinical carditis with mild valve incompetence
noted on color Doppler flow studies. The significance of this finding is
controversial, and at present it does not meet the Jones criterion
for carditis. Although this finding by itself should not be used
to diagnose acute rheumatic fever, the lesions may persist and require
long term monitoring and management.17
++
Myocarditis may be manifested by tachycardia disproportionate
to the fever, a gallop rhythm, or arrhythmias. Cardiomegaly may
be evident on x-ray. Severe myocarditis may result in congestive
heart failure with signs including jugulo-venous distention, hepatomegaly,
and pulmonary edema with rales. Prolongation of the P-R interval
is common but does not indicate carditis.
++
Pericarditis in acute rheumatic fever may appear suddenly and
may be associated with precordial pain and a friction rub. More
often, however, patients with pericarditis are asymptomatic. Pericarditis
seldom appears without endocarditis and myocarditis, the combination being
termed pancarditis. Death may occur during the acute phase of carditis
or after clinical recovery; permanent cardiac damage may result
in long-term disability, usually because of mitral or aortic valvular
insufficiency and/or stenosis.
++
Sydenham chorea is characterized by sudden,
aimless, irregular movements of the extremities frequently associated
with emotional instability and muscle weakness. Whereas carditis
and arthritis develop within 3 to 4 weeks after an inciting streptococcal
infection, chorea presents after several months and is not often
associated with other features of acute rheumatic fever except perhaps
mild carditis. The onset may be gradual, with complaints that the
child is nervous. The patient may become clumsy and stumble, fall,
or drop objects. Often there are complaints of poor attention and
deteriorating handwriting and school performance. Facial grimacing
and various speech disorders occur. As chorea becomes more severe,
irregular jerking movements can be sufficiently violent to cause injuries.
Muscle weakness may be profound. The choreiform movements subside
during sleep and are exaggerated by emotion. Characteristically,
when the patient is asked to extend the arms, hands, and fingers,
flexion of the wrists and hyperextension of the metacarpophalangeal
joints (“silver forking”) are observed. The pronator
sign may be elicited: After the arms are raised above the head there is
gradual pronation of the hands (apposition of the dorsal aspects
of the hands). Other signs are an inability to hold the tongue still
when it is protruded and spasmodic contractions of the hands when
the patient intentionally grips objects or the examiner’s
hand (milkmaid’s grip). Chorea can also be caused by diseases other
than acute rheumatic fever, such as lupus or Wilson’s disease,
and patients who present with chorea as the only manifestation of
acute rheumatic fever should undergo a full evaluation.
++
Subcutaneous nodules are rare and manifest as
painless small (0.5 to 1 cm) swellings over bony prominences, primarily
over the extensor tendons of the hands, feet, elbows, scalp, scapulae,
and vertebrae. Nodules tend to occur in crops and may persist for
days to months after the onset of acute rheumatic fever, generally with
severe carditis. Subcutaneous nodules are not specific for acute
rheumatic fever and may occur in rheumatoid arthritis as well as
systemic lupus erythematosus.
++
Erythema marginatum occurs in less than 10% of
acute rheumatic fever patients; it may be seen more frequently in
children less than 5 years old.19 The characteristic
rash consists of an evanescent, pink, erythematous macule, with
a clear center and serpiginous outline (Fig. 235-1). The rash is transient,
migratory, and nonpruritic; it blanches with pressure, is exacerbated
by warmth, and is found primarily on the trunk and proximal extremities,
sparing the face.
++
+++
Laboratory Evaluation
++
The erythrocyte sedimentation rate and C-reactive protein are
virtually always elevated in acute rheumatic fever (ARF), the degree
of elevation being influenced by previous salicylate or steroid
therapy, anemia, and congestive heart failure. Because these studies may
be abnormal in virtually any other inflammatory state, they are
of little value for the specific diagnosis of ARF. Leukopenia or urinalysis
abnormalities probably do not occur in rheumatic fever, and if found
in a patient with joint and cardiac abnormalities, they are more
suggestive of systemic lupus erythematosus.
++
Isolation of group A streptococci from the throat of a patient suspected
of having ARF provides strong evidence for the diagnosis. Caution
is needed, however, as most ARF patients clear their streptococcal
pharyngitis without antibiotic therapy, and many children may be
chronic pharyngeal carriers of streptococci unrelated to ARF without
consequence. Failure to isolate streptococci from patients with
acute rheumatic fever may be related to prior antibiotic therapy,
small numbers of organisms, or improper culture technique, but most
often reflects spontaneous clearance.
++
Elevated serum antistreptococcal antibody titers are probably
the most specific and reliable proof of previous streptococcal infection. A
rising antibody titer to specific streptococcal antigens is more
specific than a single elevated value. However, if the patient presents more
than 3 months after acute streptococcal infection, antibody titers
may be declining or low. This occurs more frequently in patients whose
initial or only manifestation of acute rheumatic fever is chorea. The
most widely used serologic test is antibody formation against streptolysin
O. Titers of at least 333 U in children and 250 U in adults are
usually considered elevated. Other available antibody tests are
antideoxyribonuclease B, antihyaluronidase, antistreptokinase, and
antinicotinamide-adenine-dineucleotidase. A fourfold rise in titer
to one or more of the above antigens can be demonstrated in virtually
all cases of acute or recurrent rheumatic fever if serum samples
are obtained within 2 to 3 months of the streptococcal infection.
Patients who present with fever, rash, arthritis, or carditis should
also have studies to exclude systemic lupus erythematosus and rheumatoid
arthritis. These include antinuclear antibodies, anti-DNA titers,
and rheumatoid factor.
++
A full course of oral or intramuscular penicillin should be given
to all patients with acute rheumatic fever even if cultures for
group A streptococci are negative. An oral cephalosporin is an acceptable
alternative; macrolide antibiotics, such as erythromycin, clarithromycin,
or azithromycin should be limited to penicillin-allergic patients.
Tetracyclines and sulfonamide drugs are not appropriate for treatment
of the streptococcal infection.
++
If a child with acute rheumatic fever is free of clinical carditis,
normal activity can be resumed once the pain and fever. If there
is mild carditis, 1 to 2 weeks at home is reasonable. The murmur
may persist indefinitely, and its disappearance is not a requisite
for return to activity. The erythrocyte sedimentation rate may remain
high for weeks, showing gradual decline. Patients with severe carditis,
as evidenced by marked cardiomegaly or congestive heart failure,
should remain at bed rest for several weeks, until the heart size
returns to normal or is at least stable.
++
Salicylates, nonsteroidal anti-inflammatory drugs, and steroids
are beneficial in controlling the acute clinical manifestations
of acute rheumatic fever. Arthritis and fever respond dramatically
to salicylate therapy, often within hours of initiation. Acetylsalicylic
acid is usually used in relatively high doses (50–70 mg/kg/d)
for a duration related to the course and severity of the disease;
the minimum period is usually 6 weeks. Prior to discontinuation,
the dose should be reduced gradually over 2 to 4 weeks. If rebound
of rheumatic activity occurs, full therapy may have to be reinstituted for
an additional 4 to 6 weeks.
++
In patients with moderate to severe carditis, neither salicylates
nor steroids demonstrate superiority over the other drug in modifying the
duration of acute disease or lessening the residual heart damage.
However, steroids are indicated in patients who develop congestive heart
failure. Digoxin may not benefit the patient with severe myocarditis,
but it is often successful in controlling congestive heart failure
in patients with valvular insufficiency. Digoxin should be used
cautiously, because toxicity may occur with relatively small doses when
acute myocarditis is present. Occasionally, severe incompetence
of aortic or/and mitral valves leads to refractory heart
failure, which requires surgical implantation of a prosthetic valve.
++
Specific treatment for chorea is not available. Physical and
mental stress should be minimized, and protective measures to prevent
injury during severe episodes should be instituted. In very severe
cases, steroids, phenobarbital, and valproic acid have been helpful.
++
Prophylaxis against recurrent acute rheumatic fever (ARF) should
be instituted immediately following acute therapy. The most effective
prophylaxis consists of benzathine penicillin G intramuscular injections
every four weeks; the injection can be painful and may lead to reactions.
Alternative therapy consists of either oral penicillin V twice daily or
oral sulfisoxazole once daily. Patients without rheumatic heart
disease are at lower risk of recurrence than are patients with carditis
or valvular disease. In pediatric ARF patients without carditis,
prophylaxis should continue for at least 5 years or until age 21,
whichever is longer. When ARF includes carditis but no clinical
or echocardiographic evidence of residual valvular disease, the
duration of prophylaxis should be extended to at least 10 years,
or well into adulthood, whichever is longer. Patients with persistent
valvular disease following ARF with carditis should continue prophylaxis
for at least 10 years since the last episode of ARF and until at
least age 40. Lifelong prophylaxis should be considered in this
group.20
++
Approximately 75% of patients with acute rheumatic fever
are well after 6 weeks. By 6 months, fewer than 5% remain
symptomatic with chorea or intractable carditis. Up to 70% of
patients who develop carditis during the initial episode of acute
rheumatic fever recover without any residual heart disease. Whereas
70% of acute rheumatic fever patients with congestive heart
failure and pericarditis develop permanent heart disease, only 20% of patients
with mild carditis are permanently affected. When more than 8 weeks
have elapsed after stopping treatment, acute rheumatic fever does
not recur in the absence of recurrent streptococcal infection. In
individual patients, the clinical features of recurrent episodes
of acute rheumatic fever tend to be similar to that of the initial
episode. Compared to a single episode, however, the likelihood of
permanent residual heart damage following carditis increases with
each recurrence. Patients who have had chorea without apparent carditis may
present years later with mitral stenosis.