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Definotion: Rheumatic fever is an inflammatory disease involving mainly
the joints and the heart and less frequently then the central nervous system, skin,
and subcutaneous tissues. It has a marked tendency to recur, and both initial and
recurrent attacks are non suppurative complications of group A streptococcal
upper respiratory infection.
Pathogenesis: Not definitely known.
1. Hypothesis of allergy to streptococcus of group A:
There is much evidence that the initial and subsequent of rheumatic fever
follow scarlet fever or upper respiratory infection due to β-hemolytic
streptococci group A. The attack of streptococcal pharyngitis may be extremely
mild or moderately severe [phase I].
In most instances, the symptoms of upper respiratory infection subside
quickly and are followed by a latent or "silent" period [phase II] usually lasting
one to three weeks. During which the patient is symptom-free. Phase II is
followed by the onset of -acute rheumatic fever [ phase III ]. If penicillin is given
early within the first 9 days and in sufficient quantity over an adequate period of
time, the patient escapes rheumatic fever. With such therapy, the hemolytic
streptocococci are eradicated from the throat in most instances.
The concept that rheumatic fever is an allergic process is based in part
upon the following points:
a) The fibrinoid degeneration of collagen is considered to be the
characteristic of allergic disease.
b) A peroid of 1 - 3 weeks commonly intervenes between the streptococcal.
infection and the onset of rheumatic fever. Such an interval is
characteristic of known allergic diseases.
c) The acute phase of rheumatic fever has clinical signs and symptoms which
are frequently indistinguishable from allergic diseases(e.g. serum
d) Recurrent attacks indicate absence of immunity.
2. Hypothesis of autoimmunity:
A more widely held theory is that rheumatic fever is an autoimmune
Several strepcococcal antigens cross-react with human tissue antigens, and
cross-reactive ["anti-heart"] antibodies have been found in rheumatic fever
patients. According to this hypothesis, streptococcal antigens immunologically
similar to tissue antigens may elicit antibodies capable or reacting, not only with
microbial products but also with the host's antigens, Thus autoimmunization may
be the underlying basis for the cardiac lesion.
Besides infection, an important factor in the etiology of rheumatic fever is
individual susceptibility. The susceptibility in child population in general Лб
between 0.2 – 1 %. The child, who gets rheumatic fever may be susceptible due
to familial predisposition: if one child in a family has rheumatic fever
approximately 10% of the children will develop it.
Age of onset: Usually between 5 - 10 years. but in some cases it does
begin at the age of 2 , 3 , or 4 years, however, it is not common. ,
Sex Rheumatic fever may occur: in children, males and females are
affected equally.
Pathology: 2 stages. There are 2 stages in the development of the disease.
1. Acute (Exudative) stagey: is characterizes by an exudative inflammatory
reaction in the connective tissues of:
a) The heart:
-Within the myocardium the cellular infiltrate [lymphocytes and
plasma celis ] form in tne interstitial tissue аs well as due to
damage of the muscle cells.
- Edema of the valvular fibrous ring and valve leaflets.
- Fibrinous or serofibrinous pericarditis.
b) Joints: Swelling of the articular and periarticular structures with
infiltration of synovial membranes and serous effusion.
This stage lasts for 2-3 weeks and is followed by:
Proliferative stage: The characterized by the appearance of
Aschoff’s nodules and a diffuse infiltration which end the fibrous. This phase is
limited to the myocardium and endocardium.
The Clinical picture and Diagnosis:
Rheumatic fever may affect a number –of isolated organs and tissues, or in
combination. No single clinical manifestation or laboratory test is characteristic
enough to be a diagnostic.
The need to bring some uniformity to the diagnosis led T.D. Jones to
formulate diagnostic criteria based on combination of clinical manifestations and
laboratory findinds.
These criteria include:
1. Major manifestations.
2. Minor manifestations.
3. Evidence of recent group A beta- hemolytic streptococcal infection of
the upper respiratory tract.
Major manifestations:
Arthritis: Rheumatic arthritis is characterized by the following criteria:
It affects the big joints mainly e.g. knees, wrists, ankles, elbows.
The affected joint shows signs of acute inflammation i.e. swollen,
tender, red , hot , limitation of movements associated with severe pain.
Several joints are commonly involved, sometimes together and
sometimes one after another (migrating arthritis).
As a rule, there is prompt improvement by salicylates; but whether
salicylates are given or not, it is rare for symptoms and signs of arthritis to
persist more than one week.
No residual deformity occurs in the affected joints.
Carditis : All layers of the heart are involved i.e. pancarditis develops.
A. Pericarditis:
- Pericarditis is recognized by hearing friction rub as superficial scratchy
sound which is heard over the precordium especially near the sternum,
and which has to and fro character.
- It is accompanied by slight pain, fever, leukocytosis and usually raised
S-T segment with inverted T wave in the ECG.
- When pericardial effusion is formed, it produces an area of enlargedcardiac dullness and distant heart sounds. Echocardiography is very
helpful in diagnosis.
B. Myocarditis:
Clinical manifestations of myocarditis include:
- Heart failure with its manifestations as gallop rhythm, congested neck
veins, edema of lower limbs,. etc.
- Cardiomegaly
- Arrhythmias
C. Endocarditis:
This leads to Mitral valve with or without Aortic valve.
1. Mitral valve:
valve leads to mitral valve incompetence which is manifested by a
pansystolic murmur, heard on the apex at maximum, selectively propagated to
the axilla. Harsh blowing in character and does not change with respiration or
change of position. The mitral valve incompetence is due to dilatation of the
fibrous ring of the valve.
The first heart sound is usually muffle and of decreased intensity which is
caused by prolonged conduction time of AV bundle which delays ventricular
contraction so that the atrioventricular valves are already more or less closed
when the ventricles contract.
In mitral valve another murmur may be heard: Carey Coomb's murmur.
It is a soft short mid-diastolic murmur, heard on the apex. It is produced by
the inflammatory thickening of the mitral cusps. This murmur occurs early in the
course of rheumatic carditis, and disappears as activity subsides ( i.e. a sign of
2. Aortic valve:
Inflammation of the aortic valve may lead to aortic incompetence which
manifests by early diastolic murmur, heard of maximum on the aortic area.
It is soft blowing in character and is associated with peripheral signs of
aortic incompetence: Water-hammer pulse, increased pulse pressure, pistol-shot,
Corrigan's sign, and Durozier's sign.
Rheumatic chorea (or Sydenham's Chorea) often appears to occur alone
rather than in the company of other rheumatic manifestations and the E S R is
usually normal . About 20% of patients with chorea alone develop rheumatic
heart disease. Chorea generally affects girls more than boys.
Clinical Features:
Involuntary movements: purposeless, irregular, non-repetitive, jerky
movements that are present at rest, become more apparent during voluntary
actions and are absent during sleep.
All limbs and often the face and tongue may be involved, with inability to
maintain the tongue in a protruded position. The tongue movements may
interfere with speech and swallowing. Respiration may be irregular and jerky.
The movements may be mild or severe, unilateral or bilateral. If unilateral, it is
called hemichorea.
Weakness of voluntary movements and hypotonia:
When the hands are held forward with palms down, they assume a typical
posture of flexion at the wrists and hyperextension at all finger joints (Dinner
fork appearance). There is often hyperpronation of the arms if they are held
above the head. The hypotonia also causes the deep reflexes to be difficult to
elicit, but when obtained they show a characteristic sustained contraction (e.g. in
knee jerk, the leg becomes held up at the height of its extension for an
appreciable interval before relaxation occurs). Hypotonia may lead also to
hyperextensibility of the joints. In some cases, hypotonia may be so severe as to
amount to paralysis.
Incoordination of the voluntary movements (caused by
superimposition of involuntary movements). This can be tested by the finger to
nose or finger to finger tests. Difficulties of talking, mastication, swallowing,
dressing, writing and walking are all examples of the incoordination. Associated
movements are also disturbed, thus if the patient while grasping the hand is asked
to protrude his tongue or clench the other fist, irregular contractions of the hand
will be felt.
Emotional instability: which may vary in severity.
In rheumatic chorea, the plantar response is flexor, and there is no sensory
loss. Tine CSF is normal. There is usually no pyrexia, the ESR and C-reactive
protein are normal. If there is fever or raised ESR, it is likely that active carditis
is present.
IV. Erythema Marginatum: It appears in rings, crescents, ovals, or in
irregular forms characterized by a thin red margin outlining a patch of normal
skin. It is distributed mainly on the trunk and proximal parts of the limbs.
Sometimes, the rash is at first composed of irregular erythematous macules but
the centers soon become clear, leaving red margins. There is no itching or
discomfort. Erythema marginatum may be fleeting or persistent.
V. Subcutaneous nodules: They are shot like hard bodies seen or felt over the
extensor surfaces of certain joints particularly elbows, knees and wrists, in the
occipital region or over the spinous processes of the thoracic or lumbar regions
At the end of 8 weeks they disappear in the majority of cases. The presence of
nodules is an indication that' the heart is involved, both being proliferative
II. Minor Manifestations:
Fever: A significant rise of temperature is a common symptom, but
because it occurs in so many-illnesses, it has little differential diagnostic value.
Approximately 50% of the cases have fever. This fever is controlled by salicylates.
Arthralgia: pain clearly located without objective findings is only a
minor criterion for diagnosis. The pain must be in the joint and not in the
muscles or other periarticular tissues. It must be distinguished from the nocturnal
pain in the extremeties occurring in normal children (called growing pains).
Arthralgia must not be used as a minor criterion when polyarthritis is
included as a major criterion.
Previous history of rheumatic fever or the presence of inactive
rheumatic heart disease.
Prolonged P-R interval in EGG: it cannot be used as a minor
criterion if carditis is already included as a major manifestation.
5. Acute Phase reactants: The positivity of one or more of these
non specific tests can be considered as a single minor criterion:
a) Elevated E.S.R.: simple and reliable test, though sometimes ESR is
normal as in heart failure, isolated chorea, erythema marginatum and in old
standing subcutaneous, nodules.
b) Presence of С - Reactive Protein (CRP): CRP tends to disappear in the
convalescent stage before ESR returns to normal. It may not appear if a rebound
occurs. It is often absent in chorea and erythema marginatum and long standing
nodules. CRP remains positive when congestive heart failure complicates active
carditis ( unlike ESR).
c) Leucocytosis.
III. Evidence of Preceding Streptococcal Infection
This must be documented by either:
A) A history of scarlet fever, or a typical clinical picture of other Betahemolytic streptococcal infection of upper respiratory tract infection. This
should precede the onset of rheumatic fever by one week to one month.
The nature of the infection must be confirmed by a history of immediate
contact with other individuals having typical streptococcal infection or by
positive culture of the nose or the throat in which Beta- hemolytic
streptococci predominate.
B) An elevated or rising ASLO titre: an ASLO of 250 Todd units or more
is considered positive. Approximately 80% of patients have an elevated
C) Patients suspected to have rheumatic fever and who do not show an
elevated ASLO (20%of cases) should be tested for other streptococcal
antibodies like anti- dsDNA.
IV. Other Manifestations of Rheumatic Fever:
These include systemic manifestations such as loss of weight, easy
fatiguability, malaise, sweating, pallor , epistaxis, erythema nodosum, abdominal
pain, headache and vomiting.
These as well as family history of rheumatic fever , provide additional
evidence of the presence of rheumatic fever , but are not to be included as
diagnostic criteria.
Diagnosis of Rheumatic Fever:
Acute rheumatic fever is diagnosed when there is:
Two major Jones' criteria + evidence of preceding Beta- hemolytic
streptococcal infection.
The presence of One Major + Two minor Jones' criteria + Evidence
of Beta-hemolytic streptococcal infection.
The main diseases with which it is necessary to differentiate acute rheumatic fever
1. non-Rheumatic myocarditis (bacterial, viral).
Typical sign:
- the presence of a chronological connection with acute nasopharyngeal (mainly
viral) infection;
- shortening (less than 5-7 days) or no latency period;
- at the onset of the disease, symptoms of asthenization, violations of
thermoregulation appear;
- gradual development of the disease;
- arthritis and severe arthralgias are absent;
- cardiac complaints have an active and emotional nature;
- there are clear clinical, ECG and EchoCG symptoms of myocarditis;
- no valvulitis;
- dissociation of clinical and laboratory parameters;
- slow dynamics under the influence of anti-inflammatory therapy.
2. Post-streptococcal arthritis.
It can occur in middle-aged people. It has a relatively short latent period (2-4 days)
from the moment of a pharyngeal BSA infection (beta-hemolytic Streptococcus
group A) and persists for a longer time (about 2 months). the Disease is not
accompanied by carditis, does not respond optimally enough to anti-inflammatory
drugs and completely regresses without residual changes.
3. Endocarditis in systemic lupus erythematosus, rheumatoid arthritis and some
other rheumatic diseases.
These diseases are characterized by characteristic features of extra-cardiac
manifestations. In systemic lupus erythematosus, specific immunological
phenomena are detected - antibodies to DNA and other nuclear substances.
4. Idiopathic mitral valve prolapse.
In this disease, most patients have an asthenic type of Constitution and phenotypic
signs indicating congenital connective tissue dysplasia (funnel-shaped chest
deformity, scoliosis of the thoracic spine, joint hypermobility syndrome, etc.). A
thorough analysis of the clinical features of extra-cardiac manifestations of the
disease and Doppler echocardiography data help to make the correct diagnosis.
Endocarditis is characterized by variability of the auscultative picture.
5. Infectious endocarditis.
Febrile syndrome in infectious endocarditis, unlike ORL, is not completely stopped
only by the appointment of NSAIDs, destructive changes in the valves quickly
progress, and the symptoms of heart failure increase. When conducting an Echo
found on the valves of the growing season. Characteristic is the allocation of
positive hemoculture. Green streptococci, staphylococci and other gram-negative
microorganisms are verified as pathogens.
6. Tick-borne migrating erythema.
It is a pathognomonic sign of early Lyme disease. Unlike anular erythema, it is
usually large (6-20 cm in diameter). In children, it often appears in the head and
face, occurs with itching and burning, regional lymphadenopathy.
7. PANDAS Syndrome.
In contrast to rheumatic chorea, this syndrome is characterized by the severity of
psychiatric aspects (a combination of obsessive thoughts and obsessive
movements), as well as a much faster regression of symptoms of the disease
against the background of adequate anti-streptococcal therapy alone.
Management of Acute Rheumatic Fever
1. Bed Rest: All children may sit up in bed and feed themselves from the day
of admission. The duration of bed rest can be as follows:
Cardiac Status
Duration of Bed Rest
No Carditis (arthritis only)
Carditis with no failure
Carditis with heart failure
Bed rest for 2 weeks and gradual
ambulation for 2 weeks even if on
Eed rest for 4-6 weeks and gradual
ambulation for 4-6 weeks.
Strict bed res~ for as long as heart failure
is present and gradual ambulation for 3
2. Eradication of streptococcal infection : The child should receive an
intramuscular injection of 400,000 I.U. procaine penicillin daily for 10
days. Patients who are allergic to penicillin can be given oral
Erythromycin in a dose of 50 mg/kg/day in 4 divided doses for 10 days.
This should be followed by either:
a) Long acting penicillin ( 1,200,000 I.U.) called Benzathine penicillin
The dose is taken every 2 weeks.
b) One tablet of Sulfadiazine (0.5 gram) for those under 25 Kg daily. Two
tablets of sulfadiazine (1 gram) for those above 25 Kg daily. This
schedule is followed in patients who are allergic to penicillin.
3. Pathogenetic treatment:
(A) Cases without cardiac involvement: are given salicylates as follows:
- 100 mg/kg/day for the first two weeks, followed by:
75 mg/kg/day in four hourly divided doses (5 times/day) to maintain
a blood level of 25 — 35 mg/dL for the following 4 - 6 weeks.
(B) Cases with evidence of cardiac involvement are given Steroid
Prednisone is started in з dose of 2 mg/kg/day in divided doses.
After about 2 weeks prednisone may be gradually withdrawn, decreasing
the daily dose by one tablet ( 5 mg) every 3 days.
When tapering is started , Salicylates should be added and continued for
one month after prednisone is stopped (dose of salicylates: 75 mg/kg/day).
4. Treatment of heart failure:
(a) Mild heart failure can.be controlled by complete bed rest, Oxygen,
fluid restriction and steroids.
(b) In severe heart failure, diuretics and digitalis are indicated.
These children are susceptible to digitalis toxicity, therefore smaller
doses than usual must be given. If digitalis is administered potassium is
given as well (KC1 2.4 mg/day for those less than 27 kg and 3.6 mg/day
for those over 27 kg). (Revise treatment of heart failure later on).
5. For Rheumatic Chorea:
Steroids and salicylates are not given unless there are also -signs of
active rheumatic inflammatory process.
Haloperidol (Haldol) in a daily dose of 1 - 6 mg in divided doses can
be given to control the involuntary -movements and agitation.
Some patients benefit from barbiturates or chlorpromazine.
Prevention of Rheumatic Fever:
Rheumatic fever is a recurrent disease which frequently can be prevented.
Infection with group A beta hemolytic streptococci precipitates both initial and
recurrent attacks; therefore prevention of rheumatic fever and rheumatic heart
disease depends upon the control of streptococcal infection. This may be
accomplished by :
Primary Prevention: by early adequate treatment of streptococcal
infection in all individuals.
Secondary Prevention: for prevention of recurrences through the
prevention and treatment of streptococcal infection in rheumatic subjects.
Rules of secondary prevention:
It should be initiated as soon as the diagnosis of rheumatic fever is
made by the long acting penicillin as mentioned before.
It should be given to all patients who have a well documented
history of rheumatic fever or chorea or who show a definite evidence of
rheumatic heart disease.
The long acting penicillin (or sulfadiazine) should be given
continuously (winter and summer).
The prophylaxis should be continued for life. However, it has been
recommended by the World Health Organization that prophylaxis should be
given for at least 5 years after the last attack of rheumatic fever.
Specific Prophylactic Measures:
(A) Benzathine Penicillin: an IM injection of 1,200.000 I.U. of long
acting penicillin every 2-3 weeks was found to be the most effective
prophylactic measure.
Penicillin rarely produces allergic reactions. These include urticaria, and
angioneurotic edema. Reactions similar to serum sickness with fever and joint
pains may occur arid may be mistaken as rheumatic fever.
A careful history of allergic reactions to penicillin should be obtained.
It is safer not to use penicillin if the reaction has been severe and
especially if angioneurotic edema has occurred.
(B) Oral Penicillin: is also effective in a dose of 200,000 units twice
daily. Its drawbacks include:
Failures occur frequently in patients who are not compliant or who
forget to ingest the drug regularly.
Oral penicillin causes emergence of resistant strains of alphastreptococci in the oral cavity, a potential hazard for patients with raeumatic
heart disease since they are at risk for bacterial endocarditis.
(C) Oral Sulfadiazine: from 0.5 - 1 mg (1 - 2 tablets) once a day. The
smaller dose is to be used in children under 25 kg. The main toxic reactions
a. Morbiliform skin eruption: the drug can be continued cautiously.
b. Urticaria or scarlitiniform rash associated with sore throat or fevers are
indicators of discontinuing the drug.
c. Leucopenia: discontinue the drug if the blood count falls below 4000
and polymorphs fall below 35% because of possible agranulocytosis
which is often associated with sore throat and rash. Because of these
reactions, weekly WBCs counts are advisable for the first two months
of prophylaxis.