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Rheumatic fever

Rheumatism – systemic inflammatory disease of the connective tissue with main localization of the process
in the cardio-vascular system, developing in connection with acute infection (group A beta-hemolytic
streptococсus) in predisposed patients; the peak age-related incidence is between 7 and15 years.
•

Factors of pathogeneсity of Streptococcus

•

М-protein – factor of virulence, has antigenic properties, promotes stability to phagocytosis .

•

Streptolysin - S –exerts direct toxic influence on the erythrocytes, platelets, cells of the myocardium
and kidney by means of increasing permeability of their cellular and lysosomic membranes.

•

Streptolysin О - inducts production of cytotoxic antibodies,

•

Streptohyaluronidase – increases permeability of tissues for the toxines

•

Streptoproteinase – causes destruction of the protein-mucopolysaccharide complex – main
substance of connective tissue.

•

Hyaluronic acid – capsule component, supresses phagocytic activity of neutrophiles.

•

Peculiarities of rheumatism:

1) Connection with acute streptococcal infection;
2) Presence of “absolute signs” of the rheumatism – Jones criteria;
3) Tendency to formation of valvular lesion.
•

The Jones Criteria for Rheumatic Fever, Updated 1992

•

Major Criteria

Carditis
Migratory polyarthritis
•

Sydenham's chorea

•

Subcutaneous nodules

Erythema marginatum
•

Minor criteria

•

Clinical

•

Fever

•

Arthralgia
•

Laboratory

•

Elevated acute phase reactants

•

Prolonged PR interval

•

The Jones Criteria for Rheumatic Fever, Updated 1992

•

plus :

•

Supporting evidence of a recent group A streptococcal infection (e.g., positive throat culture or
rapid antigen detection test; and/ or elevated or increasing streptococcal antibody test)

•

Periods of the development of rheumatism

First period

During 2 to 4 weeks after streptococcal infection.
Asymptomatic or with the signs of prolonged recovery.
•

Periods of development of rheumatism

Second period
Clinically evident disease
Development of polyarthritis, carditis, etc.
Clinical, morphologic and immunobiochemical changes, typical for the
primary rheumatism.
•

Periods of development of rheumatism

Third period
Multiform manifestations of the recurrent rheumatism.
Progression of the severity of valvular heart disease.
Development of hemodynamic failure.
•

Diagnosis of rheumatism

•

Primary rheumocarditis (70–85%)

•

Chronological association with А-streptococcal infection (pharyngitis, tonsillitis)

•

Latent period 2 – 4 weeks
•

Young age of the patient

•

Mainly acute or subacute onset

•

Polyarthritis or acute arthralgias in the beginning of the disease

•

Presence of valvulitis in connection with myocarditis or pericarditis

•

Quick modification of the symptoms of carditis

•

Correlation of laboratory and clinical data of activity of disease

•

Primary rheumocarditis
Signs of myocarditis
•
•

Cardiomegaly,

•

Weakening of the apex impulse,

•

Cardiac rhythm disturbances (tachycardia, bradycardia, atrial fibrillation)

•

А-V block,

•

Decreased heart sounds,

•
•

Precordial chest pain,

Functional systolic murmur on the apex, not connected with S1

Primary rheumocarditis
ACС Criteria of carditis
(American College of Cardiologists) :
Appearance of new organic or dynamics of previous heart murmurs
Cardiomegaly in the absence of other reasons
Congestive heart failure in young patients in the absence of other reasons
Pericarditis

•

Primary rheumocarditis
ECG peculiarities
•

Prolonged PR interval,

•

Rhythm disturbances:
Extrasystole
Atrial fibrillation
•

Disturbances of ventricular repolarization,

•

Prolongation of electric systole (Q-T interval).

•

АV block I degree in patient with acute rheumatic fever

•

EchoCG

•

Thick mitral valve leaflets

•

“Tousled” of the echosignal from the leaflets of the affected valves,

•

Decreased motion of the mitral valve leaflets,

•

Systolic dysfunction of the myocardium.

•

Recurrent rheumocarditis

•

Proceeds with combined valvular heart disease

•

Chronic lingering or latent course.

•

Rheumatic polyarthritis (60-100%)

•

Mainly big and middle joints (knees,elbows,ankles,wrists). Doesn’t affect the small joints of the
hand or feet.

•

benign

•

Short-term

•

migratory

•

Salicylates and other anti-inflammatory drugs usually cause prompt resolution of joint symptoms
(during several days or even hours)

•

Sydenham's chorea
(6-30%)

•

Appears in childhood and juvenile age.

•

Choreic hyperkinesia, most expressed in the muscles of distal parts of extremities and facial mimic
muscles

•

Muscular hypotonia,

•

coordination disorders,

•

Psychical and vegetative disturbances.

•

Duration of the attack of acute rheumatic fever in the form of chorea usually takes from 3 to 6
months.
•

Erythema marginatum
(4–17% )

•

Evanescent macular eruption with rounded borders

•

Vary in size.

•

concentrated on the trunk and proximal parts of extremities (but not on the face !).

•

Transitory migrating character

•

No itch or induration

•

Turn pale when pressed.

•

Subcutaneous nodules (1–3 %)

•

Rounded, not mobile, painless formations of different size, are found over extensor surfaces of
joints,

are seen most often in patients with long-standing rheumatic heart disease, and are extremely rare in
patients experiencing an initial attack
•

Quickly appear and disappear.

•

Rheumatic pneumonia

•

Exacerbation of dyspnea,

•

Fever,

•

A lot of rales of different calibres in the absence of dull percussion sound.

•

Chest X-rays – local intensification and deformation of lung markings with multiple small foci of
consolidation.

•

Anti-inflammatory treatment leads to prompt normalization of clinical and roentgenologic changes.

•

Rheumatic pleuritis

•

Pleuritic chest pain, exacerbated by breathing and coughing.

•

Pleural rub

•

Fever.

•

Anti-inflammatory drugs cause prompt resolution of the symptoms.

•

Additional manifestations:

GENERAL:
•

Fever

•

Adynamia, fatigue, asthenia

•

Paleness

•

Sweating

•

Nasal bleeding

•

Abdominal syndrom

•

Abdominal syndrom

•

Mainly in childhood, in acute course of primary or recurrent rheumatism.

Clinical symptoms:
•

Diffuse or localized pain in the abdomen,

•

nausea, vomiting,

•

Constipation or diarrhea.

•

Additional manifestations

Special:
•

Leucocytosis (neutrophilia)

•

Increasing of erythrocyte sedimentation rate (ESR)

•

hyperfibrinogenemia

•

positive С-reactive protein

•

Increasing of a2- and g- globulins

•

Increasing of serum mucoproteins, glycoproteins

•

Pathologic serologic indices: streptococcal antigen, increased titers
of АSL-О, АSС, АSH.

•

Increased capillary permeability

•

Degrees of activity of rheumatic process

•

Peculiarities of the course:

Acute rheumatic fever – duration of the attack to 3 months, proceeds rapidly, symptoms are evidently
progressing, high titers of antistreptococcal antibodies, prevalence of hypersensitivity of immediate type
reactions (desorganisation of connective tissue and exudative cell reactions).
•

Peculiarities of the course:

Subacute rheumatism – duration of the attack from 3 to 6 months, proceeds rapidly, symptoms are
progressing, high titers of antistreptococcal antibodies, prevalence of hypersensitivity of immediate type
reactions (desorganisation of connective tissue and exudative cell reactions).
•

Peculiarities of the course:

Lingering illness– with the constant development of symptoms and I –II degree activity more than 6
months,without clear remissions and weak, unstable effect of anti-inflammatory treatment .
•

Peculiarities of the course:

Persistently-recurrent – undulating with с exacerbations and incomplete remissions, with I – III degree
activity up to 1 year and more.
•

Peculiarities of the course:

Latent course – can’t find a disease, which may be considered as missed rheumatic attack; can’t reveal even
minimal activity of pathologic process, but clinically certain acquired valvular heart disease is estalished.
•

Plan of laboratory and instrumental examination:

•

CBC (complete blood count)

•

Thermometry during 2 hours

•

Protein fractions

•

С-reactive proteine (CRP)

•

Titers of anti-streptolysin O, anti-streptohyaluronidase and anti-deoxyribonuclease B

•

ECG

•

PhonoCG, EchoCG, Doppler-EchoCG.

•

Classification of Nesterov A. (1964)

•

TREATMENT

•

There are two necessary therapeutic approaches to patients with acute rheumatic fever: antistreptococcal antibiotic therapy and therapy for the clinical manifestations of the disease

•

Etiotropic treatment

•

Goal: eradication of group A b-hemolytic Streptococcus.

•

Benzylpenicillin in daily dose 1 500 000 – 4 000 000 units in adults and teenagers and 400 000 – 600
000 units in children for 10-14 days course.
•

Following transition to retard form of penicillin (benzathine penicillin).

•

Pathogenetic treatment
Nonsteroidal antiinflammatory drugs (NSAIDs).

•

Pathogenetic treatment

Glucocorticosteroids.
•

Prednisolon 20 – 30 mg/day up to 2 weeks with following tapering (2,5 mg every 5 – 7 days) till the
complete cancellation.

•

Triamcinolon 12 – 16 mg/day

•

Primary prophylaxis

•

Proper time diagnosis of А – streptococcal infection of pharynx and tonsils.

•

Conventional antibiotic treatment should be started immediately: a complete 10-day course in
adults of either oral penicillin V (500 mg twice daily), or erythromycin (250 mg four times daily) for
those with penicillin allergy.

•

In chronic recurrent streptococcal tonsillopharyngitis:
•

macrolides,

•

oral cephalosporines.

•

But no one above-mentioned medication (or their combination )doesn’t guarantee 100%
elimination of the streptococcus from nasopharynx.

•

Secondary prophylaxis

•

Prevention of recurrent attacks and progress of the disease in patients after acute rheumatic fever.

•

Regular infusion of prolonged penicillin (benzathine penicillin )

•

Insufficient efficacy of bicillinoprophylaxis in 13 – 37 % of patients.

•

Secondary prophylaxis

•

Benzathine penicillin G–2,4 million units intramuscular every 3 weeks

•

Since it is known that the risk of recurrence of rheumatic fever is highest during the first 5 years
after the attack, secondary prophylaxis is always given for at least this period.

•

After that the decision to continue or discontinue secondary prophylaxis is dependent upon
whether the patient has documented rheumatic heart disease and whether the patient is at high
risk of exposure to streptococci (e.g., students, school teachers, medical and military personnel,
etc.). Many believe that those with documented recurrences and/or documented rheumatic
valvular heart disease should receive secondary prophylaxis for life. The duration of prophylaxis is
often individualized for specific patients.

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6 rheumatic fever

  • 1. • Rheumatic fever Rheumatism – systemic inflammatory disease of the connective tissue with main localization of the process in the cardio-vascular system, developing in connection with acute infection (group A beta-hemolytic streptococсus) in predisposed patients; the peak age-related incidence is between 7 and15 years. • Factors of pathogeneсity of Streptococcus • М-protein – factor of virulence, has antigenic properties, promotes stability to phagocytosis . • Streptolysin - S –exerts direct toxic influence on the erythrocytes, platelets, cells of the myocardium and kidney by means of increasing permeability of their cellular and lysosomic membranes. • Streptolysin О - inducts production of cytotoxic antibodies, • Streptohyaluronidase – increases permeability of tissues for the toxines • Streptoproteinase – causes destruction of the protein-mucopolysaccharide complex – main substance of connective tissue. • Hyaluronic acid – capsule component, supresses phagocytic activity of neutrophiles. • Peculiarities of rheumatism: 1) Connection with acute streptococcal infection; 2) Presence of “absolute signs” of the rheumatism – Jones criteria; 3) Tendency to formation of valvular lesion. • The Jones Criteria for Rheumatic Fever, Updated 1992 • Major Criteria Carditis Migratory polyarthritis • Sydenham's chorea • Subcutaneous nodules Erythema marginatum • Minor criteria • Clinical • Fever • Arthralgia
  • 2. • Laboratory • Elevated acute phase reactants • Prolonged PR interval • The Jones Criteria for Rheumatic Fever, Updated 1992 • plus : • Supporting evidence of a recent group A streptococcal infection (e.g., positive throat culture or rapid antigen detection test; and/ or elevated or increasing streptococcal antibody test) • Periods of the development of rheumatism First period During 2 to 4 weeks after streptococcal infection. Asymptomatic or with the signs of prolonged recovery. • Periods of development of rheumatism Second period Clinically evident disease Development of polyarthritis, carditis, etc. Clinical, morphologic and immunobiochemical changes, typical for the primary rheumatism. • Periods of development of rheumatism Third period Multiform manifestations of the recurrent rheumatism. Progression of the severity of valvular heart disease. Development of hemodynamic failure. • Diagnosis of rheumatism • Primary rheumocarditis (70–85%) • Chronological association with А-streptococcal infection (pharyngitis, tonsillitis) • Latent period 2 – 4 weeks
  • 3. • Young age of the patient • Mainly acute or subacute onset • Polyarthritis or acute arthralgias in the beginning of the disease • Presence of valvulitis in connection with myocarditis or pericarditis • Quick modification of the symptoms of carditis • Correlation of laboratory and clinical data of activity of disease • Primary rheumocarditis Signs of myocarditis • • Cardiomegaly, • Weakening of the apex impulse, • Cardiac rhythm disturbances (tachycardia, bradycardia, atrial fibrillation) • А-V block, • Decreased heart sounds, • • Precordial chest pain, Functional systolic murmur on the apex, not connected with S1 Primary rheumocarditis ACС Criteria of carditis (American College of Cardiologists) : Appearance of new organic or dynamics of previous heart murmurs Cardiomegaly in the absence of other reasons Congestive heart failure in young patients in the absence of other reasons Pericarditis • Primary rheumocarditis ECG peculiarities • Prolonged PR interval, • Rhythm disturbances: Extrasystole Atrial fibrillation
  • 4. • Disturbances of ventricular repolarization, • Prolongation of electric systole (Q-T interval). • АV block I degree in patient with acute rheumatic fever • EchoCG • Thick mitral valve leaflets • “Tousled” of the echosignal from the leaflets of the affected valves, • Decreased motion of the mitral valve leaflets, • Systolic dysfunction of the myocardium. • Recurrent rheumocarditis • Proceeds with combined valvular heart disease • Chronic lingering or latent course. • Rheumatic polyarthritis (60-100%) • Mainly big and middle joints (knees,elbows,ankles,wrists). Doesn’t affect the small joints of the hand or feet. • benign • Short-term • migratory • Salicylates and other anti-inflammatory drugs usually cause prompt resolution of joint symptoms (during several days or even hours) • Sydenham's chorea (6-30%) • Appears in childhood and juvenile age. • Choreic hyperkinesia, most expressed in the muscles of distal parts of extremities and facial mimic muscles • Muscular hypotonia, • coordination disorders, • Psychical and vegetative disturbances. • Duration of the attack of acute rheumatic fever in the form of chorea usually takes from 3 to 6 months.
  • 5. • Erythema marginatum (4–17% ) • Evanescent macular eruption with rounded borders • Vary in size. • concentrated on the trunk and proximal parts of extremities (but not on the face !). • Transitory migrating character • No itch or induration • Turn pale when pressed. • Subcutaneous nodules (1–3 %) • Rounded, not mobile, painless formations of different size, are found over extensor surfaces of joints, are seen most often in patients with long-standing rheumatic heart disease, and are extremely rare in patients experiencing an initial attack • Quickly appear and disappear. • Rheumatic pneumonia • Exacerbation of dyspnea, • Fever, • A lot of rales of different calibres in the absence of dull percussion sound. • Chest X-rays – local intensification and deformation of lung markings with multiple small foci of consolidation. • Anti-inflammatory treatment leads to prompt normalization of clinical and roentgenologic changes. • Rheumatic pleuritis • Pleuritic chest pain, exacerbated by breathing and coughing. • Pleural rub • Fever. • Anti-inflammatory drugs cause prompt resolution of the symptoms. • Additional manifestations: GENERAL:
  • 6. • Fever • Adynamia, fatigue, asthenia • Paleness • Sweating • Nasal bleeding • Abdominal syndrom • Abdominal syndrom • Mainly in childhood, in acute course of primary or recurrent rheumatism. Clinical symptoms: • Diffuse or localized pain in the abdomen, • nausea, vomiting, • Constipation or diarrhea. • Additional manifestations Special: • Leucocytosis (neutrophilia) • Increasing of erythrocyte sedimentation rate (ESR) • hyperfibrinogenemia • positive С-reactive protein • Increasing of a2- and g- globulins • Increasing of serum mucoproteins, glycoproteins • Pathologic serologic indices: streptococcal antigen, increased titers of АSL-О, АSС, АSH. • Increased capillary permeability • Degrees of activity of rheumatic process • Peculiarities of the course: Acute rheumatic fever – duration of the attack to 3 months, proceeds rapidly, symptoms are evidently progressing, high titers of antistreptococcal antibodies, prevalence of hypersensitivity of immediate type reactions (desorganisation of connective tissue and exudative cell reactions).
  • 7. • Peculiarities of the course: Subacute rheumatism – duration of the attack from 3 to 6 months, proceeds rapidly, symptoms are progressing, high titers of antistreptococcal antibodies, prevalence of hypersensitivity of immediate type reactions (desorganisation of connective tissue and exudative cell reactions). • Peculiarities of the course: Lingering illness– with the constant development of symptoms and I –II degree activity more than 6 months,without clear remissions and weak, unstable effect of anti-inflammatory treatment . • Peculiarities of the course: Persistently-recurrent – undulating with с exacerbations and incomplete remissions, with I – III degree activity up to 1 year and more. • Peculiarities of the course: Latent course – can’t find a disease, which may be considered as missed rheumatic attack; can’t reveal even minimal activity of pathologic process, but clinically certain acquired valvular heart disease is estalished. • Plan of laboratory and instrumental examination: • CBC (complete blood count) • Thermometry during 2 hours • Protein fractions • С-reactive proteine (CRP) • Titers of anti-streptolysin O, anti-streptohyaluronidase and anti-deoxyribonuclease B • ECG • PhonoCG, EchoCG, Doppler-EchoCG. • Classification of Nesterov A. (1964) • TREATMENT • There are two necessary therapeutic approaches to patients with acute rheumatic fever: antistreptococcal antibiotic therapy and therapy for the clinical manifestations of the disease • Etiotropic treatment • Goal: eradication of group A b-hemolytic Streptococcus. • Benzylpenicillin in daily dose 1 500 000 – 4 000 000 units in adults and teenagers and 400 000 – 600 000 units in children for 10-14 days course.
  • 8. • Following transition to retard form of penicillin (benzathine penicillin). • Pathogenetic treatment Nonsteroidal antiinflammatory drugs (NSAIDs). • Pathogenetic treatment Glucocorticosteroids. • Prednisolon 20 – 30 mg/day up to 2 weeks with following tapering (2,5 mg every 5 – 7 days) till the complete cancellation. • Triamcinolon 12 – 16 mg/day • Primary prophylaxis • Proper time diagnosis of А – streptococcal infection of pharynx and tonsils. • Conventional antibiotic treatment should be started immediately: a complete 10-day course in adults of either oral penicillin V (500 mg twice daily), or erythromycin (250 mg four times daily) for those with penicillin allergy. • In chronic recurrent streptococcal tonsillopharyngitis: • macrolides, • oral cephalosporines. • But no one above-mentioned medication (or their combination )doesn’t guarantee 100% elimination of the streptococcus from nasopharynx. • Secondary prophylaxis • Prevention of recurrent attacks and progress of the disease in patients after acute rheumatic fever. • Regular infusion of prolonged penicillin (benzathine penicillin ) • Insufficient efficacy of bicillinoprophylaxis in 13 – 37 % of patients. • Secondary prophylaxis • Benzathine penicillin G–2,4 million units intramuscular every 3 weeks • Since it is known that the risk of recurrence of rheumatic fever is highest during the first 5 years after the attack, secondary prophylaxis is always given for at least this period. • After that the decision to continue or discontinue secondary prophylaxis is dependent upon whether the patient has documented rheumatic heart disease and whether the patient is at high risk of exposure to streptococci (e.g., students, school teachers, medical and military personnel, etc.). Many believe that those with documented recurrences and/or documented rheumatic
  • 9. valvular heart disease should receive secondary prophylaxis for life. The duration of prophylaxis is often individualized for specific patients.