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Rheumatic fever (RF) is an acute, immunologically mediated, multisystem inflammatory disease that occurs a few weeks following an episode of group A streptococcal pharyngitis.

Cont…

• It is believed to be caused by antibody cross-reactivity and can involve the heart, joints, skin, and brain.

• In about 3%,RF occurs 10 days to 6 weeks after an episode of pharyngitis caused by group A streptococci.

• Acute rheumatic fever commonly appears in children ages 5 -15 years, but about 20% of first time attacks occur in middle to later life.

• In developing countries, it is still the most common cause of acquired heart disease in childhood and adolescence.

• Abnormal response to infection with specific strain of Group A β- Haemolytic streptococcus (serotypes 1,3,5,6,18 etc), extracellular products (e.g. M protein) of streptococcus act as antigen.

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Etiology is unknown Strong association with beta hemolytic

streptococci of group A is indicated by a number of observation: 1. H/O sore throat in 50% of patient 2. Epidemics of streptococcal infection are followed

by higher incidence of rheumatic fever 3. Seasonal variation of rheumatic fever and

streptococcal infection are identical 4. Patient with established rheumatic heart disease

streptococcal infection is followed by reccurence of acute rheumatic fever.

Cont…

▪ 5. Penicillin prophylaxis for streptococcal infection prevents recurrence of rheumatic fever in those patients who have had it earlier▪ 6. More than 85 % of the patients with acute

rheumatic fever consistently show elevated levels of anti – streptococcal antibody titer.

Note : - Although these feature indicate the association of RF with streptococcal infection, streptococci have never been isolated from rheumatic lesions in joints, heart or the blood stream.

Cont..

Considerable evidence suggests that the RF is an antigen – antibody reaction.

Following streptococcal sore throat there is latent period of 10 days to several weeks before the onset of RF. This latent period is similar to the antigen – antibody diseases like serum sickness (type III hypersensitivity reaction that results from the injection of heterologous or foreign protein or serum) .

Cont…

Patients suffering from RF produce antibodies against streptococcal cell wall and cell membrane proteins

Streptococcal antigen and human myocardium appear to be identical antigenically. These antibodies have the capacity to react with human connective tissue specially the cardiac muscle, straited muscle and vascular smooth muscle.

Note : by immunofluorescent technique the antibodies are shown to be attached to the sarcolemma of the cardiac muscle.

Cont..

Note : - Streptococcal products against which

antibodies can be demonstrated are streptolysin, hyaluronidase, erythrogenic toxin, streptokinase, deoxyribonuclease etc. These antibodies are utilized for the identification of a previous streptococcal infection.

Cont…

Streptococcus has a hyaluronic acid capsule Hyaluronic acid capsule prevents phagocytosis

by the leukocytes Below the capsule hair – like fimbriae

containing lipoteichoic acid as well as the M,T and R proteins are present

lipoteichoic acid provides the mucosal attachment (penicillin destroy this).

M,T and R proteins are utilized for typing the streptococci.

M protein is believed to be the virulence factor of the streptococcus

Cont…

Antibodies which the immune system generates against the "M proteins" may cross react with cardiac myofiber protein myosin, heart muscle glycogen and smooth muscle cells of arteries, inducing cytokine release and tissue destruction

Cont…

One component of the streptococcal cell wall carbohydrate is N – acetyl glucosamine which is present in human connective tissue

N – acetyl glucosamine is an immunulugically active sugar

The compounds containing N – acetyl glucosamine cross – react with antiserum against human connective tissue

Cont..

Streptococcal cell wall proteins as well as carbohydrates have the capacity to produce antibodies capable of reacting with human connective tissue, resulting in RF

RF appears to be the result of the host`s unusual response at both the cellular and humoral level to the streptococcus.

Note : - Antibodies against the heart muscle (anti – heart antibodies) and nervous tissue (anti – nuronal antibodies) are found in high titers in patients with carditis and chorea

Cont..

Antibodies are specific in that they react with rheumatic tissue but not with non – rheumatic tissue.

Exact significance is not clear why some people are susceptible while others are not so susceptible to the occurrence of RF following the streptococcal infection

Cont…

Genetic susceptibility to RF : -▪ 1. HLA – DR3▪ 2. serum 883 (85%)▪ 3. D 8/17 (100% in USA)

Cont…• Extra cardiac involvement is seen

mostly in joints and skin. Histologically: • Fibrinoid degeneration can be seen in the

collagen of the connective tissues of these organs.

• Aschoff nodule (multinucleated giant cells surrounded by macrophages and T -lymphocytes, occuring in Heart) and

• Anitschkow cells are pathgnomonic histological lesion.

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Usually follows 2-3 weeks after streptococcal Pharyngitis.

Arthritis occurs in about 75%. Skin rash, Carditis and Neurological

changes may occur Other symptoms include : SOB ,Chest pain, purposeless

involuntary movement, Fever, Anorexia, and Lethargy.

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Symptoms characteristically occur 2-3 weeks after the initial attack of pharyngitis but the patient may give no history of sore throat.

Jones criteria are used to make diagnosis. The following criteria must be present for

diagnosis:

1. Two or more major criteria plus Essential criteria. Or

2. One major plus Two or more minor criteria plus Essential criteria Or

3.Two major or one major and two minor criteria plus Essential criteria 18

Major criteria :1.Carditis2.Migratory Polyarthritis3.Sydenham’s chorea 4.Erythema marginatum5.Subcutaneous nodules.

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Cont…

Minor criteria:A. Clinical

1. Fever2. Arthralgia3. Previous Rheumatic fever or RHD

B. Laboratory 1.Leukocytosis, raised ESR and C reactive

protein2.Prolonged PR interval in the ECG.

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Cont..

Essential criteria: Supporting evidence of recent Streptococcal infection as indicated by:1.Raised ASO titer or other Streptococcal

antibody titer2.Positive throat swab culture3.Recent Scarlet fever

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Arthritis:

• Early manifestation and occurs in about 75% of the patients.

• Early features: There is acute , painful , asymmetry and migratory inflammation of large joints (knee , ankle , wrist , elbow)

• Affected joints are red , warm, swollen, pain and limitation of movement.

• Pain and swelling appear more quickly, last 3 to 7 days and subside spontaneously to appear in some other joint.

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Cont…

• There is no residual damage or erosion after recovery .

• Arthritis responds well to Aspirin.

• Note : - younger the patient with acute rheumatic fever, the less the arthritis and the older the patient the more the arthritis

Carditis:

• It is a pancarditis involving endocardium , myocardium and pericardium .• Seen in 50-60% of patients.• Early manifestation of RF so that by the time a patient seeks helps, he already has evidence of carditis.• 80 % of those patients who develop carditis do so within the first two weeks of the onset of rheumatic fever.

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Pericarditis :-

Seen in 15 % of patients C/F : severe precordial pain On auscultation : friction rub ECG shows : ST elevation and T wave

inversion After the disappearance of pericardial

friction rub, one can safely exclude rheumatic fever as the cause of pericarditis.

Myocarditis Features diagnostic of myocarditis are : 1. cardiac enlargement 2. soft first sound 3. congestive cardiac failure 4. Carey Coombs murmur (delayed diastolic

mitral murmur): - Disappear after the myocarditis subsides Due to increased diastolic flow, secondary to

mitral regurgitation, across inflamed rigid cusps Disappearance can be explained by the decrease

in the left ventricular size following subsidence of myocarditis, and better function of the mitral valve – papillary complex

Endocarditis : -

Pansystolic murmur Pathologically mitral valve is involved in

100 % of cases of RF who have carditis. Clinically : -

5 – 8 % (pure aortic regurgitation) 95 % (mitral regurgitation murmur)

Tricuspid valvulitis resulting in tricuspid regurgitation in 10 – 30 %

Pulmonary valve involvement never seen

Cont…

Acute hemodynamic overload resulting from mitral regurgitation and / or aortic regurgitation leads to left ventricular failure (LVF) and is the main reasons for the morbidity and mortality of rheumaticfever and RHD

The severity of the valvar endocarditis causing acute and later chronic hemodynamic overload determines the prognosis of individuals patients

Sydenham’s chorea:

Late manifestation occurring after about 3 months of acute attack

Generally by the time a patient manifests chorea, the signs of inflammation in the form of ESR have returned to normal

More common in females and observed in about one – third cases.

Chorea is purposeless, involuntary , dancing movements of hands , feet and face (St . Vitus dance), weakness.

Untreated, it has a self – limiting course of two to six weeks

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Subcutaneous nodules

Late manifestation occurring after about 6 weeks of acute attack

• Found in about 3 – 5 % patients after a few weeks of illness.

• Appear on bony prominences like elbows, occiput and spine and are small(0.5-2cm),firm and painless nodules.

• Patients who have subcutaneous nodule almost always have carditis.

• Last from a few days to weeks but have been known to last for almost a year.

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Erythema marginatum

It is rare manifestation Rash : faintly reddish, not raised above

the skin (macules) and non – itching It is early manifestation, predominently

seen over the trunk and proximal extremities.

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Minor criteria

Clinical Fever :Temperature rarely goes above 39.5

degree C In the initial attack it is almost present

90 % of the patients.Arthralgia :Subjective painOccurs in about the 90 % of the patientsPrevious RF or RHD is applicable only

for a second attack of RF

Lab manifestations :

Acute phase reactants : Leukocytosis (1oooo – 15000/cmm) Increased ESR (for 4 – 10 weeks in

80 %) and Presence of C – reactive protein

(absence after use of steroids)

Essential criteria :

Presence of antibodies against the streptococci (ASO titer)

Rising ASO titer is a strong evidence of a recent streptococcal infection

Positive throat culture for streptococci is relatively uncommon, when a patient presents with ARF

Positive throat culture means that streptococci are present in the throat and the patient may or may not have RF

Finding of scarlet fever : desquamation of skin of palms and soles indicates that the patient has had scarlet fever within the previous two weeks.

Rheumatic heart disease at autopsy with characteristic findings (thickened mitral valve, thickened chordae tendineae, hypertrophied left ventricular myocardium).

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Evidence of systemic illness: Leucocytosis , raised ESR, raised CRP. Evidence of preceding Streptococcal

infection: Throat swab culture , Group A Beta-

hemolytic Streptococci (25-40%positive). Anti streptolysin O (ASO) antibodies : Rising titer or levels of >200 units. Evidence of carditis :1. Chest X-Ray- Cardiomegaly2. ECG-First degree heart block3. Features of Pericarditis4. Echocardiography-Cardiac dilatation or

Valve abnormality

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Treatment

No specific treatment. Management is symptomatic

combined with suppressive therapy1. Bed rest : Patients who do not have cardiac

involvment can be ambulatory in two to three weeks whereas when carditis is present, immobilization may have to be continued for two to three months specially in the presence of congestive failure.

Cont…

2. Diet : salt is restricted in case of congestion cardiac failure .

3. Penicillin : After obtaining throat cultures the patient should be put on penicillin.

Dose : Initially 400,000 units of procaine

penicillin, I.M x BD for 10 days. Followed by prophylactic penicillin using

benzathine penicillin 1.2 mega units every 21 days, or 0.6 mega units every 15 days.

Cont…

4. Suppressive therapy : Aspirin or steroids Untreated rheumatic fever subsides in 12

weeks in 80 %. Steroids are more potent than aspirin. Pericardial friction rub tends to disappear

within three to five days after starting the steroids and a new friction rub does not appear

Subcutaneous nodules tend to disappear faster with the use of steroids as compared to aspirin.

Patients who carditis with congestive cardiac failure have a much higher mortality if aspirin is used as against steroids.

Cont..

Guidelines for selecting the suppressive drug:

1. carditis with CCF, use steroids2. carditis without CCF, use either

steroids or aspirin, however, steroids are preferred

3. no carditis, use aspirin

Cont…

Total duration course : for 12 weeks Dose : Aspirin 90 – 120 mg/kg/day in 4 divided dose Full dose for 10 weeks than tapered off in

next 2 weeks Steroid : 60 mg/ day for weight >20 kg 40 mg/ day for weight < 20 kg . Continued

for 3 weeks then 50 mg/day for 1 week and 40 mg/day for another week. Following this the reduction in dose is by 5 mg/ week till it is finished

Cont…

Acute hemodynamic overload due to mitral and/ or aortic regurgitation during ARF is the main cause of RF mortality.

Management of chorea : ESR and ASO titer may be normal Reassured the patient and parents and

told the self – limiting course of the disease

Complete physical and mental rest Phenobarbitone 30mg X TDS Others drugs : promethazine,

chlorpromazine, valium

Prophylaxis

Penicillin prophylaxis is essential to prevent recurrence of RF

Primary prophylaxis : Identification of streptococcal sore throat

and its treatment with penicillin. Educate the community regarding the

consequences of streptococcal sore throat. 30 – 80 % of sore throats resulting in

rheumatic fever can be asymptomatic If RF present than oral penicillin is not

sufficient to prevent , so I.M benzathine penicillin is mandatory for prevention of RF

For prevention of recurrent attack of rheumatic fever:

Long term intramuscular Benzathine Penicilline is given 1.2 million unit 3-4 weekly or 0.6 mega units veery alternate week.

Oral Penicillin V 250mg twice a day is another choice.

Erythromycin can be used in case of Penicillin allergy

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Cont…

• Prophylaxis should be continued:For at least 5 years after last attack

OrUp to the age of 21 years

OrLife long if there is documented Rheumatic heart disease.

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Prognosis The prognosis for the primary attack is generally good, and only 1 % of patients die from fulminant RF

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