Acute Rheumatic Fever

1. ACUTE RHEUMATIC FEVER
ETIOLOGY
PATHOGENESIS
CLINICAL FEATURES
MANAGEMENT
By Devalekshmi.S
Roll no 21

2. Definition
• “It is a multi system disease resulting from an autoimmune reaction to infection
with group A streptococcus.”
• Primary sites: Heart, joints, CNS
• Almost all of manifestation resolve completely, except cardiac valvular damage(RHD),which may persist
after other features have disappeared.
• Children 5-15 years and young adults
• RHD more common in females twice as frequently as in males
• Initial episodes –less common in old adolescent
• Recurrent episodes- seen in adolescents and young adults
• Prevalence of RHD peaks 25-40 years
• India, avg age of presentation 10-14 yrs
• Declined in Europe and North America
• Remains one of the most important cause of CVS mortality and morbidity in the developing countries.

3. Etiology
Develops after latent period 2-6 weeks after an episode of pharyngitis/tonsillitis by Group A beta
hemolytic Streptococcus
• M-serotypes (particularly types 1, 3, 5, 6, 14, 18, 19, 24, 27, and 29) were associated with ARF
• Pharyngitis- produced by GABHS can lead to- ARF,RHD & post strept. Glomerulonepritis
• Skin infection- produced by GABHS leads to post streptococcal glomerulo-nephritis only not
result in Rh.Fever or carditis as skin lipid cholesterol inhibit antigenicity Group A Beta Hemolytic
Streptococcus
• GENETICS
• Familial clustering of cases particularly for chorea
• monozygotic twins > dizygotic twins and heritability estimated at 60%.
• Some human leukocyte antigen (HLA) class II alleles, particularly HLA-DR7 and HLA-DR4,
associated with susceptibility

5. B Lymphocytes produce
antibodies against
streptococcal antigens (mainly
M protein and
N-acetylglucosamine of group A
streptococcal carbohydrate)
 antibodies cross react
with human tissues
because of antigenic
similarity-
cross-reactive antibodies
bind to endothelial cells on
the heart valve--
Autoimmune damage to heart
valves, subcutaneous tissues,
tendons, joints and basal ganglia of
brain
Pathogenesis = Molecular mimicry

7. Clinical features
There is a latent period of ~3 weeks (1–5 weeks) between the precipitating group A
streptococcal infection and the appearance of the clinical features .
• The exceptions are chorea and indolent carditis, which may follow prolonged latent periods
lasting up to 6 months.
• Common Clinical features are
• polyarthritis (present in 60–75% of cases)
• carditis (50–75%).
• prevalence of chorea in ARF varies substantially between populations,
ranging from <2 to 30%
• Erythema marginatum
• subcutaneous nodules are now rare, being found in <5% of cases.

8. Heart Involvement
• 75% cases of ARF  RHD
• Valvulitis- main lesion
• Characterised by oedema, cellular infiltration of the valve and chordae tendinae causing verrucae
formation and hyaline degeneration with subsequent regurgitant valves
• Eventual fibrosis and calcification leading to stenotic valves
• ACUTE PHASE
• Carditis as a major manifestation of ARF .
• Although carditis of ARF has been considered to be a pancarditis and can involve the endocardium,
myocardium and pericardium
• Rheumatic endocarditis may involve valvular (valvular endocarditis) or mural endocardium
• (mural endocarditis).
• Rheumatic pericarditis produces pericardial effusion and thick fibrinoserous exudates.
• Carditis leaves a sequelae and permanent damage to the organ (bites the heart).
• ARF = Licks the joints

9. • On microscopic examination, myocardium shows Aschoff body that is pathognomonic
of rheumatic myocarditis.
PATHOLOGY
• Basic change: in the form of fibrinoid degeneration of the collagen:
• - Aschoff cells- modified histiocytes and pathognomic for Rheumatic carditis
• Aschoff nodule is composed of Anitschkow cells with clear nuclei and with a central bar of chromatin-
resembling a caterpiller
• Central area of fibrin
• Central necrosis- surrounded by mononuclear cell infiltrate
• Myocardial fibres adjacent to the Aschoff body undergoes fibrinoid necrosis

11. CHRONIC PHASE= VALVULAR DAMAGES
Valvular damage is the hallmark of RF.
Chronic phase is characterized by fibrosis, calcification, and stenosis of heart
valve=(fish-mouth valves)
• MC: Mitral valve with/without aortic valve
• Pulmonary / tricuspid involvement: usually secondary to increased
pulmonary pressure from Left side valvular disease
• Early will be regurgitation over yrs; leaflets thickening,scarring,
clacifications and valvular stenosis
• Clinical diagnosis based on the auscultation of typical murmurs that
indicate mitral or aortic valve regurgitation

12. Murmurs are most commonly observed during acute rheumatic fever.
1)Apical pansystolic murmur = high-pitched, blowing-quality murmur of
mitral regurgitation that radiates to the left axilla.
2). Apical soft mid-diastolic murmur (Carey Coombs murmur) =heard
during active carditis due to valvulitis with nodules forming on the mitral
valve leaflets.
It accompanies severe mitral insufficiency.
3). An early diastolic murmur of AR and is high-pitched, blowing,
decrescendo, and heard best along the right upper and mid-left sternal
border after deep expiration while the patient is leaning

13. • Subcutaneous nodules occur as
painless,small(0.5–2 cm), mobile lumps
beneath
the skin overlying bony prominences,
particularly of the hands, feet, elbows,
occiput, and occasionally the vertebrae.
• They are a delayed manifestation, appearing
2–3 weeks after the onset of disease, last
for just a few days up to 3 weeks, and are
commonly associated with carditis.

14. • JOINT INVOLVEMENT
Polyarthritis= inflammation, with hot, swollen, red, and/ or tender joints, and
involvement of more than one joint.
 Polyarthritis is typically migratory moving from one joint to another over a period of
hours.
Affects the large joints—the knees, ankles, hips, and elbows—and is asymmetric.
 Pain is severe and usually disabling until anti inflammatory medication is
commenced.
In some populations, aseptic monoarthritis ----result from early commencement of
anti-inflammatory medication before the typical migratory pattern is established.
The joint manifestations of ARF are highly responsive to salicylates and other (NSAIDs).
Joint involvement that persists for more than 1 or 2 days after starting salicylates is
unlikely to be due to ARF.

15. Skin manifestations
 The classic rash of ARF is
Erythema marginatum
begins as pink macules that clear
centrally & leaving a serpiginous,
spreading edge.
 The rash is evanescent, appearing
and disappearing before the
examiner’s eyes
 It occurs usually on the trunk,
sometimes on the limbs, but
almost never on the face.

16. CHOREA Sydenham's chorea, Saint Vitus dance, St. Johannis chorea, chorea minor,
Definition: is a syndrome charactered by chorea, muscle weakness, and emotional instability
 Commonly occurs in the absence of other manifestations, follows a prolonged latent period
after group A streptococcal infection, and is found mainly in females.
 Head = Characteristic darting movements of the tongue, the upper limbs ---- may be
generalized or restricted to one side of the body (hemi-chorea).
 Speech may be affected and may explosive and halting and fidgery
 It is difficult to diagnose and following signs are helpful in these cases
 Milkmaid's grip: When the patient is asked to squeeze the examiner's fingers, a squeezing
and relaxing motion (like milking a cow) occurs. This is described as milkmaid's grip and is
due to inability to maintain muscular contraction.

17. Jack in the box sign: When the patient is asked to keep the tongue protruded out, it retracts
involuntarily.
Pronator sign: Holding the arms outstretched may elicit "spooning" (hyperextension of the
fingers with dorsiflexion of the wrist).
 Severe forms: Patients is unable to get up or sit, and has violent continuous jerks that may
cause physical injury.
 Other features include hypotonia, pendular knee jerks, and mild generalized muscular
weakness
 Associated emotional lability or obsessive-compulsive traits, which may last longer than the
choreiform movements (which usually resolve within 6 weeks but sometimes may take up to
6 months).

18. Laboratory Investigations
EVIDENCE OF A PRECEDING GROUP A STREPTOCOCCAL INFECTION With the exception of
chorea and low-grade carditis, both of which may become manifest many months(>2months)
later,
 Because most cases do not have a positive throat swab culture or rapid antigen test, serologic
evidence is usually needed.
 The most common serologic tests are the anti-streptolysin O (ASO) and anti-DNase B (ADB)
titers
 Antistreptolysin O antibodies (ASO titers): Rising titers, or levels of >200 U (adults) or >300 U
(children). This test is positive in 80% of cases.
 ASO titers are normal in 20% of adult cases of rheumatic fever
 Anti-Dnase B
 Antihyaluronidase (AH)
 Antistreptozyme test (ASTZ) is a very sensitive indicator of recent streptococcal infection and
is also helpful ruling out rheumatic fever. Titers >200 units/ml considered positive.

19. • 2)Investigations for Evidence of a Systemic Illness (Nonspecific)
Acute phase reactants: These tests confirm the presence of an inflammatory
process, but are nonspecific.
Erythrocyte sedimentation rate (ESR) is raised.
Raised C-reactive protein (CRP) in the blood
 Other tests confirming an inflammatory reaction:
Peripheral blood: Polymorphonuclear leukocytosis and anemia (due to
suppression of erythropoiesis)
 Serum: Increase in serum complements, and increase in serum mucoproteins,
alpha 2 and y globulin levels

20. Investigations fpr Carditis
Chest radiography: Chest X-ray may show evidences of cardiac failure,
cardiomegaly, and pulmonary congestion.
ECG changes commonly include: prolongation of the PR interval and T-wave
inversion.
Other findings = second-degree AV block features of pericarditis and reduction in
QRS voltages.
Echocardiography: It can detect myocardial dysfunction, cardiac dilatation,
valvular abnormalities, and pericardial effusion.

22. • Typical clinical features +
evidence of the
precipitating group A
streptococcal infection,
+exclusion of other
diagnoses.
• This uncertainty led Dr. T. Duckett
Jones in 1944 to develop a set of
criteria (subsequently known as
the Jones criteria) to aid in the
diagnosis.

23. TREATMENT
1) ANTIBIOTICS
To treat the precipitating group A streptococcal infection.
• Penicillin is the drug of choice and can be given orally
• 1)Phenoxymethyl penicillin, 500 mg [250 mg for children ≤27 kg] PO twice daily, or
• 2)Amoxicillin, 50 mg/kg [maximum, 1 g] daily, for 10 days or
• 3)IM benzathine penicillin G a single dose of 1.2 million units (600,000 units for children
≤27 kg ,1,200,000 FOR >27 KG
Management of Acute Rheumatic Fever
Step 1: Primary prevention -- eradication of streptococci.
Step 2 Anti-inflammatory treatment (aspirin, steroids
Step 3: Supportive management and management of complications
Step 4: Secondary prevention (prevention of recurrent attacks)

24. 2) SALICYLATES AND NSAIDS
These may be used for the treatment of arthritis, arthralgia, and fever, once the diagnosis
is confirmed.
• Aspirin is a common first-line choice, = 50–60 mg/kg per day, up to 80–100 mg/kg(HIGH
DOSE) per day (4–8 g/d in adults) in 4–5 divided doses.
• At higher doses, -- monitored for symptoms of salicylate toxicity such as nausea,
vomiting, or tinnitus; if symptoms appear, lower doses should be used.
• Naproxen = 10–20 mg/kg per day(safer than aspirin and has the advantage of twice-
daily dosing
Step 3: Supportive Management and Management of
Complications
• Bed rest is important, --- reduces joint pain and cardiac workload.
• Patients without carditis: Advice bed rest until temperature and ESR are normal
• Patients with carditis: Bed rest to be continued for 2-6 weeks after the ESR and
temperature has returned to normal. Avoid exercise in patients who had carditis

25. .
1. Treatment of congestive cardiac failure: Digitalis and diuretics
• Glucocorticoids
Use remains controversial
Prednisone or prednisolone at a dose of 1-2 mg/kg/ day maximum upto 3 weeks
•Bed rest
2. CHOREA
 Milder cases = REST TO JOINTS , SUPPORTIVE SPLINTING
 Severe chorea: carbamazepine or sodium valproate for 1-2 weeks
 Recent evidence of corticosteroids being effective
 Should be considered in severe or refractory cases
 Prednisone at 0.5- 1 mg/kg/daily with weaning after 1 week
 IV Immunoglobulin
 More rapid resolution of chorea, but have shown no benefit on the short or long term
outcome of carditis in ARF without chorea

26. Step 4: Secondary Prevention of Rheumatic Fever (Prevention
of Recurrent Attacks)
directed at preventing acute group A B-hemolytic streptococcal (GABHS) pharyngitis in
patients at risk of recurrent acute rheumatic fever by long-term prophylaxis