Clinical features of acute rheumatic fever in children and its management principles

1. Dr.C.S.N.Vittal

2. INTRODUCTION
• Leading cause of Acquired Heart disease
• Non suppurative complications of Group A beta hemolytic
streptococcal pharyngitis
• Latent period of 1‐3 weeks
• A delayed immune response caused by antibody cross reactivity
that can involve the heart, joints, skin, and brain (basal ganglia)
• Serotypes M types (4,1,3,5,6,18,29)

3. EPIDEMIOLOGY
• Incidence: Peak 5 – 15 yrs.
• Prevalence of RHD India 1.5 to 2.2
• About 50% of children with ARF will suffer from
RHD
• Sex–Both sex Equally Affected
• Season – Winter
• Predisposing Factor s–
– 1.Low Socioeconomic status
– 2.Over crowding
– 3.Poor Medical Care

4. ARF - World Scenario

5. Pathologic Lesions
• Fibrinoid degeneration of connective tissue, inflammatory edema,
inflammatory cell infiltration & proliferation of specific cells
resulting in formation of Ashcoff nodules, resulting in-
-Pancarditis in the heart
-Arthritis in the joints
-Ashcoff nodules in the subcutaneous tissue
-Basal gangliar lesions resulting in chorea

6. Pathogenesis
1. Cytotoxicity theory: Enzymes like streptolysin O cause tissue
damage
2. Immune-mediated pathogenesis: The antigenicity of several GAS
cellular and extracellular epitopes and their immunologic cross
reactivity with cardiac antigenic epitopes also lends support to the
hypothesis of molecular mimicry
3. Antibody response to the collagen: Binding of an M protein N-
terminus domain to a region of collagen type IV leads to ground
substance inflammation especially in subendothelial areas like
cardiac valves and myocardium.

7. Pathogenesis

8. Diagrammatic structure of the group A beta
hemolytic streptococcus
Capsule
Cell wall
Protein antigens
Group carbohydrate
Peptidoglycan
Cyto. membrane
Cytoplasm
…………………………………………………...
Antigen of outer protein cell wall
of GABHS induces antibody
response in victim which result
in autoimmune damage to heart
valves, sub cutaneous tissue,
tendons, joints & basal ganglia of
brain

10. Histology of Myocardium in
Rheumatic Carditis (200X)

11. Fused mitral valves
in Rheumatic heart
disease

12. Jones Criteria (Revised) for Guidance in the Diagnosis of Rheumatic
Fever – 2015 revision
Major Criteria
Low Risk Population High Risk Population
Carditis (clinical or subclinical) Carditis (clinical or subclinical)
Arthritis – only polyarthritis Arthritis – monoarthritis or polyarthritis
Chorea Polyarthralgia
Erythema marginatum Chorea
Subcutaneous nodules Erythema marginatum
Subcutaneous nodules
Minor Criteria
Low Risk Population High Risk Population
Polyarthralgia Monoarthralgia
Hyperpyrexia (>38.50C) Hyperpyrexia (>380C)
ESR > 60 mm/h and/or CRP > 3.0 mg/dl ESR > 30 mm/h and/or CRP > 3.0 mg/dl
Prolonged PR interval (age related) Prolonged PR interval (age related)

13. Acute RF occur in > 2/100 000
school age children.
01
02
Rheumatic heart disease is diagnosed in
> 1/1000 patients at any age during one year
Acute RF occur in ≤ 2/100 000
school age children.
Rheumatic heart disease is diagnosed in
≤ 1/1000 patients at any age during one year
Jones Criteria (Revised) for Guidance in the Diagnosis of
Rheumatic Fever – 2015 revision
Low Risk
Population
Moderate
/ High risk
population

14. Diagnosis of a first attack Diagnosis of recurrent acute
• 2 major manifestations,
OR
• 1 major and 2 minor manifestations,
PLUS
• Evidence of recent GAS infection.
• 2 major manifestations,
OR
• 1 major and 2 minor,
PLUS
• Evidence of recent GAS infection
• 3 minor manifestations (in the
Moderate/High-Risk population),
PLUS
Supporting evidence of antecedent group A streptococcal infection:
• Positive throat culture or rapid streptococcal antigen test
• Elevated or increasing streptococcal antibody titer (>250 U/dL)
Jones Criteria (Revised) for Diagnosis of
Rheumatic Fever 2015 Revision
(Essential Criteria)

15. Exceptions to Jones criteria
1) Chorea
2) Indolent carditis with insidious onset
3) Previous h/o acute rheumatic fever in
particularly high-risk populations or RHD

17. Involve larger joints (knees, ankles, wrists, and elbows)
Resolves in six weeks
No Permanent Sequelae
Dramatic response to Aspirin
Sacroiliac, Temporomandibular & Cervical joints not involved
Earliest manifestation/ correlate with ASO titers
Migratory in nature
Arthritis

18. Peripheral and pulmonary edema.
Sleeping pulse rate raised.
Mod or severe : cardiomegaly, heart failure, hepatomegaly
Tachycardia out of proportion to fever
Tachycardia, cardiac murmurs, with or without e/o myocardial
or pericardial involvement.
Approximately 50-60% of all cases of acute rheumatic fever.
Carditis

19. Echocardiographic evidence of valvulitis
Pathological MR
(all 4 criteria need to be met)
Pathological AR
(all 4 criteria need to be met)
• Seen in at least 2 views
• Jet length ≥ 2 cm in at least 1 view
• Peak velocity >3 meters / second
• Pan-systolic jet in at least 1 envelope
• Seen in at least 2 views
• Jet length ≥1 cm in at least 1 view
• Peak velocity >3 meters / second
• Pan-diastolic jet in at least 1 envelope
• Gewitz MH, Baltimore RS, Tani LY, etal

20. Carditis
ECG: Prolonged PR interval

21. Chorea
In approximately 10-15% of patients with
acute rheumatic fever
Usually presents as an isolated, frequently
subtle, movement disorder
The latent period from acute GAS infection to
chorea is usually substantially longer

22. Chorea - demonstration
Milkmaid’s grip
Spooning and pronation of the hands when the patient’s arms
are extended
Pronator sign: Inability to hold the hand above the head with
palms facing each other it results in pronation of forearm and
palm face outwards
Wormian darting movements of the tongue upon protrusion (Jack
in the Box)
Examination of handwriting to evaluate the motor movements
Hung up Reflux: On eliciting Knee jerk: knee extends and the leg
and foot hangs up in the mid air due to chorea.

23. 3. Not pruritic
2. Erythematous, serpiginous, macular lesions, pale centers
1. In % of patients with acute rheumatic fever
4. primarily on the trunk and extremities, not on the face
Erythema marginatum
5. Can be accentuated by warming the skin.

24. Erythema marginatum

25. 3. Along the extensor surfaces of tendons near bony
prominences
2. Firm nodules approximately 1 cm in diameter
1. ≤ 1 % of patients with acute rheumatic fever
4. Correlation between the presence of these
nodules and significant rheumatic heart disease
Subcutaneous nodules

26. Subcutaneous nodules
SUBCUTANEOUS
NODULE

27. Differential Diagnosis
ARTHRITIS CARDITIS CHOREA
Juvenile idiopathic arthritis Viral myocarditis Huntington chorea
Reactive arthritis (e.g., Shigella,
Salmonella, Yersinia)
Viral pericarditis
Wilson disease
Serum sickness Infective endocarditis Cerebral palsy
Sickle cell disease Kawasaki disease Tic disorder
Systemic lupus erythematosus Mitral valve prolapse Hyperactivity
Lyme disease (Borrelia burgdorferi)
Innocent murmurs
Pyogenic arthritis Congenital heart disease
Post-streptococcal reactive arthritis

28. Some Important Terminology
Recurrence
Rebound
Relapse
Subclinical
carditis
Indolent
carditis
A new episode of rheumatic fever following
another GABHS infection, occurring after
8 weeks following stopping treatment
Manifestations of rheumatic fever
occurring within 4-6 weeks of
stopping treatment or while tapering
drugs
Worsening of rheumatic fever while
under treatment and often with
carditis
When clinical exam is normal but
echocardiogram is abnormal.
(30%)
Persistent features of CHF, murmur and
cardiomegaly. No or very few features of
carditis.
01
05
04
03
02
ARF
Course

29. Indications of recurrence of Rheumatic
Fever in established heart disease
1. New murmur / change in pre existing murmur
2. Pericardial rub (and other evidence of pericarditis
3. Unexplained congestive heart failure including cardiomegaly

30. 1. Bed rest
2. Eradication of Streptococci
3. Anti inflammatory therapy
4. Treatment of CCF
Treatment - Principles
5. Treatment of Chorea
6. Prevention of Recurrences
7. Surgical : Acute and Chronic

31. Treatment - GENERAL MEASURES
Measures ARTHRITS
ONLY
MILD CARDITIS MODERATE
CARDITIS
SEVERE
CARDITIS
BEDREST 1-2 Weeks 3-4 Weeks 4-6 Weeks As long as CHF
present
INDOOR
AMBUALTION
1-2 Weeks 3-4 Weeks 4-6 Weeks 2-3 months
• Mild : Questionable cardiomegaly.
• Moderate : Definite but mild cardiomegaly.
• Severe : Marked cardiomegaly or heart
failure.

32. Treatment - Arthritis
• Switch over to steroids if no response within 4 days of treatment.
• R/o inflammatory myeloproliferative disorders
Anti-inflammatory treatment
Aspirin Regimen I
Starting dose: 100 mg/kg/d for 2-3 weeks
Tapering dose: once symptoms resolver, 60-70 mg/kg/s
Total 12 weeks
Regimen II
50-60 mg/kg/d for total of 12 weeks
Neproxen
(if Aspirins intolerance
detected, or no response to
aspirin in 4 days)
10-20 mg/kg/d for 12 weeks

33. Treatment - Carditis
• Carditis alone – Aspirin only
• Carditis with cardiomegaly – Aspirin only
• Patients with carditis and more than minimal cardiomegaly
and/or congestive heart failure should receive corticosteroids .
• Decongestive measures
• Diuretics, digitalis
• Bed rest
• Low sodium diet
Steroids:
• Predinisalone: 2-2.5 mg/kg/d in 4 divided doses for 2 weeks (till
ESR normalizes) and by half the dose for 2-3 wk and then tapering
of the dose by 5 mg/24 hr every 2-3 days.
• When prednisone is being tapered, aspirin should be started at 50
-75mg/kg/day in 4 divided doses for 6 wk to prevent rebound of
inflammation.- (complete total 12 weeks)
• Methyl prednisolone IV: If no response to oral steroid therapy. 30
mg/kg/d for 3 days

34. Treatment - Chorea
• Anti inflammatory agents not needed
• Phenobarbitone (16-32 mg every 6-8 hr PO) – drug of choice
• Haloperidol: 0.01 - 0.03 mg/kg/d in 2 divided doses orally
• Chlorpromazine: 0.5 mg/kg Q4 or 6H Oral
• Sodium valproate: 15mg/kg/d
• Carbamazapine: 7-20 mg/kg/d
• Steroids – in some cases • Treatment should be
continued for 2-4 weeks after
clinical improvement .
• Indian pediatrics, Vol 45, july 17, 2008

35. Anti-streptococcal treatment
• A single injection of benzathine penicillin is given
when the diagnosis of rheumatic fever is made.
– 1.2 million unit (>27 kg) after sensitivity test
0.6 million units(< 27 kg)
• Penicillin V
– 250 mg four times a day for 10 days) is an alternative;
• To those with penicillin allergy. (Oral)
– Erythromycin (20 mg/kg/dose max 500 mg for 10 days OR
– Azithromycin 12.5 mg/kg once daily for 5 days

36. Management of Complications
• Heart Failure
– Reduce physical activity
– Monitro fluid balance
– Treat anemia with iron/pRBC
– Drugs
• Digoxine 10 mcg/kg total digitalization dose and 7.5 mcg/kg
maintenance dose
• Diruretics: Frusemide 0.5 – 2 mg /kg/d
• Captopril: 0.25 mg/kg/d
– Surgery
• For sever MR due to chordal rupture leading to refractory CHF

37. Prevention of RF
Primordial Preventing Strep throat - ? Vaccine – not avb
Primary Treating Strep throat infection
Secondary Preventing Rheumatic recurrence by
chemoprophylaxis
Tertiary Treating RHD

38. Primary Prophylaxis
• Vulnerable children from 5 – 15 yrs with pharyngitis
• ORAL
– Penicillin V 250-500 mg BID for 10 days
– Amoxicillin 50 mg/kg OD for 10 days
– Azithromycin 12 mg/kg/d OD for 5 days
– First gen Cephalosporin – 10 days
– Azithromycin 12 mg/kg/d OD – 5 days
• PARENTARAL
– < 27 Kg single dose IM Benzathine Penicillin 6,00,000 U
– > 27 kg single dose IM Benzathine Penicillin 12,00,000 U
AHA Recommendation

39. Secondary Prophylaxis
DRUG DOSE ROUTE
Penicillin G benzathine • 600,000 IU for children weighing ≤ 27 kg
• 1.2 million IU for children weighing > 27
kg every 4 weeks
IM
Penicillin V 250 mg, twice a day Oral
Sulfadiazine or sulfisoxazole 0.5 g once a day for < 27 kg
1.0 g once a day for > 27 kg
Oral
Macrolide or azalide Variable Oral

40. Secondary Prophylaxis – How Long to give ?
RF;
No Carditis
5 yrs from last episode OR till 21 years of age
(whichever is longer)
RF; Carditis – no residual RHD
10 yrs from last episode or till 21 yrs
(whichever is longer) *
RF Carditis; RHD
10 yrs from last episode or till 40 yrs age
(whichever is longer); sometimes lifelong
More severe valvular disease or
after valvular surgery ** Life long
• Gerber MA, Baltimore RS, Eaton CB, et al: Prevention of rheumatic fever and diagnosis and
treatment of acute streptococcal pharyngitis

41. Prognosis
• Before antibiotic prophylaxis: 75% patients develop recurrences and
residual RHD
• 50-70% with carditis during initial episode recover with no residual
disease
• Severe the initial attack – more chances of RHD
• Risk of recurrence more in first 5 yrs of initial episode
• 20% of patients with pure chorea not given sec prophylaxis develop
RHD within 20 yrs

42. • Dr. C.S.N.Vittal