1. Dr. SUSHIL SURESH KAMTANE
RHEUMATIC FEVER
Dr. SUSHIL SURESH KAMTANE

2. Introduction
Causative organisms: Group A beta haemolytic Streptococci (GABHS).
Triggered after repeated Streptococcal throat infections.
Autoimmune etiology – molecular mimicry with self antigens.
Lesions due to connective tissue involvement.
GABH streptococci are also called as streptococcus pyogenes and classified on the basis of there M surface protein into various types. Strains causing RF include 1, 3, 5, 6, 14, 18, 19 and 24
Vaccine development difficult due to 80 M type antigens.

3. Epidemiology
BMJ – Rheumatic fever
Global prevalence of rheumatic heart disease in children aged 5 to 14 years; Lancet Infect Dis. 2005;5:

4. Pathophysiology

5. Pathophysiology of rheumatic fever
Caused as a consequence of infection with Beta - haemolytic streptococci group A
Mechanism
1.Direct infection by group A streptococcus
2.Toxic effect of streptococcal extracellular products
3.Antigenic mimicry- mostly accepted

6. Antigenic mimicry
Group specific carbohydrate of group A streptococcus & glycoprotein of heart valves i.e. laminin, N-acetyl glucosamine.
Streptococcal cell membrane, M protein: A,B and C regions & other moieties of human myocardial cells i.e. myosin.
? Predisposing genetic influence
? Unique surface marker on T lymphocytes.

7. Pathologic Lesions
Figures Chronic rheumatic valvulitis of the mitral valve. This
mitral valve exhibits the characteristic features of chronic rheumatic
mitral valvulitis—short, thick, and fused chordae tendineae (arrows).
The leaflets are also thick. These changes can lead to mitral stenosis.

8. Figure 10-22. Chronic rheumatic valvulitis of the mitral valve. This
figure shows mitral stenosis (arrowhead), which resulted in left
atrial dilation. Atrial dilation can lead to atrial fibrillation, which can
in turn predispose to thrombus formation (arrow). The thrombi can
break loose and embolize to distant sites

9. Figure 10-23. Chronic rheumatic valvulitis of the aortic valve. The
valve ring has been opened, and the aortic aspect of the valve is
illustrated in the photograph. This aortic valve has the characteristic
features of chronic rheumatic aortic valvulitis; namely, fusion of
the commissures (long arrows) and thickening of the valve leaflets.
The patient also has dystrophic calcification related to healed
endocarditis (short arrow) and evidence of aortic regurgitation in
the form of endocardial fibrosis from a jet lesion (arrowhead).

10. Clinical Features Clinical features of streptococcal pharyngitis:
Fever with chills
Swelling, erythema, oedema of pharyngitis with enlarged tonsils.
Submandibular and periauricular tender, enlarged lymph nodes.
Latent period of 3 weeks between GABHS pharyngitis and acute rheumatic fever manifestations. (1-5 weeks)

11. Clinical Features: Acute Rheumatic Fever
Develops after a latent period of 3 weeks(1-5 weeks) after GABHS pharyngitis.
Patients develop fever
Polyarthritis (60-70%)
Pancarditis (50-60%)
Sydenham’s Chorea (<2%-30%)
Erythema Marginatum (<5%)
Subcutaneous Nodules (<5%)

12. Clinical Features Polyarthritis is most common presentation.
Signs of inflammation
red,
swollen,
tender, joint
asymmetric involvement.
Classically described as fleeting or migratory i.e. one joint gets involved, becomes normal and then other joint is involved.
Involves large joints esp. knees, ankle, hips and elbows.

13. Friction Rub or small effusion of pericarditis
Carditis: Pancarditis with valvulitis. Commonest valve is mitral followed by aortic valve.
Acute Lesions :
Mitral Regurgitation
Aortic Regurgitation
Chronic Lesions :
Mitral Stenosis
Aortic Stenosis
Friction Rub or small effusion of pericarditis
Cardiac failure due to myocarditis.
PR interval prolongation due to myocardial inflammation.

14. Syndenham’s Chorea: Occurs as lone feature of Acute rheumatic fever.
Female preponderance
Commonly affects head and upper limbs:
Darting tongue movement
Generalized or on one side (Hemi-chorea)
Resolves spontaneously in 6 weeks.
Severe forms of chorea patient may not be able to perform daily routine activities and at risk for harm.

15. Skin Manifestations: Erythema Marginatum is uncommon.
Distribution is Trunk, sometimes limbs and almost never on face – hence likely to be missed.
Rash is pink macula's with central clearing with serpiginous spreading edge.
Evanascent rash which continously appears and disappears in front of examiner’s eyes.
Subcutaneous Nodules
Non tender nodules
0.5 – 2 cm mobile lumps beneath skin overlying bony prominence.
Seen on hands, feet, elbows, occiput and occasionally vertebrae
Commonly associated with carditis.
Delayed manifestation at 2-3 weeks after onset of disease and last for few days to 3 weeks.

18. Investigations
Recommended Tests in Cases of Possible Acute Rheumatic Fever
Complete Blood Count
Erythrocyte sedimentation rate
C-reactive protein
Blood cultures if febrile and to r/o endocarditis
Electrocardiogram (repeat in 2 weeks and 2 months if prolonged P-R interval or other rhythm
abnormality)
Chest x-ray
Echocardiogram (consider repeating after 1 month if negative)
Throat swab (preferably before giving antibiotics)—culture for group A streptococcus
Anti-streptococcal serology: both anti-streptolysin O and anti-DNase B titres, if available (repeat 10–14 days later if 1st test not confirmatory)
Joint aspirate (microscopy and culture) for septic arthritis esp. if presents as monoarthritis.
Copper, ceruloplasmin, anti-nuclear antibody, drug screen for choreiform movements
Serology and auto-immune markers for auto-immune or reactive arthritis

19. Lab tests Elevated antistreptolysin O - Sensitivity 80%
elevated anti DNAase & anti hyaluronidase
Combined sensitivity of the three 95%
Organism in throat culture- before antibiotic therapy started .(difficult in India)
Sensitivity is less % (difficult in India so far as cost effectivess ratio is concerned )

20. Jones Criteria Diagnostic Categories Criteria *Major Manifestations.
**Minor Manifestations
Supporting evidence of a preceding streptococcal infection in last 45 days.
Carditis
Polyarthritis
Chorea
Erythema marginatum
Subcutaneous nodules
Clinical: Fever, polyarthralgia
Lab: raised acute phase reactants i.e. ESR or leucocyte count
electrocardiogram: prolonged P-R interval
elevated or rising antistreptolysin-O or
other streptococcal antibody, or
a positive throat culture, or
rapid antigen test for group A
streptococci, or
recent scarlet fever.
Table –2003 World Health Organization Criteria for the
Diagnosis of Rheumatic Fever and Rheumatic Heart Disease (Based on the
1992 Revised Jones Criteria)

21. Revised Jones Criteria
Diagnostic categories
Criteria
Primary episode of RF
Recurrent attack of RF in a patient without established RHD.
Recurrent attack of RF in a patient of established RHD
Rheumatic Chorea
Insidous onset Rheumatic carditis b
Chronic valve lesions of RHD (Patients who present for first time with lesions of pure mitral stenosis, or mixed mitral valve disease, and/or with aortic valve disease) d
Two major* or one major and two minor** manifestations + Evidence of preceding GABH streptococcal infection***.
Two minor manifestations + evidence of preceding GABHS infection.c
Other manifestations and GABHS infection evidence is not required.
Do not require any criteria for diagnosis.
aSome patient’s may present with only polyarthralgia or monoarthritis with 3 or more of other minor manifestations, together with evidence of GABHS infection and later turn out to be RF. To be considered as probable RF (once other diagnoses are excluded). These should be started on secondary prophylaxis. Cautious approach in such cases esp. when This cautious approach is particularly suitable for patients in vulnerable age groups in high
incidence settings.
b Infective endocarditis should be excluded.
c Some patients with recurrent attacks may not fulfil these criteria.
d Congenital heart disease should be excluded

22. Differential Diagnosis
Viral pharyngitis, scarlet fever
Infective endocarditis
Infective arthritis, gout
Reactive arthritis-reiter’s syndrome, IBS
post streptococcal reactive arthritis
Autoimmune arthritis such as rheumatoid, SLE
In cases of chorea alone – Atypical seizures, CVA, Wilson’s disease, SLE, medications(anti-convulsants-phenytoin, Lithium, oestrogen, cocaine, amitryptyline, metoclopramide, fluphenazine)
Myocarditis (alone) in the absence of valvulitis is unlikely to be of
rheumatic origin and by itself should not be used as a basis for such a
diagnosis.

23. Treatment Antibiotics: to treat precipitating Streptococcal infection
Drug
Dose
Route
Duration
Inj. Benzathine Penicillin G
1.2 Million Units IM
Single Dose
Oral Penicillin V
500 mg twice daily
P/O
10 days
Amoxycillin
25-50mg/kg/day 2-3 times/day
Total adult dose mg/day
Cephalosporins-1st gen.
2-3 times a day
Erythromycin
250 mg four times daily

24. NSAID’S
Drug
Dose
Route
Duration
Aspirin
mg/kg in children
4-8 gm in adults
4-5 divided doses
P/O
1-2 weeks
Naproxen
10-20 mg/kg/day
Relapse of symptoms can occur upto first 3 weeks and to be managed by recommencing aspirin.
If nausea, vomitting, tinnitus occurs with salicylates, then dose can be lowered to 60-70mg/kg/day for further 2-4 weeks.

25. Severe Carditis:
Glucocoticoids are used with the belief that they help in reducing inflammation and early resolution of carditis and failure.
not recommended, as Short term and long term studies do not prove this hypothesis.
Glucocorticoids
Drug
Dose
Route
Duration
Predisone or Prednisolone
Inj. Methyl prednisolone given in very severe carditis.
1-2mg/kg/day
P/O
1-3 weeks
Chorea: Duration or outcome does not change with treatment.
Symptom gets reduced with medication.
Sodium valproate or
carbamazepine are preferred to haloperidol.
But action takes 2 weeks to appear.
To be continued 2 weeks after symptoms subside.

26. Treatment
Patient’s with carditis should be adviced rest for atleast 4 weeks, (but variable as per patient)
Patient’s with arthritis can be ambulated on relief of symptoms.
Patient’s with mild chorea should be kept in protective calm environment.

27. Prevention Primary Prevention:
To avoid overcrowding.
To remove hygiene infrastructure inadequacies
Primary Prophylaxis: includes
Timely and complete treatment of Streptococcal sore throat
If treated with Inj. Benzathine penicillin (single dose) or oral penicillin for 10 days – within 9 days of onset of sore throat , almost all cases of RF can be prevented.
Secondary Prevention is for preventing recurrence of RF and progression of RHD

28. Secondary Antibiotic Prophylaxis
Drug
Dose
Route
Frequency
Inj. Benzathine Penicillin G
1.2MU or 6,00,000 U(<30kg) IM
Every 3-4 weeks
Penicillin V
250mg
P/O
Twice daily
Sulfonamide: Sulphadiazine,
Sulphadoxine, sulphisoxazole
>=30 kg adult and children – 1 gm
<30 kg – 500 mg
Daily
Erythromycin
250 mg
Duration of Secondary Prophylaxis
Patient Category
Duration of Prophylaxis
Patient without proven carditis
5 years from last attck or 18 years age (whichever is longer)
Patient with mild mitral regurgitation
10 years from last attack or 25 years of age (whichever is longer)
Patient with severe valvular disease and valve surgery
Lifelong

29. Prognosis Untreated it lasts for 12 weeks Treated resolves in 2 weeks
Besides carditis all other symptoms resolve completely.
Echocardiogram to be repeated after 1month for progression of carditis.

30. Conclusion Autoimmune and genetic susceptibility.
Major cause of valvular disease.
Carditis and RHD important sequelae.
Primary and secondary prophylaxis needed.