1. Dr.Said Alavi MD,DCH,DNB,FCPS Dept. of Pediatrics and Neonatology Saqr Hospital,Ras Al Khaimah UNITED ARAB EMIRATES E-mail: drsaid@emirates.net.ae

2. 05/05/1999Dr.Said Alavi2 ObjectivesObjectives l Etiology l Epidemiology l Pathogenesis l Pathologic lesions l Clinical manifestations & Laboratory findings l Diagnosis & Differential diagnosis l Treatment & Prevention l Prognosis l References

3. 05/05/1999Dr.Said Alavi3 Etiology l Acute rheumatic fever is a systemic disease of childhood,often recurrent that follows group A beta hemolytic streptococcal infection l It is a delayed non-suppurative sequelae to URTI with GABH streptococci. l It is a diffuse inflammatory disease of connective tissue,primarily involving heart,blood vessels,joints, subcut.tissue and CNS

4. 05/05/1999Dr.Said Alavi4 Epidemiology l Ages 5-15 yrs are most susceptible l Rare <3 yrs l Girls>boys l Common in 3rd world countries l Environmental factors-- over crowding, poor sanitation, poverty, l Incidence more during fall,winter & early spring

5. 05/05/1999Dr.Said Alavi5 Pathogenesis l Delayed immune response to infection with group.A beta hemolytic streptococci. l After a latent period of 1-3 weeks, antibody induced immunological damage occur to heart valves,joints, subcutaneous tissue & basal ganglia of brain

6. 05/05/1999Dr.Said Alavi6 l Strains that produces rheumatic fever - M types l, 3, 5, 6,18 & 24 l Pharyngitis- produced by GABHS can lead to- acute rheumatic fever, rheumatic heart disease & post strept. Glomerulonepritis l Skin infection- produced by GABHS leads to post streptococcal glomerulo nephritis only. It will not result in Rh.Fever or carditis as skin lipid cholesterol inhibit antigenicity Group A Beta Hemolytic Streptococcus

7. 05/05/1999Dr.Said Alavi7 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

8. 05/05/1999Dr.Said Alavi8 Pathologic Lesions l Fibrinoid degeneration of connective tissue,inflammatory edema, inflammatory cell infiltration & proliferation of specific cells resulting in formation of A shcoff nodules, resulting in- -Pancarditis in the heart -Arthritis in the joints -Ashcoff nodules in the subcutaneous tissue -Basal gangliar lesions resulting in chorea

9. 05/05/1999Dr.Said Alavi9 Rheumatic Carditis Histology (40X)

10. 05/05/1999Dr.Said Alavi10 Histology of Myocardium in Rheumatic Carditis ( 200X)

11. 05/05/1999Dr.Said Alavi11 Clinical Features l Flitting & fleeting migratory polyarthritis, involving major joints l Commonly involved joints- knee,ankle,elbow & wrist l Occur in 80%,involved joints are exquisitely tender l In children below 5 yrs arthritis usually mild but carditis more prominent l Arthritis do not progress to chronic disease 1.Arthritis

12. 05/05/1999Dr.Said Alavi12 Clinical Features (Contd) l Manifest as pancarditis (endocarditis, myocarditis and pericarditis),occur in 40- 50% of cases l Carditis is the only manifestation of rheumatic fever that leaves a sequelae & permanent damage to the organ l Valvulitis occur in acute phase l Chronic phase- fibrosis,calcification & stenosis of heart valves(fishmouth valves) 2.Carditis

13. 05/05/1999Dr.Said Alavi13 Rheumatic heart disease. Abnormal mitral valve. Thick, fused chordae

14. 05/05/1999Dr.Said Alavi14 Another view of thick and fused mitral valves in Rheumatic heart disease

15. 05/05/1999Dr.Said Alavi15 Clinical Features (Contd) l Occur in 5-10% of cases l Mainly in girls of 1-15 yrs age l May appear even 6/12 after the attack of rheumatic fever l Clinically manifest as-clumsiness, deterioration of handwriting,emotional lability or grimacing of face l Clinical signs- pronator sign, jack in the box sign, milking sign of hands 3.Sydenham Chorea

16. 05/05/1999Dr.Said Alavi16 Clinical Features (Contd) l Occur in <5%. l Unique,transient,serpiginous-looking lesions of 1-2 inches in size l Pale center with red irregular margin l More on trunks & limbs & non-itchy l Worsens with application of heat l Often associated with chronic carditis 4.Erythema Marginatum

17. 05/05/1999Dr.Said Alavi17 Clinical Features (Contd) l Occur in 10% l Painless,pea-sized,palpable nodules l Mainly over extensor surfaces of joints,spine,scapulae & scalp l Associated with strong seropositivity l Always associated with severe carditis 5.Subcutaneous nodules

18. 05/05/1999Dr.Said Alavi18 Clinical Features (Contd) Other features (Minor features) l Fever-(upto 101 degree F) l Arthralgia l Pallor l Anorexia l Loss of weight

19. 05/05/1999Dr.Said Alavi19 Laboratory Findings l High ESR l Anemia, leucocytosis l Elevated C-reactive protien l ASO titre >200 Todd units. (Peak value attained at 3 weeks,then comes down to normal by 6 weeks) l Anti-DNAse B test l Throat culture-GABHstreptococci

20. 05/05/1999Dr.Said Alavi20 Laboratory Findings (Contd) l ECG- prolonged PR interval, 2nd or 3rd degree blocks,ST depression, T inversion l 2D Echo cardiography- valve edema,mitral regurgitation, LA & LV dilatation,pericardial effusion,decreased contractility

21. 05/05/1999Dr.Said Alavi21 Diagnosis l Rheumatic fever is mainly a clinical diagnosis l No single diagnostic sign or specific laboratory test available for diagnosis l Diagnosis based on MODIFIED JONES CRITERIA

22. 05/05/1999Dr.Said Alavi22 Recommendations of the American Heart Association

23. 05/05/1999Dr.Said Alavi23 Exceptions to Jones Criteria  Chorea alone, if other causes have been excluded  Insidious or late-onset carditis with no other explanation  Patients with documented RHD or prior rheumatic fever,one major criterion,or of fever,arthralgia or high CRP suggests recurrence

24. 05/05/1999Dr.Said Alavi24 Differential Diagnosis l Juvenile rheumatiod arthritis l Septic arthritis l Sickle-cell arthropathy l Kawasaki disease l Myocarditis l Scarlet fever l Leukemia

25. 05/05/1999Dr.Said Alavi25 Treatment l Step I - primary prevention (eradication of streptococci) l Step II - anti inflammatory treatment (aspirin,steroids) l Step III- supportive management & management of complications l Step IV- secondary prevention (prevention of recurrent attacks)

26. 05/05/1999Dr.Said Alavi26 STEP I: Primary Prevention of Rheumatic Fever (Treatment of Streptococcal Tonsillopharyngitis) Agent Dose Mode Duration Benzathine penicillin G600 000 U for patients Intramuscular Once 27 kg (60 lb) 1 200 000 U for patients >27 kg or Penicillin VChildren: 250 mg 2-3 times daily Oral 10 d (phenoxymethyl penicillin) Adolescents and adults: 500 mg 2-3 times daily For individuals allergic to penicillin Erythromycin: 20-40 mg/kg/d 2-4 times daily Oral 10 d Estolate (maximum 1 g/d) or Ethylsuccinate40 mg/kg/d 2-4 times daily Oral 10 d (maximum 1 g/d) Recommendations of American Heart Association

27. 05/05/1999Dr.Said Alavi27 Step II: Anti inflammatory treatment Clinical condition Drugs

28. 05/05/1999Dr.Said Alavi28 l Bed rest l Treatment of congestive cardiac failure: -digitalis,diuretics l Treatment of chorea: -diazepam or haloperidol l Rest to joints & supportive splinting 3.Step III: Supportive management & management of complications

29. 05/05/1999Dr.Said Alavi29 STEP IV : Secondary Prevention of Rheumatic Fever (Prevention of Recurrent Attacks) Agent DoseMode Benzathine penicillin G1 200 000 U every 4 weeks*Intramuscular or Penicillin V250 mg twice daily Oral or Sulfadiazine 0.5 g once daily for patients 27 kg (60 lb Oral 1.0 g once daily for patients >27 kg (60 lb) For individuals allergic to penicillin and sulfadiazine Erythromycin250 mg twice daily Oral *In high-risk situations, administration every 3 weeks is justified and recommended Recommendations of American Heart Association

30. 05/05/1999Dr.Said Alavi30 Duration of Secondary Rheumatic Fever Prophylaxis CategoryDuration Rheumatic fever with carditis and At least 10 y since last residual heart disease episode and at least until (persistent valvar disease*) age 40 y, sometimes lifelong prophylaxis Rheumatic fever with carditis10 y or well into adulthood, but no residual heart disease whichever is longer (no valvar disease*) Rheumatic fever without carditis5 y or until age 21 y, whichever is longer *Clinical or echocardiographic evidence. Recommendations of American Heart Association

31. 05/05/1999Dr.Said Alavi31 Prognosis l Rheumatic fever can recur whenever the individual experience new GABH streptococcal infection,if not on prophylactic medicines l Good prognosis for older age group & if no carditis during the initial attack l Bad prognosis for younger children & those with carditis with valvar lesions

32. 05/05/1999Dr.Said Alavi32 References  Hoffman JIE: Rheumatic Fever. Rudolph's Pediatrics; 20th Ed: 1518 - 1521,1996.  Stollerman GH: Rheumatic Fever. Harrison's Principles Of Internal Medicine; 13th Ed: 1046 - 1052,1995.  Special Writing Group of the Committee on Rheumatic Fever,endocarditis & Kawasaki Disease of the Council on Cardiovascular Disease in the Young of the American Heart Association: Guidelines for the Diagnosis of Rheumatic Fever. In Jones Criteria, 1992 Update JAMA 268:2029,1992  Todd J: Rheumatic Fever. Nelson's Textbook Of Pediatrics; 15th Ed: 754 - 760, 1996.  Warren R, Perez M, Wilking A: Pediatric Rheumatic Diseases. Pediatric Clinics of North America; 41: 783 - 818,1994.  World Health Organization Study Group: Rheumatic Fever & Rheumatic Heart Disease,technical Report Series No. 764.Geneva,world Health Organization, 1988

33. 05/05/1999Dr.Said Alavi33