1. Rheumatic Fever Prof SC Brown M.MeD FCP (paed, cardio) DCH

2. How common is RHD? 2 -3 % of infected GABHS  RF WHO 15.6 mill RHD 300 000 of 0.5mill ARF > RHD p.a. 233 000 deaths p.a. Prevalence –Sub Saharan Africa 5.7/1000 in children 5 – 14y –Asia 2 – 3.5/100 –Developed countries 0.5/1000 Characteristics –Rare at young age (< 5% younger 5y) –F > m

3. Incidence ARF & RHD in Aboriginal Australians – Dpt of Health and community services, Northern Australia Prevalence RHD per 1000 Incidence of ARF per 1000 < 55-1415-2425-34> 34 15 35 200 400 RHD 2003 ARF 2002

4. Pathophysiology organism –high rate area: no association –type, site infection, class –repeated infection primes immune response host HLA II allelles B-cell alloantigens (D8/17 = binding site for Strep) immune response –molecular mimicry –CD4+ T-cells –host vs host –valvular disease –laminin in valvular basement membrane(  )

5. Pathogenesis ARF

6. How do we make the diagnosis?

7. First contact with Streptococcus 5 – 15 yr pharyngitis I/T 2 – 3 w Acute RF arthritis fever carditis skin Chronic RF MR, AR MS, AS Relapse / acute on chronic years Natural progression of rheumatic fever Rx Prophylaxis! Jones criteria

8. JONES CRITERIA : MAJOR –fleeting poliarhtritis –carditis –erythema marginatum –subcut nodules –Sydenhams chorea MINOR –history of previous RF –arthralgia –fever –PR prolongation - ECG –LAB  WCC, ESR, CRP EVIDENCE OF RECENT STREPTOCOCCAL INFECTION e.g. ASOT EVIDENCE OF RECENT STREPTOCOCCAL INFECTION e.g. ASOT PLUS

9. Jones criteria

10. does “Streptococcosus exist? ? ? ? ? ? ? ? ? ? ?

11. Chorea vs PANDAS Sydenham chorea 5-15y female choreoatetotic with functional impairment resolve 1-6mo Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal throat infections 3y –puberty male choreiform, no functional impairment remit/relapse

12. Post Streptococcal ReactiveArthritis arhtritis not typical, recent Streptococcal infection small joints hand not responsive to anti-inflamm Rx no risk of carditis! may go on to develop ARF recommend: –high risk population diagnosed – receive prophylaxis for 5 y (1y in low risk population)

13. Drug Therapy anti-inflammatory antibiotics prevention

14. Treatment not all tested in controlled trials e.g. longterm bedrest for carditis e.g. Pen for URTI –Not affect cardiac outcome after 1 y anti-inflammatory antibiotics

15. Anti-inflammatory Salicylates rapid resolution fever, arthritis, arhtralgia evidence: –NOT be used carditis »do not decrease incidence of residual RHD »Dorfman (Pediatrics 1961): 12 week aspirin similar incidence of murmurs as controls > 1yr meta analysis Cochrane 2003,CD003176) –No benefit over steroid or vice versa indication –symptomatic Rx of fever, arthritis, arthralgia

16. Anti-inflammatory steroids –reduce inflammatory response of ARF esp. fever & acute phase reagents –little objective evidence studies done before ECHO meta-analyses no benefit over salisylates or placebo of RHD after 1 –10 y most > 40y ago not test newer corticosteroids

17. Anti-inflammatory: other NSAIDS –Naproxen in 1 small trial Immunoglobulins –IVIG in ARF – no diff > 1y Chorea –Rx reserved moderate-severe symptoms –Valproic acid > carbamazepine or haloperidol PROBLEM – need studies –natural progression of RHD 60% regress after 10y

18. Prevention oral –once daily amoxycillin –high dose amoxycillin –azithromycin –not recommended by US intravenous –3 - 4weekly –practical aspects small gauge needles 1% lignocaine or procaine penicillin slow injection(3min) direct pressure and warming of medication (room temp)

19. prophylaxis

20. prevention treat carriers & children with sore throat 1965 possible reduction ARF 21% cost US $12 pa per child or $65 000 per ARF prevented New Zealand –school based sore throat diagnosis & treatment –no reduction in ARF incidence programmes not practical or affordable vaccine –multivalent vs M-serotype –unlikely < 2015

21. Subclinical Rheumatic carditis “silent” mitral regurgutation  ECHO –MR jet > 1 –MR in 2 planes –velocity > 2,5m/s chorea & arthritis: silent MR abn valve – murmur 2w or 18mo -5y or MS studies trivial MR 45% normal children ? higher in febrile patients New Zealand study –Affect diagnosis of ARF in 10% of cases summarise controversial problems with Echocardiography WHO addition to Jones criteria  justified

22. role of ECHO normal population MR : 2,4 – 50% AR : 0 – 33% TR : 6,3 – 95% PR : 21.9 – 92% rheumatic fever –excludes nonrheumatic causes –e.g. prolapse, bicuspid aov –acute carditis –25% nodules tip leaflets, disappear follow-up –classification of severity –1+ to 4+ –no murmur –later develop RHD

23. Clinical features of rheumatic carditis Pericarditis: Audible friction rub; can be supported by echocardiographic evidence of pericardial effusion. Simultaneous demonstration of valvular involvement generally considered essential. Pericarditis is equally diagnostic in primary episode, or a recurrence of RF. Myocarditis: Unexplained CHF or cardiomegaly, almost always associated with valvular involvement. Left ventricular function is rarely affected. In presence of RHD,CHF and minor manifestations, and elevated streptococcal antibody titers provide reasonable evidence of rheumatic carditis. Endocarditis/valvulitis: Presence of apical holosystolic murmur of mitral regurgitation(with or without apical mid-diastolic murmur, Carey Coombs), or basal early diastolic murmur in patients who do not have a history of RHD. On the other hand, in an individual with previous RHD, a definite change in the character of any of these murmurs or the appearance of a new significant murmur indicates the presence of carditis. Echocardiography can provide early evidence of valvular involvement, can confirm suspected valvular regurgitation, and can exclude non-rheumatic causes of valvular involvement

24. Indications for referral to surgical centre (WHO) symptoms have progressed beyond New York Heart Association(NYHA) Class II. Note: with aortic stenosis (AS), all symptomatic patients should be referred. patients who are asymptomatic, or mildly symptomatic, with progressive left ventricular enlargement on clinical or radiological examination (>0.5 cm/year). cardiac failure due to the valve lesion itself, rather than to an episode of rheumatic carditis. Pulmonary hypertension, with physical signs and ECG evidence of changes in right ventricular hypertrophy, and chest X-ray evidence of pulmonary artery dilatation. tricuspid regurgitation that complicates mitral valve disease. development of atrial fibrillation. thromboembolism. endocarditis is suspected to contribute to cardiac decompensation.

25. surgery during acute phase n = 254 MR + HF age: 6 – 52y rheumatic activity : n = 76 higher incidence of early cx 5 ± 3y acute mortality: 2.6% 5y mortality: 15% re-operation 27% 47% Circulation, 1994,90(5 Pt 2):II 167–174. conclusion “surgical valve repair during active carditis was associated with an acceptable survival rate, but reoperations were frequent”

26. surgery during acute phase: conclusions surgery can be safely performed during active carditis and, in of active carditis, may be preferable to the long-term use of corticosteroids. myocardial inflammation plays no significant role in the clinical pathology of active carditis. valve repair during active carditis may not constitute the best surgical option if there is macroscopic evidence of valvular inflammation, because valve repair is associated with significant reoperation rates.

27. conclusion ? are we missing ARF pathogenesis – answers Jones criteria challenge old ideas WHO Expert Consultation on Rheumatic Fever and Rheumatic Heart Disease (2001 : Geneva, Switzerland) Rheumatic fever and rheumatic heart disease

28. giving bad news gently