DIAGNOSIS & MANAGEMENT OF RHEUMATIC FEVER

1. DIAGNOSIS & MANAGEMENT OF RHEUMATIC FEVER DR.SANDEEP R SR CARDIO 87 slides

2. Introduction Rheumatic fever( RF) - a delayed autoimmune reaction in genetically predisposed individuals to group A, β-hemolytic, streptococcal (GABHS) pharyngitis characterized by inflammation of several tissues that gives rise to typical clinical characteristics including • 1)Carditis/ valvulitis • 2)Arthritis • 3)Chorea • 4)Erythemamarginatum • 5)Subcutaneous nodules • Residual damage only in the heart • Latent period of 3 weeks(1 – 5 wks) b/w GABHS infection & ARF • 3%-6% of any population

3. MAJOR MANIFESTATIONS

4. CARDITIS • Incidence varies from 50%-60% • The clinical diagnosis of carditis in an index attack of RF is based on • 1) Presence of significant murmurs (MR/AR) • 2)Pericardial rub • 3) Unexplained cardiomegaly with CHF. • Common in young • 80% of patients develop it within first 2 weeks of RF

5. ENDOCARDITIS/VALVULITIS • Almost always associated with a murmur of valvulitis • An universal finding in rheumatic carditis, whereas the presence of pericarditis or myocarditis is variable. • Valve Involvments- • 92 – 95% mitral valve involvement ( 70 – 75 % isolated MV) • 20 – 25% aortic valve involvement( 5-8% isolated AV) • MR – PSM in apex radiating to axilla> with grade 2 (MC FINDING IN CARDITIS) • AR in the absence of MR is uncommon

6. ENDOCARDITIS/VALVULITIS • First attack of RF- apical holosystolic murmur of mitral regurgitation (with or without apical MDM, Carey Coombs), or basal EDM • Pt. with previous RHD- a definite change in the character of any of these murmurs or the appearance of a new significant murmur • Severe MR • Associated with worst prognosis - fatal HF • Incidence of chronic RHD 90%. • Linear relationship between the severity of MR during the first episode of RF and subsequent RHD.

7. ENDOCARDITIS/VALVULITIS Pathogenesis of severe MR • Valvulitis • Mitral annular dilatation • Leaflet prolapse with or without chordal elongation • Chordal rupture • Carey Coombs murmur • MDM without presystolic accentuation • Associated with severe MR • Due to increased flow through diseased mitral valve

8. MYOCARDITIS • Myocarditis is always associated with valvulitis • New onset CMGLY and recent change in cardiac size - most specific sign • No definite evidence of myocarditis!! - No consistent elevation of cardiac biomarkers - No evidence of systolic dysfunction - CHF does not occur without significant valvular lesions - Radionuclide studies failed to demonstrate significant myocardial staining - Biopsy in acute RF failed to show cellular necrosis -inflammation was subepicardial, subendocardial and perivascular - Surgical valve replacement during RF and AHF reverted features of HF - Aschoff nodules do not contain myocardial cells

9. PERICARDITIS • 6 -15 % OF RF • Diagnosed by typical pain & friction rub • Always associated with rheumatic valvulitis • May be associated with normal ecg • May be associated with effusion but rarely causes constriction and tamponade • Its presence denote severe carditis

10. POLYARTHRITIS • 66-75% of patients • MC & most earliest manifestation • Typically involves larger joints – knee, ankle, wrist, & elbow • Involved joints - hot, red, swollen, and tender • Migratory in nature • Not deforming • A dramatic response to small doses of salicylates

11. POLYARTHRITIS • Synovial fluid in ARF usually has 10,000-100,000 WBC/mm3 • Exudative with normal glucose & neutrophil predominance • Self limiting & normalizes by 2 – 4 wks • Polyarthritis & sydenham’s chorea never occurs simultaneously • Inverse relationship b/w the severity of arthritis & cardiac involvement

12. SUBCUTANEOUS NODULES • Rare • 2-20% • Freely mobile,painless • 0.5 - 2 cm • Occur in crops over bony prominences or extensor tendons • Common locations - elbow,wristknee,ankle & achilles tendon

13. SUBCUTANEOUS NODULES • Self limiting –days to 1 month • Nodules may occur in SLE,RA but they tend to be larger • There is a correlation between its presence & carditis • PATHOLOGY • Fully developed nodules consist of a central zone of fibrinoid necrosis surrounded by a peripheral cellular reaction consisting of histiocytes and fibroblasts • Do not exhibit the pallisading pattern of RA

14. ERYTHEMA MARGINATUM • 3-15% • Erythematous, serpiginous, macular lesions with pale centers that are not pruritic • Multiple lesions primarily on the trunk or proximal extremities,rarely on distal extremities & never on face • It occurs early in course of RF

15. ERYTHEMA MARGINATUM • Nonpainful , nonpruritic, blanches on pressure • Accentuated by warming the skin. • Not influenced by antiinflammatory therapy • It is associated with carditis • Nodules & marginatum can occur simultaneously • It is also seen in sepsis,drugrn.,glomerulonephritis

16. CHOREA • Sydenham chorea , St.Vitus dance • 5 - 36% of ARF • Mc in females, rare > 20 yrs • Isolated, frequently subtle, neurologic behavior disorder • Emotional lability, incoordination, poor school performance, uncontrollable movements, and facial grimacing • Exacerbated by stress and disappears with sleep • Seen occasionally unilateral

17. CHOREA • Long latent period • Clinical maneuvers to elicit features of chorea include • (1) demonstration of milkmaid’s grip (irregular contractions of the muscles of the hands while squeezing the examiner’s fingers) • (2) spooning & pronation of the hands when the patient’s arms are extended • (3) wormian darting movements of the tongue upon protrusion • (4) examination of handwriting to evaluate fine motor movements • Do not cause permanent neurologic sequelae

18. CHOREA • Rheumatic chorea –marker of future carditis • 23% pure rheumatic chorea dvpd MS in 20 yr follow up & 27% in 30 yr period • Chorea is rarely associated with polyarthritis • Inflammatory markers & ASO titres may be normal

19. DIFFERENTIAL DIAGNOSIS

20. MINOR MANIFESTATIONS • Arthralgia • constitutes pain in one or more joints without evidence of inflammation, tenderness to touch, or limitation of motion. • Arthralgia + monoarticular arthritis – suggestive of RF • Fever • Temperature >100.40 F rectally-diurnal variations are seen • Children with mild carditis and pateints with chorea are afebrile • Epistaxis seen in 4% of cases • Abdominal pain • 5% 0f cases - occurs before the appearance of major maniftn • Pain usually epigastric or periumblical & may mimic appendicitis

21. MIMETIC FEATURE OF RHEUMATIC FEVER • Those patients who develop extracardiac manifestation in the initial attack ,there is a less chance for carditis during recurrence whereas if the initial attack is carditis there is a high chance of recurrent carditis

22. POST STREPTOCOCCAL REACTIVE ARTHRITIS • Relatively shorter latent period ( 7 to 10) days • May be persistent or relapsing • Slower response to aspirin • Not associated with other major manifestations • Symmetric invlnt. of large , small joints & axial skeleton • Occ . causation by non GABHS • Secondary prophylaxis for up to 1 year after the onset of their symptoms (Class IIb,LOE C)

23. ?RHEUMATIC PNEUMONIA • An acute inflammatory pneumonitis has been described in patients with RF • Presents as sudden onset respiaratory distress • Associated with carditis • CXR shows a hilar or patchy distributionn • Difficult to differentiate clinically with CHF • Responds to steroids • Uncertainity of its frequency and its existence as a distinct entity

24. JACCOUD’S ARTHRITIS

25. JACCOUD’S ARTHRITIS • Chronic postrheumatic fever arthritis • Seen in patients with severe RHD & not associated with evidence of RF • Recovery delayed & assoc. with stiffness of metacarpophalyngeal joints • Characteristic deformity due to periarticular , fascial and tendon fibrosis • Joint disease is inactive with normal ESR & negative RA factor • Deformity characterized by flexion at the metcarpophalangeal joint with ulnar deviation of 4th and 5th fingers & hyperextn of PIP • Initially the deformity is correctable & not assoc with bone destruction

26. PANDAS • Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections • Autoimmune responses that cross-react with brain tissue in response to a GAS infection • Obsessive-compulsive & tic disorders • No need of secondary prophylaxis (Class III, LOE B).

27. EVOLUTION OF JONES CRITERIA • ORGINAL JONES CRITERIA 1944

28. MODIFIED JONES CRITERIA 1956

29. REVISED JONES CRITERIA 1965 + SUPPORTING EVIDENCE OF PRECEEDING STREPTOCOCCAL INFECTION ,H/O RECENT SCARLET FEVER;POSITIVE THROAT C/S FOR GROUP A STREPTOCOCCUS; INCREASED ASO TITRE

30. REVISED CRITERIA OF 1965 WAS REVIEWED AND PUBLISHED AGAIN IN 1984 • INFERENCES MADE • 1) Premature administration of antiinflammatory drugs may modify the clinical picture • 2) Usefulness of echo in distinguishing pt with MVP & BICUSPID VALVE from RHD • 3) PR prolongation- not an indication of carditis nor does it corelate with development of RHD JONES CRITERIA WAS NOT DIAGNOSTIC-INDOLENTCARDITIS,RECURRENT RF,CHOREA

31. JONES CRITERIA UPDATE 1992 + SUPPORTING EVIDENCE OF PRECEEDING STREPTOCOCCAL INFECTION POSITIVE THROAT C/S FOR GROUP A STREPTOCOCCUS OR RAPID ANTIGEN TEST ELEVATED OR RISING STREPTOCOCCAL ANTIBODY TITRE

32. EVOLUTION OF JONES CRITERIA

33. WHO 2002 – 2003

36. LAB DIAGNOSIS OF ARF • No gold standard diagnostic technique • 1)THROAT C/S • initially considered a gold standard for diagnosis of streptococcal infection • LIMITATIONS • 1) Difficult to differentiate a carrier from active infection • 2) 1/3 of RF has no H/O preceeding pharyngeal infn. • 3) Delay in getting culture report

37. LAB DIAGNOSIS 2)RAPID ANTIGEN TEST FROM THROAT SWAB • Specificity is 95% & sensitivity 60 to 90% 3)STREPTOCOCCAL ANTIBODY TEST • Antistreptolysin O (ASO) • Anti DNAase B • Anti hyaluronidase (AH) • Streptozyme(SZ)

38. ASO TEST • Significant antibody response defined as a rise in titre > 2 dilution increments b/w acute phase and convalescent phase • Serum samples obtained 2 to 4 week intervals • ASO Titre of > 240 todd units in adults & > 320 todd units in children> 5 yrs is elevated • Appears 7 to 10 days after the infection with peak detection at 2 & 3 weeks after the onset of RF

39. ASO TEST • All cases of suspected ARF should have elevated serum streptococcal serology demonstrated. • If the initial titre is above ULN, there is no need to repeat serology. • If the initial titre is below the ULN for age, testing should be repeated 10–14 days later.

40. ANTI DNASe B • Anti DNAse B titers begin to rise 1 to 2 weeks and peak 6 to 8 weeks after infection • Antidnase 1:60 in preschool, 1:480 in school age, 1:340 in adult( NORMAL TITRE) • Single antibody test-( only ASO) -80-85% • Multiple antibody test-(ASO +ANTIDNase B)-95-100%

41. LAB INVESTIGATION • 1) B CELL MARKER • D8/17 monoclonal antibody - 90 to 100% of all patients with RF • Mode of inheritence - Autosomal recessive • 2) CRP, ESR

42. ECG CHANGES IN ARF • 1) Persistent sinus tachycardia & an elevated sleeping pulse rate are signs of carditis • 2)Sinus bradycardia 3) PR prolongation • Seen in 20- 30% of cases • Proposed theory – due to vagaloveractivity,myocardialinflmn • No correlation with carditis and future dvpnt. Of RHD • 4) High grade AV block ,CHB • 5) pericarditis • 6) QT prolongation

43. ECHOCARDIOGRAPHY • CHARACTERISTIC CHANGES IN RHEUMATIC MITRAL VALVULITIS • CHORDAL ELONGATION • ANNULAR DILATION • AML PROLAPSE • POSTEROLATERAL JET OF MR

44. ECHOCARDIOGRAPHY SUBCLINICALCARDITIS/ ECHOCARDITIS • Patients with suspected acute rheumatic carditis have no clinical murmurs but have documented regurgitation on echocardiography •  Prevalence 0 to 53%

45. ECHOCARDIOGRAPHY • ADVANTAGES • 1)Superior sensitivity in detecting rheumatic carditis • 2) Avoids misdiagnosis • DISADVANTAGES -Overdiagnosis of physiological valvular regurgitation as an organic dysfn. -Echocardiographic facilities not widely available -Ability to detect the recurrence of subclinical carditis not clear

46. WHO ECHO CRITERIA FOR CLINICAL CARDITIS • 0: Nil, including physiological or trivial regurgitant jet <1.0 cm, narrow, small, of short duration, early systolic at mitral valve or early diastolic at aortic valve. • 0+: Very mild regurgitant jet, more than 1.0cm, wider, localized immediately above or below the valve, throughout systole at the mitral valve or diastole at the aortic valve (clinically, no murmur audible). • 1+: Mild regurgitant jet. • 2+: Moderate regurgitant jet, longer and at a wider area. • 3+: Moderately severe regurgitant jet, reaching the entire left atrium (MR) or left ventricle (AR). • 4+: Severe regurgitant jet, diffusely into the enlarged LA, with systolic backward flow into pulmonary veins (mitral valve); markedly enlarged LV filled with regurgitant jets (aortic valve).

47. WHO CRITERIA FOR SUBCLINICAL CARDITIS MARIJON ET AL IN 2009 • Demonstrated that WHO criteria was inadequate • A significant difference in prevalence of RHD 7.8 (95% confidence interval, 4.6 to 12.5) and 30.4 (95% confidence interval, 23.6 to 38.5) –who vs combined criteria

48. ECHOCARDIOGRAPHY

49. OUTCOME OF SUBCLINICAL CARDITIS

50. WORLD HEART FEDERATION CRITERIA 2012 FOR RHD