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Prof. P. Krishnam Raju CARE Hospitals & CARE Foundation Hyderabad www.carehospitals.com www.carefoundation.org.in. Acute Rheumatic Fever Natural History - Indian Scenario. Historical Vignettes. Vieussens-autopsy of valvar lesions – 1715 RHEUMATISM – Baillie – 1797

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Prof. P. Krishnam Raju CARE Hospitals & CARE Foundation Hyderabad carehospitals


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    1. Prof. P. Krishnam Raju CARE Hospitals & CARE Foundation Hyderabad www.carehospitals.com www.carefoundation.org.in • Acute Rheumatic Fever • Natural History • - Indian Scenario

    2. Historical Vignettes • Vieussens-autopsy of valvar lesions – 1715 • RHEUMATISM – Baillie – 1797 • Pitcain – Rheumatism & heart disease • Peter latham---Rh:pericarditis, endocarditis. • Boulland-hallmark article-father of rheumatic heart disease. • Scolt – RHD in India. [ 1938]

    3. RF Natural History • Provides insights into pathophysiology of the disease • Permits better recognition of the disease and sequelae • Clues for more effective intervention strategies UNIVERSITY OF DISEASE

    4. RF • 19th and Early 20th century RF – leading cause of death (5 to 20 yrs group) • Second leading cause of death in the age group 20 to 30 Y • Mortality - due to carditis • 60% of all ARF deaths in the first 5 yrs (carditis / chronic RhVHD / IE ) 20th Century • Pre penicillin era – mortality from AC carditis – 8 to 30% • Decline evident by 1930s – 1 yr mortality – 4% • There after steady decline.

    5. Rheumatic Heart Disease Not gone But Almost Forgotten World congress of Cardiology 2006 Barcelona

    6. RF • Major problem in developing Nations • Children and young adults – Victims • 60% of CVD in young / children – RHD • Affects upto 20 m people World wide • 2 million children are affected / World wide • 500000 deaths / Annually / World wide • Undermines National Productivity “ Most solvable cardiac probem affecting the developing world” “Cardiac surgery for RHD “ Chews up” funds”

    7. Introduction • Acute rheumatic fever: inflammatory disease with devastating sequelae • Link to pharyngeal infection with group A beta hemolytic streptococci * Continues to be a problem worldwide: Sporadic outbreaks in developed countries Frequent occurrences in developing countries • Still gaining understanding of etiology and Link between genetic predisposition and clinical manifestations Best prevention still-- correct use of antibiotics

    8. Epidemiology (continued) • Usually occurs in people between 5 and 18 years old • Males and females equally affected • Overcrowding, poverty, lack of access to medical care contributes to transmission • Virulence of strain important • In tropics/subtropics: year-round incidence with peak in colder months

    9. Pathogenesis • Group A strep pharyngeal infection precedes clinical manifestations of ARF by 2 - 6 weeks • Antibodies made against group A strep cross-react with human tissue heart valve and brain share common antigenic sequences with GAS bacteria theory of molecular mimicry • Host immune responses may play a role in determining who gets ARF following infection • Virulent strains: rheumatogenic serotypes

    10. The Epidemiologic Triad of Rheumatic Fever

    11. RHEUMATIC FEVER Incidence : Strep. Infection Sporadic : 0.3% Epidemic : 3.0% (closed communities) Why do others escape? ? Genetic susceptibility

    12. ARF and RHD • Major health problem in developing countries including India • Approximately 2 million cases have RHD and 50,000 new episodes of RF occur/year • RHD prevalence 1 – 5.4 / 1000 school children • ARF incidence 0.3 – 0.5 / 1000 school children Padmavathi et al. 1995

    13. Epidemiology – WHO 15.6 million people – RHD 300 000 of about 0.5 million individuals who acquire ARF every year go on to develop RHD 233 000 deaths annually are directly attributable to ARF or RHD.

    14. Epidemiology ARF is a rare disease in the very young Only 5% of first episodes – children younger than age 5 years. Almost unheard of in those younger than 2 years. First episodes of ARF are most common just before adolescence Rare in adults older than age 35 years

    15. Organism – GAS RHEUMATOGENECITY – strains 1,3,6 and 18- M Serotypes Infrequently found in several communities with high burdens of ARF and RHD, where newly identified serotypes or those most often associated with skin infections have been linked with disease.

    16. “Diagnostic criteria must be subject to change as knowledge and experience increases” T Duckett Jones 1944 - Original Jones Criteria 1944 - Modified Jones Criteria 1956 (Modified in 1951 for use in a trial) - Revised Jones Criteria 1965, 1984 (Reference to Echo) - Jones Criteria update 1992 (discussed the Role of Echo) Undergone remarkably few changes - Compulsory evidence of Preceding strep infection. - Applicability only for the initial attack of RF - Recurrent episodes (1 major or 2 or more minor criteria)

    17. I T. Duckett Jones Criteria – EvolutionThe Original Jones Criteria – 1944* Major Manifestations Minor Manifestations • Carditis 1. Fever • Arthralgia 2. Abdominal pain • Chorea 3. Precordial pain • Subcutaneous 4. Rashes (erythema nodules marginatum) • History of previous 5. Epistaxis definite rheumatic 6. Pulmonary findings fever or rheumatic 7. Laboratory findings heart disease a. Electrocardiographic abnormalities b. Microcytic anemia c. Elevated total leukocyte count d. Elevated erythrocyte sedimentation rate

    18. II T. Duckett Jones Criteria – EvolutionThe Modified Jones Criteria – 1956* Major Manifestations Minor Manifestations • Carditis 1. Fever • Polyarthritis 2. Arthralgia • Chorea 3. Prolonged PR interval • Subcutaneous nodules 4. Increased erythrocyte sedimention rate, presence of C-reactive protein or leukocytosis 5.Erythema Marginatum 5. Previous history of rheumatic fever or the presence of inactive rheumatic heart disease 6. Evidence of preceding betahemolytic streptococcal infection

    19. III T. Duckett Jones Criteria – EvolutionThe Revised Jones Criteria – 1965* Major Manifestations Minor Manifestations • Carditis 1. Fever • Polyarthritis 2. Arthralgia • Chorea 3. Previous rheumatic fever or rheumatic heart disease. 4.Erythema marginatum 4. Elevated erythrocyte sedi- mentation rate, positive C- reactive protein, leukocytosis 5.Subcutaneous nodules 5. Prolonged PR interval Plus supporting evidence of preceding streptococcal infection : history of recent scarlet fever; positive throat culture for group A streptococcus; increased ASO titer or other streptococcal antibodies:

    20. IV T. Duckett Jones Criteria – EvolutionThe Jones Criteria Update – 1992* Major Manifestations Minor Manifestations • Carditis 1. Clinical findings • Polyarthritis 2. Arthralgia • Chorea 3. Fever • Erythema marginatum 4. Laboratory findings • Subcutaneous nodules Elevated acute phase reactants, erythrocyte sedimentation rate, C-reactive protein 5. Prolonged PR interval Supporting Evidence of Antecedent Group A Streptococcal Infection Positive throat culture or rapid streptococcal antigen test Elevated or rising streptococcal antibody titer IF supported by evidence of preceding group A streptococcal infection, the presence of two major manifestations of one major and two minor manifestations indicates a high probability of acute rheumatic fever.

    21. Evolution of Laboratory tests in Diagnosis of Acute Rheumatic Fever * MC indicates minor criteria; EC essential criteria; ESR. Erythrocyte sedimentation rate. CRP, C-reactive protein. ** Evidence of preceding streptococcal infection was not considered mandatory for the diagnosis of indolent carditis and Sydenham’s chorea. † History of sore throat is no longer considered adequate as evidence of a preceding streptococcal infection. ‡ Anti-DNase B and antihyaluronidase tests introduced as newer diagnostic tools. § In 1955, the hematologic and electrocardiographic criteria (prolonged PR interval) were split into separate minor criteria each of which could contribute to the diagnosis of acute rheumatic fever.

    22. WHO Criteria… WHO criteria ( 2002-03) Chorea and indolent carditis do not require evidence of antecedent group A streptococcus infection First episode – As per Jones criteria

    23. Arthritis • Most common feature: present in 80% of patients • Painful, migratory, short duration, excellent response of salicylates • Usually >5 joints affected and large joints preferred Knees, ankles, wrists, elbows, shoulders • Small joints and cervical spine less commonly involved

    24. Natural history of rheumatic arthritis Usually resolves in 3 weeks even when untreated. Usually no chronic sequale Jaccoud’s arthritis – periarticular fibrosis of metacarpophalaqngeal joints – in those with multiple recurrence.

    25. Subcutaneous Nodules • Usually 0.5 - 2 cm long Firm, non-tender, isolated or in clusters • Most common: along extensor surfaces of joint Knees, elbows, wrists • Also: on bony prominences, tendons, dorsi of feet, occiput or cervical spine • Last a few days only • Occur in 9 - 20% of cases • Often associated with carditis

    26. Erythema Marginatum • Present in 7% of patients • Highly specific to ARF • Cutaneous lesion: • Reddish pink border • Pale center • Round or irregular shape • Often on trunk, abdomen, inner arms, or thighs • Highly suggestive of carditis

    27. Rh Chorea Natural History • Isolated chorea in 10% with RF • Female Propensity • Subsides in > 75% in 6 months • Recurs in 1/3rd • No Long term neuro sequelae • Concomitant carditis – 3 to 73% (various reports) • Chronic RHD on follow up in Isolated Chorea (20-34%)

    28. Jaccoud’s Arthritis

    29. Prevalence Studies Pioneer study in India – berry et al [1972]– chandigarh population based study. Total No : 3396 Male – 1.23% Female – 2.07%

    30. ICMR Studies Prevalence in 1000 school children Agra - 5.3 Delhi - 11.0 Hyderabad - 6.7 Alappuzha - 2.2 Bombay -1.8

    31. RF / RHD in India PADMAVATHI et al 1995 Prevalence - 1-5.4/1000 ARF incidence - 0.3-0.5/1000 Koshey et al - 4.9/1000 Newdelhi study - 9.0/1000 K.S. Reddy, Delhi - 1.8/1000

    32. Studies… According to a conservative estimate [vijaykumar et al] approximately 1 million people have RHD in India and there are 50000 new episodes of RF per year.

    33. RF PREVALANCE ICMR 1970 1.8 -11 /1000 KANPUR 2000 4.5 /1000 HOSPITAL DATA SAT NEW RF 1998 - 79 1999 - 76 2000 - 97

    34. Rheumatic Fever Burden in India Population 1.2 Billion. Adults with RHD (1/1000) 12 million Children 5 to 15 yrs (25%) 30 million RF / RHD at 1/1000 3 million 0.5/1000 1.5 million.

    35. RHEUMATIC FEVER Problems in India • Juvenile sympt. RHD common • 25% present with severe valvar lesions below 20 yrs. • Majority symptomatic in II / III decade of life • Repeated hospitalisation • Expensive surgical management • Loss of productive manpower

    36. RHEUMATIC FEVER Carditis : frequency • Padmawati (1966 / 74) 14% • Sanyal (1974) 33.3% • Roy (1960) 46% • Aggarwal (1986) 51% • Vaishnava (1960) 90%

    37. SAT, Trivandrum Study 66 patients 3 years follow up, 58% had clinical & 71.2% had echo evidence of rhd.

    38. Natural History…. As high as 70% of MR in the initial attack can disappear clinically over a period of time. JUVENILE MS – in young people [<20 years] In India 23% and in the west 5% The latent period in west 5-10 years, in India as short as 1-3 years.

    39. Natural History AR Overall incidence : 50% Isolated : < 10%.– rare It has no latent period It can also disappear with time, but rare.

    40. Natural History… AS-if AS is present with MV involvement rheumatic. As below 20 years – 12% rheumatic Isolated As below 12 years is almost always congenital. TV : rare, organic TR/TS can be found in 5-8% PV: involvemnt is very rare: < 1%

    41. Natural History of ASO Appears at diagnostic titre by 7-10 days, peaks by 2-3 weeks. 70-80% positive > 240 in adults,> 320 in children. Rh: Chorea – 20-40% The ASO elevation at diagnostic titres can remain up to 3-6 months.

    42. ASO… Aso response is affected by antibiotic usage, steroid administration. Anti DNA ase B: second most useful antibody test. positive in 80% ARF may be positive in ARF even if ASO is negative. Titer: > 120 in adults, > 240 in children.