ACUTE RHEUMATIC FEVER- clinical features

ACUTE RHEUMATIC FEVER

1. ACUTE RHEUMATIC FEVER DR. ANAM SIDDIQUE MBBS., MD (General Medicine) Assistant Professor, Dept. of Medicine, IIMSR.

2. ACUTE RHEUMATIC FEVER EPIDEMIOLOGY PATHOGENESIS HISTOLOGY CLINICAL FEATURES INVESTIGATION DIAGNOSIS MANAGEMENT PROGNOSIS PROPHYLAXIS Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

3. EPIDEMIOLOGY Usually affects children and young adults in age groups 5-35 years Incidence in India ranges between 13 and 150 cases per 1 lakh population per year. Commonest cause of acquired heart disease in childhood and adolescence Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

4. ACUTE RHEUMATIC FEVER EPIDEMIOLOGY PATHOGENESIS HISTOLOGY CLINICAL FEATURES INVESTIGATION DIAGNOSIS MANAGEMENT PROGNOSIS PROPHYLAXIS Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

5. PATHOGENESIS Conventional teaching has it that ARF is exclusively caused by infection of the upper respiratory tract with GAS Certain M serotypes (1,3,5,6,14,18,19,24,27 and 29) are conventionally known to be associated with ARF Many other M serotypes are recently thought to be rheumatogenic This also points to a clear role of skin infection like Impetigo in the pathogenesis of ARF The potential role of group C and G streptococci is unclear at this time Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

6. PATHOGENESIS Triggered by an immune mediated delayed response to infection with with specific strains of group A streptococci Streptococci have antigens that cross react with cardiac myosin and sarcolemmal membrane proteins. Antibodies against streptococcal antigens cause inflammation in endocardium, myocardium and pericardium and also skin and joints. Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

7. ACUTE RHEUMATIC FEVER EPIDEMIOLOGY PATHOGENESIS HISTOLOGY CLINICAL FEATURES INVESTIGATION DIAGNOSIS MANAGEMENT PROGNOSIS PROPHYLAXIS Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

8. HISTOLOGY Fibrinoid degeneration in collagen of connective tissue Pathognomic of RF: ASCHOFF Bodies - occur only in heart Focus of fibrinoid necrosis i.e site of antibody antigen reaction. Mutinucleated giant cells and T cells Plump activated marcrophages called ANITSCHKOW / Caterpillar cells Seen only in Sabacute or chronic phases of rheumatic carditis Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

9. ACUTE RHEUMATIC FEVER EPIDEMIOLOGY PATHOGENESIS HISTOLOGY CLINICAL FEATURES INVESTIGATION DIAGNOSIS MANAGEMENT PROGNOSIS PROPHYLAXIS Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

10. CLINICAL FEATURES Multisystem disorder which presents with Fever Anorexia Lethargy Joint pain Arthritis occurs in ~75 % patients Other features include Rashes Subcutaneous nodules Carditis Neurological changes Usually 2-3 weeks following an episode of streptococcal pharyngitis Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

11. CLINICAL FEATURES CARDITIS Causes pancarditis involving endocardium, myocardium and pericardium. Incidence declines with increasing age with 90% at 3 years to 30% in adolescents Manifests as- Breathlessness Palpitations Chest pain Tachycardia Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

12. CLINICAL FEATURES Pericarditis - chest pain, pericardial friction rub and precordial tenderness New changing murmurs A soft systolic murmur due to mitral regurgitation is very common A soft mid diasystolic murmur ( Carey coombs murmur ) is typically due to valvulitis and nodules forming on mitral valve leaflets Aortic regurgitation occurs in 50% cases but pulmonary and Tricuspid valve are rarely involved Conduction defect – first degree heart block most commonly causes syncope Cardiac failure - due to myocardial dysfunction or valvular regurgitation Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

13. CLINICAL FEATURES 2) ARTHRITIS and ARTHALGIAS ARTHRITIS Most common form of joint involvement Most commonly affects large joints - knee, ankle, hips and elbows. Hot, swollen, red and/or tender joints Polyarthritis Asymmetrical involvement Migratory joint pain - moving from one joint to another over a period of hours ARTHRALGIA Without joint inflammation Migratory polyarthralgia Highly NSAID responsive - if joint involvement persist after 1-2 days of NSAID therapy, consider alternate diagnosis Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

14. CLINICAL FEATURES 3) CHOREA SYDENHAMS Chorea or St. Vitas dance Commonly occurs in absence of other manifestations Follows a prolonged latent period after GAS infection- late manifestation More common in females Associated emotional lability or obsessive compulsive traits- precede chorea and last longer Choreiform movements affect particularly head ( darting movement of tongue) and upper limbs ( milking sign ) Generalised or restricted to one side of body (hemi- chorea) Speech- explosive and halting Spontaneous recovery within 6 weeks to 6 months. 50% of chorea patients will have carditis- 2D ECHO mandatory Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

15. CLINICAL FEATURES 4) SKIN MANIFESTATIONS ERYTHEMA MARGINATUM Seen in ~ 5 % patients Classic Rash of ARF Pink macules that clear centrally leaving a serpiginous, spreading edge Usually on trunk , sometimes on limbs. Evanescent - appears and disappears infront of examiners eyes Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

16. CLINICAL FEATURES 4) SKIN MANIFESTATIONS SUBCUTANEOUS NODULES Seen in 5- 7 % patients Painless , small (0.5-2 cm), mobile lumps overlying bony prominences Involving hands, feet, elbows, occiput Delayed manifestation- 2-3 weeks after disease onset Commonly associated with carditis Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

17. ACUTE RHEUMATIC FEVER EPIDEMIOLOGY PATHOGENESIS HISTOLOGY CLINICAL FEATURES INVESTIGATION DIAGNOSIS MANAGEMENT PROGNOSIS PROPHYLAXIS Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

18. INVESTIGATIONS ESSENTIAL INVESTIGATIONS CBC- LFT/ RFT ESR CRP Streptococcal serology (ASO, anti Dnase B) ECG- conduction block – prolonged PR interval- 1 st degree hear block ST Segment elevation and T wave changes Chamber enlargement CXR- Chronic RHD- MS- straightening of left heart border ECHO Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

19. Reference: Hurst’s the heart- textbook of cardiology, 14 th edition

20. INVESTIGATIONS IN RELEVANT CASES Throat swab Blood cultures Test to exclude alternate diagnosis: ANA/ anti CCP Urine for N.gonorrhoeae Urine for C.trachomatis Serology for viral hepatitis, CMV , Parvovirus B19 Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

21. ACUTE RHEUMATIC FEVER EPIDEMIOLOGY PATHOGENESIS HISTOLOGY CLINICAL FEATURES INVESTIGATION DIAGNOSIS MANAGEMENT PROGNOSIS PROPHYLAXIS Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

22. DIAGNOSIS No definitive test for acute rheumatic fever Diagnosis based on combination of clinical manifestation and laboratory evidence of preceding streptococcal infection Preceding GAS infection maybe demonstrated by increased or rising antistreptolysin O titre , other streptococcal antibodies, a positive throat swab or rapid antigen antigen test for GAS JONES CRITERIA Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

23. JONES CRITERIA LOW RISK POPULATION : ARF incidence ≤2 per 100 000 school-aged children or all-age RHD prevalence of ≤1 per 1000 population year MODERATE/ HIGH RISK POPULATION : ARF incidence >2 per 100 000 school-aged children or all-age RHD prevalence of >1 per 1000 population year Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

24. JONES CRITERIA Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

25. JONES CRITERIA PRIMARY EPISODE of rheumatic fever TWO MAJOR or ONE MAJOR and TWO MINOR PLUS Evidence of a preceding group A streptococcal infection RECURRENT ATTACK of rheumatic fever TWO MAJOR or ONE MAJOR and TWO MINOR or THREE MINOR PLUS Evidence of a preceding group A streptococcal infection Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

26. ACUTE RHEUMATIC FEVER EPIDEMIOLOGY PATHOGENESIS HISTOLOGY CLINICAL FEATURES INVESTIGATION DIAGNOSIS MANAGEMENT PROGNOSIS PROPHYLAXIS Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

27. MANAGEMENT No treatment of ARF has been proven to alter the likelihood of developing or severity of RHD AIMS OF MANAGEMENT Follow closely to ensure the diagnosis is confirmed 2D ECHO is done to establish a baseline for cardiac involvement Treatment of all symptoms is undertaken Commencement of secondary prophylaxis Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

28. MANAGEMENT 1) ANTIBIOTICS All patients of ARF to receive antibiotics sufficient to treat the precipitating GAS infection PENICILLIN- drug of choice 1 Benzathine Penicillin G 1.2 million IM single dose (adults) 600000 units IM single dose (children <27kg) 2 Phenoxymethyl Penicillin 500mg PO BD X 10 days (adults 250mg PO BD X 10 days (children <27kg) 3 Amoxicillin 50mg/kg , max 1g, for 10 days Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

29. MANAGEMENT 2) SALICYLATES AND NSAIDS Treatment of arthralgias, arthritis, fever ASPIRIN : First line drug 50-60mg/kg , max 100mg/kg per day (4-8 g/ day in adults) in 4-5 divided doses Monitor for nausea, vomiting, tinnitus (signs of salicylate toxicity) Taper to 50-60 mg/kg per day for a futher 2-4 weeks after initial relief NAPROXEN: 10-20 mg/kg per day Safer than aspirin Twice daily dosing. Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

30. MANAGEMENT 3)CHOREA Medications to control chorea do not alter the duration/ outcome of chorea Milder cases- managed with calm environment Severe cases- CBZ or Sodium valproate- need 1-2 weeks to act, to be continued for 2 weeks after symptoms subside Refractory cases- prednisolone 0.5 mg/kg with earliest possible weaning, after 1 week if symptoms reduce IVIG- small studies show more rapid resolution of chorea. But no short or long term benefit in carditis without chorea. NOT RECOMMENDED for regular use. 4)GLUCOCORTICOIDS Controversial role Severe carditis causing HF Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

31. ACUTE RHEUMATIC FEVER EPIDEMIOLOGY PATHOGENESIS HISTOLOGY CLINICAL FEATURES INVESTIGATION DIAGNOSIS MANAGEMENT PROGNOSIS PROPHYLAXIS Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

32. PROGNOSIS If untreated ARF last 12 weeks With treatment hospital stay is 1-2 weeks Inflammatory markers to be monitored every 1-2 weeks till normalized Repeat ECHO after 1 month to monitor progression Ensure long term follow up and compliance to secondary prophylaxis Enter into local ARF registry. Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

33. ACUTE RHEUMATIC FEVER EPIDEMIOLOGY PATHOGENESIS HISTOLOGY CLINICAL FEATURES INVESTIGATION DIAGNOSIS MANAGEMENT PROGNOSIS PROPHYLAXIS Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

34. PROPHYLAXIS PRIMARY PREVENTION Elimination of major risk factors for streptococcal infection particularly overcrowding Development of a vaccine is underway Primary prophylaxis is the the cornerstone A course of penicillin if initiated within 9 days of sore throat with prevent almost all cases of ARF In high prevalence resource limited setups where microbiological confirmation of GAS is not available it is recommended to treat all sore throat patients with penicillin regimen or deployment of clinical algorithm to identify high risk individuals. With increasing evidence of impetigo being linked to ARF, prevention and proper treatment of GAS related skin infections is a priority Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

35. PROPHYLAXIS SECONDARY PROPHYLAXIS ARF patients at high risk of developing recurrent attack and Chronic RHD Long term penicillin prophylaxis is recommended in such cases Duration of secondary prophylaxis depends on Duration since last ARF episode Age Severity of RHD Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

36. PROPHYLAXIS 1 Benzathine penicillin G 1.2 million units every 4 weeks 600000 units (<27kg) every 4 weeks 2 Oral penicillin V 250 mg twice daily 3 Erythromycin 250mg twice daily ANTIBIOTICS RECOMMENDED FOR SECONDARY PROPHYLAXIS AMERICAN HEART ASSOCIATION RECOMMENDATION FOR DURATION OF SECONDARY PROHYLAXIS CATEGORY DURATION 1 Rheumatic fever without carditis For 5 years after last attack or till 21 years of age, whichever is longer 2 Rheumatic fever with carditis but no residual valvular disease For 10 years after last attack or till 21 years of age, whichever is longer 3 Rheumatic fever with persistent residual valvular disease (clinical / ECHO) For 10 years after last attack or till 21 years of age, whichever is longer, Sometimes lifelong. Reference: Harrison textbook of medicine 21st edition, Davidson's principles and practice of medicine, 24th edition

37. Exam questions

38. 18 years old male came to outpatient department with fever, joint pain and swelling of right knee and chest pain. On examination there is relative tachycardia, pansystolic murmur in mitral area and ECG shows prolongation of PR interval. Answer the following: What is your diagnosis? How do you investigate this patient? What are the features of this disease and complications? How do you manage this patient?