• Rheumatic fever is an immunologically mediated inflammatory disorder, which occurs as a sequel to group A streptococcal pharyngeal infection.• Multisystem disease affecting connective tissue particularly of the heart, joints, brain, cutaneous and subcutaneous tissues• RF – not a communicable disease but results from a communicable disease(streptococcal pharyngitis).• The illness is so named because of its similarity in presentation to rheumatism.
• RF RHD (rheumatic heart disease); a crippling disease.• Epidemiological point of view these cannot be separated. [WHO CHRONICLE 1969]• RF and RHD diseases of the poor most prevalent in underdeveloped and developing countries.• Preventable disease.
PROBLEM STATEMENT• RF and RHD is the most common cause of heart disease in 5-30 age groups throughout the world.• It accounts for 12-65% of hospital admissions related to CVD in developing countries.• There has been marked decrese in cases of RF and RHD in places that have implemented preventive programs.
IN INDIA• RHD is prevalent in range of 5-7/1000 in 5-15 age groups.• About 1 million cases of RHD• RHD constitutes 20-30% hospital admissions due to CVD.• Streptococcal infections commonin children living in under –privileged conditions and RF accounts for 1-3% of the cases.
• Important cause of chronic disease and death in developing world• Underdiagnosed and undertreated• Ages 5-15 yrs are most susceptible• Rare <3 yrs• Common in 3rd world countries• Environmental factors-- over crowding, poor sanitation, poverty,poor housing• Incidence more during fall ,winter & early spring
AGENT FACTORS• Streptococcal sore throat• Not all strains of Group A Streptococci (GAS) lead to rf• Rheumatogenic potential• Recently virus (coxsackie B-4) has been suggested as causative agent with streptococcus acting as conditioning agent.
HOST AND ENVIRONMENTAL FACTORS• AGEadolescents 5-15 yrs initial attack at younger age valvularlesion faster Juenile mitral stenosis• SEX equal• IMMUNITY Toxic –immunological hypothesis• SOCIO-ECONOMIC STATUSSocial disease• HIGH RISK GROUP 5-15 yrs school-age children living in closed community
• Based on currently based evidence, RF is caused by group A streptococcal (GAS) pharyngeal infection.• Postulated that series of preceding streptococcal infection is needed to prime the immune system prior to final infection that directly causes the disease.
• Group A strep pharyngeal infection precedes clinical manifestations of ARF by 2 - 6 weeks.• Body produce antibodies against streptococci .• These antibodies cross react with human tissues because of the antigenic similarity between streptococcal components and human connective tissues (molecular mimicry) [there is certain amino acid sequence that is similar btw GAS and human tissue]• Immunologically mediated inflammation & damage (autoimmune) to human tissues which have antigenic similarity with streptococcal components- like heart, joint, brain connective
• Epitopes present in cell wall ,CM, str. M protein are immunologically similar to molecules in human myosin, tropomyosin,keratin,actin,etc. MOLECULAR MIMICRY
• Because of the similarity btw hyaluronic acid in GAS capsule and in the connective tissue of the joints, Ab produced against GAS capsule will start to attack the joints and causes arthritis.• M-protein in GAS cell wall and the myocardium are similar, thus Ab produced against GAS cell wall will attack heart and will cause carditis and so forth.• Similarly Ab against NAG in GAS will affect cardiac valve tissue causing valvular damage.
Characteristic Aschoff bodies , composed ofswollen eosinophilic collagen surrounded bylymphocytes and macrophages can be seen onlight microscopy. The larger macrophages maybecome Aschoff giant cellsIn order for R.F. to occur: There must be throat infection by GAS.(only when there is GAS throat infection there is R.F.) Antibodies must be produced by the body rapidly & in high magnitude. These Abs will cross react with tissue of the heart, joint, brain (especially basal ganglia),
STREPTOCOCCUS SORE THROAT• Tender lymph nodes• Close contact with infected person• Scarlet fever rash• Excoriated nares( crustedlesions) in infants• Tonsillar exudates in older children• Abdominal pain• GOLD STANDARD POSITIVE THROAT CULTURE
FEATURESFollowing upper airway infection with GAS Silent period of 2 - 6 weeks Sudden onset of fever, pallor, malaise,fatigue.Commonly GAS streptococcal infection issubclinical; such cases confirmed usingstreptococcal antibody testing .
MINOR MANIFESTATIONS Involvement of lung,Fever Epistaxis kidneys and CNS Arthralgia Serositis
1.POLYARTHRITISMost common feature: present in 90% of patientsJoint is arthritic ie inflammed. Painful, migratory, short duration. Usually >5 joints affected and mainly large joints Knees, ankles, wrists, elbows, shoulders Small joints and cervical spine less commonly involved
Excellent response of salicylates and NSAIDSPain and swelling come on quickly and subsides within 5-7 daysIn children below 5 yrs arthritis usually mild but carditis more prominentArthritis do not progress to chronic disease
2.CARDITIS• Early and most serious manifestation• Manifest as pancarditis• Occur in 60-70% of cases• Carditis is the only manifestation of rheumatic fever that leaves a sequelae & permanent damage to the organ• Valvular damage is the hallmark of RF• Chronic phase- fibrosis,calcification & stenosis of heart valves(fishmouth valves)
Any cardiac tissue may be affected Valvular lesion most common: mitral and aortic Seldom see isolated pericarditis or myocarditis RHEUMATIC HEART DISEASE• Rheumatic Heart Disease is the permanent heart valve damage resulting from one or more attacks of ARF.• It is thought that 40-60% of patients with ARF will go on to developing RHD.• Sadly, RHD can go undetected with the result that patients present with debilitating heart
Another view ofthick and fusedmitral valves inRheumatic heartdisease
3.SYNDENHAM’ S CHOREA• Occur in 5-10% of cases• Mainly in girls of 1-15 yrs age• Late manifestation of RF -months after infection• Spasmodic, unintentional, jerky choreiform movements,• Speech affected, fidgety• Choreiform movements particularly affect the head(darting movement of tongue)and upper
• First sign: difficulty walking, talking, writing• Occurs in 30% of patients with ARF• Usually benign and resolves in 2 - 3 months• Disappears leaving no residual damage.
4.ERYTHEMA MARGINATUM• Occur in <7%.• Unique,transient,serpiginous-looking lesions of 1-2 inches in size• Pink macules - Clear centrally ,serpiginous spreading edge .• More on trunks & limbs & non-itchy• Almost never on face• Worsens with application of heat• Often associated with chronic carditis
5.SUBCUTANEOUS NODULES• Small,painless, mobile hard lumps beneath skin.• Most common along - extensor surfaces of joint-Knees, elbows,wrists• Also: on bony prominences, tendons, dorsi of feet,occiput or cervical spine• Appears 4 weeks after onset of RF• Delayed manifestation, disappears –leaves no residual damage.• Occur in 9 - 20% of cases• Often associated with carditis
Nodules -Firm, non-tender, isolated or in clusters
6.FEVER• Present at onset of acute illness• High grade fever >39ºC• Lasts for about 12 weeks ,tends to recur
LAB DIAGNOSIS• High ESR• Anemia, leucocytosis• Elevated C-reactive protien• Elevated ASO or other streptococcal antibody titer• Anti-DNAse B test• Throat culture-GABHstreptococci
• There is no definitive test.• Diagnosis of ARF relies on presence of combination of typical clinical features together with evidence of the precipitating GAS infection .• This uncertainty led Dr.T.Duckett Jones in 1944to develop a set of criteria Jones Criteria to aid diagnosis.• Now Diagnosis based on MODIFIED JONES CRITERIA .
2002–2003 World Health Organization Criteria for theDiagnosis of Rheumatic Fever and Rheumatic Heart Disease(Based on the 1992 Revised Jones Criteria)Diagnostic Categories CriteriaPrimary episode of rheumatic fever Two major or one major and two minor manifestations plus evidence of preceding group A streptococcal infectionRecurrent attack of rheumatic fever in a Two major or one major and two minorpatient without established rheumatic heart manifestations plus evidence of precedingdisease group A streptococcal infectionRecurrent attack of rheumatic fever in a Two minor manifestations plus evidence ofpatient with established rheumatic heart preceding group A streptococcal infectioncdiseaseRheumatic chorea Other major manifestations or evidence ofInsidious onset rheumatic carditis group A streptococcal infection not requiredChronic valve lesions of rheumatic heart Do not require any other criteria to bedisease (patients presenting for the first diagnosed as having rheumatic hearttime with pure mitral stenosis or mixed disease
Major manifestations Carditis Polyarthritis Chorea Erythema marginatum Subcutaneous nodulesMinor manifestations Clinical: fever, polyarthralgia Laboratory: elevated erythrocyte sedimentation rate or leukocyte counte Electrocardiogram: prolonged P-R intervalSupporting evidence of a preceding Elevated or rising anti-streptolysin O orstreptococcal infection within the last 45 other streptococcal antibody, ordays A positive throat culture, or Rapid antigen test for group A streptococcus, or Recent scarlet fevere
Source: Reprinted with permission from WHO ExpertConsultation on Rheumatic Fever and Rheumatic Heart Disease(2001: Geneva, Switzerland): Rheumatic Fever and RheumaticHeart Disease: Report of a WHO Expert Consultation (WHO TechRep Ser, 923). Geneva, World Health Organization, 2004.
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
• Step I - primary prevention (eradication of streptococci)• Step II - anti inflammatory treatment (aspirin,steroids)• Step III- supportive management & management of complications• Step IV- secondary prevention (prevention of recurrent attacks)
PRIMARY PREVENTION• AIM ; Prevent the first attack of RF, by identifying all patients with streptococcal throat infection and treating them with pencillin• Theoretically simple , in practise its difficult, not feasible.• Many infections are inapparent or if apparent are not brought to attention of health services• VIABLE APPROACH; concentrate on high risk groups ie school age children.• Surveillance for streptococcal pharyngitis
STEP I:Primary Prevention of RheumaticFever (Treatment of Streptococcal Tonsillopharyngitis)• Agent Dose Mode Duration• Benzathine penicillin G 600 000 U for patients Intramuscular Once 27 kg (60 lb) Least 1 200 000 U for patients >27 kg expensive or method• Penicillin V Children: 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• Ethylsuccinate 40 mg/kg/d 2-4 times daily Oral 10 d (maximum 1 g/d) Recommendations of American Heart Association
Step II: Anti inflammatory treatmentCLINICAL CONDITION DRUGArthritis only Aspirin 75-100 mg/kg/day , give as 4 divided doses for 6 weeks (attain a body level 20-30 mg/dl)Carditis Corticosteroids 1-2 mg/kg per day – for 4-6 weeks to be tapered off
3.Step III: Supportive management & management of complications• Bed rest• Treatment of congestive cardiac failure: -digitalis,diuretics• Treatment of chorea: -diazepam or haloperidol• Rest to joints & supportive splinting
STEP IV : Secondary Prevention of Rheumatic Fever(Prevention of Recurrent Attacks)Agent Dose ModeBenzathine penicillin G 1 200 000 U every 3 weeks* Intramuscular orPenicillin V 250 mg twice daily OralFor individuals allergic to penicillin and sulfadiazineErythromycin 250 mg twice daily Oral Recommendations of American Heart Association
Duration of Secondary Rheumatic FeverProphylaxis Category DurationRheumatic fever without carditis At least 5 y or until age 18 y, whichever is longerRheumatic fever with carditis and At least 10 y since last residualheart disease episode and at least until age 40 y(persistent valvar disease*), sometimes lifelong prophylaxisRheumatic fever with carditis 10 y or well into adulthood,but no residual heart disease whichever is longer(no valvar disease*)More severe valvular disease LifelongPost-valve surgery cases*Clinical or echocardiographic evidence. Recommendations of Am erican Heart Association
• Secondary prophylaxis is more effective when done on a Register based method• A register of cases of RF and RHD is kept.• This is used to improve treatment adherence in order to prevent recurrent RF and the development of RHD, necessitating surgery.
NON- MEDICATED MEASURES • Improvement of living standards. • Breaking the poverty –disease –poverty cycle. • Improvements in socio-economic EVALUATION conditions.• The prevalence of RHD in school children from periodic surveys of random samples.• Samples of school in 6-14 age groups. At 5 year interval.• Recommended sample size 20,000 to 30,000
PROGNOSIS• Rheumatic fever can recur whenever the individual experience new GABH streptococcal infection,if not on prophylactic medicines• Good prognosis for older age group & if no carditis during the initial attack• Bad prognosis for younger children & those
Rheumatic heart disease is the only trulypreventable chronic heart condition
Rapid, direct test kit for diagnosis of group Ainfections, throat swab introduced to latex beadsand monoclonal antibodiesPositive- Negativethe C-carbohydrate -milky smoothon group A streptococci reaction.causes clumping