By Dr.M.Sharif Akhter MCPS-COM.MED By Dr.M.Sharif Akhter MCPS-COM.MED A.P.COMMUNITY MEDICINE SZMC RAHIM YAR KHAN

Objectives Etiology Epidemiology Pathogenesis Pathologic lesions Clinical manifestations & Laboratory findings Diagnosis & Differential diagnosis Treatment & Prevention Prognosis References

PROBLEM, i I - World, RF and RHD present a problem in all parts of the world, especially the developing countries. II - The reported prevalence rates in school age children in various parts of the world range from very low about 0.2 (Havana-Cuba) to 77.8 / 1000 in Samoa-.

PROBLEM, ii III - RF is the most common cause of heart disease in the 5 – 30 year age group. Iv - There has been marked decrease in mortality, incidence, prevalence, hospital morbidity, and severity of RF and RHD in some places that have implemented prevention programmes. In the Western countries, it became fairly rare since the 1960s, probably due to widespread use of antibiotics to treat streptococcus infections. While it is far less common in the United States since the beginning of the 20th century, there have been a few outbreaks since the 1980s.

PROBLEM, iii V – In 1994, about 12 million individuals suffered from RF and RHD in the world. VI – The mortality rate for RHD varied from 0.5 to 8.2/lac population.

EPIDEMIOLOGYCAL FACTORS. 1 – AGENT FACTORS, A - AGENT, the onset of the RF is usually preceded by a streptococcal sore throat. Of the streptococci, it is the group A. it has been suggested that not all strain of group A streptococci lead to RF; it is believed that there might be some strains with “rheumatogenic potential”. These serotype that has attracted special emphasis is M type 5 which is frequently associated with RF.

Diagrammatic structure of the group A beta hemolytic streptococcus Capsule Cell wall Protein antigens Group carbohydrate Peptidoglycan Cyto.membrane Cytoplasm …………………………………………… ……... Antigen of outer protein cell wall of GABHS induces antibody response in victim which result in autoimmune damage to heart valves, sub cutaneous tissue,tendons, joints & basal ganglia of brain

Epidemiologycal factors (AGENT FACTORS) Recently the virus (coxsackie B-4) has been suggested as a causative factor and streptococcus acting as a conditioning agent. B – CARRIERS, convalescent, transient and chronic carriers. In view of the high carrier rate, their eradication is not even theoretically possible.

Epidemiologycal factors Host and enviornment, AGE, RF is typically a disease of childhood and adolescence ( 5 – 15 years). The initial attack of RF occurs at a young age, progresses to valvular lesions faster and is associated with pulmonary arterial hypertension. B – SEX, the disease affects both sexes equally.

Epidemiologycal factors (Host and enviornment) continue D – SOCIOECONOMIC STATUS; RF is a social disease linked to poverty, overcrowding, poor housing conditions, inadequate health services, inadequate expertise of health care providers and a low level of awareness of the disease in the community. It declines sharply when the standard of living is improved. E – HIGH RISK GROUP, the school age children between 5 and 15 years, slum dwellers, and those living in a closed community (barracks)

Strains that produces rheumatic fever - M types l, 3, 5, 6,18 & 24 Pharyngitis- produced by GABHS can lead to- acute rheumatic fever rheumatic heart disease & post strept. Glomerulonepritis Skin infection- produced by GABHS leads to post streptococcal glomerulo nephritis only. It will not result in Rh.Fever or carditis as skin lipid cholesterol inhibit antigenicity Pathogenesis Group A Beta Hemolytic Streptococcus Pathogenesis

Pathogenesis (continue) Delayed immune response to infection with group.A beta hemolytic streptococci. After a latent period of 1-3 weeks, antibody induced immunological damage occur to heart valves,joints, subcutaneous tissue & basal ganglia of brain

Pathologic Lesions Fibrinoid degeneration of connective tissue,inflammatory edema, inflammatory cell infiltration & proliferation of specific cells resulting in formation of Ashcoff nodules, resulting in- - Pancarditis in the heart -Arthritis in the joints -Ashcoff nodules in the subcutaneous tissue -Basal gangliar lesions resulting in chorea

Clinical Features Flitting & fleeting migratory polyarthritis, involving major joints Commonly involved joints- knee,ankle,elbow & wrist In children below 5 yrs arthritis usually mild but carditis more prominent Arthritis do not progress to chronic disease 1.Arthritis

Clinical Features (Contd) Manifest as pancarditis(endocarditis, myocarditis and pericarditis),occur in 40-50% of cases Carditis is the only manifestation of rheumatic fever that leaves a sequelae & permanent damage to the organ Valvulitis occur in acute phase Chronic phase- fibrosis,calcification & stenosis of heart valves(fishmouth valves) 2.Carditis

Rheumatic heart disease. Abnormal mitral valve. Thick, fused chordae

Another view of thick and fused mitral valves in Rheumatic heart disease

Clinical Features (Contd) Occur in 5-10% of cases Mainly in girls of 1-15 yrs age May appear even 6/12 after the attack of rheumatic fever Clinically manifest as abnormal jerky purposeless movements of the arms, legs, and the body. It gradually disappears leaving no residual damage. 3.Sydenham Chorea

Clinical Features (Contd) Occur in <5%. Unique,transient,serpiginous- looking lesions of 1-2 inches in size Pale center with red irregular margin More on trunks & limbs & non-itchy Worsens with application of heat Often associated with chronic carditis 4.Erythema Marginatum

Clinical Features (Contd) Occur in 10% Painless,pea-sized,palpable nodules Mainly over extensor surfaces of joints,spine,scapulae & scalp Associated with strong seropositivity Always associated with severe carditis 5.Subcutaneous nodules

Clinical Features (Contd) Other features (Minor features) Fever-(upto 101 degree F) Arthralgia Pallor Anorexia Loss of weight

Laboratory Findings High ESR Anemia, leucocytosis Elevated C-reactive protien ASO titre >200 Todd units. (Peak value attained at 3 weeks,then comes down to normal by 6 weeks) Anti-DNAse B test Throat culture-GABHstreptococci

Laboratory Findings (Contd) ECG- prolonged PR interval, 2nd or 3rd degree blocks,ST depression, T inversion 2D Echo cardiography- valve edema,mitral regurgitation, LA & LV dilatation,pericardial effusion,decreased contractility

Diagnosis Rheumatic fever is mainly a clinical diagnosis No single diagnostic sign or specific laboratory test available for diagnosis Diagnosis based on MODIFIED JONES CRITERIA

Recommendations of the American Heart Association

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

Differential Diagnosis Juvenile rheumatiod arthritis Septic arthritis Sickle-cell arthropathy Kawasaki disease Myocarditis Scarlet fever Leukemia

Treatment 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)

I- PRIMARY PREVENTIONI The main aim is to prevent the first attack of RF, by identifying all patients with streptococcal throat infection and treating them with penicillin.

STEP I: Primary Prevention of Rheumatic Fever (Treatment of Streptococcal Tonsillopharyngitis) Agent Dose Mode Duration Benzathine penicillin G U for patients Intramuscular Once 27 kg (60 lb) U for patients >27 kg or Penicillin VChildren: 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: mg/kg/d 2-4 times daily Oral 10 d Estolate (maximum 1 g/d) or Ethylsuccinate40 mg/kg/d 2-4 times daily Oral 10 d (maximum 1 g/d) Recommendations of American Heart Association

Step II: Anti inflammatory treatment Clinical condition Drugs

Bed rest Treatment of congestive cardiac failure: - digitalis,diuretics Treatment of chorea: -diazepam or haloperidol Rest to joints & supportive splinting 3.Step III: Supportive management & management of complications

SECONDARY PREVENTION Basic Aim, To Stop The Recurrence Rheumatic Fever by, Idenifing those have had RF. Treatment with penicillin. This prevents streptococcal sore throat and therefore recurrence of RF and RHD

SECONDARY PREVENTION Steps, Treatment with penicillin. A i/m inj. of benzathine benzyl Penicillin according to age at intervals of 3 weeks. Ideally penicillin prophylaxis should be continue life long. Less than the ideal would to be continue till the age of 35 years The least satisfactory approach is to give it for 5 years from the last attack of RF.

SECONDARY PREVENTION TREATMENT, Ideally penicillin prophylaxis should be continue life long. Less than the ideal would to be contonue till the age of 35 years The least satisfactory approach is to give it for 5 years from the last attack of RF.

STEP IV : Secondary Prevention of Rheumatic Fever (Prevention of Recurrent Attacks) Agent DoseMode Benzathine penicillin G U every 4 weeks*Intramuscular or Penicillin V250 mg twice daily Oral or Sulfadiazine 0.5 g once daily for patients 27 kg (60 lb Oral 1.0 g once daily for patients >27 kg (60 lb) For individuals allergic to penicillin and sulfadiazine Erythromycin250 mg twice daily Oral *In high-risk situations, administration every 3 weeks is justified and recommended Recommendations of American Heart Association

Duration of Secondary Rheumatic Fever Prophylaxis CategoryDuration Rheumatic fever with carditis and At least 10 y since last residual heart disease episode and at least until (persistent valvar disease*) age 40 y, sometimes lifelong prophylaxis Rheumatic fever with carditis10 y or well into adulthood, but no residual heart disease whichever is longer (no valvar disease*) Rheumatic fever without carditis5 y or until age 21 y, whichever is longer *Clinical or echocardiographic evidence. Recommendations of American Heart Association

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 with carditis with valvar lesions

References  Hoffman JIE: Rheumatic Fever. Rudolph's Pediatrics; 20th Ed: ,1996.  Stollerman GH: Rheumatic Fever. Harrison's Principles Of Internal Medicine; 13th Ed: ,1995.  Special Writing Group of the Committee on Rheumatic Fever,endocarditis & Kawasaki Disease of the Council on Cardiovascular Disease in the Young of the American Heart Association: Guidelines for the Diagnosis of Rheumatic Fever. In Jones Criteria, 1992 Update JAMA 268:2029,1992  Todd J: Rheumatic Fever. Nelson's Textbook Of Pediatrics; 15th Ed: ,  Warren R, Perez M, Wilking A: Pediatric Rheumatic Diseases. Pediatric Clinics of North America; 41: ,1994.  World Health Organization Study Group: Rheumatic Fever & Rheumatic Heart Disease,technical Report Series No. 764.Geneva,world Health Organization, 1988