RHEUMATIC FEVER PROF.DR. AYÇA VİTRİNEL

A postinfectious, immune-mediated, inflammatory reaction that affects the connective tissue of multiple organ systems (heart, joints, central nervous system, blood vessels, subcutaneous tissue) and that follows infection with certain strains of group A beta-hemolytic streptococci(GABHS).

 In the developing world, acute rheumatic fever and rheumatic heart diseases are the leading causes of cardiovascular death during the first five decades of life

ETIOLOGY  GROUP A ß HEMOLYTIC STREPTO- COCCUS.  Certain serotypes ( M-types 1,3,5*,6,14,18, 19,24) are more frequently isolated from patients with ARF than other serotypes.  ARF; most frequently observed in the age group susceptible to GABHS infections, children from 5-15 years of age. Increased numbers of cases also occur in socially and economically disadvantaged group

ETIOLOGY  The increased incidence of GABHS pha- rangitis in the fall, winter and early spring is associated with an increased number of cases of ARF during these same periods of the year.

 GABHS impetigo doesn’t result in ARF the reasons for this aren’t fully understood;  Differences of rheumatogenic potential of skin strains and throat strains as well as observed difference in the immunologic response to GABHS impetigo compared with URI with GABHS

Group A ß HS

PATHOLOGY  1) Exudative, degenerative-» Reversible.fibrinoid,T-lenf,B- lenf,macrophage,mast cells  2) Proliferative-» Aschoff nodules.Fibrinoid center+multinuclear cells  Attack rate of ARF after URI ; individual of untreated, inadequately treated, strain of infecting organism, certain host factors.

PATHOLOGY Aschoff nodules  Aschoff nodules

PATHOLOGY Two basic theories for development of ARF: -TOXIC EFFECT: produced by an extracel- lular toxin of GABHS on target organs; myocardium, valves, synovium, brain.(Streptolysin S and O) -ABNORMAL IMMUNE RESPONSE: The resulting Abs cause the immunological damage ; clinical manifestations.

PATHOLOGY  Polisaccaride/group spesific carbohydrates have similarities with valves ( endocardium).  The possibility of abnormal immune response is based on cross reactivity between group A streptococcus M protein and human tissue  Hyaluranate has a similar antigenic properties with cartilage tissue.

 M protein shares certain aminoacid sequences with some human tissues and this has been proposed as a possible source of cross reactivity between the microorganism and its host leading to the abnormal immune response.(myocardium)

PATHOLOGY  Some people appear to be susceptible to developing ARF.(genetic predisposition)  A spesific alloantigen is present on the surface of non T lymphocytes in 70-90% of rheumatic individuals but fewer than 30% of control nonrheumatic individuals.

 The marker is more common in families in which there’s an index case of RF than in nonaffected members of control families.  In Turkey ARA is mostly seen in patients with HLA A20 and HLA DRw 11

CLINICAL MANIFESTATIONS  CARDITIS: PANCARDITIS; pericardium, epicardium, myocardium and endocardium  Residual of ARF -» chronic changes.Valvular insufficiency = most frequently mitral valve, aortic valve.---» later stenosis of the valve.  Occurs 40-80% of patients with RF.  Pericarditis.  Arrythmias  Cardiomegaly

 New murmurs appear within the first 2 weeks in 80% of patients, and they rarely occur after the second month of illness.  Hence, during an episode, one normal echocardiogram in the first 2 weeks should be sufficient to eliminate carditis

Rheumatic carditis (verrucae)

Mitral stenosis

Rheumatic carditis (before treatment)

Rheumatic carditis (posttreatment-4 wk later)

CLINICAL MANIFESTATIONS  POLYARTHRITIS: Tender, joints are red, warm and swallen. Migratory, several dif- ferent joints; elbows, knees, ankles, wrists. Need not be symmetric. Doesn’t result in chronic joint disease  untreated it may persist for a week.

CLINICAL MANIFESTATIONS  CHOREA: Occurs much later than other manifestations. (as long as several months)  Marked deterioration is handwriting.  Emotional lability  Affect all four extremities or may be unila- teral.  Frequently the only symptom of RF  Usually disappears within weeks to months.  Dissapears during sleeping

CLINICAL MANIFESTATIONS  ERYTHEMA MARGINATUM: Occurs very infrequently, nonspesific pink macules  over the trunk  can be made worse with application of heat  migratuar.

ERYTHEMA MARGINATUM

CLINICAL MANIFESTATIONS  SUBCUTAN NODULES: Infrequently and are most commonly observed in patients with severe carditis.  Nontender  No inflammation  Seen on the extansor surfaces of the joints such as knees, elbows, over the spine

SUBCUTAN NODULES

CLINICAL MANIFESTATIONS MINOR MANIFESTATIONS:  FEVER: 37.8 C- 40 °C  ARTHRALGIA

DIAGNOSIS

 Two major criteria OR  one major + two minor criteria ; +  evidence of preeceding strep infection. Indicate high probability of RF

In three situtations ARF may be diagnosed in the absence of these rules: 1) Chorea (if other cause have been pre- clude. 2) Insidious or late onset of carditis with no other explanation 3) Rheumatic reccurence

DIAGNOSIS  WHO CRITERIA ( )  FIRST ATTACK: JONES CRITERIA  RECURRENCE:  R.H.D. (-): first attack criteria  R.H.D. (+): 2 minor criteria + eviden- ce of preceeding strep. İnfection.

Differential diagnosis of rheumatic fever   Juvenile rheumatoid arthritis   Systemic lupus erythematosus   Infective endocarditis   Reactive arthritis   Sickle cell disease   Drug reactions   Other connective tissue diseases   Septicaemia   Leukaemia   Gonoccocal arthritis   Tuberculosis   Lyme disease   Serum sickness

LABORATORY FINDINGS  Throat culture  ASO, reaches its peak 3-6 weeks after infection.  ESR   CRP   ECG  Chest Roentgram  ECHO

Rheumatic carditis (ECG)

COMPLICATIONS  Development of rheumatic valvular heart disease.

TREATMENT  1) Treatment of GABHS  2) Antiinflamatuar agents  3) Supportive therapy (therapy of conges- tive heart failure)

TREATMENT  1) Ten full days of an appropriate oral agent  A single IM injection of U of benzathin penicillin G  2) Arthritis salicylates mg/kg/day in 4 divided doses  Mild carditis: salicylates

TREATMENT  2)Congestive hearth failure/significant manifestations of carditis CORTICOSTEROIDS ( 2 mg/kg/day prednisone (d2) 2-3 wk and taper the drug (add salicylates during tapering)  3)SYDENHAM CHOREA: Phenobarbital, cholorpromazine, benzodiazepine, halope- ridol.

PREVENTION  PRIMARY PROPHYLAXIS: Antibiotic treatment of strep URI.  SECONDARY PROPHYLAXIS: Prevention of colonisation or infection of URI with GABHS:  IM B.pen. Every 3-4 wk  Oral pen V 250 mg twice daily  Sulfadiazine 500 mg daily  Erytromycin 250 g twice daily

PREVENTION  The necessary duration of secondary prophylaxis--» 5 years or reaching 21. birthday  Carditis without residual heart disease-10 yrs or 21 years age  Residual rheumatic heart disease--» 10 years or until age 40.  Severe heart disease or risc of continous exposure- lifelong.