10 Rheumatic Fever


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  • All right , provide some little tips You should remember the word – MY HEART to help to review the clinical features of KD. M ,h,e ------------------may respectly respectively ------------------------------------- The whole word may remind us the abnormalities of coronary arteries and heard.
  • 10 Rheumatic Fever

    1. 1. MBBS.weebly.com Rheumatic Fever
    2. 2. <ul><li>Rheumatic fever is an immunological inflammatory disease </li></ul><ul><li>follows infection with certain strains of group A streptococci </li></ul><ul><li>easily recur without prophylaxis </li></ul>carditis chorea migratory polyarthritis subcutaneous nodules permanent valvular disease erythema marginatum
    3. 3. <ul><li>incidence : 22/100000 in China </li></ul><ul><li>season : winter or spring </li></ul><ul><li>age : 5 – 15y </li></ul>Epidemiology
    4. 4. Etiology ☆ a nonsuppurative complication of group A streptococcal infection of the upper respiratory tract ☆ occurs 1 - 4 weeks after convalescence of infection ☆ individual propensity ☆ environmental factors latitude altitude humidity nutrition crowding age
    5. 5. Pathogenesis <ul><li>molecular mimicry of bacterial antigens </li></ul><ul><li>similarity between bacterial and self molecules as recognized by immune cells leading to across-react with target organs in the body </li></ul><ul><li>circulating immune complexes (CIC) </li></ul><ul><li>circulating immune complexes activate the complement system leading to the inflammatory changes </li></ul><ul><li>Genetic proneness </li></ul><ul><li>HLA-B35 、 HLA-DR4 </li></ul>
    6. 6. capsule ( synovial membranes ) Cell wall protein ( myocardium, endocardium ) Cell wall polysaccharides ( myocardium, endocardium ) cell membrane protein ( myocardium 、 subthalamic nucleus 、 caudate nucleus ) The antigens of Group A streptococci and molecular mimicry
    7. 7. pathology 急性渗出期( acute exudative period ) 增生期( proliferative period ) 硬化期 (sclerotic period) 1 month 3~4 months 2~3 months connective tissue edemas ,effuse, and degenerate, infiltrated with inflammatory cells. Aschoff body in myocardium, muscle, endocardium, subcutaneous tissue collagen fiber hyperplasia and scar tissue formation mitral >aortic>tricuspid>pulmonary
    8. 8. acute exudative period edema and degeneration of collagen and exudation in pericardium pericardial effusion fibrinous pericarditis
    9. 9. proliferative period Aschoff body in endocardium 中心: fibrinoid necrosis of collagen 外周: lymphocytes, plasma cells and Aschoff giant cells Aschoff giant cell large cells with two or more pale nuclei that have prominent nucleoli.
    10. 10. sclerotic period mitral valve shows thickening distorted cusps, adherent commissures with calcification and thrombus deposition, fusion and shortening of chordae tendinae. stenotic mitral valve shows fusion of commissures, thickening and calcification of the cusps. commissures are fused; cusps are severely thickened. The valve is both incompetent and stenotic.
    11. 11. Clinical Manifestation <ul><li>Major clinical manifestations: </li></ul><ul><li>carditis; polyarthritis; chorea; </li></ul><ul><li>subcutancous nodules; </li></ul><ul><li>erythema marginatum </li></ul><ul><li>Ordinary complaints: </li></ul><ul><li>fever / arthralgia </li></ul><ul><li>Duration of acute rheumatic fever: </li></ul><ul><li>≤ 6 months </li></ul>
    12. 12. rheumatic carditis <ul><li>Incidence: 40~50% </li></ul><ul><li>One and only permanent damage </li></ul><ul><li>Endocarditis </li></ul><ul><li>Myocarditis </li></ul><ul><li>Pericarditis </li></ul><ul><li>Congestive heart failure during the initial episode: 5%~10% </li></ul>Pancarditis
    13. 13. Myocarditis <ul><li>Tachycardia disproportionate to the fever </li></ul><ul><li>Congestive heart failure </li></ul><ul><li>Gallop rhythm </li></ul><ul><li>Soft systolic murmur heard at the apex </li></ul><ul><li>ECG abnormalitis : </li></ul><ul><li>arrhythmias; </li></ul><ul><li>prolongation of the P-R interval; </li></ul><ul><li>atrioventricular block (AVB) </li></ul><ul><li>Cardiomegaly on x-ray </li></ul>Before treatment after treatment
    14. 14. Endocarditis <ul><li>Mitral regurgitation: </li></ul><ul><li>Apical systolic murmur at the apex </li></ul><ul><li>Relative mitral stenosis: </li></ul><ul><li>Low-pitched mid-diastolic rumble </li></ul><ul><li>Aortic regurgitation: </li></ul><ul><li>Diastolic murmur in the third costa at the left side of the sternum </li></ul>
    15. 15. Pericarditis <ul><li>Precordial pain </li></ul><ul><li>A friction rub </li></ul><ul><li>Striking increase in heart size on X-ray </li></ul><ul><li>Echocardiography: pericardial effusion > 50ml </li></ul>
    16. 16. Rheumatic arthritis <ul><li>Incidence: 50%~60% </li></ul><ul><li>Acute migratory polyarthritis </li></ul><ul><li>Larger joints of the extremities are affected: </li></ul><ul><li>knee 、 ankle 、 elbow 、 wrist </li></ul><ul><li>Red, hot, swollen, exquisitely tender and painful if moved </li></ul><ul><li>as one joint recovered, another joint may be involved </li></ul><ul><li>arthritis lasts less than 1 month without deformity </li></ul>
    17. 17. Chorea <ul><li>Incidence: 3%~10% </li></ul><ul><li>Female > male; 8~12 yeas old </li></ul><ul><li>Sudden, aimless, irregular movements of the extremities and facial muscles that subside during sleep and exaggerated by emotions </li></ul><ul><li>Emotional instability: nervous </li></ul><ul><li>Muscle weakness and ataxia: </li></ul><ul><li>clumsy, stumble, handwriting or speech disorders </li></ul>
    18. 18. erythema marginatum <ul><li>The characteristic rashes consist of an evanescent , pink, erythematous maculae, with a clear center and serpiginous outline. The rash is transient, migratory and nonpruritic , which found primarily on the trunk and proximal extremities . </li></ul>
    19. 19. subcutaneous nodules <ul><li>Subcutaneous nodules are painless small swellings over bony prominences , primarily over the extensor tendons of the hands, feet, elbows, scalp, scapulae, and vertebrae. Nodules tend to occur in crops and may persist for days to months after the onset of acute rheumatic fever. </li></ul>
    20. 20. Other clinical features <ul><li>Variable fever </li></ul><ul><li>Tiredness </li></ul><ul><li>paleness </li></ul><ul><li>Pneumonia </li></ul><ul><li>Nosebleed </li></ul><ul><li>sweating </li></ul><ul><li>Abdominal angina </li></ul>
    21. 21. Laboratory findings <ul><li>Blood routine test: WBC↑,mild anemia </li></ul><ul><li>Acute phase reactants : ESR↑, CRP↑ </li></ul><ul><li>Isolation of group A streptococci (+) </li></ul><ul><li>Serum antibody against the specific strptococci : </li></ul><ul><li>ASO↑, ASK ↑, AH ↑, anti-DNase B ↑ </li></ul><ul><li>Immune system: IgG ↑, IgA ↑, C 3 ↑ </li></ul><ul><li>ECG: P-R interval ↑, second degree AVB </li></ul><ul><li>Routine roentgenogram </li></ul><ul><li>Echocardiography </li></ul>
    22. 22. The Jones Criteria Revised with Addition of World Health Organization Recommendations Major Criteria Minor Criteria Carditis Fever Polyarthritis, migratory Arthralgia Erythema marginatum increased acute-phase reactants Chorea ESR↑, CRP↑ Subcutaneous nodules Prolonged P-R interval Plus Evidence of a preceding group A streptococcal infection (culture, rapid antigen, antibody titers rise/elevation, scarlet fever) ★ two major manifestations + Evidence of S.I (streptococcal infection ) ★ one major + two minor manifestations + Evidence of S.I
    23. 23. <ul><li>Fever, body weight ↓, tireness </li></ul><ul><li>Tachycardia or arrhythmias </li></ul><ul><li>ESR↑, CRP↑, neutrocyte↑, antibody titer↑ </li></ul>Dignosis of active rheumatic fever
    24. 24. Differential diagnosis <ul><li>Fever </li></ul><ul><li>Carditis </li></ul><ul><li>Arthritis </li></ul>
    25. 25. Differential diagnosis of carditis <ul><li>Infective endocarditis : </li></ul><ul><li>anemia, splenomegaly, petechia, embolism </li></ul><ul><li>blood culture ( + ) </li></ul><ul><li>vegetations on endocardium / valves </li></ul><ul><li>Viral myocarditis : </li></ul><ul><li>arrhythmias ( premature contraction) </li></ul><ul><li>evidence of viral infection </li></ul>
    26. 26. Differential diagnosis of arthritis <ul><li>Systemic lupus erythematosus (SLE) : </li></ul><ul><li>malar rash, proteinuria, hypertension, </li></ul><ul><li>leukopenia, Coombs(+) hemolytic anemia, </li></ul><ul><li>antinuclear antibodies(+) </li></ul><ul><li>Juvenile rheumatoid arthritis (JRA) : </li></ul><ul><li>morning stiffness, iridocyclitis, </li></ul><ul><li>progression of joint destruction, ANA(+), </li></ul><ul><li>rheumatoid factor(+) </li></ul>
    27. 27. <ul><li>Bed rest </li></ul><ul><li>antibiotics </li></ul><ul><li>anti-rheumatism therapy </li></ul><ul><li>heteropathy </li></ul>Management
    28. 28. <ul><li>( 1 ) Bed rest </li></ul>carditis cardiamegaly congestive heart failure -- -- -- 2 w 2 w + -- -- 4 w 4 w + + -- 6 w 6 w + + + 8 w 3 mon
    29. 29. <ul><li>( 2 ) antibiotics </li></ul><ul><li>Procaine penicillin G: </li></ul><ul><li>4.8 millon U ~ 9.6 millon U / d , iv drip ×2~3 w </li></ul><ul><li>PG AST ( + ) : </li></ul><ul><li>Erythromycin p.o ×10 d </li></ul><ul><li>( 3 ) anti-rheumatism therapy </li></ul><ul><li>Carditis : Prednisone, 2mg/kg.d ( ≤ 60mg/d ) × 2~4w; reduce dose gradually; full duration = 8~12 w </li></ul><ul><li>arthritis : Aspirin , 80~100mg/kg.d ( ≤ 3g /d ) until remission; gradually reduce to half dose for 4~6w </li></ul>
    30. 30. <ul><li>( 4 ) heteropathy </li></ul><ul><li>congestive heart failure : </li></ul><ul><li>steroid; oxygen therapy; diuresis; </li></ul><ul><li>captopril ; digitalis ( small dose) </li></ul><ul><li>chorea : tranquilizer (chlorpromazine, </li></ul><ul><li>barbital ) </li></ul><ul><li>arthralgia: immobilization of affected joints </li></ul>
    31. 31. prophylaxis <ul><li>Recurrent rheumatic fever </li></ul><ul><li>benzathine Penicillin: 1.2million U , Q4W,≥5 years </li></ul><ul><li>patients with established heart disease may continue </li></ul><ul><li>for ≥ 10 years, even the whole life. </li></ul><ul><li>PG AST ( + ) : </li></ul><ul><li>Erythromycin p.o ×6 ~7 d, every month </li></ul><ul><li>Bacterial myocarditis </li></ul><ul><li>Patients with rheumatic heart disease should receive antibiotic prophylaxis before and after operation to prevent bacterial infection. </li></ul>
    32. 32. Emphases <ul><li>Five major clinical manifestations </li></ul><ul><li>Jones criteria </li></ul><ul><li>Features of active rheumatic fever </li></ul><ul><li>treatment : </li></ul><ul><li>prophylaxis : long-acting PG </li></ul>
    33. 33. Kawasaki disease ( Mucocutaneous lymph node syndrome ) 川 崎 病
    34. 34. <ul><li>Tomisaku Kawasaki described KD in 1967 </li></ul><ul><li>KD is a acute generalized systemic vasculitis of unknown etiology with fever and rashes. </li></ul><ul><li>Coronary artery dilation or aneurysms </li></ul><ul><li>KD has replaced acute rheumatic fever as the most common cause of acquired heart disease in children In developed countries </li></ul>
    35. 35. <ul><li>Age : < 4 years old (80%) </li></ul><ul><li>< 2 years old (50%) </li></ul><ul><li>Sex : more often in males than in females (1.5:1) </li></ul><ul><li>Season : clusters in winter / spring </li></ul><ul><li>Racial background: Asian children, especially those of Japanese descent. </li></ul>Epidemiology
    36. 36. Etiology and Pathogenesis <ul><li>etiology of KD remains undiscovered. </li></ul><ul><li>immunopathogenic mechanism for </li></ul><ul><li>coronary disease </li></ul><ul><li>organism super-antigen </li></ul><ul><li>mimic antigen ( HSP65) </li></ul><ul><li>T cell - mediated immune response </li></ul><ul><li>cytokine – mediated immune damage </li></ul>
    37. 37. <ul><li>stageⅠ : 1~10 d , acute small periarteritis ; </li></ul><ul><li>cardiac inflammatory changes </li></ul><ul><li>stageⅡ : 10~25 d , coronary arteritis; elastic </li></ul><ul><li>laminae and muscular layers split, leading </li></ul><ul><li>to thrombus and aneurysms. </li></ul><ul><li>stage Ⅲ : 26~31 d , acute inflammation remission; </li></ul><ul><li>fibrous tissue proliferates; intima thickens; </li></ul><ul><li>coronary arteries narrow or occlude . </li></ul><ul><li>stage Ⅳ :≧ 40 d, cicatrization in myocardium; </li></ul><ul><li>occluded arteries reopen. </li></ul>Pathophysiology — systemic vasculitis (coronary arteries)
    38. 38. normal coronary artery stageⅠ stage Ⅱ
    39. 39. 10 days after the onset of symptoms, elastic laminae splits , intima proliferates and thickens in branch of coronary artery.
    40. 40. Huge coronary artery aneurysm
    41. 41. Clinical manifestation <ul><li>Mucocutaneous lymph node abnormalities </li></ul><ul><li>Cardiovascular abnormalities </li></ul><ul><li>Other nonspecifically manifestations </li></ul>
    42. 42. Main clinical features <ul><li>1. Fever </li></ul><ul><li>usually more than 39°C, for at least 5 days </li></ul><ul><li>High spiking and remittent </li></ul><ul><li>not responds to antibiotics </li></ul><ul><li>Generally persists 1-2 weeks without treatment </li></ul><ul><li>usually resolves in 1-2 days after treatment with intravenous gamma globulin (IVIG) </li></ul>
    43. 43. <ul><li>2. Bilateral conjunctiva injection without exudate </li></ul>Main clinical features
    44. 44. Main clinical features <ul><li>3. inflammation of the lips and oral cavity </li></ul><ul><li>Injected, dry, fissured- lips </li></ul><ul><li>injected oral and pharyngeal mucosa </li></ul><ul><li>Strawberry tongue with prominent papillae and erythema </li></ul><ul><li>no oral exudates, ulcerations, or Koplik spots </li></ul>
    45. 45. Main clinical features <ul><li>4. Hands and feet </li></ul><ul><li>Erythema, or indurative edema of palms and soles </li></ul><ul><li>Periungual membranous desquamation of fingers and toes about 2 weeks after onset </li></ul><ul><li>Transverse grooves across the nails </li></ul>
    46. 46. Main clinical features <ul><li>5. rash of various forms </li></ul><ul><li>diffuse, scarlatiniform or </li></ul><ul><li>erythema polymorphous rash </li></ul><ul><li>erythema or desquamation in perineal region </li></ul>
    47. 47. Main clinical features <ul><li>6. non- purulent cervical lymphadenopathy </li></ul><ul><li>50-75% of patients </li></ul><ul><li>With a node size of 1.5 cm or greater in diameter </li></ul><ul><li>tenderness, not red </li></ul>
    48. 48. <ul><li>1. carditis </li></ul><ul><ul><li>Tachycardia </li></ul></ul><ul><ul><li>Gallop rhythm </li></ul></ul><ul><ul><li>systolic murmurs </li></ul></ul><ul><ul><li>Arrhythmia </li></ul></ul><ul><li>2. myocardial ischemia </li></ul><ul><ul><li>angina </li></ul></ul><ul><ul><li>myocardial infarction </li></ul></ul>Cardiovascular abnormalities
    49. 49. 3. Coronary arterial changes — 2~4 weeks after onset / convalescent phase <ul><li>coronary arteritis </li></ul><ul><li>vessel intima roughened </li></ul><ul><li>coronary arteries narrow </li></ul><ul><li>coronary arteries dilation </li></ul><ul><li>coronary artery aneurysm </li></ul>
    50. 50. Aneurysm at left anterior descending ( LAD) coronary artery LAD Coronary Artery Aneurysm — 20~30% of untreated children normal coronary artery
    51. 51. High risk factors of CA aneurysm <ul><li>age: < 6 month or > 3 years </li></ul><ul><li>male sex </li></ul><ul><li>fever for more than 16 days or recurrence </li></ul><ul><li>cardiomegaly or arrhythmia </li></ul><ul><li>lab findings: </li></ul><ul><li>Hb < 80g/L, WBC > 16~30X10 9 /L, </li></ul><ul><li>PLT > 1000X10 9 /L, ESR > 100mm/h </li></ul><ul><li>KD recurrence </li></ul>
    52. 52. Less-common features <ul><li>aseptic </li></ul><ul><li>meningitis </li></ul><ul><li>abdominal </li></ul><ul><li>pain </li></ul><ul><li>otitis media </li></ul><ul><li>jaundice </li></ul><ul><li>diarrhea </li></ul><ul><li>gallbladder </li></ul><ul><li>hydrops </li></ul><ul><li>hepatic </li></ul><ul><li>dysfunction </li></ul><ul><li>arthralgia </li></ul><ul><li>arthritis </li></ul><ul><li>urethritis </li></ul>
    53. 53. <ul><li>Blood analysis : </li></ul><ul><li>WBC↑; mild anemia; </li></ul><ul><li>PLT↑in 2nd~3th week ; </li></ul><ul><li>ESR↑ ; </li></ul><ul><li>CRP↑ ; </li></ul><ul><li>ALT↑; AST↑ </li></ul>Laboratory findings
    54. 54. <ul><li>Immune system </li></ul><ul><li>IgG 、 IgM 、 IgA 、 IgE↑ ; </li></ul><ul><li>Circulating Immune Complexes ↑ ; </li></ul><ul><li>C3 normal or ↑ </li></ul>
    55. 55. <ul><li>ECG : ST-T abnormalities of pericarditis </li></ul><ul><li>or myocardial infarction </li></ul><ul><li>Chest roentgenogram : nonspecific </li></ul><ul><li>perihilar or parenchyma infiltrates ; </li></ul><ul><li>cardiamegaly. </li></ul>
    56. 56. <ul><li>Echocardiography </li></ul><ul><li>coronary arteritis </li></ul><ul><li>intima roughened </li></ul><ul><li>coronary arteries </li></ul><ul><li>narrow or dilation </li></ul><ul><li>coronary artery </li></ul><ul><li>aneurysm </li></ul><ul><li>pericardial effusion </li></ul><ul><li>mitral , aortic, or </li></ul><ul><li>tricuspid disturbed </li></ul><ul><li>flow </li></ul><ul><li>coronary artery aneurysm </li></ul><ul><li>right coronary artery trunk </li></ul><ul><li>aorta </li></ul>
    57. 57. <ul><li>Coronary angiography </li></ul><ul><li>— myocardial ischemia / multiple coronary aneurysms </li></ul>normal aneurysm LAD dilation and narrow
    58. 58. Diagnostic guidelines ( for typical cases) <ul><li>fever lasting more than 5 days + 4 of the following 5 criteria (other illnesses must be excluded): </li></ul><ul><li>1. polymorphous rash </li></ul><ul><li>2. bilateral conjunctival injection without exudate </li></ul><ul><li>diffuse injection of oral mucosa, erythema or fissuring of </li></ul><ul><li>the lips, strawberry tongue </li></ul><ul><li>4. nonpurulent cervical lymph node enlargement (one lymph node >1.5 cm) </li></ul><ul><li>5. extremity changes: erythema of palms / soles, </li></ul><ul><li>indurative edema of hands / feet, Membranous desquamation of the fingertips </li></ul>
    59. 59. Diagnostic guidelines ( for atypical cases) <ul><li>fever lasting more than 5 days </li></ul><ul><li>≤ 3 of the 5 criteria </li></ul><ul><li>coronary arteries dilation or aneurysm detected by echocardiography </li></ul>
    60. 60. Differential diagnosis <ul><li>Scarlet fever </li></ul><ul><li>Red rash blanches with pressure, which is diffuse but spares the palms, soles, and face. The face appears flushed. The skin rash fades in a week and is followed by extensive desquamation. Patient has good response to PG. </li></ul>
    61. 61. Differential diagnosis <ul><li>Exudative and Erythema Multiforme </li></ul><ul><li>polymorphous Erythema, herpes and extensive desquamation; oral ulcers; conjunctival exudate; no indurative edema of palms or soles </li></ul>
    62. 62. <ul><li>Treatment & Medication </li></ul><ul><li>relieve vasculitis </li></ul><ul><li>inhibit PLT aggregation </li></ul>
    63. 63. <ul><li>( 1 ) aspirin </li></ul><ul><li>administered for anti-inflammatory and </li></ul><ul><li>antithrombotic effects </li></ul><ul><li>a cute phase : 80-100 mg/kg/d PO in tid/qid </li></ul><ul><li>72h after defervescence: reduce dose </li></ul><ul><li>gradually </li></ul><ul><li>2 weeks after defervescence: 3-5 mg/kg/d p.o×6~8 weeks until ESR , PLT and coronary arteries return to normal </li></ul>
    64. 64. <ul><li>reduce the prevalence of coronary abnormalities and lead to rapid defervescence </li></ul><ul><li>2 g/kg IV infusion over 8-12 h within 10d after onset </li></ul><ul><li>Patient with incomplete response can receive a second course of IVIG. </li></ul><ul><li>defer using live viral vaccines until about 11 months after IVIG administration </li></ul>(2) intravenous gammaglobulin ( IVIG)
    65. 65. <ul><li>indications of administration </li></ul><ul><li>pancarditis </li></ul><ul><li>no available IVIG </li></ul><ul><li>no response to IVIG </li></ul><ul><li>prednisone / methylprednisolone </li></ul><ul><li>combination with aspirin + persantine </li></ul>(3) corticosteriods
    66. 66. <ul><li>persantine 3~5mg/kg/d </li></ul><ul><li>maintenance treatment in patient with huge or multiple coronary aneurysms </li></ul><ul><li>aspirin 3~5mg/kg/d + warfarin </li></ul>(4) inhibit PLT aggregation (5) Other therapy <ul><li>Liquid therapy </li></ul><ul><li>thrombolytic drug </li></ul><ul><li>coronary artery bypass graft </li></ul>
    67. 67. Prognosis <ul><li>principal cause of death: </li></ul><ul><li>myocardial infarction </li></ul><ul><li>fatality rate : 0.5-1% </li></ul><ul><li>recurrence rate: 1-2% </li></ul><ul><li>incidence of CA aneurysms: </li></ul><ul><li>20~30% in untreated patient </li></ul><ul><li>15% in IVIG treated patient </li></ul>
    68. 68. outpatient follow-up <ul><li>systemic examination </li></ul><ul><li>no CA abnormality: </li></ul><ul><li>the first 1,3,6,12 month </li></ul><ul><li>CA abnormality: </li></ul><ul><li>the first 1,3,6 month, then </li></ul><ul><li>every 6-12 month until CA return to normal </li></ul>
    69. 69. Emphases <ul><li>acute generalized systemic </li></ul><ul><li>vasculitis </li></ul><ul><li>coronary artery abnormalities </li></ul><ul><li>diagnostic guidelines </li></ul><ul><li>treatment : </li></ul><ul><li>goals / medication </li></ul><ul><li>out patient follow-up </li></ul>
    70. 70. M(y) Heart <ul><li>M : m ucocutaneous </li></ul><ul><li>H : h and / feet </li></ul><ul><li>E ( e ye) : conjunctiva </li></ul><ul><li>A : a denopathy </li></ul><ul><li>(lymphadenopathy) </li></ul><ul><li>R : r ash </li></ul><ul><li>T ( t empreture ): fever </li></ul>