PENYAKIT JANTUNG. REMATIK. Abdullah Afif Siregar. Departemen Kardiologi
dan Kedokteran Vaskuler. Departemen Kardiologi dan Kedokteran Vaskuler.
DEMAM REMATIK dan PENYAKIT JANTUNG REMATIK Abdullah Afif Siregar Departemen Kardiologi dan Kedokteran Vaskuler Fakultas Kedokteran USU Medan
Rheumatic fever is an immunologically mediated inflammatory disease disease, that occurs as a delayed sequel to group A streptococcal throat infection, in genetically susceptible individuals. Rheumatic heart disease is the most serious complication of rheumatic fever A Acute rheumatic h i fever f and d rheumatic h i heart h disease are thought to result from an autoimmune response, response, but the exact pathogenesis remains unclear
The rheumatic fever follows 0.3% of cases of group A beta-hemolytic streptococcal pharyngitis in children. • As A many as 39% off patients ti t with ith acute t rheumatic h ti ffever may develop varying degrees of pancarditis with associated valve insufficiency, heart failure, pericarditis, and even death. • With chronic rheumatic heart disease, patients develop valve stenosis with varying degrees of regurgitation regurgitation, atrial dilation, arrhythmias, and ventricular dysfunction. • Chronic rheumatic heart disease remains the leading cause off mitral it l valve l stenosis t i and d valve l replacement l t iin adults and children •
Pathophysiology: Rheumatic fever develops in children and adolescents following pharyngitis with group A beta-hemolytic Streptococcus (ie, Streptococcus pyogenes) pyogenes). • The organisms attach to the epithelial cells of the upper respiratory tract and produce a battery of enzymes allowing them to damage and invade human tissues tissues. • After an incubation period of 2-4 days, the invading organisms elicit an acute inflammatory response with 3-5 days of sore throat, f fever, malaise, l i h headache, d h and d an elevated l t d lleukocyte k t count. t • In 0.3-3% of cases, infection leads to rheumatic fever several weeks after the sore throat has resolved. Only infections of the pharynx h iinitiate ii or reactivate i rheumatic h i ffever. • The organism spreads by direct contact with oral or respiratory secretions, and spread is enhanced by crowded living conditions. •
Etiopathogenesis : • The Th pathogenic th i mechanisms h i i involved l d iin th the d development l t off RF remain i
unclear. But it is evident that an abnormal humoral and cellular immune response occurs. • Antigenic mimicry between streptococcal antigens antigens, mainly M-protein M protein epitopes and human tissues, such as heart valves, myosin and tropomyosin, brain proteins, synovial tissue and cartilage has been proposed as the triggering factor leading to autoimmunity in individuals with genetic predisposition. • Several genetic markers of susceptibility have been studied but no consistent association found. Associations with different HLA class II antigens have been observed in several populations. • Molecular mimicry was first demonstrated by humoral immune response. Streptococcal antibodies cross-react with several human tissues including heart, skin, brain, glomerular basement membrane, striated and smooth muscles. • The presence of CD4+ T cells at lesions sites in the heart has been demonstrated ssuggesting demonstrated, ggesting a direct role of these cells in the pathogenesis of RHD.
Etiopathogenesis :
• Infiltrating T lymphocytes from
heart lesions of severe RHD patients and peripheral T lymphocytes were capable of recognising immunodominant myocardium M5 peptides and valve proteins. These results showed the significance g of molecular mimicry between beta hemolytic streptococci and heart tissue assessing the T-cell repertoire leading to local tissue damage in RHD. Figure 1 Fi 1: S Schematic h ti representation t ti of the aetiopathogenic events occurring during the development of carditis
DIAGNOSIS :
Sambungan Tabel 4.1
Carditis (40% )
Carditis (40% )
Clinical picture of carditis : • The clinical picture includes high pulse rate, congestive heart failure, failure arrhytmias and pericardial friction rubs rubs. • On the first attack, valvulitis is suspected in the presence of a new apical systolic murmur of mitral regurgitation (associated or not with an apical mid-diastolic murmur) and/or a basal diastolic murmur of aortic regurgitation. • Cardiomegaly g y is noted on X-Rayy and on echocardiogram. g • Myocarditis and/or pericarditis in the absence of valvular involvement is unlikely due to acute RF
Polyarthritis (75%) • Arthritis is the most common manifestation, present in 60-80% of patients. patients • It usually affects the peripheral large joints; small joints and axial skeleton are rarely involved. • Knees, ankles, elbows and wrists are the most frequently affected. The joints are red, warm and swollen. • Arthritis is characteristically asymmetrical, migratory, and very painful, although some patients may present mild joint complaints. It usually resolves spontaneously at the most in 2 or 3 weeks. • Arthritis in ARF has an excellent response to salicylates
Sydenham Chorea :
Sydenham’s chorea is characterized by involuntary movements specially of the face movements, and limbs, muscle weakness, disturbances of speech and gait. Children usually exhibit concomitant psychologic dysfunction,, especially dysfunction obsessiveobsessi e-compulsive obsessive comp lsi e disorder, diso de increased emotional lability, hyperactivity, irritablility and age--regressed age d behavior. b h i It is usually a delayed manifestation,, and is often the manifestation sole manifestation of ARF.
Erythema marginatum : This is an evanescent, erythematous, nonnon-pruritic rash with pale l centers and d rounded d d or serpiginous margins. Lesions occur mainly on the trunk and proximal extremities and mayy be induced byy application pp of heat
Diagnosis g :
Based on Jones Criteria, 1992 Update : - 2 Major criteria + 1 Minor criteria, criteria or - 1 Major criteria + 2 minor criteria
* plus supporting evidence off preceding GAS infection
Table : Differential diagnosis of rheumatic fever
Juvenile rheumatoid arthritis
Systemic lupus erythematosus
Infective f i endocarditis d di i
Reactive arthritis
Sickle cell disease
Drug reactions
Other connective tissue diseases
Septicaemia
Leukaemia
Gonoccocal arthritis
T b Tuberculosis l i
Lyme disease
Serum sickness
Treatment : Medical therapy involves the following 5 areas: 1. Treat group A streptococcal infection regardless of organism detection. 2 Steroids and salicylates are useful in the control of pain and 2. inflammation. The nonsteroidal anti-inflammatory drug (NSAID) naproxen has also been studied. It is effective and may be easier to use than aspirin aspirin. 3. Heart failure may require digitalis. 4. Administer prophylaxis to patients who have developed ARF. Patients with ARF should receive prophylaxis against future GABHS infections. Available regimens include benzathine penicillin G 1.2 million U IM every month, penicillin V 200,000 U or 250 mg PO bid, bid or erythromycin 250 mg PO bid bid. Most authorities suggest that prophylaxis be given for 5 years. For those who have rheumatic carditis, some authorities suggest lifel long prophylaxis. h l i 5. Haloperidol may be helpful in controlling chorea.
Drug Name
Penicillin G benzathine (Bicillin LA)
Penicillin G procaine (Crysticillin, Wycillin)
Penicillin VK (Beepen (Beepen--VK, Betapen--VK, Robicillin VK, Veetids) Betapen
Description
Interferes with synthesis of cell wall mucopeptide during active multiplication resulting in bactericidal activity against susceptible bacteria. Because of its prolonged blood level,, several authors believe this to be the DOC. Others prefer daily injections.
Long-acting parenteral penicillin Long(IM only) indicated in the treatment of moderately severe infections caused by penicillin G-sensitive microorganisms. Some prefer 10 10--d therapy. Administer byy deep p IM injection j only into the upper outer quadrant of the buttock.
Inhibits the biosynthesis of the cellcellwall mucopeptide and is effective during the stage of active multiplication. Inadequate concentrations may produce only bacteriostatic effects. Penicillin VK is the oral alternative for the treatment of rheumatic fever.
Adult Dose
2.4 million U IM once
2.4 million U IM once
500 mg PO q6h for 10 d
Pediatric Dose
Infants and children 10 years: 10-15 mcg/kg PO M i t Maintenance dose: d 25-35% 25 35% off PO loading l di dose d
Contraindications
Documented hypersensitivity; beriberi heart disease; idiopathic hypertrophic subaortic stenosis; constrictive pericarditis; carotid sinus syndrome
Interactions
Medications that may increase digoxin levels include alprazolam, benzodiazepines, bepridil, captopril, cyclosporine propafenone, cyclosporine, propafenone propantheline, propantheline quinidine, quinidine diltiazem diltiazem, aminoglycosides, aminoglycosides oral amiodarone, amiodarone anticholinergics, diphenoxylate, erythromycin, felodipine, flecainide, hydroxychloroquine, itraconazole, nifedipine, omeprazole, quinine, ibuprofen, indomethacin, esmolol, tetracycline, tolbutamide, and verapamil; medications that may decrease serum digoxin levels include aminoglutethimide, anti histamines, cholestyramine, neomycin, penicillamine, aminoglycosides, oral colestipol, hydantoins,hypo glycemic g y agents, g , antineoplastic p treatment combinations (including ( g carmustine,, bleomycin, y , methotre xate, cytarabine, doxorubicin, cyclophosphamide, vincristine, procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
yp mayy reduce positive p inotropic p effect of digitalis; g IV calcium mayy produce p arrhythmias y ; Hypokalemia hypercalcemia predisposes patient to digitalis toxicity, and hypocalcemia can make digoxin ineffective; magnesium replacement therapy must be instituted in patients with hypomagnesemia; patients diagnosed with incomplete AV block may progress to complete block when treated with digoxin; exercise caution in hypothyroidism, hypoxia, and acute myocarditis
Table : Secondary prevention of rheumatic fever.
Agent Therapeutic Scheme Benzathine penicillin G 1,200,000 U every 4 weeks*, IM or
Penicillin V
250mg twice daily, PO or
Sulfadiazine
500mg once daily for patients < 27kg; 1g once daily for patients > 27kg, PO
For individuals allergic to penicillin and sulfadiazine:
Erythromycin
250mg twice daily daily, PO
*In high-risk situations, administration every 3 weeks is recommended.
Table. Guidelines for Bed Rest and Ambulation and Recommended antiinflammatory agents
Bed Rest
Arthritis alone
Carditis minimal
Carditis Carditis moderate severe
1-2 wk
2-3 wk
4-6 wk
2-4 mo
I d Indoor ambulation b l ti
1 2 wkk 1-2
2-3 2 3 wkk
4-6 4 6 wkk
2-3 2 3 mo
Outdor activity ( (school) )
1-2 wk
2-3 wk
4-6 wk
2-3 mo
Full activity
1-2 wk
2-3 wk
4-6 wk
2-3 mo
Prednisone Aspirin
0 0
0 0
2-4 2 4 wk 2-4 wk
2 2-6 6 wk 2-6 wk
Minimal Carditis Questionable cardiomegaly ; Moderate carditis definite but mild cardiomegaly, Severe carditis, marked cardiomegaly or CHF
Complications Carditis Mitral stenosis Congestive heart failure (CHF)
Prognosis Sequelae q are limited to the heart and are dependent upon the severity of the carditis during the acute attack. .
Rheumatic Heart Disease
Rheumatic heart disease is the most serious complication of rheumatic fever. A t rheumatic Acute h ti fever f ffollows ll 0 3% off cases off group A 0.3% beta--hemolytic streptococcal pharyngitis in children. As beta many as 39% of patients with acute rheumatic fever may develop varying degrees of pancarditis with associated valve insufficiency, heart failure, pericarditis, and even death. With chronic rheumatic heart disease, disease, patients develop valve stenosis with varying degrees of regurgitation, atrial dilation, arrhythmias, arrhythmias, and ventricular dysfunction. dysfunction. Chronic rheumatic heart disease remains the leading g cause of mitral valve stenosis and valve replacement in adults
Frequency: In the US: Prevalence of rheumatic heart disease in the United States now is less than 0.05 per 1000 population Internationally: Th incidence The i id off rheumatic h i ffever and d rheumatic h i h heart di disease h has not decreased in developing countries. Retrospective studies reveal developing countries to have the highest figures for cardiac involvement and recurrence rates of rheumatic fever. fever Estimations worldwide are that 5-30 5 30 million children and young adults have chronic rheumatic heart disease, and 90,000 patients die from this disease each year. There were no data available in Indonesia
Mortality/Morbidity: Rheumatic heart disease is the major cause of morbidity from rheumatic fever and the major cause of mitral insufficiency and stenosis in the Indonesia and the world. Variables that correlate with severity y of valve disease include the number of previous attacks of rheumatic fever, the length of time between the onset of disease and start of therapy, and sex. (The disease is more severe in females than in males.) Insufficiency from acute rheumatic valve disease resolves in 60-80% of patients who adhere to antibiotic prophylaxis.
Race: The race (when controlled for socioeconomic variables) has not been documented to influence disease incidence.
Sex: Rheumatic fever occurs in equal numbers in males and females, but the prognosis is worse for females than for males.
Age: Rheumatic fever is principally a disease of childhood, with a median age of 10 years, although it also occurs in adults d lt (20% off cases). ) Socio-economic factors : It is well known that socioeconomic and environmental factors play an indirect, but important, role in the magnitude and severity off RF and RHD. Such S factor f as a shortage off resources for providing quality health care, inadequate expertise p of health-care p providers,, and a low level of awareness of the disease in the community can all impact the expression of the disease in populations. Crowding adversely affects rheumatic fever incidence
Cardiac manifestations of chronic rheumatic heart disease : • Valve deformities, • thromboembolism, • cardiac hemolytic anemia, and • atrial arrhythmias are the most common cardiac manifestations of chronic rheumatic heart disease. Valve deformities • Mitral stenosis – Mitral regurgitasi occurs in 25% of patients with chronic rheumatic heart disease and in association with mitral insufficiency in another 40%. • Aortic regurgitasi g g – Aortic stenosis are typically yp y from chronic rheumatic heart disease. The valve commissures and cusps become adherent and fused, and the valve orifice becomes small with a round or triangular g shape. p
• Thromboembolism occurs as a complication of mitral
stenosis. t i It is i more likely lik l tto occur when h th the lleft ft atrium ti is dilated, cardiac output is decreased, and the patient is in atrial fibrillation. • Cardiac hemolytic anemia is related to disruption of the red blood cells by a deformed valve. Increased d t ti and destruction d replacement l t off platelets l t l t also l may occur. • Atrial arrhythmias typically are related to a chronically enlarged left atrium (from a mitral valve abnormality). Successful cardioversion of atrial fibrillation to sinus rhythm is more likely to be successful if the left atrium is not markedly enlarged, the mitral stenosis is mild, and the patient has been in atrial fibrillation for less than 6 months.
TREATMENT 1.
2.
3.
4 4.
M di l Care: Medical Care C : Medical therapy is directed toward eliminating the group A strepto coccal pharyngitis Treatment of the acute inflammatory manifestations of acute rheumatic fever consists of administering salicylates li l t and d steroids. steroids t id . If moderate moderate--toto-severe carditis is indicated by cardiomegaly, g y, congestive g heart failure,, or thirdthird-degree g heart block, oral prednisone should be added to salicylate therapy. therapy. Preventive and prophylactic therapy is indicated after rheumatic fever and rheumatic heart disease to prevent further damage to valves.
TREATMENT Surgical Care: When heart failure persists or worsens after aggressive medical therapy for acute rheumatic heart disease disease, surgery to decrease valve insufficiency may be life life-saving. Forty percent of patients with acute rheumatic fever subsequently develop mitral stenosis as adults. In patients with critical stenosis, mitral valvulotomy, percutaneous balloon valvuloplasty, p p y, or mitral valve replacement may be indicated. Due to high rates of recurrent symptoms after p y or other repair p procedures, p , valve annuloplasty replacement appears to be the preferred surgical option.
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