RHEUMATISM , INFECTI VE ENDOCARDITIS

1. RHEUMATISM,INFECTIVE ENDOCARDITIS Prof. Vatutin N.T.

2. RHEUMATISM

3. Definition: The rheumatism (a Rheumatic fever) is systemic, immune, aseptic inflammatory disease which affect the connecting tissue and develops as a deferred consequence of Streptococcal (usually pharyngeal) infection. It affects joints, central nervous system, skin and subcutaneous tissues, but the most serious its complication is heart damage.

4. Epidemiology: In most cases rheumatism begins at the age of 5-15 years. More often (70 %) it affects women. In the past 30-40 years the incidence of rheumatism has decreased significantly in USA and Europe, however it is still common and widespread in developing countries. Rheumatic heart disease remains a leading cause of the valve insufficiency, of disability and mortality of the population, especially in children and young adults.

5. Etiology The rheumatism is caused by Lancefield Group A beta-hemolytic Streptococcus. The most common “gate” of streptococcal infection is the throat (streptococcal pharyngitis). In development of disease the certain role play genetic (presence of alloantigenes against B-lymphocytes) and social (poor financial-household conditions) factors.

6. Pathophysiology: The mechanism, according to which streptococcus starts the pathological process, remains unclear. Although M-serotype β-hemolytic streptococcal antigens are revealed to be structurally similar to those in the human heart. When such serotypes involve into human organism, the immune system produces the antistreptococcal antibodies, which may cross react with heart valve tissue (because of antigenic mimicry) and some other organs.

7. Pathological anatomy The rheumatism leads to systemic inflammatory damage of connective tissue, however the most severe pathologic changes can be found in the heart. Three stages of such lesion can be histologically allocated: • mucoid swelling; • Аshoff-Таlаlаеv’s granulomas; • fibrosis and sclerosis.

8. Classification In classification of rheumatism should be specified: • Phase of disease (acute - «acute rheumatic fever», chronic - «chronic rheumatic heart disease»); • Activity of inflammatory process (active – the I, the II or the III degree, inactive); • Clinical manifestations of the disease (carditis, arthritis, Sydenham’s chorea, erythema marginatum, subcutaneous nodules etc.); • Complications (the presence or absence of the heart valve deformities); • Presence and severity of heart failure (stage, functional class)

9. Clinical manifestations In typical cases the rheumatism begins (starts, recurrens) in 1-3 weeks after antecedent streptococcal infection. Among general symptoms of disease are marked a fever, weakness, fatigue, sweating, anorexia, weight-loss. The basic signs of rheumatism are: • carditis; • polyarthritis; • Sydenham’s chorea; • erythema marginatum; • subcutaneous nodules.

10. Carditis All structures of heart are involved into inflammatory process - endocardium, myocardium and pericardium. The following signs are specific for carditis: • Occurrence new or change of old noises; • Inappropriate to a fever tachycardia; • Cardiomegaly; • Rhythm of gallop; • Arrhythmias and conduction disturbances of heart; • Rubbing noise of pericardium; • Occurrence or intensifying of heart failure; • Formation of heart affects.

11. Polyarthritis At acute flow of disease typical reactive synovitis with sweat into joint’s cavity develops, edema and hyperemia of periarthicular tissues can be observed, expressed pain and restriction of movements are present. The defeat of large joints of extremities is typical, it can be migratory, flying character arthritis, the process is usually symmetry. The arthritis is complete and fast convertibility under influence of treatment. Enough frequently, especial at repeated attacks of rheumatism polyarthritis can be present.

12. Chorea It is a sign of rheumatic lesion of the central nervous system, which is characterized by muscle weakness, aimless and chaotic movements, emotional instability. In severe cases there can be frustration of walking, paralyses, loss of ability to movement. It is interesting, that chaotic and involuntary bounces of muscles of extremities and mimic muscles disappear during slipping.

13. Erythema marginatum represents by itself rose-red stains up to 5-7 см in a diameter ring-shaped (less often stellation) forms which are turning pale at pressing, not accompanying with itch and packing of skin. Typical localization is on stomach, breast, back, extremities. The spontaneous disappearance and rare recurrence are the characteristic features of this sign.

14. Subcutaneous nodules represent by themselves dense, round, painless formations in periarthricularis tissues with size from several millimeters up to 1-2 sm. They are observed seldom, basically at the patients with recurrent rheumocarditis. They can disappear in some days (weeks).

15. Other features Extremely seldom rheumatic polyserositis develops. It can be pleuritis, peritonitis, pericardiotis, vasculitis with defeat of lungs and kidneys.

16. Additional methods of research The laboratory data. The specific tests, which are characteristic for rheumatism are not present, however with the help of the laboratory data it is possible to determine presence of inflammatory process and degree of its expression. Particularly, in patients suffering from active rheumatism in blood quite often can be revealed: • Leukocytosis (neutrophilia); • Raised ESR; • Raised C-reactive protein; • Increased level of antistreptococcus antibodies ASL-O, from the throat of such patients frequently Group А β-haemolytic streptococci can be seeded.

17. ECG The various arrhythmias (sinus tachycardia, bradycardia, extrasystolic arrhythmia, atrial fibrillation) and blockades, particularly prolonged PQ-interval more than 0.2 msec with carry can be observed. (minor diagnostic criteria of rheumatism).

18. Echo-CG The method is descriptive in revealing of carditis and valvular abnormalities, it is especial used in dynamics. The signs of rheumatic endocarditis are regional thickening of valvular leaves, valve regurgitation.

19. X-ray It is usually used to specify the character of heart defects, to reveal serositis, pneumonitis, haemodynamic changes, and also in differential diagnostics. At the same time there are no specific for rheumatism X-ray changes.

20. Diagnosis Criteria of T.D.Jones Major criteria: • carditis; • polyarthritis; • Sydenham’s chorea; • erythema marginatum; • subcutaneous nodules. Minor criteria: • fever, • raised ESR or CRP, • arthralgia (but not if arthritis is one of the major criteria) • prolonged P-R interval (but not if carditis is major criteria) • previous rheumatic fever. • The diagnosis of rheumatism is considered probable at the patients who have recently transferred streptococcus infection, at presence at them two major or one major and two minor criteria.

21. Differential diagnosis Rheumatism has to be differentiated with infective endocarditis, autoimmune connective tissue diseases, first of all, with systemic lupus erythematosus, juvenile rheumatoid arthritis, reactive arthritis, serous disease, measles, sarcoidosis, hemorrhagic vasculitis and some other diseases.

22. Management • Treatment of active rheumatism must be carried out in a special-purpose hospital. Bed regimen until CRP becomes normal for two weeks (may be 3 month). • Benzylpenicillin - 2 weeks • Aspirin. Alternative: NSAIDs (indometacin, voltaren, ibuprofen) - 3-5 months . • Corticosteroids (prednisolon). They are usually used at acute rheumocarditis and the high activity recurent rheumocarditis (1-3 mg/kg/d of, then dose can be reduced). • Joints immobilization in case of severe arthritis. • Haloperidol or diazepam can be used for the chorea. • At occurrence of heart failure, arrhythmias or blockades the appropriate treatment should be prescribed.

23. Prognosis In 60% of patients with carditis chronic rheumatic heart disease is usually developed. This correlates with the severity of the carditis. Acute attacks last an average of 3 months. Recurence may be precipitated by further streptococcal infections, pregnancy, or use of the Pill. Cardiac sequelae affect mitral (70%), aortic (40%), tricuspid (10%), and pulmonary (2%) valves.

24. Primary prophylaxis • Improvement of social conditions of life of the population; • Propagation of a healthy life style (sports activities); • Obligatory treatment of acute streptococcal infections by antibiotics. For this purpose penicillin, or amoxicillin, or erythromycin can be used.

25. Secondary prophylaxis • The American Rheumatological College at presence of rheumocarditis recommends continuous preventive bicillinotherapy during 10 years (or up to 25-year's age of the patient); without rheumocarditis - 5 years (or up to 18-year's age). • Infective endocarditis prophylaxis.

26. INFECTIVE ENDOCARDITIS

27. Definition Infective endocarditis (IE)is an inflammation of heart valves and endocardium due to direct influence of infective agent.

28. Epidemiology The frequency of IE changes from 0.16 up to 5.4 cases on 1 thousand of the patients, who were hospitalized. Most vulnerable considers a population in the age of 20- 50 years. IE occurs in males 3 times more often than in females. For the last quarter of XX century the increase in morbidity is registered. The reasons are: • surgical interventions on heart; • intravascular devices and procedures; • drug addiction.

29. Etiology The cause of IE can be any infectious agent, but more often it can be • streptococci(30-80 %), • staphylococci (20-35 %) • enterococci (5-15 %). Less often IE is caused by other microorganisms, fungi.

30. Pathogenesis It is considered that IE develops under influence of some factors. For example, it can be at weakening of bacterial resistance, high virulence of infectious agent. But the most significant are two of them: • Damage of endothelium of heart valves or epistenotic endocardium. • Bacteremia (transient or long).

31. Causes of endothelium damage: • congestive or acquired valvular diseases; • prothetic valves; • placement of an intravascular line (eg, Swan-Ganz catheter). • Bacteremia can result from various invasive procedures: oral, otolaryngologic, genitourinary surgery, infected injury of extremities

32. The initial lesion involves the deposition of fibrin and platelets in areas of damaged endothelium, producing a nonbacterial thrombus. It could be infected during a bacteremic episode with formation of vegetation. The infective agent can reproduce, and hide from macro-organism’s immune system and antibiotics inside vegetations - at valvular leaflets or outside – in fibrin thrombus.

33. Infected vegetation is a dynamic formation. It can damage valvular leaflets and epistenotic endocardium, enlarge, divide, occasionally or permanently eject a big amount of infective agent into the blood, what leads to appearance of septic areas in organs and systems. The most common areas of deposition are the coronary arteries, kidneys, brain, and spleen. Further persistent bacteremia stimulates cellular and humoral immunity and starts up immuno-mediated mechanism of inflammation.

34. Pathological anatomy Pathomorphological base of IE is a polypoulserosa endocarditis. More often are damaged aortic and mitral valves with destruction of shutters and formation of insufficiency, less often (approximately at 6 %) - tricuspid (as a rule, at drug addicts or persons who receive cytostatics). In many organs (kidneys, spleen, lungs, brain) can be found the septic centers and infarctions caused by dissemination of infection and emboli (by fragments of destroyed shutters and vegetations).

35. Classification According to the recommendations of European cardiological society (2004) there are active, healed and recurrent IE. Secondary IE develops on the background of congenital or acquired valvular diseases. Initial IE occurs in people without cardiac pathology. IE can be caused by Streptococci, Staphylococci, Fungi etc.IE of prothetic valves is divided into early (during the year after the operation) and backward IE.

36. Clinical features The main signs of IE are : • fever; • emboli; • haemorrhage rash; • valvular leaflets destruction. In most cases IE are developed in some days after invasion of infective agent (for example, after dental procedures, in case of infected wounds, illegal abortion etc.).

37. Fever as a rule, is hectic, accompanied by sweats and algor. Approximately 8-10% of patients with IE (primarily elderly and chronically ill individuals) have normal or subnormal temperature.

38. Emboli are observed in 15-60 % of the patients. They result from breakaway of infective vegetations or parts of destroyed valves. Their localization is quite different - cerebral arteries, spleen, kidney, coronary arteries, retinal arteries and so on. Further infarctions, abscess and septic aneurysms form in zones of embolization.

39. Haemorrhage rash It is caused by microthrombosis and vasculitis - petechial skin rash, Osler nodes,Janeway lesions and Roth spots.

40. Valvular leaflets destruction The onset of illness is abrupt, with rapidly progressive destruction of the infected valve. The valvular leaflets are destroyed rapidly by bacteria that multiply rapidly within the ever-growing friable vegetations. More frequently the left heart involves in the process, the right part involves rarely. Appearance or transformation of heart murmur at auscultation gives the opportunity for early diagnostics of IE.

41. Other clinical features • Heart: besides endocarditis - myocarditis, pericarditis, abscess and heart attacks, heart failure; • Kidneys: artery embolism, infarction, abscess, pyelonephritis, glomerulonephritis, amiloidosis, renal failure; • Brain: emboli, septic aneurysm, abscess, encephalitis, meningitis; • Spleen: splenomegaly, infarction, abscess; • Liver: hepatitis; • Musculoskeletal system: myalgia, arthralgia, arthritis (including septical), osteomyelytis.

42. Additional methods of investigationLaboratory studies The criterion standard test for diagnosing IE is the documentation of bacteremia based on blood culture results. Frequently can be revealed: • anemia; • thrombocytopenia; • high level of ESR; • leucocytosis; • neutrophylesis; • pathological changes in urine.

43. ECG Changes at IE are nonspecific. At the quickly destroying of valves is possible the appearance of acute overload of the left or right heart.

44. Echocardiography diagnostic method of choice, especially in patients who present with clinical picture of IE but who have nondiagnostic blood culture results. Vegetations are usually formed after 2-3 weeks from a beginning of disease and are kept within several months after recovery. Unfortunately, at transthoracic echocardiography as a rule, are visible vegetations of the size 5 mm and more, only.

45. The diagnostic criteria of IE • Fever; • Heart murmur; • Emboli; • Bacteremia; • Vegetations. The absence of the vegetations makes the diagnosis IE probable, and the absence of bacteremia makes it possible.

46. The differential diagnosis As the signs of IE are rather various, it should be differentiated with many diseases, more often with systemic lupus erythematosus, vasculitis, atrial myxoma, rheumatism, cardiologic, haematologic, nephrologic and neurologic pathologies.

47. Treatment The base of the therapy are bactericidal antibiotics in bactericidal doses. Antibiotic therapy should be started as soon as possible to minimize valvular damage. The choice of antibitiotic depends on infective agent and its drug sensitivity. If the etiological agent is not known, empirically benzilpenicillin (10-30 mln МЕ/d iv, im through 4 h)is administered in combination with gentamycin (240 mg/d. IV, IM each 8h). Reserved antibiotics are vancomycin combinated with gentamycin.

48. For IE caused by streptococci, the following regimens are recommended: benzilpenicillin or ampicillin in a combination with gentamycin, vancomycin or cefalosporins. • For IE caused by S. aureus oxacillin, kaficillin, methyciclin, vancomycin or cefalosporins are used. Rather effective is vancomycin in combination with gentamycin or rifampicin. • For IE caused by gram-negative organisms are used cefalosporins, ampicillin, gentamycin or doxicycline. • For fungal IE amphotericin B therapy and fluocytosine are used. As a rule antibiotic treatment lasts during 4-8 weeks.

49. Indications for surgical intervention • Fungal IE; • Recurrent septic emboli; • IE of prothetic valves; • Congestive heart failure refractory to standard medical therapy; • Recurrent or repeated IE; • Conduction disturbances caused by a septal abscess or pyogeneous pericarditis.

50. Clinical course and prognosis for a disease At duly diagnostics and adequate antimicrobial therapy at the majority of the patients affected with IE after 3-5 days after the beginning of treatment can be observed reduced temperature. The 5-year's probability of survival achieves 70 %. The most favourably are endocarditis, which are caused by alpha-haemolytic streptococcus. The highest mortality (up to 80 % and more) is observed at fungi endocarditis. Without treatment IE, as a rule, is fatal.