Просмотров: 7 964

Acute Rheumatic Fever

Irina Alexandrovna Zborovskaya – doctor of medical sciences, professor,cathedral professor of hospital therapy with the course of clinical rheumatology of the doctors improvement faculty of Volgograd state medical university, director of the Federal Budgetary State Institution (FBSI) “Research and development institute of clinical and experimental rheumatology” of the RAMS, head of the regional Osteoporosis Center, presidium member of the Association of rheumatologists of Russia, member of the editorial boards of the magazines “Scientific and practical rheumatology” and “Modern rheumatology” Definition. Acute rheumatic fever (ARF) is a systemic disease of the connective tissue which can develop in relation to group A streptococcal pharyngitis. It often occurs in predisposed people in relation to autoimmune response to group A streptococcal epitope and cross-reactivity which are identical to human tissue epitopes which are found in the skin, joints, heart and brain. Epidemiology. The incidence of acute rheumatic fever in Russia is 0.03 and the incidence of rheumatic heart disease is 0.065 cases per 1000 population. The incidence of rheumatic acute fever and rheumatic heart disease among children and adolescents (teenagers) is 0.5 – 1.3 cases per 1000 population. The incidence of rheumatic acute fever and rheumatic heart disease among adults is 3 cases per 1000 population. At the beginning of the 90-s as many as 0.96 cases per 10 000 population were found to be disabled due to rheumatic heart disease. Clinical manifestations of rheumatic acute fever have changed dramatically. Now 44 – 60 % of new cases occur when chorea, carditis, and arthritis are specific clinical manifestations of primary rheumatism. These cases usually result in the development of heart disease in 30% of patients with undetected acute rheumatic fever. The peak age of acute rheumatic fever is 7 – 15 years. Girls and females are more likely to develop acute rheumatic fever (up to 70%) than boys and males. First-degree relatives of patients with acute rheumatic fever also have an increased frequency of the disease. Aetiology and pathogenesis. ARF is caused by group A beta-hemolytic Streptococci. Inflammation of the upper respiratory tracts typically caused by group A beta-hemolytic Streptococci results in the development of rheumatic inflammation. Three aspects in the pathogenesis of acute rheumatic fever should be focused on. They are the following: common features of the causative agent, specific features of the interaction between group A Streptococci and the human body as well as peculiarities of the human body in which the disease develops. 1. Infection. Group A beta-hemolytic Streptococci (Streptococcus pyogenes, Sptreptococcus haemolyticus) are presented by 80 various strains. Virtually, acute rheumatic fever is caused by some of them. M1, M3, M5, M6, M14, M18, M19, M24, M27, M29 strainsseem to be most likely to result in acute rheumatic fever. Group A Streptococcus antigens which can cross-react with tissue antigens of the human body are thought to play an important role in induction of autoimmune reactions. Nowadays similar antigenic structures are known. They are the following: cellular membrane of group A Streptococcus, muscular cells of the myocardium (cardial myosin, sarcolemma of cardiomyocytes, fibroblasts of the connective tissue of the heart) and its vascular wall. Other similar antigenic structures are structural glycoprotein of the connective tissue of heart valves, cytoplasm of subthalamic and caudate nuclei of the brain, epithelium of cortical and medullar areas of the thalamus. The idea of the presence of “antigen mimicry” between antigen determinants of Streptococcus components and human tissues enables us to the explain the variety of clinical manifestations of rheumatism. 2. Genetic predisposition. 3 – 4% of people who suffered from respiratory infection develop rheumatism in case of epidemic and 0.3% of patients develop rheumatism in sporadic cases. Family incidence is 3 times more than the population incidence, suggesting genetic predisposition to rheumatism. Acute rheumatic fever is associated with the presence of B-lymphocytes alloantigen D8/17, which is found in 96.0 – 98.0% of patients with rheumatism, in 40.3% of healthy kinsmen (relatives by blood), in 66.7% of children whose mothers suffer from rheumatism, in 11.8% of relatives by marriage and in 9.5% of healthy people. Studying the association of acute rheumatic fever with certain HLA antigens enabled us to obtain a great variety of findings depending on peculiarities of the studied populations. There is evidence that acute rheumatic fever is associated with HLA  A11, B35, DR2, DR4, DR7 antigens. In patients with mitral valve involvement HLA  A3 is most commonly the cause of acute rheumatic fever. However, in patients with aortic valve involvement it is HLA B15 that is responsible for rheumatic acute fever 3. Body susceptibility. Besides genetic predisposition, body susceptibility to Streptococcus plays an important role in the development of rheumatic inflammation, i.e. (that is) repeated infection of the body by the causative agent. It is accounted for by the fact that children under 3 years of age do not have rheumatism. 4. Systemicity of lesions. 1. Systemic lesions are caused by prolonged circulation of forming immune complexes and their fixation in organs and tissues. 2. Multiple intracellular and extracellular (exoenzymes) antigens of Streptococcus have a direct unfavourable effect on human body tissues and myosin of muscular fibers. They also interfere with immune regulation resulting in the development of an immunopathologic process. Pathomorphology. Four stages are singled out in the development of a pathologic process in the connective tissue. They are the following: 1. Mucoid swelling: depolimerization and breakdown of glycosaminoglycans of the ground substance of the connective tissue as well as accumulation of hyaluronic acid. The changes occurring at this stage are fully reversible. 2. Fibrinoid swelling: an amorphous mass, called fibrinoid, is formed which is precipitated in tissues resulting in the appearance of local foci of necrosis. 3. Granulematosis (formation of rheumatic granulomas or Aschoff’s bodies/nodules): proliferation of connective tissue cells around the foci of fibrinoid necrosis. Granulomas consist of large, irregular basophile cells of histiocytic origin, gigantic multicellular cells of mitogenic origin with eosinophile cytoplasm, cardiohystiocytes (Anitschkow myocytes) with typical arrangement of chromatin, lymphoid and plasmatic cells, labrocytes (mast cells), single leukocytes. The duration  of the development of granuloma is 3 to 4 months. It is considered to be a specific morphologic feature of rheumatic carditis. 4. Sclerosis and hyalinosis. Morphologic peculiarities of various tissues. 1. Heart: edema of the intermuscular connective tissue, fibrin effusion, infiltration by cellular elements, mainly by polymorphonuclear leukocytes and lymphocytes. 2. Muscular fibers: hypertrophy, atrophy, different kinds of dystrophy and necrobiosis resulting in lysis. 3. Endocardium (valve involvement): development of severe deformative sclerosis. Mitral valve is most commonly affected. Aortal valve ranks second and tricuspid valve is the least commonly affected. 4. Articular tissues: disorganization of the connective tissue, exudative inflammation, vasculitis resulting in moderate fibrosis. 5. Subcutaneus fat: rheumatic nodules 0.5 – 2.5 cm in diameter may occur. However, they typically disappear within a month. 6. Serous membranes: serous, serous-fibrinous and fibrinous inflammation. 7. Lungs: vasculitis and perivasculitis; infiltration of alveolar septa by lymphoid-hystiocytic elements; protein membranes on the internal surface of alveoli. Sometimes small foci of fibrinoid necrosis with large cell proliferation may be found (Masson bodies). 8. Kidneys: inflammation and sclerotic changes in vessels and focal, less commonly diffuse glomerulonephritis. 9. Nervous system: vasculitis of the vessels of microcirculatory bloodstream, atrophic and dystrophic changes of ganglious cells (in chorea). Lympho-hystiocytic infiltrates are found in pia mater, in the stroma of sensory ganglia, endoneurium and perineurium. Management. In most cases patients develop signs or symptoms of acute rheumatic fever in 1.5 – 4 weeks following streptococcal nasopharyngeal infection. The patients often complain of fever, malaise, fatigue, hyperhydrosis, anorexia and decreased body weight. The severity of the initial stage of this condition depends on the patient’s age. In 50% of cases in 2 – 3 weeks following tonsillitis children may have increased temperature, symmetric migrating pain in large joints (most commonly in knee joints) and clinical sings of carditis (pericardial pains, dyspnea, palpitation, etc.). Outbreaks of acute rheumatic fever have also been reported in older schoolboys who had beta-hemolytic streptococcal tonsillitis. Other children develop a monosyndromal course of acute rheumatic fever with predominance of clinical signs of arthritis, carditis or chorea (less commonly). Adolescents and young adults typically have a gradual onset of the disease. They usually have increased temperature, pain in large joints or clinical signs of carditis following tonsillitis. An exception includes recruits (soldiers) who had epidemic beta-hemolytic streptococcal tonsillitis. They typically have an acute onset of the disease. The initial stage of the disease is followed by the extensive one. Heart involvement which determines nosologic specificity of the process and the outcome of the disease is the most significant clinical presentation. Rheumatic carditis is characterized by involvement of all cardiac membranes. Myocardium involvement is typical of this condition, although the findings on the incidence of myocardium involvement are controversial. Rheumatic heart disease may be primary (first attack) and recurrent (recurrent attacks). Rheumatic heart disease may be characterized by valve involvement as well. Children with primary rheumatic fever develop carditis in 79 – 83% of cases, adults – in 90 – 93% of cases. Adults with recurrent acute rheumatic fever develop rheumatic heart disease in 100% of cases. Rheumatic heart disease is characterized by consistent involvement of myocardium, endocardium and pericardium into a pathologic process. The person may develop isolated diffuse or focal myocarditis, endomyocarditis or pancarditis. Rheumatic heart disease is manifested clinically by the involvement of cardiac membranes, active rheumatic process and the specific character of the course of the disease:
  • dyspnea and orthopnea (they may be absent in mild or moderate carditis);
  • cardialgia is characterized by prolonged stabbing, dull pain in the area of the heart, typically without irradiation. It is also manifested clinically by the sense of heaviness in the area of the heart;
  • cardiomegalia (in primary carditis cardiac enlargement is revealed in 31% of cases, in recurrent carditis – in 63% of cases);
  • decreased myocardium contractility (it is most commonly revealed with the help of echocardiography);  in primary carditis decreased myocardium contractility is found in 21% of cases, in recurrent carditis in 31% of cases;
  • arrhythmia: sinus tachycardia, atrial fibrillation (most commonly in stenosis of the mitral valve), superventricular or ventricular (less commonly) extrasystole, atrioventricular heart block.
The most significant finding of rheumatic heart disease is considered to be valvulitis which is manifested clinically by new or changing heart murmurs while the size of the heart remains unchanged. The changing heart murmurs may be of the following frequency:
  • Low-frequency middiastolic murmurs. They are best heard in the left lateral decubitus at an expiration after holding your breath. They are most commonly heard after the 3rd heart sound or they may fuse with it.
  • Basal protodiastolic murmurs are typical of aortal regurgitation. They are typically heard right after the 2nd heart sound. These are high-frequency heart murmurs and have a blowing, subsiding nature. They are best heard along the left margin of the breastbone after a deep expiration when the patient bends forward.
As a result of rheumatic valvulitis, the person may develop heart disease. People usually have mitral valve involvement in 78% of cases, aortal valve involvement in 7% of cases and both valves are involved in 20% of cases. Pericarditis is most commonly associated with pancarditis, pleuritis or pneumonia. Two forms of pericarditis are singled out:
  • acute fibrinous (pericarditis sicca) pericarditis. It is characterized by an acute onset, severe pain (sometimes retrosternal pain, abdominal pain), fever, pericardial murmurs.
  • exudative (serous) pericarditis. It is characterized by coronary pain, dyspnea (corresponding to the amount of fluid), tachypnea, orthopnea. As soon as fluid is accumulated, the pain subsides, pericardial friction rub subsides or disappears, muffled heart sounds are heard.
Rheumatic polyarthritis is common reactive synovitis characterized by effusion of fluid into the articular cavity. It is manifested clinically by swelling and reddening of periarticular tissues, less commonly by severe pain, tenderness and limited range of active and passive motions. Major manifestations include:
  1. Involvement of large joints;
  2. Symmetric involvement;
  3. Migratory, shifting nature of arthritis;
  4. Reversibility of the articular syndrome.
Juvenile [rheumatic, Sydenham’s] chorea is most commonly observed in children. It may precede the first rheumatic attack, may be associated with it or may develop following it. Chorea is characterized by a number of symptoms: hyperkinesia, muscular dystonia, statics and coordination disturbances, vascular dystonia, mental disorders. Hyperkinesis of muscles associated with their hypotonia is typically the first manifestation. Clinical presentations include chaotic involuntary twitching of the musculature of the extremities and mimic muscles. The symptoms subside when the patient sleeps. Choreic hyperkinesia increases when the person is excited and less commonly on physical exertion. Erythema annulare is manifested clinically by pale pinkish-red spots 5 – 7 cm in diameter with well marked, not always even margins. The edges of the spots usually protrude above the surface of the skin and become pale under pressure. The spots are usually localized at the abdomen, back, breast and extremities. They most commonly occur in 6 – 12% of patients. Subdermal rheumatic nodules are grain or pea-sized lesions which are typically localized at periarticular tissues. They may occur in rheumatic attack (they are observed in 3 – 6% of patients). They usually do not cause concern in patients. They are painless and the skin above them does not change. Rheumatic pneumonia or pulmonary vasculitis is found mainly in children. It is manifested clinically by dyspnea, poorly marked auscultative symptoms, cough, fever and sputum. X-ray examination enables us to reveal small multiple foci of sclerosis or a bilateral periapical process which  resembles “butterfly’s wings”. Vasculitis is manifested clinically by cough, blood spitting, moist rales on auscultation without any changes revealed on percussion. Diffuse enhancement of lung pattern is observed on X-ray. Rheumatic pleuritis is most commonly bilateral. It is characterized by pain in the chest, cough, dyspnea. On auscultation the doctor usually reveals pleural friction rub and crackling rales. Abdominal syndrome is a rare sign of the disease in children. It is often associated with rheumatic peritonitis. It is characterized by a sudden appearance of diffuse or localized pains in the abdomen and associated with nausea or less commonly vomiting, constipation  or diarrhea. Pains are migrating, varying in extent, often associated with fever, slight tension of the muscles of the abdominal wall, tenderness on palpation. Peritoneal symptoms disappear within several days, and usually there are no recurrences. Renal manifestations are various. They vary from urinary syndrome (albuminuria, hematuria) caused by infectious nephritis to diffuse glomerulonephritis. Skin manifestations are also common features, for example, cellulitis, eye manifestations (conjunctivitis, episcleritis), endocrine manifestations. In order to determine the activity of the inflammatory process the following laboratory data are considered:
  • White cell count – moderate neutrophile leukocytosis;
  • Elevated erythrocyte sedimentation rate (ESR);
  • Non-specific reactions of the connective tissue:
–         Increased amount of alfa2-globulins >10% (more than 10%); –         Increased amount of gamma-globulins >20% (more than 20%); –         Increased amount of plasma fibrinogen (>0.5 g%); –         Elevated C-reactive protein; –         Progression of the values yielded by diphenylamine test; –         Increased amount of  seromucoid. For definitive diagnosis other lab tests, such as bacteriological analysis of the throat swab may be helpful. It helps to reveal beta-hemolytic Streptococci (BHSC). However, positive results of microbiologic tests do not indicate true infection from mere carriage of the organism. Commercially distributed group A streptococcal antigen detection kits for a rapid estimation of BHSC-antigens are often used. Serologic tests indicate high titres of anti-streptococcal antibodies, such as antistreptolysin-O (ASO), antistreptokinase (ASK), antistreptohyaluronidase (ASG) and, what is more important, an elevated titer of these antibodies. Diagnosis. Making a diagnosis of acute rheumatic fever is somewhat difficult, because there are not any specific tests for definitive diagnosis. Diagnostic criteria of rheumatism developed by Kisel-Johnes and supplemented by Nesterov, have been used since 1940. They have been revised by the American Heart Association (AHA) American Rheumatology Association. Diagnostic criteria of rheumatism developed by Kisel-Johnes and revised by the American Rheumatology Association (2003).
Major manifestations Minor manifestations Lab tests indicating A-streptococcal infection
Carditis   Polyarthritis   Chorea   Erythema annulare   Subdermal rheumatic nodules Clinical manifestations: – arthralgias; – fever. Laboratory studies: – elevated acute phase reactants: – elevated ESR; – elevated C-reactive protein; Other tests: – prolonged PR interval; – symptoms of mitral/aortal regurgitation on Doppler-echocardiography. A throat culture with positive results for Streptococcus or positive results of a rapid estimation of BHSC-antigens.   Increased or increasing titres of antistreptococcal antibodies, such as ASO, anti-DNAase B.
Presence of at least two major manifestations or one major and two minor manifestations combined with laboratory tests indicating prior history of group A streptococcal infection testifies to a high probability of acute rheumatic fever. However, there are some special cases: 1) an exception includes chorea, which can present as the sole manifestation of acute rheumatic fever; 2) another possible exception is indolent carditis with valvulitis which typically develops within 2 months and can present as the sole manifestation of acute rheumatic fever; 3) recurrent acute rheumatic fever associated with rheumatic heart disease (or without it). Classification of ARF
Clinical forms Activity criteria Extent of activity Outcome Stage of CF

Basic criteria

Additional criteria
Acute rheumatic fever Carditis associated with heart involvement   Carditis without any heart involvement   Arthritis   Chorea   Erythema annulare   Rheumatic nodules   Arthralgias   Abdominal syndrome   Serositis III   II   I Without heart disease               Rheumatic heart disease I


Recurrent rheumatic fever
Diagnosis: ARF: carditis, polyarthritis, extent of activity III, CFI. Recurrent rheumatic fever: carditis, extent of activity I, combined mitral valvular disease, CI II. Rheumatic heart disease: combined mitral-aortal valvular disease, CI II B. Rheumatic heart disease: rheumocarditis in past history.
Evaluation of the extent of activity
I degree II degree III degree
Early monosyndromal signs are typical. Indolent carditis is often observed. Neurological disorders, persistent arthralgias are common. Imaging Studies: cardiomegaly. Other Tests: coronary circulation disturbances, signs of myocardiosclerosis, arrhythmia (in recurrent rheumocarditis) are typical. Lab Studies: slightly elevated or normal ESR; C-reactive protein is not found or it is I plus; slightly elevated or normal gamma-globulin level; the values yielded by diphenylamine test are normal; the values of yielded by seromucoid test are also normal; titres of ASO, ASK, ASG are  normal. High temperature is an early clinical manifestation. Carditis may be associated with circulation disturbances of the 1st and 2nd degree. Early symptoms of polyarthritis, monooligoarthritis and chorea may be observed. Imaging Studies: cardiomegaly. Other Tests: arrhythmia, prolonged PQ interval, coronary circulation disturbances. Lab Studies: neutrophil leukocytosis 8*109 – 10*109; ESR – 20 – 40 mm/h. C-reactive protein is I – III plus; the amount of alfa2-globulins is 11 – 16%; the amount of gamma-globulins is up to 21 – 23%; the values yielded by diphenylamine test are 0.25 – 0.3; the values yielded by seromucoid test are 0.3 – 06; 1.5 elevation of ASO, ASK, ASG titres. Fever is considered to be the major clinical manifestation. Other findings include: migrating polyarthritis, diffuse myocarditis, pancarditis. Some symptoms of pleuritis, peritonitis, rheumatic pneumonia, glomerulonephritis, subdermal nodules, erythema annulare, and  chorea are typical.  Imaging Studies: cardiomegaly, decreased contractility of the  myocardium. Other Tests: arrhythmia and conduction disturbances. Lab Studies: neutrophil leukocytosis is higher than 10,0*109; ESR is more than 40 mm/h; C-reactive protein is III – IV plus; fibrinogen is more than 9-10 g/l; the values yielded by seromucoid test are more than 0.6; the values yielded by diphenylamine test are more than 0.35 – 0.5; the amount of alfa2-globulins is 17%; the amount of gamma-globulins is more than 23 – 25%; titres of ASO, ASG, ASK are 3 – 5 times higher than normal.  
Differential diagnosis. Rheumatism must be differentiated from diseases with similar clinical manifestations:
  • Rheumatoid arthritis
  • Juvenile rheumatoid arthritis
  • Gout, gouty arthritis
  • Gonorrheal polyarthritis
  • Viral polyarthritis
  • Reiter’s syndrome
  • Poststreptococcal reactive arthritis
  • Lane’s disease
  • Rubella
  • Lupus systemic erythematosis
  • Antiphospholipid syndrome
  • Nodular polyarteritis
  • Dermatomyositis
  • Löffler’s endocarditis
  • Subacute infectious endocarditis
  • Myocarditis
  • Abramov-Fiedler myocarditis

Treatment of rheumatism.

Methods of treatment. I. The treatment usually involves three main stages. They are the following: 1 stage. Treatment of the active phase of the disease in the hospital. 2 stage. Rehabilitation in a sanatorium or at home (the patient is put on sick-leave for some days). 3 stage. Regular medical check-ups and preventive treatment. II. Differentiation of active and inactive phases of the disease is important. III. Early diagnostics is beneficial (in early diagnostics the treatment is usually more successful). IV. Early initiation of treatment. V. Complex therapy (aetiological, pathogenetic, restorative, symptomatic). Inpatient treatment (1 stage). Common regimen: the patient should stay in bed during the period of acute and subacute manifestations of the disease as well as in severe carditis. In polyarthritis and chorea the patient should not stay in bed. Diet: N 10 Drug therapy:
  • Using the methods of desensitizating and anti-inflammatory therapy;
  • Restoring general reactivity of the body;
  • Symptomatic therapy (in circulatory insufficiency, etc);
  • Elimination of the foci of infection;
  • Functional therapy and rehabilitation.
Indications for the use of corticosteroids:
  • In primary carditis with the 2nd or 3rd extent of disease activity and associated with a well pronounced exudative component of inflammation. In this case the risk of heart disease is very high;
  • In patients with recurrent rheumocarditis with suspicion of progressing valvulitis;
  • At the decompensation stage where acute rheumatic fever is associated with active carditis.
The initial dose of Prednisone should be 0.7 – 0.8 g daily increasing it to 1.0 mg/kg daily. The maximum dose should not exceed 20 – 30 mg daily. After 2 weeks the dosage is reduced by 2.5 mg every 5 – 7 days until complete withdrawal of the drug. Non-steroidal anti-inflammatory drugs should be administered during this period to prolong the anti-inflammatory treatment up to 9 – 12 weeks. Non-steroidal anti-inflammatory drugs (NSAD) are administered in rheumatic arthritis, chorea, mild and moderately severe rheumocarditis, in mild and moderately severe extent of the disease activity, in subacute indolent and latent course of the disease. Nowadays the derivates of indolacetic (Indomethacin) and arylacetic acids (Voltaren) are beneficial. The initial dose of the drug is usually 150 mg daily. Acetylsalicylic acid may be also administered. Doses of up to 3 –4 g daily are typically used. Ibuprofen may be also given 800 – 1200 mg daily reducing it up to maintenance dose. Aminocholine derivates are poor immunosuppressive agents and stabilizers of lyzosome membranes which help to prevent the destruction caused by proteolytic lizosomal enzymes. Patients with an indolent and recurrent course of the disease should be prescribed long-term administration of quinoline drugs, such as Chlorochin (Chingamin, Delagil). Doses of up to 0.25 mg twice a day are typically used. 0.2 g of Plaquenil twice a day are also beneficial. Antibiotics. In most patients with rheumatism and those who have chronic foci of streptococcal infection the use of antibiotics is justified. The doctor in charge decides on a certain antibiotic and determines the way of its administration considering the clinical situation. Benzylpenicillin is usually the first antibiotic to be administered. Doses of up to 1 500 000 to 4 000 000 activity units daily are typically used. Intramuscular injections are given for 10 – 14 days. If there are not any risk factors, such as burdened heredity, poor living conditions, etc., oral administration of Penicillin drugs are advisable. The course of treatment usually lasts for 10 days. These drugs include the following: Phenoxymethylpenicillin should be given 0.5 – 1.0 g 4 times a day, Ampicillin – 0.25 g 4 times a day, Amoxicillin – 0.5 g 3 times a day or 1 g twice a day. Amoxicillin is considered to be the most beneficial of all the above mentioned drugs, because it is  as effective as Ampicillin and Phenoxymethylpenicillin, but it is more bioavailable. Cephalosporins I, such as Cephalexin, Cefradin, Cefadroxil 0.5 g 4 times a day, or Cephalosporins II, such as Cephaklor, Cephuroxim 0.25 g 3 times a day may be also used. If the patient is intolerant of Penicillin preparations, macrolide antibiotics may be used. Erythromycin is one of them. It may be given 0.25 g 4 times a day. There are some other new preparations, such as Azitromycin which should be given for 5 days increasing the dose from 0.5 g on the first day and by 0.25 g daily from the 2nd to 5th day. Roxitromycin should be given 0.15 g twice a day. The course of treatment usually lasts for 10 days. Cardiac glycosides are used if there are signs of congestive heart failure. In patients with severe carditis they are effective only in combination with anti-rheumatic drugs. Nitrates worsen the prognosis in patients suffering from rheumatism. Rehabilitation of patients with rheumatism in a local specialized rehabilitation centre (e.g. sanatorium) or at home (the patient is put on sick-leave for some days) (2-nd stage). This stage is important for consideration when rheumatism turns into an inactive phase. At this stage hormones are discontinued, the administration of non-steroidal anti-inflammatory drugs is controlled, and the drugs improving metabolism of the myocardium are administered. Specialists in physical and social rehabilitation work with the patients at this stage. Regular medical check-ups (3-d stage). The objectives of regular medical check-ups are the following: 1. Treatment of patients aimed at complete elimination of the active rheumatic process. 2. Symptomatic therapy of circulatory disturbances and receiving symptomatic therapy by patients with heart diseases. Ways of treating heart diseases. 3. Solving the problems of rehabilitation, work capability and employment of patients who had acute rheumatic fever. 4. Secondary prevention of rheumatism. Prevention of recurrences. Prevention. Primary prevention. The objective of primary prevention consists in organization of a complex of individual, social and national measures aimed at eliminating primary disease incidence, i.e. (that is) preventing healthy people from falling ill with rheumatism. The following factors should be focused on: I. Treatment of streptococcal infection: 1)                Revealing the carriers ( bacteriologic examination in nasopharyngeal infection is obligatory); 2) Obligatory treatment of streptococcal nasopharyngeal infections with antibiotics. Beta-lactam antibiotics (adult dose – Amoxicillin 1.5 g daily for 3 doses; children dose 0.375 g daily for 3 doses; the course usually lasts for 10 days). Benzatin-benzylpenicillin should be considered if the patient is unable to take antibiotics orally. It should be also administered if the patient or one of his relatives had acute rheumatic fever, if the patient’s living conditions are poor,   if there are outbreaks of BHSA-infection in pre-school establishments, at schools, hostels, in colleges, in the army, etc. If the patient is intolerant of beta-lactam antibiotics, macrolide antibiotics, such as Midekamycin, Roxitromycin, Erythromycin, Claritrimycin, Spiramycin, Azitromycin, are used and if the patient is intolerant of macrolides, lincosamines, such as Clindamycin, Linkomycin, are typically used. Antimicrobial therapy of recurrent BHSA-tonsillitis includes Amoxicyclin, Klavulanat, Clindamycin, Cefuroxim, or Aksetil. 3) Sanation of chronic foci of streptococcal infection. II. Education of the population about the necessity to visit the doctor in case of tonsillitis and pharyngitis. III. Taking measures aimed at strengthening the defensive forces of the human body (e.g. taking exercises, hardening, gymnastics, etc.). Secondary prevention. After finishing the course of treatment of acute rheumatic fever secondary prevention is carried out. It is performed in order to prevent recurrences of the disease in people who had acute rheumatic fever. Antibiotics are the main means of preventing recurrent rheumatic attacks. Perspective antibiotics with a prolonged action are considered to be Benzylpenicillin antibiotics, such as Extencillin, Retarpen, Pendepon, Benzatin-benzilpenicillin which are administered 2 400 000 activity units once every 3 weeks. In this case intramuscular injections are usually used. The duration of secondary prevention should not exceed 5 years after the last rheumatic attack if acute rheumatic fever was associated with carditis. Secondary prevention should not exceed 3 years if acute rheumatic fever was not associated with heart involvement and the patient did not have chronic foci of infection. According to the WHO, if acute rheumatic fever is not associated with carditis, secondary prevention should not exceed 5 years. However, it should be completed earlier than the patient is 18 years old. Sometimes, however, it can be prolonged. Patients who had acute rheumatic fever associated with carditis should have secondary prevention till the age of 25. Patients with valvular heart disease and those who underwent a surgery correcting heart disease should have secondary prevention throughout the life. Pregnant women with rheumatism should be monitored by rheumatologist and obstetrician at an early gestational age. Pregnant women who had acute rheumatic fever should be continued on Bicillin prevention. However, if it had been completed by the time the woman became pregnant, it can be renewed at weeks 10 or 12 of gestation. The prognosis of the disease is determined by the efficacy of treatment of primary rheumocarditis and by the presence of complications.