Rheumatic fever

Rheumatic fever (PL) is a post-infection complication of A-streptococcal tonsillitis or pharyngitis in predisposed individuals with the development of an autoimmune response to epitopes of group A streptococcus and cross reactivity with similar epitopes of human tissues (heart, joints, CNS).

[1], [2], [3],

Epidemiology of rheumatic fever

The epidemiology of rheumatic fever is closely related to the epidemiology of A-streptococcal infections of the upper respiratory tract. A high level of rheumatic fever began to decline even before the use of antibiotics in clinical practice, the use of antibiotics since 1950 has rapidly accelerated this process. Thus, in developed countries, the incidence of rheumatic fever has dropped from 100-250 to 0.23-1.88 per 100 000 population. Nevertheless, around 12 million people suffer from rheumatic fever and rheumatic heart disease at the moment. Most of them live in developing countries, where the incidence of RL is in the range of 1.0 per 100 000 population in Costa Rica, 72.2 per 100,000 in French Polynesia, 100 per 100,000 in Sudan, to 150 per 100,000 in China In some areas, such as Havana (Cuba), Costa Rica, Cairo (Egypt), Martinique and Guadeloupe, where preventive programs were introduced, there was a marked decrease in the mortality, prevalence and severity of RL and RBS. Socioeconomic indicators and environmental factors play an indirect but important role in the prevalence and severity of rheumatic fever and RBS. Factors such as a lack of resources to ensure quality health care, a low level of awareness of the disease in society, population crowding, can significantly affect the incidence in the population. However, rheumatic fever is not a problem only in socially and economically disadvantaged populations. This was demonstrated by local outbreaks of rheumatic fever. Recorded in the 80-90-ies. XX century. In some areas of the USA, Japan and a number of other developed countries of the world.

[4], [5], [6], [7], [8], [9]

Causes of acute rheumatic fever

The etiological relationship between infections caused by BSCA, followed by the development of acute rheumatic fever (ARF) is well known. Despite the lack of evidence of direct involvement of group A streptococcus in the damage to tissues of patients with acute rheumatic fever, there are significant epidemiological immunological evidence of the indirect involvement of BGA in the initiation of the disease:

• outbreaks of rheumatic fever closely follow each epidemic of angina or scarlet fever;
• adequate treatment of documented streptococcal pharyngitis markedly reduces the number of subsequent attacks of rheumatic fever;
• appropriate antimicrobial prophylaxis prevents recurrence of the disease in patients undergoing ARV;
• The presence of elevated titers in at least one of the anti-streptococcal antibodies in most patients with ORL.

Rheumatic fever and rheumatic heart disease are observed only after upper respiratory infections caused by Group A streptococci. Although beta-hemolytic streptococci of serogroups B, C, O and P can cause pharyngitis and be triggers of the host's immune response, they are not associated with the aetiology of RL.

Streptococcal pharyngitis / tonsillitis is the only infection associated with ARF. For example, there are many descriptions of outbreaks of skin streptococcal infections (impetigo, erysipelas), which were the cause of post-streptococcal glomerulonephritis, but never - the cause of rheumatic fever.

Streptococcus strains of group A, colonizing the skin, differed from strains that caused rheumatic fever. Bacterial genetic factors may be an important determinant of the place of occurrence of group A streptococcal infection. The structure of antigens coding for M- and M-like surface proteins of streptococcus is recognized and labeled from A to E. Pharyngeal strains have the structure of A-C, while all skin strains have D and E structure.

Another factor affecting the localization in the pharynx can be the CD44 receptor, a hyaluronic acid-bound protein that serves as a pharyngeal receptor for group A streptococci. In the experiment, it was shown that, after intranasal administration of group A streptococcus, the oropharynx is colonized in normal mice and not colonized in transgenic mice that do not express CD44.

Many theories try to explain why acute rheumatic fever is associated only with streptococcal pharyngitis, but there is still no exact explanation. The group of streptococcus A is divided into two main classes, the basis of this division is the difference in the C-sequences of the M-protein. One class is associated with streptococcal pharyngeal infection, the other (with some exceptions) with strains most often causing impetigo. Thus, the characteristics of streptococcal strains are decisive in initiating the disease. Pharyngeal infection with its involvement of a large amount of lymphoid tissue in itself can be important for initiating an abnormal humoral response to microbial antigens with the formation of cross reactivity to the tissues of the body. Skin strains can colonize the pharynx, but they are unable to induce such a strong immunological response to M-protein, as pharyngeal strains.

Rheumatic fever occurs as a result of an abnormal immune response to pharyngitis caused by group A streptococci. Clinical manifestations of this response and its expression in a particular individual depend on the virulence of the microbe, the host's genetic susceptibility and the "appropriate" environmental conditions.

One of the well-studied determinants of bacterial virulence is M-protein. Streptococcal M-protein is located on the surface of streptococcal cells and has structural homology with the myosin of cardiomyocytes, as well as with other molecules: tropomyosin, keratin, laminin. It is assumed that this homology is responsible for histological changes in acute rheumatic carditis. For example, laminin, an extracellular matrix protein secreted by endothelial cells lining the heart valves, is an important component of the valve structure. It also serves as a target for polyreactive antibodies that "recognize" M-protein, myosin and laminin.

Of the more than 130 identified types of M-protein, M-types such as 1, 3, 5, 6, 14, 18, 19 and 24 are associated with rheumatic fever. It is postulated that these M-types of group A streptococcus have a rheumatogenic potential. These serotypes are usually hard to encapsulate and form large mucoid colonies rich in M-protein. These characteristics enhance the ability of bacteria to tissue adhesion and resistance to phagocytosis in the host.

Another factor of virulence is streptococcal superantigens. This is a unique group of glycoprotein holes that can bind class II molecules of the main histocompatibility complex to the T-lymphocyte V receptors, simulating the binding of the antigen. Thus, T cells become susceptible to antigen-nonspecific, and autoreactive stimulation. In the pathogenesis of rheumatic fever, some fragments of M-protein and streptococcal erythrogenic exotoxin are considered as superantigens. Streptococcal erythrogenic toxin can behave like a superantigen for B cells, resulting in the production of autoreactive antibodies.

The development of rheumatic fever also requires a genetic predisposition of the macroorganism. This is currently the only explanation for the fact that rheumatic fever occurs only in 0.3-3% of individuals with acute A streptococcal pharyngitis. The concept of the genetic predisposition of RL intrigues researchers for more than 100 years. All this time, it was believed that the disease gene has an autosomal dominant transmission pathway, autosomal recessive with limited penetrance or transmission is carried out by a gene associated with the secretory status of the blood group. Again, interest in the genetics of ARF has grown in connection with the discovery of a complex histocompatibility in humans. The results of the studies suggest that the immune response is genetically controlled and that there is high reactivity to the Streptococcus cell wall antigen expressed through a separate recessive gene and low reactivity expressed through a single dominant gene. Modern data confirm that the genetic control of a low response to streptococcal antigen is closely related to histocompatibility class II antigens. However, the relationship between susceptibility to rheumatic fever and class II antigens HLA varies widely, depending on ethnic factors. For example, DR4 is more frequent in patients with RL - Caucasians; DR2 - in Negroids, DR1 and DRw6 - in patients from South Africa; DRS is more often found in patients with RL from India (who also report a low incidence of DR2); DR7 and DW53 - in patients from Brazil; DQW2 - for the Mongoloids. Most likely, these genes are located next to the gene for predisposition to rheumatic fever, possibly in the same locus, but not identical to it.

Somewhat later, surface alloantigens of B lymphocytes, called D8 / 17 alloantigens, were named after a clone of monoclonal antibodies, with the help of which they were isolated. According to the world data, the alloantigen of B-lymphocytes D8 / 17 is infected in 80-100% of patients with ORL and only in 6-17% of healthy individuals. The involvement of alloantigen B-lymphocytes of patients in the pathogenesis of rheumatic fever continues to be studied. It is most plausible that the predisposition to ORL is polygenic, and the D8 / 17 antigen can be associated with one of the genes responsible for the predisposition; another may be a histocompatibility complex encoding DR antigens. Although there is no precise explanation, an increased number of D8 / 17 positive B cells is a sign of a particular risk of acute rheumatic fever.

[10], [11], [12],

Pathogenesis of rheumatic fever

Streptococcal infection begins with the binding of surface ligands of the bacterium with specific receptors of cells of the host organism and the subsequent inclusion of specific processes of adhesion, colonization and invasion. Binding of surface bacterial ligands to surface host receptors is a key event in the colonization of the host organism, it is initiated by fibronectin and streptococcal fibronectin-binding proteins. Streptococcal lipoteichoic acid and M-protein also play a significant role in bacterial adhesion. The host organism responds to streptococcal infection with opsonization and phagocytosis. Streptococcal infection in genetically susceptible organism under suitable ambient conditions results in the activation of T and B lymphocyte antigens and streptococcal superantigens, which in turn contributes to the production of cytokines and antibodies directed against streptococcal N-acetyl-beta-D-glucose (carbohydrate) and myosin.

It is believed that damage to the valvular endothelium with anticarbohydrate antibodies leads to an increase in the production of adhesion molecules and the influx of activated CD4 + and CD8 + T cells. Violation of the integrity of the endothelium of the heart valves leads to the exposure of subendothelial structures (vimentin, laminin and valvular interstitium cells), which contributes to the development of a "chain reaction" of valvular destruction. After the valve flaps are involved in the inflammation process, thanks to newly formed microvessels, the valve endothelium infiltrates with T cells, supporting the process of valve destruction. The presence of T-cell infiltration even in old mineralized lesions serves as an indicator of the persistence of the disease and the progression of valve damage. Under the influence of pro-inflammatory cytokines, valvular interstitial cells and other valve components lead to "improper restoration" of the valve.

The pathogenetic mechanism described above is most probable, but to date there is no direct and conclusive evidence of the pathogenetic role of cross-reacting antibodies in vivo and there is no suitable animal model for the study of rheumatic fever.

In 2000-2002, The European Society of Cardiology has published data on the possible trigger role of viruses and stress stress proteins of heat stress proteins in the formation of relapses of rheumatic fever and rheumatic heart disease, but this theory still requires further study.

Thus, the modern understanding of rheumatic fever is based on the recognition of the etiological role of BGA and the hereditary predisposition to the disease, which is realized by an anomaly of the immune response of the organism.

Symptoms of rheumatic fever

Rheumatic fever occurs in the form of attacks. In 70% of patients, the rheumatic attack subsides, according to clinical and laboratory data, for 8-12 weeks, 90- 95% - 12-16 weeks, and only 5% of patients continue to attack more than 6 months, i.e. Takes a long or chronic course. In other words, in most cases the rheumatic process has a cyclic course, and the attack ends and the average for 16 weeks.

In more than half of cases, patients complain of shortness of breath, heartbeats, palpitations that occur against the background of general symptoms of rheumatic fever: rapid fatigue, lethargy, sweating, fever. Adults may have pain in the heart of an uncertain nature.

Rheumatic carditis, rheumatoid arthritis, chorea, ring-shaped erythema and subcutaneous nodules serve as diagnostic signs of acute rheumatic fever.

Subcutaneous nodules and annular erythema

Subcutaneous nodules and annular erythema are rare manifestations of rheumatic fever, they occur in less than 10% of cases.

Subcutaneous nodules are round, dense, easily displaced, painless formations from 0.5 to 2 cm in size, more often localized on the extensor surfaces of the elbows, knees and other joints, in the occipital region and along the tendon sheaths, are extremely rare in the first attack of rheumatic fever. The number of nodules varies from one to several tens, but usually 3-4. It is believed that they are easier to feel than to see. They last from several days to 1-2 weeks, less often - more than a month. Subcutaneous nodules are almost always associated with cardiac involvement and are found more often in patients with severe carditis.

Ring-shaped erythema are transitory ring-shaped spots with a pale center, usually appearing on the trunk, neck, proximal parts of the extremities. Ring-shaped erythema is never localized on the face. Due to the fleetingness of the changes and the absence of associated symptoms, ring-shaped erythema can be missed if it is not specifically looked for, especially in black patients. Individual elements can arise and disappear within minutes or hours, sometimes changing form in the eyes of a specialist, merging with neighboring elements to form complex structures (therefore, in some sources they are described as "cigarette smoke rings"). Ring-shaped erythema usually appears at the onset of a rheumatic attack, but it can persist or recur for months or even years, remaining after other manifestations of the disease have subsided; It is not affected by anti-inflammatory treatment. This skin phenomenon is associated with carditis, but, unlike subcutaneous nodules, not necessarily with heavy. Nodules and annular erythema are often combined.

Ring-shaped erythema is not unique to rheumatic fever, it is also described in sepsis, allergic reactions to medications, glomerulonephritis and in children without any diagnosed diseases. It should be distinguished from toxic erythema in febrile patients and rash with juvenile idiopathic arthritis. Ring erythema in Lyme disease (chronic migrainea of erythema) may also resemble annular erythema in rheumatic fever.

Clinical small criteria for rheumatic fever

Arthralgia and fever are referred to as "small" clinical manifestations of rheumatic fever in the diagnostic criteria of T. Jones, not because they are less common than the five large criteria, but because they have less diagnostic specificity. Fever is observed and the beginning of almost all rheumatic attacks and usually is 38.4-40 C. As a rule, there are fluctuations during the day, but there is no characteristic temperature curve. Children who have only mild carditis without arthritis may have a low-grade fever, and patients with "pure" chorea are afebrile. Fever rarely persists more than a few pedes. Arthralgia without objective changes is often found in rheumatic fever. Pain usually occurs in large joints and can be minor and very severe (up to the impossibility of movements), it can persist for several days to weeks, changing in intensity.

Although abdominal pain and nasal bleeding occur in about 5% of patients with RL, they are not considered part of T. Jones's criteria because of the lack of specificity of these symptoms. However, they can be of clinical importance, since they appear several hours or days before the development of large manifestations of RL, abdominal pain is usually localized in the epigastrium or near the umbilical region, may be accompanied by symptoms of muscular defenses and often simulates various acute diseases of the abdominal cavity organs.

[13], [14], [15],

Clinical observation

Patient S., 43, is counseled in the Moscow City Rheumatology Center on 20.01.2008, where she is sent from the city polyclinic to clarify the diagnosis.

When examined, she complained of general weakness, sweating, fast fatigue, dyspnoea with physical exertion. In December 2007, she underwent acute pharyngitis, because of which she received no antibacterial treatment. After 3-4 weeks, shortness of breath and palpitations appeared with a slight physical exertion, pain in the precardial region of a different nature, an increase in body temperature to 37.2 C, an increase in ESR to 30 mm / h.

It is also known from an anamnesis that since childhood, a cardiologist has observed a primary prolapse of the mitral valve, a mesodiastolic click and late systolic murmur over the apex at auscultation of the heart were constantly heard. During the last month, the cardiologist noted an increase in systolic murmur with the acquisition of a pansystolic sound, which became the basis for suspicion of the ORL and referral to a consultation with the revmocenter.

Objectively: the skin of normal color, normal nutrition. Peripheral edema is absent. Tonsils hypertrophied, loosened. In the lungs vesicular breathing, wheezing was not heard. The boundaries of relative dullness of the heart are not expanded. Attenuation of I tone above the apex, pansystolic murmur is heard with irradiation to the left axillary region and the interscapular area of the 5th gradation, as well as systolic murmur over the tricuspid valve and pulmonary artery valve of the 3rd grade. Extracosystia. Heart rate - 92 per minute, blood pressure - 130/70 mm Hg. The abdomen is soft, painless when palpated. Percutaneous liver and spleen are not enlarged.

Clinical blood test from 16.01.08: Hb ~ 118 g / l, leukocytes - 9.4х10 ⁹ / l, ESR - 30 mm / h

The general analysis of urine from 16.01.08 without pathological changes. In the immunological analysis of the blood of 16.01.08: C-reactive protein - 24 mg / l, antistreptolysin-O - 600 ED.

On the ECG - the normal position of the electric axis of the heart, rhythm sinus, heart rate - 70 per minute, single atrial extrasystoles, PQ - 0.14 s, QRS - 0.09 s.

With Doppler-echocardiosis from 20.01.08, both mitral valve flaps prolapse into the left atrial cavity, the marginal compaction of the anterior valve, their movements in antiphase. Fibrous ring - 30 mm, hole size 39x27 mm, peak gradient - 5.8 mm Hg, mitral regurgitation of the third degree. Left atrium 44 mm, left ventricular dilation: finite-diastolic size (CRD) - 59 mm, finite-systolic size (CSF) - 38 mm, end-diastolic volume (BWW) - 173 ml, finite-systolic volume (CSR) - 62 ml, shock volume - 11 ml, ejection fraction (FB) - 64%. Aorta 28 mm, unchanged. Aortic valve is tricuspid, small marginal compaction of valves, fibrous ring - 24 mm, peak pressure gradient - 4 mm Hg. Right atrium - 48 mm, right ventricle - small dilatation (equal to left volume), estimated pressure - 22 mm Hg. The pulmonary artery is moderately expanded, the pulmonary valve is not changed, the fibrous ring is 29 mm, the systolic pressure gradient on the pulmonary artery valve is 3 mm. Hg, there is no regurgitation. The tricuspid valve prolapses, the fibrous ring is 30 mm, the 1st degree is riguritisation. Conclusion: prolapse of both mitral valve flaps, marginal compaction of mitral and aortic valve flaps, mitral regurgitation of the third degree, tricuspid regurgitation of the 1st degree, dilatation of the heart cavities.

Taking into account the connection between the worsening of the patient's state with the acute pharyngitis and the evidence of the transferred A-streptococcal infection (the detection of an elevated titer of antistreptolysin-0), the enhancement of the existing systolic murmur over the apex of the heart, as well as the cardiomegaly detected by echocardiography, an increase in the C-reactive protein level and an increase in ESR was diagnosed: "Acute rheumatic fever: carditis of medium degree (mitral and aortic valvulitis). Mitral regurgitation of the third degree. Tricuspid regurgitation of the 1 st degree. Nadzheludochkovaya extrasystoles. NK 1 st, II FC. "

The patient was hospitalized in GKB No. 52, where he was treated with streptococcal amoxicillin for 10 days at a dose of 1500 mg / day, diclofenac at a dose of 100 mg / day for 14 days, strict bed rest for 2 weeks was observed with further expansion of the exercise regime . The patient's condition improved, the size of the heart decreased. At the time of discharge from the hospital for outpatient care, the patient did not present any complaints. In blood tests, the ESR was 7 mm / h, the C-reactive protein was 5 mg / l, and the antistreptolysin-O less than 250 units. Secondary prophylaxis of rheumatic fever of benzathine with benzylpenicillin was started at a dose of 2.4 million units IM intramuscularly once every 4 weeks, which was recommended for the next 10 years.

[16], [17], [18], [19], [20], [21]

Classification of rheumatic fever

At present, the Russian Federation has adopted a national classification of rheumatic fever.

Classification of rheumatic fever (RDA, 2003)

Clinical Options	Clinical symptoms		Exodus	Stages of circulatory failure (NK)
	Basic	Additional		SWR *	NYHA **
Acute rheumatic fever Repeated rheumatic fever	Carditis Arthritis Chorea Erythema ring-shaped	Fever Arthralgia Abdominal syndrome Serosites	Recovery Rheumatic heart disease without heart disease *** heart disease ****	0	0
				I	I
				IIA	II
				IIB	III
				III	IV

• * According to the classification of ND, Strazhesko and V.Kh., Vasilenko.
• ** Functional class of heart failure according to the New York classification.
• *** There may be post-inflammatory marginal fibrosis of valvular flaps without regurgitation, which is specified with the help of echocardiography.
• **** In the presence of "the first detected heart disease, it is necessary to exclude, as far as possible, other causes of its formation (infective endocarditis, primary antiphospholipid syndrome, calcification of valves of degenerative genesis, etc.).

[22], [23]

Diagnosis of rheumatic fever

In the history of patients with suspected rheumatic heart disease, it is necessary to describe in detail the family history of the presence of rheumatic fever in the immediate family and the documented confirmation of this diagnosis, and to establish the presence or absence of documented tonsillopharyngitis, scarlet fever, otitis, rhinitis, lymphadenitis of the anterior lymph nodes during last 2-3 weeks. The presence of risk factors should also be considered:

• hereditary predisposition (detection of a specific antigen of B-lymphocytes D8 / 17, as well as a high prevalence of class II antigens of the NLA system);
• "Vulnerable" age;
• crowding;
• unsatisfactory housing and sanitary and hygienic living conditions (small living space, large families);
• low level of medical care,

Currently, in accordance with the recommendations of the WHO as international, diagnostic criteria for rheumatic fever T. Jones, revised in 2004

Diagnostic criteria for rheumatic fever

Big criteria		Small criteria				Data confirming the preceding A-streptococcal infection
Carditis Migrating polyarthritis of Chorea Sydengam (small chorea) Ring-shaped erythema Subcutaneous rheumatic nodules		Clinical: arthralgia, fever Laboratory: increased content of acute phase reactants - ESR, C-reactive protein Elongation of the PQ interval on the ECG				Positive A-streptococcal culture isolated from throat, or positive test for rapid determination of A-streptococcal hypertension Increased or increasing titers of streptococcal antibodies

To confirm the primary attack of the disease, large and small criteria for rheumatic fever, laboratory changes and evidence of a prior streptococcal infection are needed in accordance with the recommendations of WHO 2004. In the context of a streptococcal infection, two large criteria or a combination of one large and two small are sufficient grounds for diagnosing ARF . The diagnosis of repeated rheumatic fever in a patient with established RBS may be based on small criteria in combination with evidence of a recent history of streptococcal infection.

Criteria for diagnosis of rheumatic fever and rheumatic heart disease (WHO, 2004, based on T. Jones' revised criteria)

Diagnostic categories

Criteria

0RL (a) Repeated attacks of rheumatic fever in patients without established RBS (s) Repeated attacks of rheumatic fever in patients with established RBS Rheumatic chorea; latent rheumatic heart disease (s)

Two large or one large and two small criteria + evidence of a transplanted infection caused by Group A streptococci Two large or one large and two small criteria + evidence of a transected infection caused by Group A streptococci Two small criteria + evidence of a transmitted infection caused by group A streptococcus ) Other large criteria or evidence of group A streptococcal infection are not required

(a) - Patients may have polyarthritis (or only polyarthralgia or monoarthritis) and several (3 or more) other small manifestations, as well as evidence of a recent infection caused by BHSA. Some of these cases may later go to the radar. They can be considered as cases of "possible RL" (if other diagnoses are excluded). In these cases, regular secondary prevention is recommended. Such patients should be observed and regularly examined by the heart. This cautious approach is especially important for patients of "vulnerable" age.

(b) - Infective endocarditis should be excluded.

(c) - Some patients with repeated attacks may not fully meet these criteria.

[24], [25], [26], [27], [28]

Laboratory diagnostics of rheumatic fever

In the presence of rheumatic fever in the active phase, an increase in nonspecific "acute phase indices" is revealed with the help of a blood test, which includes:

• neutrophilic leukocytosis (not more than 12 000-15 000);
• disproteinemia with an increase in the level of a-2 and y-globulins;
• increased ESR (already in the first days of the disease);
• increase in the level of C-reactive protein (from the first days of the disease).

Bacteriological examination of the throat swab makes it possible to detect BGSA, but not to differentiate the active infection and streptococcal carriage.

Evidence of recent streptococcal infection is an increase in the titres of streptococcal antibodies detected in paired sera that occurs during the first month after the onset of the disease, persists, as a rule, for 3 months, normalizing after 4-6 months.

Normal, borderline and high numbers of streptococcal antibodies

Antibodies	Titles, unit / ml
	Normal	Borderline	High
ASL-0	<250	313-500	> 625
LRA	<250	330-500	> 625
ASA	<200	300-500	> 600
ADPK-8	<600	800-1200	> 1200

Instrumental diagnosis of rheumatic fever

When ECG-study can detect a violation of rhythm and conductivity: transient atrioventricular block (lengthening PQ) 1 st, rarely 2 nd degree, extrasystole, changes tooth to T as a decrease in its amplitude until the appearance of negative teeth. These ECG changes are characterized by instability and rapidly disappear during treatment.

The phonocardiography study helps to refine the auscultation of the heart and can be used to objectify the changes in tones and noise during dynamic observation.

Chest X-ray is performed to determine cardiomegaly and signs of stagnation in a small circle of blood circulation.

EchoCG criteria of the mitral valve endocarditis are:

• clavate marginal thickening of the mitral valve;
• hypokinesia of the posterior mitral valve;
• mitral regurgitation;
• transient domed diastolic bending of the anterior mitral valve.

Rheumatic endocarditis of the aortic valve is characterized by:

• edge thickening of valve flaps;
• transient prolapse of valves;
• aortic regurgitation.

It should be remembered that isolated damage to the aortic valve without the noise of mitral regurgitation is not characteristic of acute rheumatic carditis, but does not exclude its presence.

Example of the formulation of the diagnosis

• Acute rheumatic fever: carditis of medium degree (mitral valvulitis), MP I degree, migrating polyarthritis. НК 0, 0 FC.
• Acute rheumatic fever: mild carditis, chorea. НК 0, 0 FC.
• Repeated rheumatic fever: carditis, severe RBC: combined mitral heart disease: insufficiency of mitral valve of mild degree, stenosis of left atrioventricular aperture of mild degree. NK IIA, II FC.

Treatment of rheumatic fever

The main goal of treating rheumatic fever is eradication of beta-hemolytic streptococcus from the nasopharynx, as well as inhibition of rheumatic process activity and prevention of severe disabling complications of RL (RBS with heart disease).

All patients with suspected acute rheumatic fever should be hospitalized to clarify the diagnosis and treatment.

Drug treatment of rheumatic fever

Since the establishment of rheumatic fever, treatment with penicillins is prescribed, which ensures removal of BGSA from the nasopharynx. Of the penicillins, benzathine benzylpenicillin or phenoxymethylpenicillin is most often used. Recommended daily doses of benzathine benzylpenicillin: for children - 400 000- 600 000. ED, adults - 1.2-2.4 million ED intramuscularly once. Phenoxymethylpenicillin is recommended to adults for 500 mg orally 3 times a day for 10 days.

Algorithm for the treatment of streptococcal pharyngitis:

• Phenoxymethylpenicillin (Ospen 750) 1,5 g / day, 10 days: 500 mg (tablets) 3 times a day or 750,000 IU / 5 ml (syrup) 2 times a day.
• Amoxicillin 1,5 g / day, 10 days: - 500 thousand (tablets) 2-3 times a day and inside regardless of food intake.
• Benzathine benzylpenicillin 1,2-2,4 million units is single-intramuscularly. It is advisable to appoint when:
  • dubious patient compliance with oral antibiotic intake;
  • the presence of rheumatic fever in an anamnesis in the patient or next of kin;
  • unfavorable social and living conditions;
  • outbreaks of A-streptococcal infection in preschool institutions, schools, boarding schools, schools, military units, etc.
• Cephalexin - 10 days by: - 500 mg 2 times a day inside.
• When intolerance of ß-lactam antibiotics - macrolides - 10 days (including azithromycin - 5 days).
• When intolerance of ß-lactam antibiotics and macrolides - clindamycin 300 mg 2 times a day inside, washed down with a large amount of water, 10 days.

Penicillins should always be considered as a drug of choice in the treatment of ARF, except for cases of their individual intolerance, when macrolides or lincosamides are prescribed. Of macrolides, erythromycin is most often used 250 mg orally 4 times a day.

Patients with intolerance of both ß-lactams and macrolides are prescribed lincosanides, in particular, lipcomycin 0.5 g per day 3 times a day (10 days).

When studying the long-term prognosis of rheumatic fever and analyzing the frequency of heart disease within a year after the attack, according to Cochrane review, there is no reliable effect of anti-inflammatory treatment. However, the conclusion drawn about the ineffectiveness of this effect is not sufficiently justified, since in the meta-analysis of eight studies cited by the authors, most of them belonged to the 50-60's. XX of. These works lacked the most important principles of good clinical practice, for example the principle of randomization. In this regard, the authors of the meta-analysis consider it necessary to conduct multicenter randomized placebo-controlled studies on the effectiveness of anti-inflammatory effects in rheumatic carditis.

[29], [30], [31],

Prevention of rheumatic fever

The goal of prevention is to prevent recurrence of rheumatic fever. Relapses are most common within 5 years after the first attack. Despite the fact that the number of relapses decreases with the age of the patient, they can develop at any time.

Primary prevention of rheumatic fever includes a number of strategic aspects:

• diagnostics of streptococcal infection;
• treatment of streptococcal infection;
• streptococcal immunization;
• socio-economic measures;
• development of methods for predicting the disease.

Secondary prevention is a set of measures aimed at preventing acute respiratory streptococcal infection in patients who have undergone a rheumatic attack.

Prevention of recurrence of rheumatic fever should be prescribed immediately in a hospital after the end of a 10-day treatment with penicillins (macrolides, lincosamides). The classical parenteral regimen is benzenzothine benzylpenicillium 1.2-2.4 million units intramuscularly once every 3-4 weeks. If you are allergic to penicillins, you can use erythromycin 250 mg twice daily.

Secondary prevention of rheumatic fever

A drug		Dosage
Benzazine benzylpenicillium		1.2-2.4 million units every 3-4 weeks intramuscularly
When allergic to penicillins - erythromycin		250 mg twice daily

Patients who underwent heart surgery for rheumatic heart disease are exposed to secondary prophylaxis for life.

The duration of secondary prevention of rheumatic fever

Category of patients	Duration
RL with carditis and valvular lesion	At least 10 years after the last episode and at least up to 40 years of age. Sometimes lifelong prevention
RL with carditis but without valvular lesion	10 years or up to 21 years
RL without carditis	5 years or up to 21 years

Prevention of infectious endocarditis is shown to all patients who have suffered rheumatic fever with the formation of heart disease, and in the following situations:

• dental procedures causing bleeding;
• operations on ENT organs (tonsillectomy, adenoidectomy);
• procedures on the airways (bronchoscopy, mucosal biopsy);
• surgical interventions in the abdominal cavity, urogenital tract, gynecological area.

Forecast of rheumatic fever

Relapses of rheumatic fever are more common in childhood, adolescence and adolescence and occur mainly in people who have undergone moderate and severe carditis, especially in cases of the formation of rheumatic heart disease.

[32], [33], [34], [35]

Rheumatic fever - history

Rheumatic fever is one of the most ancient human diseases: references to it are found in the early literature of China, India, Egypt. In Hippocrates' "Book of Diseases" (460-377 BC), a description of typical rheumatic arthritis is first described: the intermittent inflammation of many joints, with swelling and redness, severe pain, not life-threatening, and observed mainly in young people. The first use of the term "rheumatism" for the designation of arthritis is attributed to Galician, a second-century Roman physician. The term "rheumatism" comes from the Greek word "rheumatismos" and means "spreading" (on the body). Being an active representative of the humoral concept of the origin of various diseases, including arthritis, Galen considered these diseases as a kind of catarrh. The great authority of Galen and the slow progress of knowledge in this field contributed to the fact that Galen's understanding of the essence of the clinical picture of the disease lasted until the 17th century, when the work of Baillou (Bayu), who called himself Ballonius, appeared. The study "Liber cle Rheumatismo etpleuritiddorsal" was published posthumously by his nephew only in 1642. It contained a description of the disease. "Rheumatism is in the whole body and is accompanied by pain, tension, fever, sweats ... With arthritis pains are repeated at regular intervals and through certain periods."

An outstanding therapist of the XVII century. Sydenham, somewhat later, Baiilou clearly characterized rheumatoid arthritis: "Most often, the disease occurs in the fall and affects people of young and middle age - in the prime of life ... In patients there is a strong pain in the joints; this pain moves from place to place, in turn in all joints, and eventually afflicts one joint with redness and swelling, "Sydenham belongs to the merit of the first description and recognition of chorea rheumatic disease.

The first reports of heart damage in rheumatic joint diseases appeared at the end of the 18th century, but these facts were viewed as an ordinary combination of two different diseases, and not as a single disease.

English physician Pitcairn (1788) was one of the first who recognized the connection of rheumatic fever with heart disease. For the first time Pitcairn noted frequent heart lesions with rheumatism. He admitted the common cause of heart and joint disease and introduced the term "rheumatism of the heart."

NO. Sokolsky and J. Buyo (Bouillaud) simultaneously, but independently of each other, established a direct organic connection of rheumatic polyarthritis and rheumatic heart disease. The majority of scientists of that time attached paramount importance to the development of rheumatism of endocarditis and pericarditis, Professor of Moscow University GI. Sokolsky in his work On Rheumatism of the Muscle of the Heart (1836) singled out the clinical and anatomical forms of rheumatic heart disease - myocarditis, endocarditis and pericarditis, with a special place for rheumatic myocarditis, ßouillaud in the Clinical Manual on Heart Disease (Paris, 1835) and " Clinical guidelines for articular rheumatism and the law of coincidence of cardiac inflammation with this disease "(Paris, 1840) noted the high prevalence of rheumatic heart disease in the form of valvulitis and pericarditis and formulated his famous law of owls Aden rheumatic fever and heart disease.

The works of Bouillaud and GI. Sokolsky in the history of the development of the theory of rheumatic fever had the value of scientific achievement and became a turning point in the understanding of this disease. From the historical and scientific point of view, the definition of rheumatic fever as Sokolsky-Buyo disease is justified.

In 1894 Romberg found in 2 dead patients significant infiltrates in the place of attachment of the valves, and in the myocardium - numerous small calluses from the connective tissue, which confirmed rheumatic myocardial damage. Later it was proved in the classic works of Aschoff, who described rheumatic granulomas in the myocardium in 1904. Talalaeva (1929) has an exceptional merit in studying the stages of development of the rheumatic process. "The value developed by Aschoff and VT. Talalayevym morphological criteria of rheumatic heart disease, - wrote A.I., Nesterov, - is so great that rheumatic granulomas are rightly called Ashot-talalayevsky,

Many outstanding clinicians of the 20th century. Devoted themselves to the study of problems of rheumatic fever and rheumatic heart disease (RBS) (Botkin SP, Davydovsky IV, Nesterov AI, Strukov AI, etc.). For the clinical-anatomical characterization of rheumatic carditis in children, MA's research is of great importance. Skvortsova. In 1944 r. T. Jones (Jones) presented the first classification of radar, which in improved form is used to this day. However, when studying Russian literature, it was established that 5 years before the appearance of T. Jones's work, the outstanding Soviet pediatrician AA Kissel described the five main criteria of T. Jones, calling them "absolute signs of rheumatism." He argued that "rheumatic nodules, circular erythema, chorea and a special form of arthritis, which quickly pass from one joint to another, serve as absolute attributes for rheumatism. The presence of only one of these signs finally solves the question of the presence of rheumatism in the child. Perhaps, to absolute attributes should be attributed still quite a kind of heart damage in rheumatism, since when the heart is damaged in children from other causes of a similar clinical picture, we do not observe. To defeat the heart of rheumatic origin is characterized by a constant progression of heart disease, and often the patient does not complain about anything. This feature is almost never happens when a heart of another origin is affected. "

The discovery in 1958 by the French scientist J. Dass of the main histocompatibility system and the clinical development of the topic "Association of HLA with various diseases", which began in 1967, turned out to be prerequisites for studying the relationship of HLA with rheumatic fever. In 1976, Academician A.I. Nesterov wrote that "the modern concepts of rheumatism lack something very important, intimate, probably, in the individual features of the molecular structure of lymphocytes or features of an individual gene pool." This statement by the largest Russian scientist, a world-renowned rheumatologist, turned out to be prophetic. Since 1978, a new direction has arisen in our country in studying the mechanisms of predisposition to rheumatic fever.

Thanks to the works of the outstanding scientist and our teacher, Academician A.I. Nesterov developed additions to the diagnostic criteria of rheumatic fever, which increased their differential diagnostic significance. Deep study of the etiology, clinic and diagnosis of rheumatic fever allowed AI. Nesterov put forward the problem of an active pathological process and develop a classification of the degrees of activity of the rheumatic process, approved at a symposium of socialist countries in 1964 and served as the basis for the creation of such classifications in other rheumatic diseases. He wrote: "Each new classification is not a complete system of knowledge and experience, but only the nodal stage of scientific progress, which, with the accumulation of knowledge, will be replaced by a new stage that opens and explains new facts and new scientific and practical horizons." Given the aetiological role of streptococcus in the development of rheumatic fever in the Institute of Rheumatism of the USSR Academy of Medical Sciences (GU "Institute of Rheumatology RAMS"), created by Academician A.I. Nesterov, the original technique of bicillin-aspirin prevention of recurrence of the disease was developed.

The ideas about the nature of rheumatic fever and its clinical-anatomical forms formed in different countries served as an occasion for various signs of the disease in the historical aspect: rheumatic fever of Anglo-Saxon authors, acute articular rheumatism (rhumatisme areculaire aigu) or, more rarely, the disease of Buyo (maladie de Bouillaud) of French authors, rheumatic polyarthritis or acute rheumatic fever of German authors. It is now generally accepted to refer to the disease as rheumatic fever.

To date, acute rheumatic fever is one of the few rheumatic diseases, the etiology of which is proven. Undoubtedly, this disease is caused by beta-hemolytic streptococcus group A (BHSA). According to the figurative expression of Academician A.I. Nesterov, "without streptococcus there is neither rheumatic fever, nor its relapse."