Acute rheumatic fever – a post-infectious complication of tonsillitis (sore throat) or pharyngitis caused by p-hemolytic streptococcus group A, manifested as a systemic inflammatory disease of the connective tissue with a primary lesion of the cardiovascular system (carditis), joints (migrating polyarthritis), brain (chorea) and skin (annular erythema, rheumatic nodules). Acute rheumatic fever develops in predisposed persons, mainly young (7-15 years old), and is associated with an autoimmune response of the body due to cross-reactivity between Ar streptococcus and Ar affected human tissues (the phenomenon of molecular mimicry).
Chronic rheumatic heart disease is a disease characterized by damage to the heart valves in the form of marginal fibrosis of the valve cusps of inflammatory genesis or heart disease (insufficiency and / or stenosis) formed after acute rheumatic fever.
The incidence of acute rheumatic fever in US is 2.7 per 100 000 population, chronic rheumatic heart disease – 9.7 per 100 000 population, including rheumatic heart disease – 6.7 per 100 000 population. The incidence of chronic rheumatic heart disease is 28 cases per 100,000 children and 226 per 100,000 adults. Persons of 7–15 years of age predominate. Sexual dimorphism is not clearly traced.
ETIOLOGY
β- Hemolytic Streptococcus
Acute rheumatic fever develops 2-4 weeks after suffering a sore throat or pharyngitis caused by highly contagious ” rheumatogenic ” strains of p-hemolytic streptococcus group A (serotypes M3, M5, M18, M24). M-protein (a specific protein that is part of the cell wall of p-hemolytic streptococcus group A and suppresses its phagocytosis) contains antigenic determinants having similarities with components of the heart muscle, brain and synovial membranes.
Genetic factors
The role of genetic factors is evidenced by the higher prevalence of acute rheumatic fever and chronic rheumatic heart disease (including rheumatic heart disease) in individual families. In 75-100% of patients and only in 15% of healthy people, there is a specific alloantigen 883 (D8 / 17) on B-lymphocytes, detected with the help of special monoclonal.
PATHOGENESIS AND PATHOMORPHOLOGY
Several mechanisms are involved in the development of acute rheumatic fever. Direct toxic damage to the components of the myocardium by the cardiotropic enzymes of the p-hemolytic streptococcus group A may play a role. However, the development of cellular and humoral immune responses to various AH streptococci is of primary importance. The synthesized anti-streptococcal AT cross-reacts with myocardial artery Ag (a phenomenon of molecular mimicry), as well as with cytoplasmic Arg nerve tissue localized in the subtalamic and caudal regions of the brain (mainly in the striatum). In addition, M-protein has the properties of superantigen – causes a strong activation of T-and B-lymphocytes without its preliminary processing by Ar- representing cells and interaction with molecules of the main histocompatibility complex of class II.
Stages of the pathological process
In acute rheumatic fever, there are 4 stages of the pathological process in the connective tissue:
• stage of mucoid swelling;
• stage of fibrinoid necrosis (irreversible phase of disorganization of the connective tissue);
• the stage of proliferative reactions, during which the formation of Aschoff-Talalaev granulomas occurs as a result of necrosis of heart tissue and proliferation of connective tissue cells;
• stage of sclerosis.
Rheumatic granuloma consists of large, irregularly shaped basophilic cells, giant multinucleated cells of myocyte origin with eosinophilic cytoplasm, and lymphoid, plasma cells. Granulomas are usually located in the myocardium, endocardium, perivascular connective tissue of the heart. Currently, granulomas are less common. When trochee cells of the striatum change. Damage to the skin and subcutaneous tissue due to vasculitis and focal inflammatory infiltration.
CLINICAL PICTURE
The onset of acute rheumatic fever is closely related to the age of the patients. In more than half of the children, the disease occurs 2-3 weeks after a sore throat with a sudden increase in body temperature, the appearance of asymmetrical migrating pains in large joints (most often in the knee) and signs of carditis (chest pain, shortness of breath, palpitations, etc.). In some cases, a monosymptomatic course is observed with a predominance of signs of arthritis or carditis (or very rarely, chorea).
Equally acute in the type of outbreak, acute rheumatic fever develops in recruiting soldiers who have had a sore throat. For adolescents and young people, after remitting the clinical manifestations of angina, a gradual onset of subfebrile body temperature, arthralgia in large joints, or only moderate signs of carditis is more characteristic.
Repeated attack of acute rheumatic fever is also associated with a streptococcal etiology of a pharyngeal infection and is manifested mainly by the development of carditis.
Arthritis
Arthritis (or arthralgia) of several large joints is one of the leading symptoms of the disease in 60-100% of patients with the first attack of acute rheumatic fever. Pain in the joints is often so pronounced that they lead to a significant restriction of their mobility. Simultaneously with the pain, swelling of the joints due to synovitis and damage to the periarticular tissues, sometimes reddening of the skin over the joints. Often affects the knee, ankle, wrist and elbow joints.
The prevailing form of injury in modern conditions is transient oligoarthritis and, less commonly, monoarthritis . The characteristic features of rheumatoid arthritis are the migratory nature (signs of damage to some joints almost completely disappear within 1-5 days and are replaced by an equally pronounced damage to other joints) and rapid full reversal under the influence of modern anti-inflammatory therapy.
Carditis
Carditis is a manifestation of acute rheumatic fever (observed in 90-95% of cases), which determines the severity and outcome of the disease. The main component of carditis is considered to be valvulitis (mainly mitral, less often aortic valve), which can be combined with damage to the myocardium and pericardium. Symptoms of rheumatic valvulitis :
• “Blowing” systolic murmur of apical localization associated with tone I (with mitral regurgitation );
• unstable low-frequency mesodiastolic murmur in the area of listening to the mitral valve;
• high-frequency decreasing protodiastolic noise heard along the left edge of the sternum (with aortic regurgitation ).
Myocardium and pericardium may be involved in the pathological process with the development of tachycardia, expansion of the boundaries of cardiac dullness, muffled heart sounds, pericardial friction noise, conduction disorders, etc. However, isolated heart damage as myopericarditis in the absence of valvulitis is not typical for acute rheumatic fever, and in these cases differential diagnosis with carditis of a different etiology is required.
On the background of pronounced arthritis or minor chorea, the clinical symptoms of carditis in acute rheumatic fever may be mild. In this regard, the diagnostic significance of EchoCG using the Doppler mode increases .
The most important feature of carditis during the first attack of acute rheumatic fever is the clear positive dynamics of its clinical manifestations under the influence of active antirheumatic therapy.
In the overwhelming majority of cases, the normalization of heart rate, the restoration of sonorous tones, a decrease in the intensity of systolic and diastolic murmurs, a reduction in the borders of the heart, the disappearance of symptoms of circulatory failure occur during the treatment.
The social significance of acute rheumatic fever is determined by acquired rheumatic heart defects, which, as it progresses, lead to permanent disability and shortened life expectancy. The frequency of formation of rheumatic heart disease after the first attack of acute rheumatic fever in children is 20-25%. Isolated heart defects predominate, often mitral insufficiency.
Rarely, aortic valve insufficiency, mitral stenosis and concomitant mitral-aortic heart disease are formed (for more details, see the chapter “Acquired heart defects”). In about 7–10% of children, after prolapsed carditis, mitral valve prolapse is formed.
In adolescents who have experienced the first attack of acute rheumatic fever, heart defects are diagnosed in one third of cases. In adult patients, this figure is 39-45%, with the maximum incidence of rheumatic heart disease (> 75%) observed during the first three years from the onset of the disease. In patients
after the first attack of acute rheumatic fever aged 23 years and older, combined and combined rheumatic heart defects are formed in 90% of cases.
Chorea
Rheumatic chorea (small chorea, Sidegenam chorea ) is a typical manifestation of acute rheumatic fever associated with the involvement of various brain structures (striatum, subthalamic nuclei and cerebellum) in the pathological process . It is diagnosed in 6-30% of cases, mainly in children, less often in adolescents 1-2 months after suffering acute streptococcal infection. More often girls and girls are affected. The clinical picture of minor chorea includes various combinations of the following syndromes:
• choreic hyperkinesis, i.e. involuntary twitching of the limbs and facial muscles, accompanied by a violation of handwriting, slurred speech, awkwardness of movements;
• muscle hypotension (up to flaccidity of the muscles with imitation of paralysis);
• static and coordination disorders (inability to perform coordination tests, for example, finger-bearing);
• vascular dystonia;
• psycho-emotional disturbances (instability of mood, irritability, tearfulness, etc.).
Characteristic complete disappearance of symptoms in a dream.
Small chorea, as a rule, is combined with other clinical manifestations of acute rheumatic fever (carditis, polyarthritis), however in 5-7% of patients it may be the only sign of the disease. In these situations, i. in the absence of other criteria for acute rheumatic fever, the diagnosis of rheumatic chorea is valid only after excluding other causes of damage to the nervous system.
Ring erythema
Ring-shaped (anular) erythema is observed in 4-17% of patients at the height of acute rheumatic fever. It is characterized by pale pink ring-shaped rashes with a diameter from a few millimeters to 5-10 cm with a predominant localization on the body and proximal parts of the extremities (but not on the face), has a transient migrating character, does not rise above the skin, is not accompanied by itching or induction, turns pale when pressed, quickly regresses without residual effects.
Subcutaneous rheumatic nodules
Subcutaneous rheumatic nodules in recent years are observed very rarely (in 1-3% of cases). These are round, dense, sedentary, painless formations of various sizes, often on the extensor surface of the joints, in the ankles, calcaneal tendons, spinous processes of the vertebrae, in the occipital region of the supracranial aponeurosis with a reverse development cycle from 2 weeks to 1 month.
Despite a significant reduction in the frequency of ring-shaped erythema and rheumatic nodules in the pediatric patients and the actual absence of such in adolescents and adults, the specificity of these symptoms in acute rheumatic fever remains very high, which is why they retain their diagnostic value.
DIAGNOSTICS
Diagnosis of acute rheumatic fever is often a big problem, since the main clinical manifestations of the disease (with the exception of ring-shaped erythema and rheumatic nodules, which develop very rarely) are not specific.
Differential diagnostics
Although in classic cases the diagnosis of acute rheumatic fever is not difficult, the presence of only one of the main manifestations (carditis, polyarthritis or chorea) often leads to overdiagnosis of this disease and dictates the need for differential diagnosis with many other diseases.
• If the streptococcal infection is fuzzy due to the development of carditis (or its absence), it is necessary to exclude other diseases of the heart, such as viral myocarditis (for example, caused by the Coxsackie B virus ), mitral valve prolapse (especially in hypermobile syndrome characterized by excessive
viscosity of joints and other connective tissue derivatives, including chords of the valvular apparatus), infective endocarditis, and myxoma of the heart.
• Rheumatic polyarthritis is a classic example of reactive arthritis. In this regard, it is necessary to exclude other forms of reactive arthritis. The definition of Ag HLA-B27, whose carriage is not typical for patients with rheumatic polyarthritis, can have some help , unlike reactive arthritis associated with intestinal and urogenital infections.
• It is very difficult to distinguish rheumatic fever from post-streptococcal reactive arthritis, which can develop in adolescents and young people after streptococcal infection. In this case, careful cardiac examination and observation of patients for at least 5 years is necessary.
• Unlike classical rheumatic chorea, for PANDAS ( Pediatric Autoimmune Neuropsychiatry Disorders Associated with group a Streptococcal infections – childhood autoimmune neuropsychiatric disorders associated with infections caused by group A streptococcus) are characterized by pronounced psychiatric aspects (a combination of obsessive thoughts and obsessive movements), as well as much faster and complete regression of the psychoneurological symptoms only with adequate anti- streptococcal therapy.
• The development of arthritis, carditis, CNS (encephalitis) and skin lesions (chronic migrating erythema) are characteristic of Lyme disease (tick-borne borreliosis ). Pathogen – spirochete Borrelia burgdorferi, transmitted by tick bites. For the differential diagnosis of these diseases, a thorough analysis of the anamnesis data and the serological examination of patients in relation to the detection of AT to B. burgdorferi are necessary.
• Sometimes acute rheumatic fever needs to be distinguished from APS, which can be manifested by a lesion of the heart valves and the development of chorea. In the differential diagnosis should take into account the anamnesis and the results of the determination of antiphospholipid AT.
TREATMENT
Treatment of acute rheumatic fever – a complex, consisting of etiotropic, pathogenetic, symptomatic therapy and rehabilitation measures.
Hospitalization with bed rest during the first 2-3 weeks of the disease, with the inclusion in the diet of a sufficient amount of high-grade proteins (≥1 g per 1 kg of body weight) and the restriction of table salt is shown to all patients .
Pathogenetic treatment
Pathogenetic treatment of acute rheumatic fever is the use of glucocorticoids and NSAIDs. N Prednizo previously widely used, is currently used mainly in children cardiorheumatology, especially in patients with severe polyserositis and carditis. The drug is prescribed in a dose of 20-30 mg / day to achieve a therapeutic effect, as a rule, within 2 weeks of eating . In the future, reduce the dose (2.5 mg every 5-7 days) until the full cancellation.
In the treatment of acute rheumatic fever with predominant migrating polyarthritis or chorea, as well as with the repeated attack of the disease against the background of chronic rheumatic heart disease, NSAIDs are prescribed – diclofenac in a dose of 100-150 mg / day for 2 months This drug is also considered as the drug of choice for the treatment of acute rheumatic fever in adults.
Taking into account the specific features of the effects of HA on mineral metabolism, as well as a fairly high level of dystrophic processes in the myocardium, especially in patients with recurrent acute rheumatic fever against the background of chronic rheumatic heart disease, the following drugs are indicated:
• potassium and magnesium asparaginate 3-6 tablets per day for 1 month;
• inosine in a dose of 0.2-0.4 g 3 times a day for 1 month;
• nandrolone in a dose of 100 mg intramuscularly weekly, for the course – 10 injections.