Rheumatic fever is an autoimmune disease caused by streptococcal infection, which can involve multiple systems such as joints, heart, and skin. The resultant joint lesions used to be called “rheumatoid arthritis” and are typically characterized by multiple, large-joint, wandering arthritis.
Causes
Group B hemolytic streptococcal throat infection is the cause of rheumatic fever. It is generally believed to be related to the specific composition of the bacterium. Its pod membrane composition has common antigens with hyaluronic acid in human synovial membrane and joint fluid, and the protein composition of cell wall and cell membrane is similar to that of human heart, kidney and nerve tissue, which can induce immune damage by cross-reaction. In addition, certain viruses such as coxsackievirus B4 infection may also be involved in the pathogenesis of rheumatic fever, but further studies are needed to confirm this.
Pathogenesis
The mechanism by which streptococci cause rheumatic fever is not fully understood. Studies have confirmed the presence of elevated autoantibodies and immune complexes in patients with rheumatic fever compared with streptococcal pharyngitis alone, and the presence of a large infiltration of lymphocytes and phagocytes in the damaged tissues of patients, suggesting that tissue damage in rheumatic fever is associated with humoral and cellular immune-mediated immune damage. In addition, rheumatic fever, like other autoimmune diseases, has a genetic susceptibility, and multiple genes may be closely associated with the development of rheumatic fever. Studies suggest that the D8/17 antigen is a marker gene for identifying people at risk for rheumatic fever.
Clinical manifestations
Prevalent population
The age of onset of the disease is 9-17 years old, mainly in adolescents. In areas with crowded living rooms, poor economy and lack of medicine, it is conducive to the reproduction and spread of streptococci, which can easily constitute an epidemic of the disease. At present, the incidence of the disease in western developed countries has been significantly reduced, but the incidence in developing countries, such as Southeast Asia, Africa and vast areas of Central and South America is still high. The incidence is higher in rural than in urban areas.
Disease symptoms
(1) Prodromal symptoms: 1-6 weeks before the appearance of typical symptoms, there may be laryngitis or tonsillitis and other manifestations of upper respiratory tract infection, such as fever, sore throat, swollen submandibular lymph nodes, etc. 50%-70% of patients have irregular fever, mild to moderate fever is more common, there may also be high fever. More than half of the patients have mild or transient prodromal symptoms and are not noticed.
(2) Rheumatoid arthritis: Wandering, polyarthritis. Large joints such as knees, ankles, elbows and shoulders are mainly involved, and there may be localized redness, swelling, heat and pain. Joint pain rarely lasts more than a month and usually subsides within 2 weeks. There is no joint deformity but recurrent attacks are common. Mild and atypical cases may show single or few joint involvement, or involve some uncommon joints such as hip, finger joint, mandibular joint, sternoclavicular joint, and thoracic intercostal joint, the latter often being mistaken for cardiac inflammatory symptoms.
(3) Other manifestations of rheumatic fever: In addition to wandering polyarthritis, rheumatic fever may manifest as carditis, subcutaneous nodules, annular erythema, and chorea. These manifestations may occur separately or in combination. Skin and subcutaneous tissue manifestations are uncommon and usually occur only in patients with preexisting arthritis, chorea, or chorea.
①Cardiac inflammation: Patients with mild disease may have only progressive palpitations, increased shortness of breath with no other explanation, or only subclinical manifestations of cardiac inflammation such as dizziness and fatigue. Sinus tachycardia is often an early manifestation of carditis, and the heart rate is disproportionate to the increase in body temperature. In severe cases, valvular disease such as mitral stenosis and aortic valve closure insufficiency may be present. Pericarditis is mostly mild. Cardiac inflammation can occur alone or in combination with other symptoms.
②Erythema annulare: the rash is a light red ring-shaped erythema with a pale center, which appears and disappears suddenly and fades in a few hours or 1-2 days, often distributed in the proximal extremities and trunk. Annular erythema often appears later after streptococcal infection.
③Subcutaneous nodules: they are slightly hard, painless small nodules, located in the subcutaneous tissue of the joint extension, especially at the elbow, knee, wrist, occipital or thoracolumbar spine, with no adhesion to the skin and no erythematous inflammatory changes on the surface skin, often appearing simultaneously with cardiac inflammation, and are one of the manifestations of rheumatic activity.
Chorea: common in children aged 4~7 years old, it is an involuntary trunk or limb movement, with facial manifestations such as squeezing eyebrows and blinking eyes, shaking head and neck, pouting mouth and tongue. The limbs show rhythmic alternating movements in all directions, which are aggravated by excitement and disappear during sleep.
⑤ Other symptoms: excessive sweating, epistaxis, petechiae, abdominal pain, etc. may occur. In the presence of renal damage, red blood cells and protein may appear in the urine.
Auxiliary tests
(1) Laboratory tests: positive pharyngeal swab culture for streptococci and positive anti-streptococcal hemolysin “O” (ASO) suggest that the patient has had a recent group A group B hemolytic streptococcal infection. Acute inflammatory reactants such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated in the acute phase. Serum glycoprotein electrophoresis alpha 1 and alpha 2 are increased by up to 70%. Non-specific immune markers such as immunoglobulins (IgM, IgG), circulating immune complexes (CIC) and complement C3 are increased in about 50-60% of cases. Positive anti-cardiac antibody (AHRA), anti-group A streptococcal wall polysaccharide antibody (ASP), and peripheral blood lymphocyte procoagulant activity test (PCA) also have good sensitivity and specificity in the diagnosis of rheumatic fever.
(2) Electrocardiogram and imaging tests: have greater significance in rheumatic heart disease. Electrocardiography helps to detect sinus tachycardia, prolonged P-R interval and various arrhythmias. Echocardiography can detect early, mild cardiac inflammation as well as subclinical cardiac inflammation and pericardial effusion. Echocardiography (ECT) can detect mild and subclinical myocarditis.
Complications
Patients with recurrent rheumatic fever or during treatment of rheumatic fever are prone to pulmonary infections and severe cases may result in cardiac insufficiency, sometimes complicated by endocarditis, hyperlipidemia, hyperglycemia, and hyperuricemia. Patients may also be combined with coronary artery disease to acute heart attack. These conditions may be related to the patient’s decreased body resistance or long-term treatment with hormones and aspirin.
Diagnosis and Differentiation
Disease diagnosis
(1)The American Heart Association revised Jones’ diagnostic criteria in 1992.
(2)2002~2003 WHO diagnostic criteria for rheumatic fever and rheumatic heart disease.
Differential diagnosis
1, rheumatoid arthritis: the difference with this disease is that arthritis is persistent, symmetrical metacarpophalangeal, proximal interphalangeal and wrist joints and other small joints are mainly involved, morning stiffness is obvious, rheumatoid factor and anti-cyclic citrulline antibodies and other autoantibodies are positive, bone and joint destruction is common, and joint deformity often occurs without active treatment.
2. Systemic lupus erythematosus: The main difference with this disease is that the disease has a special rash, such as butterfly-shaped erythema, and may have multi-system damage such as kidney and blood system.
3, ankylosing spondylitis: the disease has obvious manifestations of sacroiliac arthritis, spondylitis and attachment pointitis, HLA-B27 positive, with a family tendency to develop, while rheumatic fever usually does not have these manifestations;
4, tuberculosis rheumatism: the main difference with this disease is a history of tuberculosis infection, positive tuberculin skin test, poor efficacy of non-steroidal anti-inflammatory drugs, and effective anti-tuberculosis treatment.
5, subacute infective endocarditis: the disease has progressive anemia, petechiae, splenomegaly, embolism, and positive blood cultures, while rheumatic fever usually has none of these manifestations.
6, viral cardiac inflammation: the main difference with this disease is that the disease has prodromal symptoms of viral infection such as nasal congestion, runny nose and lacrimation, significantly higher viral antibody potency, and significant and intractable arrhythmias.
Disease treatment
Treatment goals
include: clearing streptococcal infection and removing the cause of rheumatic fever; 2) controlling clinical symptoms; 3) managing various complications and improving the patient’s quality of life.
Treatment measures
1. General treatment.
Pay attention to keep warm, avoid moisture and cold. Early acute arthritis should be bed rest until blood sedimentation and body temperature are normal and then start activities. Those with cardiac inflammation should continue bed rest for 3~4 weeks before resuming activities after body temperature is normal, tachycardia is controlled and ECG is improved.
2. Elimination of streptococcal foci of infection.
Penicillin is the drug of choice. For those who are allergic or resistant to penicillin, erythromycin or roxithromycin can be used instead.
3.Anti-rheumatic treatment.
For rheumatoid arthritis, non-steroidal anti-inflammatory drugs are preferred and aspirin is commonly used, with a starting dose of 3~4g/day for adults and 80~100mg/kg/day for children, divided into 3~4 oral doses. For cardiac inflammation, glucocorticoids are generally used for treatment. To prevent rebound after discontinuation of hormones, aspirin can be added 2 weeks or earlier before discontinuation of hormones, and aspirin can be discontinued only after 2~3 weeks of hormone discontinuation. The course of anti-rheumatic therapy is 6-8 weeks for simple arthritis and at least 12 weeks for cardiac inflammation. If the disease is prolonged, the course of therapy should be extended until the disease is fully recovered according to clinical manifestations and laboratory test results.
Management of subclinical cardiac disease: No previous history of cardiac disease, recent history of rheumatic fever, no special treatment, regular follow-up and adherence to long-acting penicillin prophylaxis. For those who have had cardiac fever or are suffering from rheumatic heart disease, if there are only slight changes in signs and normal laboratory, echocardiographic and electrocardiographic examinations, anti-rheumatic treatment is not necessary and should be followed up; if the changes in the above examinations are obvious and there is no other explanation, anti-rheumatic treatment can be carried out for 2 weeks on a trial basis, and if the laboratory examinations return to normal, no further treatment is needed. If it is still not negative and there are suspicious symptoms and signs or echocardiographic or electrocardiographic changes, formal anti-rheumatic treatment is required.
4. Chorea.
Avoid bright light and noise stimulation, and add sedatives, such as Valium, barbiturates or chlorpromazine. Hormone therapy is effective, especially for those patients for whom the above drug therapy is ineffective or intolerable. Plasma exchange and intravenous gammaglobulin can be used as experimental treatment.
5. Treatment of complications.
For cardiac insufficiency, small doses of digitalis and diuretics should be given; if infection should be treated for different conditions and effective antibiotics should be selected; metabolic abnormalities and coronary artery disease should also be promptly detected and treated.
Disease prognosis
The prognosis of polyarthritis alone is good, and the majority of patients can be cured. About 70% of patients with rheumatic fever recover within 2 to 3 months. In the acute phase, about 65% of patients have heart involvement, and if not treated promptly and reasonably, 70% may develop valve disease.
Disease prevention
Prevention of rheumatic fever includes primary prevention and secondary prevention.
Primary prevention
That is, to strengthen health care and health education work, block the transmission of group A beta hemolytic streptococcal infection and stop the occurrence of rheumatic fever. Specific measures include.
(1) Improving the socio-economic situation;
(2) Improving the living environment and avoiding dense population;
(3) prevent malnutrition, physical exercise, enhance physical fitness, and improve resistance to disease;
(4) Prevention of cold and moisture, active prevention of upper respiratory tract infections, and thorough treatment of acute and chronic foci of streptococcal infections;
(5) Health education.
Secondary prevention
It is to prevent recurrence of rheumatic fever or secondary rheumatic heart disease. For secondary prophylaxis of recurrent rheumatic fever or rheumatic heart disease: the above dose should be injected intramuscularly once every 1~3 weeks depending on the condition, until the streptococcal infection no longer recurs, then it can be changed to once every 4 weeks.
For those who are allergic or resistant to penicillin, erythromycin 0.25g 4 times daily or roxithromycin 150mg 2 times daily for 10 days can be used instead. Or Lincomycin, cephalosporins or quinolones can also be used. In recent years, Azithromycin 5 days course method, patients over 16 years old 500mg/d in two doses on the first day, 250mg dose on the second to fifth day, after the above full course of treatment, can be followed by erythromycin 0.5g/d or sulfadiazine (or sulfathiazole) 0.5g once a day (weight <27kg), or 1g once a day (weight ≥27kg) for long-term prophylaxis It is important to drink plenty of water and to review regularly.
It is important to pay attention to drink more water and review the blood picture regularly to prevent leukopenia. The duration of secondary prophylaxis is decided according to the patient’s age, streptococcal susceptibility, the number of episodes of rheumatic fever, and the presence of valvular disease left behind. In simple arthritis, the duration of prophylaxis can be slightly shortened, at least until the age of 21 years or for 8 years in pediatric patients and at least 5 years in adult patients. In young patients, those with susceptibility, those with recurrent rheumatic fever episodes, those with a history of heart inflammation or residual valve disease, the duration of prophylaxis is at least 10 years or until the age of 40, or even for life. For those who have had heart inflammation but do not have residual valve disease, the duration of prevention is at least 10 years, and for pediatric patients until adulthood.