Rheumatic fever
Overview
Rheumatic fever (rheumatic fever) is an autoimmune disease caused by the infection of group A beta-hemolytic streptococcus in the upper respiratory tract, which can have systemic connective tissue lesions, especially invading the joints, heart, skin, and occasionally involving the nervous system, blood vessels, plasma membranes, and internal organs such as lungs and kidneys. The disease has a tendency to recur, and recurrent episodes of cardiac inflammation can lead to the development of rheumatic heart disease.
The disease occurs most often in the winter and spring rainy seasons, and humidity and cold are important triggers. The age of first occurrence is 9-17 years old, mainly in the school age, and the onset is rare before the age of 4 years, and less common after the age of 25 years. The proportion of males and females is equal. Overcrowding, low nutrition, and lack of medicine are conducive to the reproduction and spread of streptococci, which mostly constitute an epidemic of the disease. Although the incidence of the disease has declined significantly in Western developed countries, the incidence in developing countries, such as Southeast Asia, Africa and large areas of Central and South America is still very high. The incidence of rheumatic fever in patients with untreated streptococcal infection during the epidemic period is 1~3%. 1992~1995, the annual incidence rate of primary and secondary school students in China was 20/100,000, rheumatic heart disease was 22/100,000, and the prevalence of rheumatic fever was about
80/100,000. The incidence rate in urban and rural areas is higher than that in urban areas.
Clinical manifestations
1.Symptoms and signs
(1) Prodromal symptoms: 2-6 weeks before the appearance of typical symptoms, there are often upper respiratory tract streptococcal infection manifestations such as pharyngitis or tonsillitis, such as fever, sore throat, swollen submandibular lymph nodes, cough and other symptoms. However, more than half of the patients fail to complain of this presenting history clinically because of mild or transient prodromal symptoms.
(2) Typical manifestations: Rheumatic fever has five main manifestations: wandering polyarthritis, carditis, subcutaneous nodules, annular erythema, and chorea. These manifestations can occur alone or in combination and can give rise to many clinical subtypes. Cutaneous and subcutaneous manifestations are uncommon and usually occur only in patients with existing arthritis, chorea, or cardiac disease. 50-70% of patients have irregular fever, moderate fever is common, and high fever may be present, but fever is not diagnostically specific.
Arthritis” is the most common clinical manifestation. It is a wandering, multiple arthritis. Large joints such as knees, ankles, elbows, wrists and shoulders are mainly involved, with localized redness, swelling, burning, pain and pressure, sometimes with exudation. Joint pain rarely lasts more than a month and usually subsides within 2 weeks. No deformity remains after an arthritic episode. Salicylic acid preparations are very effective in relieving joint symptoms. Arthralgia may occur or worsen with cold or rainy weather. Mild and atypical cases may present with mono- or oligo- or oligo-articular involvement, or involve some uncommon joints such as hip, finger, mandibular, sternoclavicular and thoracic intercostal joints, the latter often being mistaken for cardiac inflammatory symptoms.
②Cardiac inflammation: Patients often have complaints of palpitations, shortness of breath, and precordial discomfort after exercise. In mitral valve inflammation, there may be a high-pitched, systolic blowing murmur or a short, low-pitched mid-diastolic murmur (Carey coombs murmur) in the apical region. A soft mid-diastolic murmur may be heard at the base of the heart in aortic valve inflammation. Sinus tachycardia (heart rate >100 beats/min after falling asleep) is often an early manifestation of cardiac inflammation. Pericarditis in rheumatic fever is mostly mild, with pericardial effusion detectable on echocardiography and congestive heart failure in severe cases of cardiac fever. Mild patients may have only progressive palpitations and increased shortness of breath without any other pathologic or physiologic explanation (signs of hypocapnia), or only subclinical manifestations of cardiac inflammation with dizziness, fatigue, and weakness. Cardiac inflammation may occur alone or in conjunction with other symptoms. Approximately 50% of patients with rheumatic fever with initial onset of arthritis have cardiac inflammation. In approximately 50% of adult patients with cardiac involvement, the cardiac damage is detected much later.
(iii) Erythema annulare: 6-25% of patients have a pale red erythema annulare with a pale center, which appears and disappears suddenly and fades within a few hours or one to two days, and is found on the proximal extremities and trunk. Erythema annulare often appears later after streptococcal infection.
④Subcutaneous nodules: small, slightly hard, painless nodules, located in the subcutaneous tissue of the joint extension, especially at the elbow, knee, wrist, occipital or thoracolumbar spine, without adhesion to the skin and without erythematous inflammatory changes on the surface skin, often appearing at the same time as cardiac inflammation. The incidence is 2%~16%.
⑤ Chorea: often occurs in children aged 4 to 7 years. It is a purposeless, involuntary trunk or limb movement, and the face can be characterized by eyebrow squeezing and blinking, head shaking and neck turning, mouth pouting and tongue stretching. The limbs may exhibit rhythmic alternating movements such as straightening and flexion, inversion and abduction, forward and backward rotation, etc. The movements are aggravated during excitement and disappear during sleep, and the mood is often unstable. The incidence is about 3% in domestic reports, but up to 30% in foreign reports.
(6) Other symptoms: excessive sweating, epistaxis, petechiae, and abdominal pain are not uncommon. The latter is sometimes misdiagnosed as appendicitis or acute abdomen, which may be due to mesenteric vasculitis. When there is renal damage, red blood cells and protein may appear in the urine. As for pneumonia, pleurisy and encephalitis, they are rare in recent years.
2, laboratory tests: streptococcal infection indicators, increased acute phase reactants and a number of abnormal immune indicators can be measured. The positive rate of streptococcus in pharyngeal swab culture is about 20-25%, and the positive rate of anti-streptococcal hemolysin “O” (ASO) and anti-DNA enzyme-B are about 50-85%, respectively, and the latter lasts for a long time, which is of great significance to determine the cause of streptococcal infection. The erythrocyte sedimentation rate (ESR) and C-reactive protein positivity rate are higher in the acute phase of first-episode rheumatic fever, up to 80%. However, the positive rate of ESR acceleration is only about 60% for late onset or prolonged rheumatic fever, and the positive rate of CRP can be reduced to 25% or lower, but the increase of serum glycoprotein electrophoresis α1 and α2 can reach 70%, which is more sensitive than the former two. Non-specific immune indicators such as immunoglobulins (IgM, IgG), circulating immune complexes (CIC) and complement C3C are increased in about 50-60%.
Specific immune indicators are important for the diagnosis of rheumatic heart disease. Among them, the positive rate of anti-cardiac antibody (AHRA) is 48.3% and 70% by indirect immunofluorescence and ELISA, respectively; the positive rate of anti-group A streptococcal wall polysaccharide antibody (ASP) is 70%~80%; the positive rate of peripheral blood lymphocyte procoagulant activity test (PCA) is above 80%, and the latter has higher sensitivity and specificity.
3, electrocardiography and imaging examinations: have greater significance for rheumatic heart disease. Electrocardiography can help detect sinus tachycardia, prolonged P~R interval and various arrhythmias. Echocardiography can detect early, mild cardiac inflammation as well as subclinical cardiac inflammation, and is more sensitive to mild pericardial effusion. Myocardial nuclear examination (ECT) can detect mild and subclinical myocarditis.
Diagnostic points]
1. Typical acute rheumatic fever: The Jones criteria, revised in 1992, are traditionally used, which include
Primary manifestations: carditis, polyarthritis, chorea, annular erythema, subcutaneous nodules.
Secondary manifestations: arthralgia, fever, increased acute phase reactants (ESR, CRP), and prolonged P~R interval.
Evidence of antecedent streptococcal infection: i.e. positive pharyngeal swab culture or rapid streptococcal antigen test, or elevated streptococcal antibody potency.
If there is evidence of antecedent streptococcal infection and two major manifestations or one major manifestation plus two minor manifestations, it is highly suggestive of possible acute rheumatic fever. However, in the following three cases, and no other etiology can be found, it is not necessary to strictly follow the above diagnostic criteria, namely: chorea as the only clinical manifestation; insidious onset or slowly occurring cardiac inflammation; history of rheumatic fever or current rheumatic heart disease, when reinfected with group A streptococcus, there is a high risk of rheumatic fever recurrence.
2, atypical or mild rheumatic fever: often fail to meet the revised criteria of Jones (1992), the diagnosis can be made according to the following steps.
Careful questioning and examination to determine the presence of primary or secondary manifestations. For example, mild cardiac fever often presents with progressively worse palpitations and shortness of breath without any cause. Hypothermia can be detected by periodic temperature measurements and may be clinically indicated by complaints of dizziness and fatigue.
Specific immune tests can be performed in hospitals where available. Such as anti-cardiac antibodies, which can be performed with only fluorescence microscopy, and positive ASP and PCA are highly suggestive of the presence of rheumatic heart disease.
Color Doppler echocardiography, electrocardiography, and myocardial nuclear examinations can detect mild and subclinical forms of cardiac inflammation (sometimes positive results can be measured in cases with clinical manifestations of simple arthritis).
Other possible diseases are ruled out. The following diseases should be differentiated from.
① rheumatoid arthritis: the difference with this disease is persistent arthritis with morning stiffness, elevated rheumatoid factor potency, and significant bone and joint damage;
(ii) Systemic lupus erythematosus: there is a specific rash, such as butterfly erythema, high potency anti-nuclear antibodies, anti-dsDNA and anti-Sm antibodies positive, there may be kidney and blood system damage.
③Ankylosing spondylitis: with obvious manifestations of sacroiliac arthritis and tendon telangiectasia, positive for HLA-B27, with a family tendency to develop;
④Other reactive arthritis: history of intestinal or urinary tract infection, mainly arthritis of the lower extremities. With tendonitis, lumbago, HLA-B27 positive;
⑤ Allergic arthritis of tuberculosis infection (Poncet’s disease): history of tuberculosis infection, positive tuberculin skin test, poor efficacy of non-steroidal anti-inflammatory drugs, effective anti-tuberculosis treatment;
(6) Subacute infective endocarditis: progressive anemia, petechiae, splenomegaly, embolism, and positive blood cultures;
(vii) Viral cardiac inflammation: there are prodromal symptoms of viral infection such as nasal congestion, runny nose and lacrimation, significantly increased viral neutralization test and antibody potency, and significant and intractable arrhythmias.
Early stages of the above diseases are often confused with rheumatoid arthritis or cardiac inflammation, which can easily lead to misdiagnosis. Exclusionary diagnosis is an indispensable diagnostic step to confirm the diagnosis of rheumatic fever.
Treatment plan and principles]
Treatment goals: clear streptococcal infection, remove the cause of induced rheumatic fever; control clinical symptoms, so that cardiac inflammation, arthritis, chorea and other symptoms are rapidly relieved, and relieve the pain caused by rheumatic fever; deal with various complications and comorbidities, improve patients’ physical quality and quality of life, and prolong life expectancy.
1.General treatment: pay attention to keep warm, avoid moisture and cold. Those with cardiac inflammation should rest in bed. After the body temperature is normal, tachycardia is controlled and ECG is improved, continue to rest in bed for 3~4 weeks and then resume activities. Acute arthritis should also be bed rest in the early stage, until the blood sedimentation and body temperature is normal, then start activities.
2, eliminate streptococcal infection foci: this is an important measure to remove the cause of rheumatic fever, otherwise the disease will be recurrent or prolonged. At present, it is recognized that benzathine penicillin is the drug of choice, for the first streptococcal infection, weight below 27Kg can be injected benzathine penicillin 600,000u, weight above 27Kg with 1.2 millionu a dose can be. For secondary prophylaxis of re-emerging 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, it can be changed to once every 4 weeks. For those who are allergic or resistant to penicillin, erythromycin 0.25g, 4 times a day or roxithromycin 150mg, 2 times a day 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 of age on the first day 500mg/day, divided into two doses, the second to fifth day 250mg dose, after the above full course of treatment, can be followed by erythromycin 0.5/day or sulfadiazine (or sulfathiazole) 0.5g, once a day (body weight < 27kg), or 1g, once a day (body weight ≥ 27kg) for long-term prophylaxis. However, attention should be paid to drinking more water and reviewing the blood picture regularly to prevent leukopenia.
Duration of secondary prophylaxis: It should be based on the patient’s age, streptococcal susceptibility, the number of episodes of rheumatic fever, and the presence or absence of valvular disease legacy. In young patients, those with susceptibility, those with repeated episodes of rheumatic fever, those with previous heart infections or legacy valve disease, the duration of prophylaxis should be as long as possible, at least 10 years or up to 40 years of age, or even lifelong prophylaxis. For those who have had heart inflammation but do not have residual valve disease, the duration of prevention should be at least 10 years, or until adulthood for children. For simple arthritis, the duration of prevention can be slightly shortened to at least 21 years or 8 years for pediatric patients and at least 5 years for adult patients.
3.Anti-rheumatic therapy: For simple joint involvement, non-steroidal anti-inflammatory drugs are preferred, commonly used acetylsalicylic acid (aspirin), the starting dose is 3~4g/day for adults and 80~100mg/kg/day for children, divided into 3~4 oral doses. Other non-steroidal anti-inflammatory drugs, such as naproxen and anti-inflammatory pain, can also be used. For those who have heart inflammation, glucocorticoid therapy is generally used. Prednisone is commonly used, with a starting dose of 30~40mg/day for adults and 1.0~1.5mg/kg/day for children, divided into 3~4 oral doses, and the dose is reduced to 10~15mg/day for maintenance treatment after the condition is relieved. To prevent rebound after discontinuation of hormone, aspirin can be added 2 weeks or earlier before discontinuation of hormone, and aspirin can be discontinued only after 2~3 weeks of hormone discontinuation. For serious conditions, such as pericarditis, cardiac inflammation and acute heart failure, dexamethasone 5~10mg/day or hydrocortisone 200mg/day can be given intravenously until the condition improves, and then oral hormone therapy can be changed. 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 complete recovery according to clinical manifestations and laboratory test results.
Management of subclinical cardiac disease: Those with no previous history of cardiac disease and recent rheumatic fever need only regular follow-up and adherence to long-acting penicillin prophylaxis, no special treatment is needed. For those who have had cardiac fever or are suffering from rheumatic heart disease, specific treatment measures can be formulated according to the changes in laboratory tests (such as blood sedimentation, anti-heart antibodies or ASP, PCA, etc.), echocardiogram, electrocardiogram and physical signs: ① If there is only a slight change in physical signs and the above-mentioned tests are normal, anti-rheumatic treatment is not necessary, and follow-up should be continued; ② If the changes in laboratory tests are obvious, but there is no other explanation, anti-rheumatic treatment can be 2 weeks of trial anti-rheumatic therapy (usually with aspirin), if the laboratory tests return to normal after 2 weeks, no further treatment is required, if the laboratory tests are still abnormal, the relevant items can be rechecked after 2 weeks of continued anti-rheumatic therapy. If it is still not negative, and there are suspicious symptoms and signs or echocardiogram or ECG changes, regular anti-rheumatic treatment is needed; ③ If laboratory tests, ECG and echocardiogram have obvious changes without other reasons to explain, although there are no obvious symptoms, further observation and a course of anti-rheumatic treatment should be made.
For patients with chorea, sedatives such as Valium, barbiturates or chlorpromazine should be added on top of the above treatment, and strong light and noise stimulation should be avoided as much as possible.
4, complications and comorbidities treatment: in the process of rheumatic fever treatment or rheumatic heart disease repeated rheumatic fever activity, etc., patients are prone to lung infection, severe cases can lead to cardiac insufficiency, sometimes complicated by endocarditis, hyperlipidemia, hyperglycemia, hyperuricemia, senior rheumatic heart disease patients will also be combined with coronary heart disease and even acute myocardial infarction. These conditions may be related to the decrease of resistance of patients or long-term treatment with glucocorticoids and aspirin, and may also be related to the tendency of rheumatic fever to become milder in recent years, and the longer life expectancy of rheumatic heart disease patients compared with the past and the complication of various diseases of the elderly. Therefore, the dose and course of hormones and NSAIDs should be appropriate in the treatment process to avoid the emergence and aggravation of various complications and comorbidities. At the same time, during the treatment process, we need to be alert to various possibilities and deal with them in time, such as cardiac insufficiency, small doses of digitalis and diuretics should be given; such as infection, effective antibiotics should be selected for different conditions; metabolic abnormalities and treatment of coronary heart disease should also be detected and dealt with in time.