Rheumatic fever
Rheumatic fever is an inflammatory disease that occurs after a septic streptococcal infection (such as streptococcal pharyngitis or scarlet fever) and is caused by a cross-reaction of antibodies that involve the heart, joints, skin and brain. Acute rheumatic fever is usually seen in children between the ages of 6 and 15, with an initial prevalence of only 20% in adults. The disease is so named because its presentation is similar to that of rheumatism.
Diagnosis
Dr. T. Duckett Jones first publicly published the revised Jones criteria in 1944, and since then the American Heart Association has worked with other groups to revise the criteria on a regular basis. According to the revised Jones criteria, a diagnosis of rheumatic fever requires two primary criteria; or one primary criterion, plus two secondary criteria; along with the manifestations of streptococcal infection: elevated or rising streptococcal hemolysin O titers or DNA enzymes. To be excluded are chorea and chronic heart inflammation, each of which by itself can indicate rheumatic fever.
Major criteria
Polyarthritis: short migration of inflammation of large joints, usually starting in the legs and moving upwards.
Cardiac inflammation: Inflammation of the heart muscle (myocarditis), which can manifest as congestive heart failure with shortness of breath; pericarditis with a scraping murmur or a new heart murmur.
2. Subcutaneous nodules: painless, aggregated collagenous fibrous masses on bone or tendon, tense and fixed. They are usually found on the back of the wrist, outside the elbow, and in front of the knee.
3. Marginal erythema: a persistent, patchy, pale red rash flat against the skin that begins on the trunk or arms and spreads outward, forming a clear ring in the middle of the patch that continues to spread outward and merges with other ring spots, eventually forming a snake-like appearance. This rash does not usually appear on the face and can become more severe due to fever.
4. Sydenham’s chorea (St. Vitusch’s dance): A characteristic series of rapid, aimless movements of the face and arms. It may occur very late and may be infested with infection for at least 3 months after its onset.
Secondary criteria
Fever of 38.2-38.9 °C (101-102° F) ? Arthralgia: joint pain, not swelling (this will not be included if polyarthritis is present as a primary symptom)? Elevated erythrocyte sedimentation rate or C-reactive protein? Leukocytosis? ECG showing cardiac block, such as prolonged PR interval (this will not be included if carditis is present as a major symptom)? Previous rheumatic fever or rheumatic heart disease in an inactive state Other signs and symptoms? Abdominal pain? Nasal bleeding? Prior streptococcal infection: recent scarlet fever, elevated anti-streptococcal hemolysin O or other streptococcal antibody titers, or positive pharyngeal swab culture Pathophysiology Rheumatic fever is a systemic disease that affects the connective tissue of the small peripheral arteries and can present after untreated group A beta-hemolytic streptococcal pharyngeal infection. It is thought to be caused by cross-reactivity of antibodies. This cross-reactivity is a type II hypersensitivity reaction, called molecular mimicry. Usually, self-reactive B cells have no stress response in the periphery if there is no T-cell co-stimulation. During streptococcal infection, mature antigens of such cells as B cells are provided, and bacterial antigens are provided to CD4+ T cells, which differentiate into helper T2 cells. Helper T2 cells then activate B cells to become plasma cells and contribute to the production of antibodies against the streptococcal cell wall. However, antibodies may also react against the heart muscle and joints, producing symptoms of rheumatic fever.
Group A Streptococcus pyogenes has a cell wall composed of branched polymers, which sometimes contain M proteins and are highly antigenic. Antibodies produced by the immune system to stress M proteins cross-react with cardiac myofibrillar proteins of myosin, cardiac myoglycogen and smooth muscle cells of arteries, inducing cytokine release and tissue destruction. However, only cross-reactivity with the connective tissue surrounding the blood vessels has been demonstrated so far. The development of this inflammation requires the complementation of directly attached complement and crystalline segment receptor-mediated neutrophils and macrophages. The characteristic Athoff’s vesicles are visible under light microscopy and consist of swollen eosinophilic collagen surrounded by lymphocytes and macrophages. Larger macrophages can become Ashov’s giant cells. Acute rheumatic heart valve injury may involve a cell-mediated ? immune response, and these injuries are primarily in helper T cells and macrophages.
In acute rheumatic fever, these lesions are seen in all layers of the heart and are therefore referred to as total carditis . The inflammation may cause a plasmacytic fibrinous pericardial exudate, described as “bread and butter” pericarditis, which can usually be resolved without sequelae. Involvement of the endocardium in the lesion results in typical fibrin-like necrosis and wart formation along the closed edge of the left side of the heart valve. The amount of deposit formed varies, resulting in a subendocardial plaque that may cause irregular thickening of the dentate plaque, the MacCallum plaque.
Chronic rheumatic heart valve disease is characterized by recurrent episodes of inflammation with fibrinolytic images. Major anatomic changes in the valves include leaflet thickening, fusion of adhesions at the commissures, and shortening and thickening of the valve tendons.
Prevention
Prevention of recurrent disease depends on prevention through elimination of acute infection and use of antibiotics. The American Heart Association recommends daily or monthly prophylaxis, maintained over time, perhaps for life.
Treatment
Treatment of acute rheumatic fever is to reduce inflammation with drugs such as aspirin or glucocorticoids. Patients with streptococcal culture-positive laryngitis should also be treated with antibiotics. Aspirin is the drug of choice and should be given at a high dose of 100 mg/kg/day. Patients should be aware of drug side effects, such as gastritis and salicylic acidosis. In children and adolescents, the use of aspirin and medications containing aspirin may be associated with Reye’s syndrome, a serious and potentially fatal condition. Therefore, both risks and benefits must be considered when using aspirin and medications containing aspirin. Rheumatic fever studies have shown that ibuprofen targets pain and discomfort and corticosteroids alleviate severe inflammatory responses and should be considered in pediatric and adolescent patients. Steroid use should be reserved when there is evidence of cardiac involvement. The use of steroids may prevent further healing of tissue scars and may prevent improvement of sequelae such as mitral stenosis. Patients who have suffered a single blow of rheumatic fever should be given monthly injections of long-acting penicillin for five years. If there is evidence of cardiac fever, the course of treatment can be up to 40 years. Another important cornerstone of treating rheumatic fever includes the continued use of low-dose antibiotics (such as penicillin, sulfadiazine, or erythromycin) to stop relapses.
Vaccines
There is no vaccine to prevent infection with Streptococcus pyogenes, although research has been ongoing. The difficulties in developing a vaccine include the presence of various strains of Streptococcus pyogenes in the environment, the amount of time required, and the need to test the safety and efficacy of the vaccine.
Patients with positive cultures for Streptococcus pyogenes infection should be treated with penicillin promptly, provided they are not allergic to penicillin. This treatment does not alter the course of the acute disease.
The Oxford Handbook of Clinical Medicine expresses the most appropriate treatment for rheumatic fever – benzathine penicillin.
Patients with significant symptoms of inflammation may need glucocorticoids. Salicylates are useful for pain.
Heart Failure
Some patients present with significant heart inflammation, which manifests as congestive heart failure. This usually requires treatment of heart failure: angiotensin-converting enzyme inhibitors, diuretics, beta-blockers, digoxin. Unlike general heart failure, rheumatic heart failure responds well to corticosteroids.
Epidemiology Rheumatic fever is common worldwide and causes damage to the heart valves. In Western countries, it has become quite rare since the 1960s, probably due to the widespread use of antibiotics to treat streptococcal infections. In the United States, although very uncommon since the early 20th century, there have been several outbreaks since the 1980s. Although the disease is rare, the disease is severe, with a mortality rate of 2-5%.
Rheumatic fever primarily affects adolescents between the ages of 5 and 17 years and develops approximately 20 days after streptococcal pharyngitis. In up to one-third of people with streptococcal infection may not cause any symptoms.
About 3% of untreated streptococcal infections develop rheumatic fever. A very large proportion (about 50%) of those with recurrent infections without subsequent treatment develop rheumatic fever. Those treated with antibiotics develop rheumatic fever at a much lower rate. Patients who have had rheumatic fever have a tendency to have sudden exacerbations if they have recurrent streptococcal infections.
Relapses are quite common in those patients with rheumatic fever who do not maintain low-dose antibiotic therapy, especially three to five years after the first rheumatic fever infection. Cardiac complications can be long-term and severe, especially when heart valves are involved.
Survivors of rheumatic fever often have to use penicillin to prevent streptococcal infections, which otherwise have proven fatal in cases.