Rheumatic Fever (ARF)

Acute rheumatic fever (ARF) is an inflammation of the heart, skin, joints and/or brain which develops after infection with Group A streptococci, such as "strep" throat, or scarlet fever. Although the incidence of ARF has declined in Europe and North America over the past 4 to 6 decades, the disease remains one of the most important causes of cardiovascular morbidity and mortality in the developing countries that are home to the majority of the world's population. There is a 2-3 weeks delay between the strep infection and the development of ARF. Less than 3% of those with untreated strep infection may develop ARF. Most of the affected patients are between six and fifteen years of age.

Pathology

Group A streptococcal (GAS) infection of the pharynx is usually the precipitating cause of rheumatic fever. During epidemics over a half a century ago, as many as 3% of untreated acute streptococcal sore throats were followed by rheumatic fever; in endemic infections, the incidence of rheumatic fever is substantially less. Appropriate antibiotic treatment of streptococcal pharyngitis prevents acute rheumatic fever in most cases. Unfortunately, at least one third of episodes of acute rheumatic fever result from inapparent streptococcal infections. In addition, some symptomatic patients may not seek appropriate medical care. Among the most widely accepted concepts in support of an autoimmune hypothesis involving the GAS was the observation by Stollerman. He noted a correlation between outbreaks of GAS upper respiratory tract infections associated with a relatively limited number of M-protein types which were followed by outbreaks of rheumatic fever. Subsequent reports demonstrated that only a limited number of specific M-types (M-5, M-6, M-18) were isolated during rheumatic fever outbreaks. These findings supported the concept of antigenic mimicry. In ARF, antibodies against the M antigen found in the streptococcal cell wall cross react with cardiac myosin causing carditis.

Prevention of rheumatic fever requires adequate therapy for GAS pharyngitis. In selecting a regimen for the treatment of GAS pharyngitis, physicians should consider various factors, including bacteriologic and clinical efficacy, ease of adherence to the recommended regimen (frequency of daily administration, duration of therapy, and palatability), cost, spectrum of activity of the selected agent, and the potential side effects.

Clinical presentation

Signs and symptoms of rheumatic fever include fever, migratory arthritis in large joints, abdominal pain, erythema marginatum (a ring-shaped rash located on trunk and upper parts of arms and legs), Sydenham chorea, subcutaneous nodules, epistaxis, shortness of breath and chest pain.

Making the diagnosis

According to Jones Criteria, there must be evidence of previous streptococcal infection.

Any of the following may serve as evidence of GAS infection:

1. Increased or rising ASO titer or other streptococcal antibody such as Anti DNAase B
2. A positive throat Cx for GAS
3. A positive rapid test for GAS

Major Criteria:

• Polyarthritis. This is the most common manifestation of ARF, usually involves large joints, and is migratory in nature. It responds dramatically to high-dose salicylates.
• Carditis. Occurring in ~50% of patients with ARF, carditis presents with tachycardia out of proportion to the fever.   A heart murmur of mitral or aortic insufficiency indicates valvulitis. Pericarditis may present with chest pain, friction rub, pericardial effusion and EKG changes. Signs of CHF may be present. Recent recommendations require echocardiography to be performed in all cases of suspected ARF. It may be performed to assess the presence of carditis in the absence of auscultatory findings in certain high risk populations. As per the AHA, specific Doppler criteria for valvulitis are: i) MR seen in ≥ 2 views, jet length ≥ 2 cm, peak velocity > 3m/s, pan-systolic and ii) AR, seen in ≥ 2 views, jet length ≥ 1 cm, peak velocity > 3 m/s, pan-diastolic.
• Chorea. Sydenham chorea occurs in about 15% of patients with ARF and is more common in prepubertal girls. It is characterized by emotional lability, personality changes, poor motor coordination and the classic purposeless spontaneous movements. It is also characterized by hyperextension of the fingers (spooning) and irregular contractions of the muscles of the hands (milkmaid's grip). It usually resolves within 2-4 weeks. This may be the only manifestation of rheumatic fever and may occur in isolation and is considered pathognomonic for rheumatic fever.
• Erythema marginatum. It is an uncommon sign of ARF and presents as a truncal rash that is non pruritic and serpiginous with well-defined borders.
• Subcutaneous nodules. The least common signs of ARF; these are found on the extensor surfaces of the extremities or along the spine. The nodules are usually small, non-tender, and freely mobile.

Minor Criteria:

• Fever > 38.5 C
• ESR > 30 mm/hr or CRP > 3 mg/dl
• Prolonged PR interval on EKG (unless carditis is a major criteria)
• Polyarthalgia

 For ARF diagnosis, 2 major OR one major + two minor criteria are needed.

Management Principles:

• Treatment of the group A streptococcal infection

General treatment of the acute episode:

• Anti-inflammatory agents are used to control the arthritis, fever, and other acute symptoms. Salicylates are the preferred agents, although other nonsteroidal agents are probably equally efficacious. Steroids are also effective but should be reserved for patients in whom salicylates fail. None of these anti-inflammatory agents have been shown to reduce the risk of subsequent rheumatic heart disease.
• Bed rest is a traditional part of ARF therapy and is especially important in those with carditis. Patients are typically advised to rest through the acute illness and to then gradually increase activity; some clinicians monitor the patient's ESR and restart activity only as it normalizes .
• Intravenous immunoglobulin has not been shown to reduce the risk of rheumatic heart disease or to substantially improve the clinical course.
• Chorea is usually managed conservatively in a quiet non-stimulatory environment. Valproic acid is the preferred agent if sedation is needed. Intravenous immunoglobulin, steroids, and plasmapheresis have all been used successfully in refractory chorea, although conclusive evidence of their efficacy is limited.

Cardiac management:

• Bed rest is essential in patients with cardiac involvement. Carditis resulting in heart failure is treated with conventional measures. Diuretics are the mainstay of therapy. Close monitoring is needed for development of arrhythmias in patients with active myocarditis.

Prevention

Patients with a documented history of ARF should receive antibiotic prophylaxis until the age of 21 or for a minimum of five years if there is no cardiac involvement. Patients with valvular abnormalities should receive lifetime prophylaxis.   Prophylaxis consists of monthly injections of benzathine penicillin; alternatively, twice daily oral penicillin V may be used. Oral sulfadiazine may be used for patients with penicillin allergy, but it is not as effective as penicillin.

Prevention of Rheumatic Fever and Diagnosis and Treatment of Acute Streptococcal Pharyngitis: A Scientific Statement From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: Endorsed by the American Academy of Pediatrics, 2004.

Bach DS. Revised Jones Criteria for Acute Rheumatic Fever ACC, May 2015