Introduction
Rheumatic fever and its complication of chronic rheumatic heart disease remains a major public health problem, especially in developing countries. This is particularly unfortunate because the condition occurs as a result of preventable and easily treatable suppurative pharyngeal infections.
There have been no significant new advances in the treatment of rheumatic fever in the last 3 decades. Treatment is largely based on the use of antibacterials, salicylates and other symptom-specific treatments. Current therapy does not alter the natural course of the disease.
Recent research has focused on understanding the aetiology of rheumatic fever and its prevention. However, the development of a vaccine is still some way off.Aetiological Details Unclear
Rheumatic fever is a characteristic constellation of multisystem disease which occurs after a lag period following pharyngeal infection with group A streptococci in 3% of individuals.[1] The mechanism for development of the disease, which has never been shown to occur after a cutaneous streptococcal infection, is unclear. There is no evidence to support direct infection of the heart. The most likely explanation is antigenic mimicry between human and bacterial antigens.Changing Epidemiology
For a variety of reasons, including wide availability of penicillin, the incidence of rheumatic fever in industrialised countries declined dramatically between 1950 and 1980. In developing countries, however, where the spread of bacterial infection is facilitated by poverty, limited access to healthcare and overcrowding, rheumatic fever and its sequelae account for 25 to 40% of cardiac admissions to hospital. Outbreaks of rheumatic fever have also been reported in developed nations, probably because of periodic reappearance of rheumatogenic strains of streptococci.Making the Diagnosis
Rheumatic fever typically occurs 10 days to 5 weeks after an episode of streptococcal pharyngitis. According to the Jones criteria for diagnosis, the probability of rheumatic fever is high when evidence of a previous streptococcal pharyngeal infection (e.g. positive throat culture) is detected together with either 2 major manifestations (carditis, migratory polyarthritis, Sydenham's chorea, subcutaneous nodules, erythema marginatum) or 1 major and 2 minor disease manifestations (fever, arthralgia, elevated acute phase reactants, prolonged PR interval).[3]
The diagnosis of rheumatic fever is made mainly on clinical grounds and requires a high index of suspicion, especially as in at least one-third of cases, a history of preceding pharyngitis may not be recounted. Laboratory studies provide only ancillary evidence of streptococcal infection. The role of echocardiography in the diagnosis of rheumatic fever remains controversial.
Introduction
Aetiological Details Unclear
Changing Epidemiology
Making the Diagnosis
Treatment of Acute Attack Depends on Carditis
Cardiac Sequelae Common
Preventing Rheumatic Fever
References
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Information from Industry
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Treatment of Acute Attack Depends on Carditis
Treatment should be directed against the extensive and widespread non-suppurative inflammatory process that involves various organ systems. The duration and nature of therapy are mainly dependent upon the presence and severity of carditis during the initial attack.[1]
An approach to the management of rheumatic fever is outlined in the Patient care guidelines.
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Patient Care Guidelines.
Bed Rest is Essential
All patients with acute rheumatic fever should be placed on bed rest (generally in hospital) and monitored closely for onset of carditis. Patients can become ambulatory when the signs of acute inflammation have subsided. At least 4 weeks' bed rest is recommended for patients with carditis.[1]
Streptococci Must be Eradicated
The first step in the treatment of rheumatic fever is eradication of pharyngeal streptococci, thus avoiding chronic, repetitive exposure to streptococcal antigens. The drug of choice is penicillin, which in adequate concentrations for a 10-day period eradicates the organism.[4] Since compliance is often not optimal, a single intramuscular dose of benzathine benzylpenicillin is the most effective form of initial treatment.[5] Antimicrobial therapy, however, does not alter the course, frequency or severity of cardiac involvement.
Anti-inflammatories Usually Have Dramatic Effects
Salicylates remain first-line agents in the treatment of rheumatic fever and usually bring about a dramatic clinical improvement.[1] Therapy should be initiated at 80 to 100 mg/kg/day in children and 4 to 8 g/day in adults to achieve plasma concentrations of 200 to 300 mg/L. After achieving the desired initial steady state concentrations for 2 weeks, the dosage can be reduced to 60 to 70 mg/kg/day for an additional 3 to 6 weeks. Laboratory and clinical rebound may occur 2 to 3 weeks after cessation of anti-inflammatory therapy but usually resolves spontaneously.
Corticosteroids Proven Only in Severe Carditis
Several studies have shown that corticosteroids are no more effective than salicylates in altering the course of rheumatic fever and subsequent development of heart disease. [1] Thus, corticosteroids should be reserved for patients with severe carditis, in whom they appear to reduce mortality during an acute attack.[6] The agent of choice is oral prednisone, starting with an initial dosage of 1 to 2 mg/kg/day (maximum 80 mg/day). In extreme cases, therapy may be initiated with intravenous methylprednisolone. After 2 to 3 weeks of steady therapy, the dosage may be tapered, reducing by 20 to 25% each week. During corticosteroid tapering a period of overlap with salicylates is recommended to prevent rebound of disease activity.
Heart Failure May Require Specific Treatment
Heart failure in rheumatic fever generally responds to bed rest and corticosteroids; diuretics and then digoxin may be necessary in patients with more severe disease.[1] Digoxin should be used with caution because of its lowered therapeutic index in active myocarditis and the possibility of exacerbation of heart block. Surgical therapy, e.g. valve replacement, is occasionally required.
Chorea is Not Always Benign and Self-Limiting
While Sydenham's chorea is generally considered to be benign, self-limiting and requiring no therapy, a protracted course leading to disability and/or social isolation has been reported.[1] Haloperidol (initial dosage 0.5 to 1 mg/day with increments of 0.5 to 1 mg/day every 3 days up to a maximum of 5 mg/day) has been recommended. Corticosteroids are ineffective. Plasmapheresis and intravenous immunoglobulins may be useful in resistant disease. All patients with Sydenham's chorea should receive long-term antistreptococcal prophylaxis.Cardiac Sequelae Common
Acute episodes of rheumatic fever are self-limited with an average duration for untreated attacks of approximately 3 months. In the absence of rebound activity, an episode of rheumatic fever is considered to be over 8 weeks after withdrawal of treatment. After this it usually does not reactivate without new streptococcal infection. Recurrence tends to occur within the first few years after the acute attack and is most common in the setting of pre-existing heart disease.[1]
The most common presentation in patients with carditis is isolated mitral valve disease, which affects nearly 60% of patients with carditis. Aortic valve involvement alone occurs in 10% of patients with carditis; 30% have both mitral and aortic valve involvement. Most (i.e. 65 to 75%) patients with carditis will experience resolution without any sequelae; resolution is rare in those with cardiomegaly or heart failure during the initial attack.[1] Continuous fibrosis and scarring leads to valve deformity, which manifests as regurgitation and/or stenosis. Surgical valve repair/replacement or balloon mitral commissurotomy may be required to treat chronic rheumatic valvular heart disease.
Introduction
Aetiological Details Unclear
Changing Epidemiology
Making the Diagnosis
Treatment of Acute Attack Depends on Carditis
Cardiac Sequelae Common
Preventing Rheumatic Fever
References
Information from Industry
Small particle ICS (~1 micrometer) improves small airway function in asthma
Learn more about other consequences of improved airway ICS deposition with a small particle ICS.
Cardiac Sequelae Common
Although prevention of rheumatic fever has been largely achieved in industrialised nations, the reverse is true in impoverished, overcrowded parts of the world, where self-limited episodes of throat infection in children do not usually receive medical attention.[1]
Primary Prevention
Primary prevention of rheumatic fever depends on correct diagnosis of group A streptococcal infection and eradication of the organism with appropriate antimicrobial therapy. Primary prophylaxis should be recommended for all patients with streptococcal pharyngitis using a single intramuscular injection of benzathine benzylpenicillin [600 000 units for patients weighing ≤27kg (60lb) or 1 200 000 units for those >27 kg].[1] Oral antibacterial agents are poor alternatives because of compliance and cost factors, and their efficacy in eradicating streptococci has been questioned.[1] Erythromycin is the traditional agent of choice for penicillin-allergic patients; however oral cephalosporins can also be considered in these circumstances. The latter have been shown to be superior to oral penicillin in eradicating group A streptococci in patients with streptococcal pharyngitis.[7] Clindamycin is effective for persistent and recurrent streptococcal pharyngitis.[1]
Secondary Prevention
The most reliable method of preventing recurrence of rheumatic fever is prolonged prophylaxis (≥5 years) of previously affected individuals with intramuscular benzathine benzylpenicillin (1 200 000 units every 4 weeks† ).[1] However, there is controversy over whether administration every 3 weeks is advantageous for individuals living in high-risk areas. Oral prophylaxis is less reliable but may be necessary in patients unable to tolerate intramuscular injections.[1]A choice of agents is available between phenoxymethylpenicillin (250mg twice daily) and sulfadiazine [0.5g once daily for patients weighing ≤27kg or 1g once daily for those >27kg]. Patients who are truly allergic to penicillin or sulfadiazine should be treated with oral erythromycin (250mg twice daily).
There is no consensus on the required duration of antibacterial prophylaxis. As the risk of recurrent rheumatic fever is greatest during the first 3 to 5 years after an episode, a minimum of 5 years of prophylaxis after the last acute attack is usually recommended.[1] The American Heart Association recommends prophylaxis to be continued for at least 10 years after the last episode of rheumatic fever or until patients are well into adulthood.[5] As a general rule, indefinite continuation is probably unnecessary in developed countries with a low incidence of rheumatic fever. However, patients with heart disease who are at risk of repeated exposure should probably receive prophylaxis indefinitely.[8]
The decision to withdraw antibacterial drugs should be individualised after carefully assessing the risk of repetitive exposures.
Vaccine Prospects
Research is currently underway to develop a group A streptococcal vaccine active against M-protein in streptococci. The numerous serotypes and different rheumatogenic strains of group A streptococci present the greatest hurdle to vaccine development.[1]
†In France, secondary prophylaxis with benzathine benzylpenicillin is given at the rate of 2 400 000 units every 15 days.
