1. Rheumatic fever, cardiac complications and how to prevent them Rüdiger Schultz MD, PhD Pediatrician Ilembula Hospital

2. Epidemiology of rheumatic fever In western societies RF and its complications have almost disappeared, whereas in developing countries it is still the main course of fatal, chronic heart disease. Worldwide, an estimated 5 to 30 million children and young adults have chronic rheumatic heart disease (RHD) and 90.000 patients die of this disease each year.

3. Predispostion to rheumatic fever Age, family history, season, recurrency of streptococcal infection, host factors affecting susceptibility. The first attack usually occurs in patients between 5-15 years of age. No gender preference exists. Constitutional susceptibility may be a factor, but no evidence for genetic markers in rheumatic patients exists. Like streptococcal pharyngitis, RF occurs more commonly during winter and spring.

4. Predispostion to rheumatic fever Recurrent streptococcal infections are the most important predisposing factor in the occurence of RF. Approximately 1- 5% of streptococcal throat infections lead to RF. Once a patient has suffered from RF he/she is much more likely to experience reactivation of the condition. The recurrence rate is approximately 50% during the first year after the initial attack. After the first year recurrence decreases sharply down to 10%.

5. Clinical course of RF RF develops, when children or adolescents develop pharyngitis with group A beta-hemolytic streptococcal infection. The incubation period is 2-4 days, after that the patient develops sore throat, fever, malaise, headache and an elevated leucocyte count that lasts for 3-5 days. The interval between the onset of pharyngitis and the manifestation of RF is 1-5 weeks. However, clinical evidence for preceding streptococcal infection may be lacking in 1/3 of patients.

6. Clinical course of RF Polyarthritis: Inflammation affects the large joints and moves from one to another. The affected joint is hot, red, swollen and tender. The arthritis characteristically leaves the joints without sequelae and responds almost immediatly to salicylates. The severity of joint diesease is inversely proportional to the severity of cardiac disease. Carditis: Produces NO symptoms of its own and is usually diagnosed during examination of a patient with polyarthritis or chorea.

7. Signs of cardiac disease Development of apical, systolic murmur, propagated to the axilla accompanied with a distorted S1 and a S3 indicates mitral insuffiency. Middiastolic murmur over the apex region indicates mitral valvulitis Occurrence of a high pitched early diastolic murmur at the base indicates aortic valvulitis The murmurs of aortic and mitral valvulitis may disappear and be followed by signs of valve regurgitation and or stenosis

8. Signs of cardiac disease Myocarditis is usually accompanied by valvulitis and leads to tachycardia. Pericarditis accompanies valvulitis in 5-10% of cases. Effusion may be low or moderate. Amount and degree of valve lesions are critical for the development of later appearing congestive heart failure.

9. Other sequelae of RF Chorea: Involuntary, incordinate, jerky movements of hands combined with emotional disturbance Rheumatic nodules: usually indicate severe carditis and are seen over the extensor surfaces of tendon sheaths. Erythema marginatum: area of erythema with progressive margins and clearing of the center. The erythema occurs mainly over the trunk and proximal parts of the limbs.

12. Prevention of initial attacks In epidemics as many as 3% of untreated acute streptococcal sore throats are followed by rheumatic fever. In endemic infections the incidence is substantially less. Unfortunately, at least one third of episodes of acute rheumatic fever result from inapparent streptococcal infections.

13. Diagnose the GAS infection GAS pharyngitis is primarily a disease of children 5-15 years of age and occurs usually during the winter and spring months. Sore throat, pain on swallowing, fever of varying degree, headache, abdominal pain, nausea, and vomiting may occur. On investigation tonsillo-pharyngeal erythema with or without exudates, anterior, cervical lymphadenitis, soft palate petechiae, beefy, red swollen uvula and sometimes a scarlatinoform rash. A history of close contact with a well documented case of GAS infection may be helpful in making the diagnosis.

14. Diagnose the GAS infection Some form of microbiological confirmation, with either a throat culture or a rapid antigen detection test (RADT) is usually required for the diagnosis of GAS pharyngitis. Such a test should be only considered if the patient has clinical findings suggestive for GAS pharyngitis. If a positive test result in a patient is established, family members should also be tested, especially in families of a child with rheumatic fever. Or if the family history presents with recurrent epidodes of GAS infection.

15. Throat culture Is the standard for the diagnosis of GAS pharyngitis Properly obtained swab of both tonsils and the posterior pharynx is almost always positive if GA streptococci are present. A negative throat culture permits the physician to withhold antibiotic therapy from the large majority of patiens with sore throat.

16. Rapid antigen detection test A number of commercial test packages are availabe, most of them with a very high degree of specificity but there sensitivity varies, which means that a negative test result does not rule out infection with GAS but a positive test result establishes it well. For this reason RADTs should be followed, if possible also by a culture swab.

17. Primary preventive treatment Treat acute GAS pharyngitis effectively (V-penicillin. Children 50 mg/kg/day in two or three doses, adults 1000-1500 mg x2/day, for ten days). For individuals allergic to penicillin: Clindamycin 20 mg/kg/day divided in 3 doses, Kefalexin 50 mg/kg/day devided in 2 doses. If recurrent attacks of GAS pharyngitis occurs in the same family, treat the whole family, also asymptomatic members.

18. Prevention of recurrent attacks of rheumatic fever An individual with a previous attack of rheumatic fever is at high risk for a recurrent attack. Prevention of recurrent episodes of GAS pharyngitis is the most effective method to prevent the development of severe rheumatic heart disease. Since a GAS infection needs not to be symptomatic to trigger a recurrence, prevention chronic heart disease requires continous antimicrobal prophylaxis rather than recognition and treatment of acute episodes. Continuous prophylaxis is recommended for patients with well- documented histories of rheumatic fever.

19. Duration of secondary Prophylaxis CategoryDuration after last attackRating __________________________________________________________ Rheumatic fever with carditis10 years or until 40 years of ageIC and residual heart disease(whichever is longer), sometimes (persistent valvular disease *)lifelong prophylaxis Rheumatic fever with carditis10 years or until 21 years of ageIC but no residual heart disease (no valvular disease *) Rheumatic fever without carditis5 years or until 21 years of ageIC *Clinical or echocardiographical evidence

20. Secondary prevention of rheumatic fever AgentDoseModeRating --------------------------------------------------------------------------------------------- Benzathine Penicillin G600.000 U for 27 kgIM IA every 3-4 weeks Penicillin V250 mg twice dailyoral IB Sulfadiazine0.5 g once daily for 27 kgoral IB For individuals allergic macrolides like erythromycin, clarithromycinoral IC to penicillin or sulfioxazoleor azithromycin

21. Reference Circulation, Journal of the American Heart Association Prevention of Rheumatic Fever and Diagnosis and Treatment of Acute Streptococcal Prahyngitis: A Scientific Statement From the American Association Rheumatic Fever, Endocarditis and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young Michael A Gerber, Robert S. Baltimore, Charles B. Eaton, Michael Gewitz, Anne H. Rowley, Stanford T. Shulman and Kathrin A. Taubert Circulation 2009; 119:1541-1551