Acute Rheumatic Fever and Sydenham's Chorea

1. Acute Rheumatic FeverandSydenham's Chorea Great cases only seen at PEC! Dan Imler Morning Report 2/13/08

2. Epidemiology • Usually 5 – 18 yrs old. • M:F equally except Sydenham’s chorea which is more common in girls • Huge decline in incidence of ARF even before antibiotic age. Lower than 1 per 100000 • Small outbreaks still occur esp. in lower income populations • Decline thought to be due to use of antibiotics and changing GAS serotypes in US to less rheumatogenic strains

3. Changing incidence of ARF in Alaska in rural populations

4. Pathogenesis • ARF associated with pharyngitis caused by certain M-serotypes • Different serotypes from strains causing impetigo or glomerulonephritis • Molecular mimicry? M-proteins may share epitopes with myosin; may be responsible for chorea as well

5. Diagnosis • Jones Criteria – Diagnosis of ARF requires 2 major criteria OR one major and two minor criteria PLUS evidence of recent streptococcal infection

7. Diagnosis • Evidence of recent streptococcal infection can include: • Increased antistreptolysin O or other streptococcal antibodies (anti-DNAse B) • Positive throat culture for Group A beta-hemolytic streptococci • Positive rapid direct Group A strep test • Recent scarlet fever

9. Heart Disease • Rheumatic Heart Disease – usually occurs years after initial attack. Mitral valve is more commonly involved than aortic valve. Classically, pts have mitral stenosis as a result of calcification.

10. Treatment • Primary prophylaxis • Timely diagnosis of GAS pharyngitis and appropriate treatment. Treatment of choice is still Penicillin as all GAS is susceptible. • Treatment administered within 10 days of onset of illness has been shown to prevent ARF. • Alternatives – amoxicillin, erythromycin, 1st generation cephalosporin

11. Treatment • Secondary prophylaxis • Pts diagnosed with ARF need to undergo secondary prophylaxis to prevent relapses. • Prophylaxis regimens include oral Pen VK BID, Pen G IM qmonth, oral sufisoxazole qday, or oral erythromycin BID.

12. Duration of treatment

13. Sydenham chorea • Also known as St. Vitus dance, St. Johannis' chorea, chorea minor, and rheumatic chorea, is one of the major clinical manifestations of acute rheumatic fever (ARF) and is the most common form of acquired chorea in childhood. It is a movement disorder characterized by chorea, emotional lability, and hypotonia. • Chorea is still a common manifestation of rheumatic fever, particularly in developing countries. In recent studies of rheumatic fever in the United States, chorea has occurred in 18 to 36 percent of cases

14. Pathophysiology • In acute rheumatic fever, antibodies are mounted against N-acetyl-beta-D-glucosamine (NABG or GlcNAc), the immunodominant carbohydrate antigen of group A streptococci. • These antibodies likely play a role in valvular injury in rheumatic carditis, and in other manifestations of ARF. • In Sydenham chorea, the antibodies bind to lysoganglioside on the neuronal cell surface, where they are capable of triggering a signaling cascade, and also recognize the intracellular protein tubulin. • These tubulin-specific antibodies are not found in patients with acute rheumatic fever but no SC, or in patients who have recovered from SC. Moreover, the genes encoding these antibodies are similar to the genes encoding antibodies implicated in the pathogenesis of motor neuropathies. • From a pathologic viewpoint, the available data are consistent with involvement of the basal ganglia and cortical structures. In individual case reports, magnetic resonance imaging studies performed during and after an acute episode of SC showed reversible abnormalities of the striatum and positron emission tomography and SPECT imaging showed striatal hypermetabolism and hyperperfusion

15. Epidemiology • The initial presentation of SC typically occurs in patients between 5 and 13 years of age. • Females are affected more frequently than are males by a ratio of 2:1. Chorea appears to be less common in adults, particularly men. • SC appears to have a familial predisposition, as illustrated by the following observations: • a family history of rheumatic fever occurs in up to 30 percent of families with a history of chorea • and in an older study, SC occurred in 3.5 percent of families with rheumatic fever and 2.1 percent of siblings in the same family

16. Clinical Manifestations • The onset of chorea usually occurs one to eight months after the inciting infection, in contrast to carditis and arthritis, which typically present within 21 days. • The onset is typically insidious but may be abrupt. Emotional changes, such as easy crying or inappropriate laughing, may precede the development of chorea and, in some cases, regression in school performance is the initial concern.

17. Clinical Manifestations • The chorea typically begins with distal movements of the hands, but generalized jerking of the face and feet may emerge as the chorea becomes more active. The movements are rapid, irregular, and nonstereotypic jerks that are continuous while the patient is awake but improve with sleep. The chorea usually is generalized but may be more prominent on one side; 20 to 30 percent have hemichorea. • Motor symptoms, including ballismus, facial grimacing, and gross fasciculations of the tongue, often are observed in addition to frank chorea. In one review of 79 children with Sydenham chorea, handwriting changes were noted in 29 percent. • Muscle weakness is best revealed by asking the patient to squeeze the examiner's hands; the pressure of the patient's grip increases and decreases continuously and capriciously, a phenomenon known as "milkmaid's grip" or "milking sign." The hypotonia can be so severe that the extremities may look paretic. The cranial nerves are not involved, but speech often is abnormal and is described as "jerky" with sudden changes in pitch and loudness. • Holding the arms outstretched may elicit "spooning" (hyperextension of the fingers with dorsiflexion of the wrist) or a "pronator sign" (supination of the extended pronated arm). No sensory loss occurs, and the deep tendon reflexes are unaffected except for delayed relaxation of the patellar reflex.

18. Treatment • Previously recommendation was prednisone + AEDs +/- plasmapheresis • However… most new studies have shown to benefit from immunomodulation. • “The best small study comparing plasmapheresis, prednisone and IVIG conducted at the National Institute of Mental Health as referenced in the "Journal of Child Neurology," volume 20, #5, pages 424-429, by Dr. Garvey, et. al., suggests IVIG at 1 gram per kg over a 2-day course to appear better than plasmapheresis and prednisone”

19. OFF TO HAITI!! Area - comparative: slightly smaller than Maryland Population: 8,706,497 Age structure:0-14 years: 42.1% (male 1,846,175/female 1,817,082) 15-64 years: 54.4% (male 2,313,542/female 2,426,326) 65 years and over: 3.5% (male 134,580/female 168,792) (2007 est.)

20. Infant mortality rate:total: 63.83 deaths/1,000 live births male: 68.45 deaths/1,000 live births female: 59.07 deaths/1,000 live births (2007 est.) Life expectancy at birth:total population: 57.03 years male: 55.35 years female: 58.75 years (2007 est.) Total fertility rate: 4.86 children born/woman (2007 est.) HIV/AIDS - adult prevalence rate: 5.6% (2003 est.)

21. Unemployment rate: widespread unemployment and underemployment; more than two-thirds of the labor force do not have formal jobs (2002 est.) Population below poverty line: 80% (2003 est.) GDP (official exchange rate): $6.311 billion (2007 est.) GDP - per capita (PPP): $1,900 (2007 est.) Literacy:definition: age 15 and over can read and write total population: 52.9% male: 54.8% female: 51.2% (2003 est.)