Immune treatment in SC

Support for the autoimmune hypothesis of SC comes from the fact that Group A Beta Haemolytic Streptococus is the proven trigger of disease and immune therapy can shorten disease and possibly improve outcome (reviewed in Mohammad et al., 2013). Despite indicators of autoimmunity (Kirvan et al., 2003), and identification of D2R antibodies in a proportion (10/30) of SC patient (Dale et al., 2012), a definitive autoimmune process or autoantibody remains to be consistently identified.

Immune therapy with steroids, IVIG and plasmapheresis has been used empirically, utilising a common pragmatic therapeutic strategy with some evidence of efficacy (Fusco et al., 2012; Garvey et al., 2005).

There have been two key randomised trials, one with steroids and the other IVIG: –

• In one study by Paz and colleagues (Paz et al., 2006), 22 children were randomised to steroids (2 mg/kg/day during 4 weeks, followed by a gradual discontinuation) and 15 to placebo; with both group sharing similar demographics and important chorea. Each patient was evaluated by the same paediatric neurologist weekly during the first month, followed by evaluation on weeks 8 and 12, with further evaluations as necessary if choreic movements persisted. A significant difference was observed after 1 week of medication with a larger reduction in the prednisone group that continued until the end of the study (P < 0.001). Decrease in chorea intensity scale score also was persistently and significantly greater in the prednisone group (P < 0.001). Chorea complete remission time with prednisone (mean 54.3 days) was significantly shorter when compared with the placebo group (mean 119.9 days; P < 0.001)
• In the other evaluator blinded study, Walker and colleagues (Walker et al., 2012) randomised 20 children with SC to receive either IVIG (N=10) or no treatment. The mean clinical rating scores, comprising of chorea and behavioural measures, of the 2 treatment groups showed that those treated with intravenous immunoglobulin had significantly improved outcome scores (1 month P = 0.006, 3 months P =0 .011, 6 months P = .034).

As longer follow-up of SC patients often reveal an indolent course, significant persistent symptoms and recurrence risk (Cardoso, 2011); and significant psychiatric morbidity (Mohammad et al., 2013), careful consideration need to be given to evaluate the impact of immune treatment on these.

[Prepared by Dr Ming Lim, Consultant Paediatric Neurologist, Evelina London Children’s Hospital, and Adjunct Reader in Paediatric Neurology at King’s College London, May 2021]

References

 

• Cardoso, F., 2011. Sydenham’s chorea. Handb Clin Neurol. 100, 221-9.
• Dale, R.C., et al., 2012. Antibodies to surface dopamine-2 receptor in autoimmune movement and psychiatric disorders. Brain. 135, 3453-68.
• Fusco, C., et al., 2012. Acute and chronic corticosteroid treatment of ten patients with paralytic form of Sydenham’s chorea. Eur J Paediatr Neurol. 16, 373-8.
• Garvey, M.A., et al., 2005. Treatment of Sydenham’s chorea with intravenous immunoglobulin, plasma exchange, or prednisone. J Child Neurol. 20, 424-9.
• Kirvan, C.A., et al., 2003. Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea. Nat Med. 9, 914-20.
• Mohammad, S.S., et al., 2013. Autoantibody-associated movement disorders. Neuropediatrics. 44, 336-45.
• Paz A et al., 2006. Randomized double-blind study with prednisone in Sydenham’s chorea. Pediatr Neurol 34(4):264-9.
• Walker, K., et al., 2012. Treatment of sydenham chorea with intravenous immunoglobulin. J Child Neurol. 27, 147-55.by