Treatments and Outcomes Among Patients With Sydenham Chorea
abstract
This abstract is available on the publisher's site.
Access this abstract nowIMPORTANCE
Sydenham chorea is the most common acquired chorea of childhood worldwide; however, treatment is limited by a lack of high-quality evidence.
OBJECTIVES
To evaluate historical changes in the clinical characteristics of Sydenham chorea and identify clinical and treatment factors at disease onset associated with chorea duration, relapsing disease course, and functional outcome.
DATA SOURCES
The systematic search for this meta-analysis was conducted in PubMed, Embase, CINAHL, Cochrane Library, and LILACS databases and registers of clinical trials from inception to November 1, 2022 (search terms: [Sydenham OR Sydenham's OR rheumatic OR minor] AND chorea).
STUDY SELECTION
Published articles that included patients with a final diagnosis of Sydenham chorea (in selected languages).
DATA EXTRACTION AND SYNTHESIS
This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Individual patient data on clinical characteristics, treatments, chorea duration, relapse, and final outcome were extracted. Data from patients in the modern era (1945 through 2022) were entered into multivariable models and stratified by corticosteroid duration for survival analysis of chorea duration.
MAIN OUTCOMES AND MEASURES
The planned study outcomes were chorea duration at onset, monophasic course (absence of relapse after ≥24 months), and functional outcome (poor: modified Rankin Scale score 2-6 or persisting chorea, psychiatric, or behavioral symptoms at final follow-up after ≥6 months; good: modified Rankin Scale score 0-1 and no chorea, psychiatric, or behavioral symptoms at final follow-up).
RESULTS
In total, 1479 patients were included (from 307 articles), 1325 since 1945 (median [IQR] age at onset, 10 [8-13] years; 875 of 1272 female [68.8%]). Immunotherapy was associated with shorter chorea duration (hazard ratio for chorea resolution, 1.51 [95% CI, 1.05-2.19]; P = .03). The median chorea duration in patients receiving 1 or more months of corticosteroids was 1.2 months (95% CI, 1.2-2.0) vs 2.8 months (95% CI, 2.0-3.0) for patients receiving none (P = .004). Treatment factors associated with monophasic disease course were antibiotics (odds ratio [OR] for relapse, 0.28 [95% CI, 0.09-0.85]; P = .02), corticosteroids (OR, 0.32 [95% CI, 0.15-0.67]; P = .003), and sodium valproate (OR, 0.33 [95% CI, 0.15-0.71]; P = .004). Patients receiving at least 1 month of corticosteroids had significantly lower odds of relapsing course (OR, 0.10 [95% CI, 0.04-0.25]; P < .001). No treatment factor was associated with good functional outcome.
CONCLUSIONS AND RELEVANCE
In this meta-analysis of treatments and outcomes in patients with Sydenham chorea, immunotherapy, in particular corticosteroid treatment, was associated with faster resolution of chorea. Antibiotics, corticosteroids and sodium valproate were associated with a monophasic disease course. This synthesis of retrospective data should support the development of evidence-based treatment guidelines for patients with Sydenham chorea.
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Additional Info
Treatments and Outcomes Among Patients with Sydenham Chorea: A Meta-Analysis
JAMA Netw Open 2024 Apr 01;7(4)e246792, M Eyre, T Thomas, E Ferrarin, S Khamis, SM Zuberi, A Sie, T Newlove-Delgado, M Morton, E Molteni, RC Dale, M Lim, M NosadiniFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Sydenham chorea (SC) is the most common cause of autoimmune chorea and is typically seen in childhood. Chorea is a major criterion for the diagnosis of acute rheumatic fever (ARF), is noted in 10% to 25% of ARF cases, and is a delayed manifestation of group A beta hemolytic streptococcal (GABHS) infection occurring 4 to 8 weeks of the initial infection.1 The pathophysiology of SC is related to antibodies against GABHS that cross-react with neuronal antigens in the basal ganglia.2 Treatment of SC is mostly based on the personal experience of clinicians and low levels of scientific evidence drawn from case reports, case series, and retrospective observational studies. In this comprehensive meta-analysis, the authors aimed to provide evidence-based data on the clinical course and treatment outcomes in patients with SC. The evidence was synthesized through an extensive literature search including 1325 individual patient data from various articles published between 1945 and 2022, covering both high- and low-income countries.
This meta-analysis provides valuable insights into the clinical course of SC. Overall, 85% of the patients had laboratory evidence of preceding GABHS infection, but evidence of active infection (positive throat culture and high ESR) was noted in only approximately 50%. Most patients initially presented with chorea, but few had coexisting psychiatric or behavioral issues. Carditis was present in approximately 50% of the patients, and arthritis was noted in 25%. Chorea lasted for 1 to 6 months with a median duration of 3 months. Most of the patients (90%) were doing well after 6 months of the disease onset, with a modified Rankin Scale score of 0 to 1. One-third of the patients had relapse after a median duration of 16 months, and the majority of these patients had only a single relapse.
Antibiotic (penicillin) prophylaxis reduces the risk of carditis recurrence in patients with ARF, but its role in SC is not clear. Previous observational studies have shown that secondary antibiotic prophylaxis likely reduces the recurrence rate but does not completely prevent it.3 This meta-analysis revealed that the use of antibiotics during the first episode of SC was associated with a lower risk of relapse (OR, 0.28; 95% CI, 0.09–0.85; P = .020) but does not influence the functional outcome or the disease duration. The clinical severity of cases reported before 1945 appears to be greater in the pre-penicillin era, but publication bias cannot be ruled out. Use of corticosteroids was associated with a favorable response in most of the previous studies.3 This meta-analysis showed that the use of corticosteroids during the initial episode was associated with a significantly shorter mean duration of illness (HR for chorea resolution during treatment, 1.51; 95% CI, 1.05–2.19; P = .030), and a reduced risk for relapse (OR, 0.32; 95% CI, 0.15–0.67; P = .003). Notably, a reduction in chorea duration was noted only in the subgroup that received corticosteroids for 1 month or longer. Among the various symptomatic medications (haloperidol, valproate, benzodiazepines, chlorpromazine, and second-generation antipsychotics) analyzed in this study, only valproate was associated with a significant reduction in relapse rate.
In summary, this meta-analysis provides good evidence for the use of antibiotics, corticosteroids, and valproate for use in patients with SC. However, clinicians need to be aware about a few caveats of this study. Most importantly, the effect of combined use of multiple medications in individual patients was not analyzed in this study. The comparative effects of antibiotics or corticosteroids alone and antibiotics combined with corticosteroids need to be assessed in well-designed randomized controlled trials. Lack of a specific diagnostic marker for SC is another factor to be considered. Autoimmune encephalitis or GABHS-related basal ganglia encephalitis could have been possibly misdiagnosed as SC, especially in those with severe clinical presentation diagnosed before the discovery of antibodies. Lack of standardization in documenting treatment response and the heterogeneity in the exact antibiotic/corticosteroid drug (and dosage) used are problems inherent to the retrospective nature of data collection in most of the studies included in this meta-analysis. Despite these limitations, the authors have succeeded in providing comprehensive data on the clinical course and treatment outcome in patients with SC that can be used for designing randomized controlled trials in the future for addressing the unanswered questions that remain.
References