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Meta-Analysis
. 2024 Apr 1;7(4):e246792.
doi: 10.1001/jamanetworkopen.2024.6792.

Treatments and Outcomes Among Patients with Sydenham Chorea: A Meta-Analysis

Michael Eyre  1   2 , Terrence Thomas  3 , Emanuela Ferrarin  4 , Sonia Khamis  2 , Sameer M Zuberi  5   6 , Adrian Sie  6   7 , Tamsin Newlove-Delgado  8 , Michael Morton  6 , Erika Molteni  9 , Russell C Dale  10 , Ming Lim  11   2 , Margherita Nosadini  12   13 ; Sydenham’s Chorea Systematic Literature Review Working Group
Collaborators, Affiliations
Meta-Analysis

Treatments and Outcomes Among Patients with Sydenham Chorea: A Meta-Analysis

Michael Eyre et al. JAMA Netw Open. .

Abstract

Importance: 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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Ferrarin reported being a permanent collaborator of the Sydenham’s Chorea Association. Dr Sie reported being the chair of the Sydenham’s Chorea Association. Dr Newlove-Delgado reported receiving grants from the British Association for Childhood Disability, British Medical Association Helen H Lawson Award, and Sydenham’s Chorea Association during the conduct of the study. Dr Morton reported being the honorary president of the Sydenham’s Chorea Association. Dr Molteni reported receiving support from the Medical Research Council Skills Development Fellowship Scheme. Dr Dale reported receiving support from National Health and a Medical Research Council Investigator grant (Australia), and the Petre Foundation. Dr Lim reported receiving personal fees from Octapharma, Roche, Novartis, Amgen; receiving grants from the Dancing Eye Syndrome Society, Great Ormond Street Hospital Charity, Multiple Sclerosis Society UK, and the Sparks Charity; receiving research support grants from the London Clinical Research Network and the Evelina Appeal, National Institute of Health Research, Action Medical Research, Boston Children’s Hospital Research Fund, and the GOSH charity outside the submitted work; and being the UK Clinical lead for the MR-MinMo study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Historical Trends in Sydenham Chorea
Plotted points represent patients grouped into 10 epochs: 1883-1912, 1913-1942, and 10-year intervals thereafter. IVIG indicates intravenous immunoglobulin.
Figure 2.
Figure 2.. Patient Demographics and Clinician-Reported Response to Symptomatic Medications at the First Episode of Sydenham Chorea
Data are shown for the first episode of Sydenham chorea in 1325 patients with disease onset since 1945. The top 20 countries of 50 total are shown. Data on year of onset were available in 416 patients and inferred from year of publication in the remaining. Seven patients with disease onset after 32 years of age are not shown. Significance indicated for comparisons of proportion with clinician-reported benefit in pairwise χ2 tests (Bonferroni-corrected). aP = .001 vs sodium channel blockers. bP < .001 vs sodium channel blockers. cP = .04 vs antihistamines. dP = .01 vs antihistamines. eP < .001 vs antihistamines.
Figure 3.
Figure 3.. Time to Chorea Resolution at the First Episode of Sydenham Chorea
Shading indicates 95% CIs.
Figure 4.
Figure 4.. Independent Associations of Clinical and Treatment Factors With Disease Course and Outcome
Data are shown for variables significant at P < .05 in the Cox proportional hazards regression model (A) and logistic regression models (B, C).
See this image and copyright information in PMC

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