Dear Editor,

Rheumatic chorea is the most common acquired etiology of childhood chorea, especially in low-income countries, and it can be the only manifestation of rheumatic fever, making it suitable for diagnosing the latter disease. It often occurs in children aged 5 and 14 years, among whom it is rarely the initial manifestation [1,2]. The key contributors to its occurrence include poverty, overcrowding, and limited access to high-quality health care services [3]. The incidence and prevalence of rheumatic chorea have changed over time, primarily due to improvements in patient care and widespread prophylactic antibiotic use [4]. Although it has become uncommon in developed countries, rheumatic chorea persists in significant percentages in developing nations. Despite decades of research, several knowledge gaps remain regarding the pathophysiology, diagnosis, treatment, and long-term outcomes of rheumatic chorea. By addressing these gaps, future research could lead to better prevention strategies, more targeted treatments, and improved outcomes for affected individuals. This retrospective study provides the detailed demographic, clinical, laboratory, and therapeutic profiles of patients with rheumatic chorea over the past 12 years (from 2012 to 2024) from a tertiary neurology referral center in South India. Data were collected from the hospital database, and patient videos recorded after obtaining written informed consent were reviewed. Values are presented as the medians and interquartile ranges (IQRs) for continuous variables and as frequencies (%) for categorical variables.

Our study included 35 patients (22 males) diagnosed with rheumatic chorea on the basis of clinical features and the exclusion of alternative etiologies of childhood chorea [1]. The median age at presentation was 14 years (IQR: 11–17 years). The demographic, clinical, imaging, treatment, and follow-up details are shown in Figure 1 and Supplementary Table 1 (in the online-only Data Supplement). The clinical examination videos of the patients are provided in Supplementary Videos 1-4 (in the online-only Data Supplement). Generalized chorea was observed in 22 (62.9%) patients, and hemichorea was observed in 12 (34.3%) patients. Nine patients (25.7%) had gait disturbances, eight (22.9%) had difficulty speaking, and three (8.6%) had difficulty swallowing. In eight (22.9%) patients, behavioral symptoms included irritability, fear, emotional lability, and hyperactivity. The milkmaid’s grip was observed in all the patients, and lingual dyskinesia (darting tongue) was observed in 19 (54.3%) patients. None of the patients had fever, arthralgia, arthritis, or skin rashes at presentation. A history of previous arthritis or arthralgia was noted in five (14.3%) patients. A preceding infection was reported by 14 (40.0%) patients, with a median time interval of 2 weeks (IQR: 1–16 weeks). Only one (2.9%) patient had previously documented rheumatic heart disease. Asymptomatic cardiac involvement was present in 23 (69.7%) out of 33 patients for whom the data were available, the most common of which was mitral valve regurgitation (60.6%). Ventricular function and electrocardiography were normal in all 33 patients. Evidence of preceding streptococcal infection was present in 18 (66.7%) out of 27 patients who underwent streptococcal testing. The anti-streptolysin O titer was elevated in 18 (69.2%) out of 26 patients. The anti-DNase B titer was elevated in two (50.0%) of the four patients. A throat swab for Streptococcus was negative in all four patients for whom it was performed. Other inflammatory markers, such as elevated erythrocyte sedimentation rates (ESRs), were observed in eight (30.8%) out of 26 patients, and elevated C-reactive protein (CRP) levels were observed in five (19.2%) out of 26 patients. Brain magnetic resonance imaging was performed in 17 patients, and abnormal basal ganglia and white matter changes were observed in only four (23.5%) of these patients.

All patients received antibiotics; 31 (88.6%) received intramuscular benzathine penicillin, and two patients each (5.7%) received oral penicillin and amoxicillin. Immunotherapy in the form of corticosteroids was administered to nine (25.7%) patients. The median duration of steroid therapy was 28 days (IQR: 13–56 days). No patients received intravenous immunoglobulin or plasma exchange. Symptomatic pharmacological treatment included sodium valproate in 18 (51.4%) patients, tetrabenazine in 14 (40.0%) patients, haloperidol in nine (25.7%) patients, and benzodiazepines in six (17.1%) patients. The median duration of symptomatic therapy was 3 months (IQR: 2–15 months). Follow-up data were available for 30 patients; 23 (76.7%) had complete resolution of chorea in the initial episode within a median duration of 2 months (IQR: 1–3 months). Among the 23 patients who experienced complete resolution, 10 patients (43.5%) eventually experienced relapse. At the final follow-up (median duration 12 months [IQR: 3–24 months]), 12 (40.0%) of the 30 patients still had chorea, and three (10.0%) patients had ongoing psychiatric symptoms.

The incidence and prevalence of rheumatic chorea remain relatively high in underdeveloped countries, making this disease a remarkable public health challenge. This study provides the comprehensive clinical and therapeutic profiles, follow-up and outcomes of 35 patients diagnosed with rheumatic chorea at a tertiary care center in India over the past decade. Our study’s median age at presentation aligns with that reported in the literature. The consistently observed female preponderance (2.2:1) was not evident in our patients [5]. This study illustrates that chorea can be the only manifestation of rheumatic fever, making it pivotal in the diagnosis of the latter disease. Evidence of preceding streptococcal infection (i.e., elevated ASO titers) can aid in the diagnosis, although other inflammatory markers, such as the ESR and CRP level, may remain within normal limits. Early diagnosis and prompt immunotherapy, including corticosteroids or other symptomatic treatments, can lead to favorable long-term functional outcomes. A recent individual patient data meta-analysis revealed that the relapse rates of rheumatic chorea range from 16% to 42%, and corticosteroid-based immunotherapy was associated with prompt patient recovery during the first episode of chorea [6]. Furthermore, antibiotics, corticosteroids, and sodium valproate were linked to lower relapse rates, which occurred in 34.3% of patients [7]. This finding is in accordance with that of our study, where the relapse rate was 36.7%. In the present study, 76.7% of patients experienced complete symptom resolution, while the remaining patients experienced symptom improvement.

In conclusion, rheumatic chorea can be the sole manifestation of rheumatic fever, underscoring the need for thorough cardiac evaluations to detect asymptomatic heart disease. Although it is increasingly less prevalent in developed nations, it remains a significant concern in underdeveloped countries, necessitating prompt evaluation of clinically suspected patients to ensure timely diagnosis and intervention and prevent complications, including relapse or permanent neurological sequelae.

Supplementary Materials

Video 1.

Classical clinical signs of rheumatic chorea observed in our cohort. The video reveals darting tongue (Segment-1), the milkmaid’s grip (Segment-2), spooning of the fingers (Segment-3), the piano sign (Segment-4), the touchdown sign (Segment-5), the hung-up knee reflex (Segment-6), the pendular knee reflex (Segment-7), and lurching gait (Segment-8).

Video 2.

Video demonstrating generalized chorea in a 14-year-old boy before treatment (Segment-1) and complete resolution of his symptoms at the 3-month follow-up after treatment (Segment-2).

Video 3.

Video revealing right hemichorea in an 18-year-old girl.

Video 4.

Video revealing left upper limb-predominant chorea in a 15-year-old boy (Segment-1) and left lower limb-predominant chorea in an 18-year-old boy (Segment-2).

Notes

Conflicts of Interest

The authors have no financial conflicts of interest.

Funding Statement

None

Acknowledgments

None

Author Contributions

Conceptualization: Madathum Kuzhiyil Farsana, Vikram V Holla, Ravi Yadav. Data curation: Madathum Kuzhiyil Farsana, Vikram V Holla. Formal analysis: Madathum Kuzhiyil Farsana. Investigation: Madathum Kuzhiyil Farsana, Vikram V Holla, Ravi Yadav. Methodology: Madathum Kuzhiyil Farsana, Ravi Yadav. Project administration: all authors. Resources: Vikram V Holla, Nitish Kamble, Rohan R Mahale, Faheem Arshad, Pramod Kumar Pal, Ravi Yadav. Supervision: Vikram V Holla, Nitish Kamble, Rohan R Mahale, Faheem Arshad, Pramod Kumar Pal, Ravi Yadav. Writing—original draft: Madathum Kuzhiyil Farsana. Writing—review & editing: Vikram V Holla, Nitish Kamble, Rohan R Mahale, Faheem Arshad, Pramod Kumar Pal, Ravi Yadav.

Figure 1.

Clinical and investigation findings of the cohort. A and B: Bar plot depicting the clinical presentations and investigations. C: Pie chart depicting the distribution of cardiac involvement. D-G: T2/FLAIR hyperintensity (D and E) in the head of the left caudate nucleus, left internal capsule associated with foci of T1 hyperintensity (F), patches of diffusion restriction, and postcontrast peripheral enhancement (G) in one patient. H: Discrete white matter FLAIR hyperintensities in the bilateral periventricular and subcortical white matter, suggestive of demyelination, in one patient. I: Increased mineralization in the bilateral globus pallidum, substantia nigra, and dentate nuclei in one patient. MRI, magnetic resonance imaging; ECG, electrocardiogram; ASO, anti-streptolysin O; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; FLAIR, fluid-attenuated inversion recovery.

REFERENCES

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