Clinical and epidemiological features of juvenile-onset systemic sclerosis from a nationwide survey in Japan

Objectives: To evaluate clinical and epidemiological features of juvenile-onset systemic sclerosis (jSSc) in Japan and to identify racial and generational differences. Methods: We surveyed patients with jSSc (developed before the age of 18 years) who visited selected facilities in Japan between January 2016 and December 2020. We estimated the number of patients with jSSc and the annual incidence rate in Japan. Thereafter, differences in clinical characteristics by disease subtype, autoantibody, and age at investigation were analyzed and compared with previous cohorts. Results: Of the 3,005 institutions selected for the first survey, 1,845 (61.8%) responded. The estimated number of patients with jSSc was 299, while the estimated annual incidence rate ranged from 0.98 to 1.59 per 1,000,000 children (aged <18 years) from 2016 to 2020. In the second-stage survey, 130 cases were analyzed, of which 85 (65.4%) had diffuse cutaneous SSc (dcSSc), 77.7% were female, while the median ages at onset and survey was 11 and 21 years, respectively. Autoantibody positivity was 62.4% for anti-topoisomerase I antibody (ATA) and 12.9% for anti-centromere antibody, while anti-PM-Scl antibody was very rare. In total, interstitial lung disease was present in 40.8% of patients (predominantly dcSSc and ATA positive), gastrointestinal lesions in 36.9%, pulmonary arterial hypertension in 7.7%, and no renal crisis. Conclusions: This is the largest national survey of jSSc characteristics analyzed in detail by autoantibody and disease subtype. Japanese jSSc was characterized by very high ATA-positivity rate. However, the frequency of major organ involvement was similar to previous reports of jSSc in the west.