Background Juvenile onset systemic sclerosis is thought to have distinct features compared to adult onset systemic sclerosis (SSc). There is currently little data on patients with juvenile onset of Raynaud's phenomenon who subsequently develop SSc.
Objectives To examine the characteristics of subjects in an adult cohort of SSc who developed juvenile onset Raynaud's (JoR), defined as onset of Raynaud's prior to the age of 16 years.
Methods Data from patients registered in a Canadian adult SSc cohort were extracted. Baseline registry demographic, clinical and serological characteristics of patients with JoR were compared to those with adult onset Raynaud's (i.e. onset after the age of 16 years; AoR). Chi-squared tests, Fisher's exact tests and Mann Whitney U tests were used as appropriate. Kaplan Meier curves and Cox proportional hazard models were generated to compare survival of JoR and AoR subjects. P-values less than 0.05 were considered significant. All statistical analyses were performed with SAS v.9.2 (SAS Institute, USA).
Results There were 78 JoR and 1311 AoR subjects. The proportion of females was similar in JoR (86%) and AoR (87%). Mean age of onset of Raynaud's was 12.1±3.1 years in JoR compared to 42.8±13.5 years in AoR. Mean age of onset of the first non-Raynaud's disease symptom was 28.8±16.0 years in JoR compared to 45.8±12.8 years in AoR. Mean disease duration at cohort entry was 16.7±12.3 years in JoR compared to 10.2±9.2 years in AoR.
Limited cutaneous disease was more common in JoR compared to AoR (71.8% vs 63.1%, p=0.121), although anti-centromere antibodies were less common in JoR compared to AoR (24.2% vs 35.6%, p=0.060). Pulmonary hypertension was significantly less common in JoR compared to AoR (4.0% vs 18.3%, p=0.004). Scleroderma renal crisis was present equally in JoR and AoR (6.5% vs 4.8%, p=0.423), although anti-RNA polymerase III antibodies were significantly less common in JoR compared to AoR (4.4% vs 18.2%, p=0.016). Interstitial lung disease (35.9% vs 42.9%, p=0.222) and anti-topoisomerase I antibodies (18.2% vs 15.4%, p=0.546) were present equally in JoR and AoR. The prevalence of digital ulcers (26.9% vs 28.2%, p=0.804) and the number of gastrointestinal symptoms (4.2±3.2 vs 4.2±3.1, p=0.766) were also similar in JoR and AoR.
HAQ (0.6±0.7 vs 0.8±0.7, p=0.005) and SF-36 PCS scores (42±12.1 vs 37.5±11.3, p=0.001) were significantly better in JoR compared to AoR.
During follow up, 5/71 (7.0%) JoR and 185/1109 (16.7%) AoR subjects died. In unadjusted analysis, survival was significantly better in JoR compared to AoR subjects (log-rank p<0.001). After adjusting for sex and disease subset (limited versus diffuse), the risk of death in JoR was significantly less compared to that in AoR (hazard ratio 0.10, 95% CI 0.04-0.88, p<0.001).
Conclusions Patients with juvenile onset Raynaud's have distinct clinical profiles and better survival compared to those with onset of Raynaud's after the age of 16 years. However, there was considerable uncertainty around the estimates and survival bias may have contributed to the results. Further studies in large samples of subjects with incident disease are needed to confirm these results. This contributes to the rationale for the emerging INSYNC (INternational Systemic sclerosis iNception Cohort) inception cohort.
Disclosure of Interest None declared