Background Anti-topoisomerase antibodies (ATA) in systemic sclerosis (SSc) have been associated with poorer prognosis including diffuse skin involvement, pulmonary fibrosis, cardiac involvement and increased mortality. However, 30–60% of ATA-positive SSc patients demonstrate only limited skin involvement and some have only mild disease course. In SSc, optimal risk stratification is of utmost importance for tailored clinical management at the patient level.
Objectives We aimed to determine the prevalence of mild disease among ATA positive patients and to investigate which readily available clinical parameters best identify patients with highest disease severity.
Methods Clinical baseline data from SSc patients included in the Combined Care In Systemic Sclerosis (CCIS) cohort of the Leiden University Medical Center were extracted. Patients fulfilling ACR 2013 criteria and ATA positive were included. Descriptive statistics were used to summarize sociodemographic, clinical and serological features. Patients with grade 3 or 4 disease on any of the Medsger severity subscales were considered to be severely diseased. We compared presence of diffuse cutaneous involvement, Raynaud's, pitting scars, calcinosis, proximal muscle weakness, >10% weight loss, interstitial lung disease and pro-BNP between the severity groups and corrected for confounding by disease duration (time since non-Raynaud) by stratifying into quartiles.
Results Of 422 SSc patients in the database, 344 patients had SSc meeting ACR criteria. 89 patients were exclusively ATA-positive, of which n=42 with mild disease and n=47 with severe disease. Patients with severe disease appeared to be younger (mean age 50 vs 55 yr), more often non-caucasian (51 vs 12%), with a longer time since non-Raynaud (median 4 vs 2 yr) and more often diffuse skin involvement (dcSSc;62 vs 41%), calcinosis (6 vs 0%) and weight loss (23 vs 7%). Stratification by disease duration, however revealed there are no real differences between mild en severe disease. Overall 47% of ATA+ patients in our cohort presented with mild SSc. When stratifying patients according to time of non-Raynaud, 55% of ATA+ patients presented with mild disease in the first disease duration quartile (median follow-up 0.5 years, range 0–0.8 years). In the forth disease duration quartile, according non-Raynaud time (median follow-up 12.7 years, range 8.2–44.1) the percentage with mild disease was still 27% (Figure 1).
Conclusions In our cohort, 47% of ATA-positive patients presented with mild systemic sclerosis, which could not be explained by disease duration. This suggests that solely the presence of ATA is of limited clinical relevance. Readily available sociodemographic and clinical parameters including type of skin involvement seem to have only limited value in identifying ATA patients with more severe SSc. More complex serological findings as antibody titers and fine-specifity of ATA should be defined for optimal serological subsetting.
Disclosure of Interest None declared