Systemic sclerosis sine scleroderma: a time of re-appraisal.

OBJECTIVE: Systemic sclerosis sine scleroderma (ssSSc), formally described in 1962, is a subset of SSc which, unlike limited (lcSSc) and diffuse cutaneous (dcSSc) forms, lacks skin fibrosis. According to the 2013 ACR/EULAR criteria, SSc can be diagnosed in the absence of skin thickening, even if this is expected to develop later in disease course. Driven by a fatal case of ssSSc with cardiac involvement, we analysed published data on ssSSc prevalence and severity.

METHODS: A systematic literature review and qualitative synthesis of SSc cohorts with data on ssSSc was performed.

RESULTS: Thirty-five studies on a total of 25,455 SSc patients published between 1976 and 2023 were identified. The mean prevalence of ssSSc, albeit using different definitions, was almost 10% (range 0-23%), with the largest study reporting a cross-sectional prevalence of 13%. In 5 studies with a follow-up period of up to 9 years, reclassification of ssSSc into lcSSc or dcSSc ranged from 0% to 28%. Interstitial lung disease, pulmonary arterial hypertension, scleroderma renal crisis, and cardiac diastolic dysfunction were present in 46% (range 9.3-59.1%), 15% (range 5.9-24.6%), 5% (range 1.6-24.6%), and 26.5% (range 1.8-40.7%) of ssSSc patients, respectively. Survival across studies was comparable to lcSSc and better than dcSSc.

CONCLUSION: Published data on ssSSc vary widely regarding prevalence, clinical expression and prognosis partly due to underdiagnosis and misclassification. Although classification criteria should not impact appropriate management of patients, updated ssSSc subclassification criteria, which will take into account time from disease onset, should be considered.