Systemic Sclerosis Sine Scleroderma: A Time of Reappraisal.

ABSTRACT

OBJECTIVE: Systemic sclerosis sine scleroderma (ssSSc), formally described in 1962, is a subset of SSc that, unlike limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) forms, lacks skin fibrosis. According to the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology 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 analyzed published data on ssSSc prevalence and severity. METHODS: A systematic literature review and qualitative synthesis of SSc cohorts with data on ssSSc were performed. RESULTS: Thirty-five studies involving a total of 25,455 patients with SSc, published between 1976 and 2023, were identified. Although different definitions were used, the mean prevalence of ssSSc 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 0-28%. 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), respectively, of patients with ssSSc. Survival across studies was comparable to lcSSc and better than dcSSc. CONCLUSION: Published data on ssSSc vary widely on prevalence, clinical expression, and prognosis, partly due to underdiagnosis and misclassification. Although classification criteria should not affect appropriate management of patients, updated ssSSc subclassification criteria that takes into account time from disease onset should be considered.