Systemic sclerosis sine scleroderma: a multicenter study of 1417 subjects

Area of Science:

• Rheumatology
• Immunology
• Dermatology

Background:

• Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrosis, vascular abnormalities, and autoantibodies.
• SSc is classified based on the extent of skin involvement, including limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc).
• Systemic sclerosis sine scleroderma (ssSSc) presents without characteristic skin thickening, posing diagnostic challenges.

Purpose of the Study:

• To characterize the clinical and serological features of patients with ssSSc within a large, multicentered SSc cohort.
• To compare the phenotype of ssSSc with established SSc subtypes, lcSSc and dcSSc.

Main Methods:

• Data from 1417 subjects in the Canadian Scleroderma Research Group registry were analyzed.
• Subjects were classified as ssSSc if diagnosed with SSc by a rheumatologist but lacking sclerodactyly or skin involvement at baseline or during follow-up.
• Clinical and serological data of ssSSc patients were compared to those with lcSSc and dcSSc.

Main Results:

• Only 57 subjects (4.0%) initially met ssSSc criteria; 30 were later reclassified as lcSSc, leaving 27 (1.9%) as persistent ssSSc.
• ssSSc patients exhibited milder clinical profiles than dcSSc and similar or milder profiles than lcSSc, with comparable rates of interstitial lung disease.
• Serologically, ssSSc patients showed high rates of anticentromere antibodies (50.0%) and low rates of antitopoisomerase I (16.7%) and anti-RNA polymerase III (0%), mirroring lcSSc profiles.

Conclusions:

• Systemic sclerosis sine scleroderma (ssSSc) is a rare manifestation of SSc.
• The clinical and serological features of ssSSc closely resemble those of limited cutaneous SSc (lcSSc).
• These findings suggest ssSSc is likely a forme fruste of lcSSc, with potential misclassification due to subtle or early skin involvement, rather than a distinct SSc subset.