Distinctive clinical phenotype of anti-centromere antibody-positive diffuse systemic sclerosis

The aim was to define clinical characteristics and long-term survival of patients with dcSSc and positive ACA.

We identified all cases of ACA⁺ SSc in our cohort (n = 1313). Those with dcSSc (ACA⁺ diffuse) were compared with representative groups of consecutive ACA⁺ patients with limited subset (ACA⁺ limited) and ACA^- dcSSc (non-ACA diffuse).

Thirty-five patients (2.7%) were ACA⁺ diffuse. The peak modified Rodnan skin score was not significantly different between the dcSSc subgroups, but it occurred later in the disease course in ACA⁺ diffuse (88.54 vs 30.65 months, P < 0.001). Patterns of organ involvement were different between the groups. ACA⁺ diffuse had a higher incidence of interstitial lung disease than ACA⁺ limited (22.86 vs 4.43%, P = 0.001), but lower than non-ACA diffuse (41.18%, P = 0.042). More patients developed pulmonary hypertension in the ACA⁺ diffuse group (28.5 vs 12.0% ACA⁺ limited or 12.0% non-ACA diffuse), although this was attributable to the longer follow-up in these patients. The cumulative incidence of pulmonary hypertension was not different from the other two groups. The incidence of cardiac involvement was similar between the dcSSc groups, and scleroderma renal crisis was more frequent in the non-ACA diffuse group. Survival in ACA⁺ patients was similar in both subsets, whereas non-ACA diffuse had higher mortality.

ACA⁺ dcSSc is uncommon and has a distinct clinical phenotype, with a more insidious onset of skin and organ involvement. Even in dcSSc, ACA appears protective for organ-based complications, namely interstitial lung disease and scleroderma renal crisis, and is associated with a better survival than expected in dcSSc.