Phenotype of diffuse cutaneous systemic sclerosis patients with positive anticentromere antibodies: A systematic literature review and meta-analysis.

Objectives: Anticentromere antibodies (ACA) are typically found in limited cutaneous systemic sclerosis (lcSSc), whereas patients with anti-topoisomerase I antibodies (ATA) usually exhibit diffuse cutaneous involvement (dcSSc). We aimed to investigate the clinical phenotype and outcome of ACA-dcSSc.

Methods: A systematic literature review was conducted (January 1970 to April 2023) across MEDLINE, Scopus and OVID, to define whether SSc patients (population) within the ACA-dcSSc subset (exposure) had higher/lower risk for major organ involvement (interstitial lung disease-ILD, pulmonary hypertension-PH, primary myocardial involvement-PMI, scleroderma renal crisis-SRC) and mortality (outcomes) compared to ACA-lcSSc and ATA-dcSSc. Inclusion criteria were: 1) adult SSc patients with identifiable demographic and clinical features by subtype; 2) observational studies. The quality of the studies was evaluated by the Newcastle-Ottawa Scale. Random-effects meta-analysis was performed to compare odds ratios (OR) for major organ involvement, and the 5- and 10-year mortality of ACA-dcSSc with the other subsets.

Results: Out of 1570 hits, six articles were included, identifying 177 ACA-dcSSc patients. In ACA-dcSSc, ILD was more frequent than in ACA-lcSSc (OR 2.60; 95 %CI 1.39-4.87) but less frequent compared to ATA-dcSSc (OR 0.17; 95 %CI 0.10-0.29). ACA-dcSSc patients had a higher prevalence of PH vs. both conventional subsets; PMI and SRC were more frequent in ACA-dcSSc compared to ACA-lcSSc, and similar to ATA-dcSSc. While 5-year survival rates were comparable among the subsets, ACA-dcSSc patients exhibited a lower 10-year mortality than ATA-dcSSc (OR 0.42; 95 %CI 0.2-0.85).

Conclusion: Although uncommon, the ACA-dcSSc subset appears to have a distinct clinical phenotype, with a better prognosis than ATA-dcSSc.