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Background: Systemic sclerosis (SSc) is currently classified, based on the extent of skin involvement, into diffuse (dcSSc) and limited (lcSSc) cutaneous forms. However, recent evidence suggests that this historical classification fails to capture the heterogeneity of the SSc spectrum 1. Anticentromere antibodies (ACA) are typically found in lcSSc, whereas patients with anti-topoisomerase I antibodies (ATA) usually exhibit dcSSc. Nevertheless, few studies have reported less common and as yet poorly characterised associations (e.g., ACA-dcSSc) 2. Objectives: We aimed to clarify the clinical phenotype and outcome of scleroderma patients with ACA-dcSSc by performing a systematic literature review (SLR) and meta-analysis. Methods: A comprehensive literature search was conducted (January 1970 to April 2023) across the MEDLINE, Scopus and OVID databases in accordance with the PRISMA guidelines. The population of interest comprised ACA-dcSSc patients, and the outcome of interest was all-cause mortality at 5 and 10 years. Pre-defined inclusion criteria were adult ACA-dcSSc patients, with separately identifiable demographic and clinical features, and organ involvement. The quality of the selected studies was evaluated by the Newcastle-Ottawa Scale for cross-sectional, cohort, and case-control studies. Random-effects meta-analysis was performed to compare major organ involvement and the 5- and 10-year mortality risk of ACA-dcSSc with those of ACA-lcSSc and ATA-dcSSc patients. Results: From a total of 1570 hits generated by the database search, six articles were selected for review, identifying 177 cases of ACA-dcSSc patients (Figure 1). The mean age at SSc onset in SLR population was 47.3 ± 7.4 years with a mean disease duration of 12.5 ± 3.1 years. The mean modified Rodnan Skin Score (mRSS) was 15.9 ± 2.8. Among musculoskeletal manifestations, inflammatory arthritis and myositis were identified in 44 (33.6%) and 11 (8.4%) out of 131 patients with available data, respectively. Oesophageal involvement was reported in 75.6% of ACA-dcSSc patients, followed by interstitial lung disease (ILD) in 27.7%, pulmonary hypertension in 20.3% and primary myocardial involvement in 16.3%. Overall, ILD was less frequent in the ACA-lcSSc subset vs. ACA-dcSSc (OR 0.44; 95% CI: 0.27, 0.71; p Conclusion: Although uncommon, rheumatologists should be aware of the existence of the ACA-dcSSc subset, which appears to have a distinct clinical phenotype, with a better prognosis than ATA-dcSSc. This further highlights the urgent need for a novel classification combining skin subtype and serology status to enhance risk stratification and the management of scleroderma patients. REFERENCES: 1 Sobanski V, Giovannelli J, Allanore Y, et al. Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis. Arthritis Rheumatol. 2019; 71(9): 1553-1570. 2 Mierau R, Moinzadeh P, Riemekasten G, et al. Frequency of disease-associated and other nuclear autoantibodies in patients of the German Network for Systemic Scleroderma: correlation with characteristic clinical features. Arthritis Res Ther. 2011; 13(5): R172. Acknowledgements: NIL. Disclosure of Interests: None declared.
Binda et al. (Sat,) studied this question.