Background/Purpose: Antiphospholipid antibodies (aPL) can be present in the sera of systemic sclerosis (SSc) patients. Important variations of their prevalence are observed in the literature. Their clinical associations remain largely unknown. The aim of this study was to perform a systematic review of published reports and a meta-analysis to estimate the prevalence of aPL in SSc.

Methods: A systematic review of the literature was carried out in PubMed and Embase between May 1975 and November 2015 by 3 of the authors (AL, VS and DL). We used combinations of the terms “systemic sclerosis”, “antiphospholipid antibodies”, “antiphospholipid syndrome”, “anticardiolipin antibodies”, “lupus anticoagulant”, “anti-β2GP1”, “anti-phosphatidylethanolamine”, “thrombosis”, “pulmonary embolism”, “deep vein thrombosis”, “stroke”, “myocardial infarct”, “pregnancy”. We adapted the search strategy to the specificities of each database. After screening the titles and abstracts, studies were selected after a full-length review. Inclusion criteria were: French or English-language publication, adult patients with SSc, and at least 30 patients with SSc tested for lupus anticoagulant (LA), or/and anticardiolipin (aCL) or/and anti- β2Glycoprotein 1 (anti-β2GP1) antibodies. Meta-analysis was performed using number of aPL positive (at least one of the three antibodies positive) and negative patients.

Results: 1291 references were retrieved as result of search, 79 articles were included for full text review after reading the titles and abstracts. Of these articles, 31 were assessed for eligibility. Finally, 23 studies were included in the meta-analysis, representing a total population of 2937 SSc patients. Prevalence of aPL positivity (one or more) in SSc in literature ranged from 0 to 58%. The overall pooled prevalence of aPL in SSc was 16% (95%CI [10-22]). LA was found in 0 to 16% of patients; aCL in 0 to 34% and anti-β2GpI in 0 to 50%. The prevalence of aCL was 11% (95%CI [7-15]), and prevalence of anti-β2GP1 was 9% (95%CI [3-19]). Clinical manifestations associated with aPL positivity were more frequently pulmonary arterial hypertension (PAH) or digital ulcer (DU). Six studies out of 11 found an association between aPL and PAH (aCL in 5, one or more aPL in 1). Two studies out of 8 found an association between aPL (aCL) and DU and 2 studies found a trend.

Conclusion: The prevalence of aPL in SSc was highly variable (range 0-58%). The overall pooled prevalence was 16% (95%CI [10-22]). The most frequent clinical manifestation associated with aPL positivity was PAH. AL and VS have contributed equally to this work.