Antiphospholipid Antibodies in Inflammatory and Autoimmune Rheumatic and Musculoskeletal Diseases Beyond Lupus: A Systematic Review of the Available Evidence

Abstract

Background: The diagnosis of antiphospholipid syndrome (APS) requires the presence of thrombosis and/or recurrent miscarriages along with one or more anti-phospholipid antibodies (aPL). The role of aPL has been largely investigated in systemic lupus erythematosus (SLE) with minimal data on other autoimmune rheumatic diseases. In this review, we aim to assess the prevalence of aPL in patients with inflammatory and autoimmune rheumatic and musculoskeletal diseases (RMDs) other than SLE, and their association with thrombosis. Results: A total of 20 studies, including 3242 patients, measured aPL in different inflammatory and autoimmune RMDs. The overall median percentage of aPL-positive patients was 14.05% (from 0 to 57.5%). For systemic sclerosis (SSc) patients, the median positivity was 14.05% for aPL, with IgG aCL being detected in up to 35.48% of all SSc aPL-positive patients. Only six studies (30%) performed an antibody confirmation test after 12 weeks, with the median prevalence being 10.88% (from 0 to 29.79%). Only six studies also assessed the number of double or triple aPL-positive patients. A total of eight (40%) studies including 1071 patients investigated the association between aPL and thrombotic events, namely five for SSc, one for SS, one for ANCA associated vasculitides (AAV), and one for RA. A median of 18.75% (7.69–71.43%) of aPL-positive patients experienced an arterial event in comparison to a median of 13.66% (7.69–31.25%) who underwent venous thrombotic event. Taking into consideration only the studies that performed a confirmation test, a median value of 34.36% (12.9–71.43%) of aPL-positive patients underwent an arterial event and a median value of 16.32% (9.68–25%) of aPL-positive patients underwent a venous event. Conclusions: Anti-phospholipid antibodies can be detected in up to a third of patients with inflammatory and autoimmune RMDs, especially in SSc. However, there was a large heterogeneity among the retrieved studies. Available data supporting a general screening for aPL in all inflammatory and autoimmune RMDs are still insufficient. Screening for aPL in selected scenarios (e.g., pregnancy planning) could be considered. © 2021, The Author(s).