Top

Rheumatology and Therapy

Published in:

Open Access 01-03-2021 | Systemic Lupus Erythematosus | Review

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

Authors: Georges El Hasbani, Mario Viola, Savino Sciascia, Ali T. Taher, Imad Uthman

Published in: Rheumatology and Therapy | Issue 1/2021

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.

Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295–306. https://doi.org/10.1111/j.1538-7836.2006.01753.x.CrossRefPubMed

Ortel TL. Antiphospholipid syndrome: laboratory testing and diagnostic strategies. Am J Hematol. 2012;87(Suppl 1):S75-81. https://doi.org/10.1002/ajh.23196.CrossRefPubMedPubMedCentral

Tubach F, Hayem G, Marchand JL, et al. IgG anti-beta2-glycoprotein I antibodies in adult patients with systemic lupus erythematosus: prevalence and diagnostic value for the antiphospholipid syndrome. J Rheumatol. 2000;27:1437–43.PubMed

Long AA, Ginsberg JS, Brill-Edwards P, et al. The relationship of antiphospholipid antibodies to thromboembolic disease in systemic lupus erythematosus: a cross-sectional study. Thromb Haemost. 1991;66:520–4.CrossRef

Sebastiani GD, Passiu G, Galeazzi M, et al. Prevalence and clinical associations of anticardiolipin antibodies in systemic lupus erythematosus: a prospective study. Clin Rheumatol. 1991;10:289–93. https://doi.org/10.1007/bf02208692.CrossRefPubMed

Merashli M, Alves J, Ames PRJ. Clinical relevance of antiphospholipid antibodies in systemic sclerosis: a systematic review and meta-analysis. Semin Arthritis Rheum. 2017;46:615–24. https://doi.org/10.1016/j.semarthrit.2016.10.004.CrossRefPubMed

Gupta R, Thabah MM, Gupta S, et al. Clinical significance of antiphospholipid antibodies in Indian scleroderma patients. Rheumatol Int. 2009;30:277–9. https://doi.org/10.1007/s00296-009-1107-0.CrossRefPubMed

Marie I, Jouen F, Hellot M-F, et al. Anticardiolipin and anti-beta2 glycoprotein I antibodies and lupus-like anticoagulant: prevalence and significance in systemic sclerosis. Br J Dermatol. 2008;158:141–4. https://doi.org/10.1111/j.1365-2133.2007.08309.x.CrossRefPubMed

Pasoto SG, Chakkour HP, Natalino RR, et al. Lupus anticoagulant: a marker for stroke and venous thrombosis in primary Sjögren’s syndrome. Clin Rheumatol. 2012;31:1331–8. https://doi.org/10.1007/s10067-012-2019-z.CrossRefPubMed

10.

Olech E, Merrill JT. The prevalence and clinical significance of antiphospholipid antibodies in rheumatoid arthritis. Curr Rheumatol Rep. 2006;8:100–8. https://doi.org/10.1007/s11926-006-0049-8.CrossRefPubMed

11.

Giannakopoulos B, Krilis SA. The pathogenesis of the antiphospholipid syndrome. N Engl J Med. 2013;368:1033–44. https://doi.org/10.1056/NEJMra1112830.CrossRefPubMed

12.

Martin M, Martinez C, Arnaud L, et al. Association of antiphospholipid antibodies with active digital ulceration in systemic sclerosis. RMD Open. 2019. https://doi.org/10.1136/rmdopen-2019-001012.CrossRefPubMedPubMedCentral

13.

Touré AO, Ly F, Sall A, et al. Antiphospholipid antibodies and systemic scleroderma. Turk J Haematol. 2013;30:32–6. https://doi.org/10.4274/tjh.2012.0059.CrossRefPubMedPubMedCentral

14.

Wielosz E, Dryglewska M, Majdan M. Antiphospholipid antibodies and kidney involvement in patients with systemic sclerosis. Clin Rheumatol. 2009;28:955–9. https://doi.org/10.1007/s10067-009-1188-x.CrossRefPubMed

15.

Boin F, Franchini S, Colantuoni E, et al. Independent association of anti-beta(2)-glycoprotein I antibodies with macrovascular disease and mortality in scleroderma patients. Arthritis Rheum. 2009;60:2480–9. https://doi.org/10.1002/art.24684.CrossRefPubMedPubMedCentral

16.

Egiziano G, Widdifield J, Rahman A, et al. Antiphospholipid antibody testing in a general population sample from the USA: an administrative database study. Sci Rep. 2020;10:3102. https://doi.org/10.1038/s41598-020-59990-5.CrossRefPubMedPubMedCentral

17.

Morrisroe KB, Stevens W, Nandurkar H, et al. The association of antiphospholipid antibodies with cardiopulmonary manifestations of systemic sclerosis. Clin Exp Rheumatol. 2014;32:S133–7.

18.

Sobanski V, Lemaire-Olivier A, Giovannelli J, et al. Prevalence and clinical associations of antiphospholipid antibodies in systemic sclerosis: new data from a French cross-sectional study, systematic review, and meta-analysis. Front Immunol. 2018. https://doi.org/10.3389/fimmu.2018.02457.CrossRefPubMedPubMedCentral

19.

Brandt JT, Triplett DA, Rock WA, et al. Effect of lupus anticoagulants on the activated partial thromboplastin time Results of the College of American Pathologists survey program. Arch Pathol Lab Med. 1991;115:109–14.PubMed

20.

Galli M, Luciani D, Bertolini G, et al. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood. 2003;101:1827–32. https://doi.org/10.1182/blood-2002-02-0441.CrossRefPubMed

21.

Reynaud Q, Lega J-C, Mismetti P, et al. Risk of venous and arterial thrombosis according to type of antiphospholipid antibodies in adults without systemic lupus erythematosus: a systematic review and meta-analysis. Autoimmun Rev. 2014;13:595–608. https://doi.org/10.1016/j.autrev.2013.11.004.CrossRefPubMed

22.

Radin M, Schreiber K, Cuadrado MJ, et al. Pregnancy outcomes in mixed connective tissue disease: a multicentre study. Rheumatology. 2019;58:2000–8. https://doi.org/10.1093/rheumatology/kez141.CrossRefPubMed

23.

Rai R, Swetha T. Association of anti-phospholipid antibodies with connective tissue diseases. Indian Dermatol Online J. 2015;6:89–91. https://doi.org/10.4103/2229-5178.153009.CrossRefPubMedPubMedCentral

24.

Jackson J, McDonald M, Casey E, et al. Mixed connective tissue disease with arterial thrombosis, antiphospholipid antibodies and heparin induced thrombocytopenia. J Rheumatol. 1990;17:1523–4.PubMed

25.

Doria A, Ruffatti A, Calligaro A, et al. Antiphospholipid antibodies in mixed connective tissue disease. Clin Rheumatol. 1992;11:48–50. https://doi.org/10.1007/BF02207083.CrossRefPubMed

26.

Mok MY, Lau CS, Chiu SSH, et al. Systemic sclerosis is an independent risk factor for increased coronary artery calcium deposition. Arthritis Rheum. 2011;63:1387–95. https://doi.org/10.1002/art.30283.CrossRefPubMed

27.

Bortoluzzi A, Furini F, Campanaro F, et al. Application of SLICC classification criteria in undifferentiated connective tissue disease and evolution in systemic lupus erythematosus: analysis of a large monocentric cohort with a long-term follow-up. Lupus. 2017;26:616–22. https://doi.org/10.1177/0961203316671814.CrossRefPubMed

28.

Radin M, Schreiber K, Cecchi I, et al. A multicentre study of 244 pregnancies in undifferentiated connective tissue disease: maternal/fetal outcomes and disease evolution. Rheumatology. 2020. https://doi.org/10.1093/rheumatology/kez620 (Published online first: 14 Jan 2020).CrossRefPubMed

29.

Lockshin MD, Levine AB, Erkan D. Patients with overlap autoimmune disease differ from those with “pure” disease. Lupus Sci Med. 2015;2:e000084. https://doi.org/10.1136/lupus-2015-000084.CrossRefPubMedPubMedCentral

30.

Price EJ, Collins D, Williamson L, et al. The burden of systemic disease in patients with primary Sjögren’s syndrome. Rheumatology. 2016;55:i179–80.CrossRef

31.

Jeleniewicz R, Majdan M, Targońska-Stępniak B, et al. Prevalence of antiphospholipid antibodies in rheumatoid arthritis patients and relationship with disease activity. Pol Arch Med Wewn. 2012;122:480–6. https://doi.org/10.20452/pamw.1415.CrossRefPubMed

32.

Jordan N, D’cruz DP. Association of lupus anticoagulant with long-term damage accrual in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Care Res. 2016;68:711–5. https://doi.org/10.1002/acr.22723.CrossRef

33.

Sebastian JK, Voetsch B, Stone JH, et al. The frequency of anticardiolipin antibodies and genetic mutations associated with hypercoagulability among patients with Wegener’s granulomatosis with and without history of a thrombotic event. J Rheumatol. 2007;34:2446–50.PubMed

Title: Antiphospholipid Antibodies in Inflammatory and Autoimmune Rheumatic and Musculoskeletal Diseases Beyond Lupus: A Systematic Review of the Available Evidence
Authors: Georges El Hasbani
Mario Viola
Savino Sciascia
Ali T. Taher
Imad Uthman
Publication date: 01-03-2021
Publisher: Springer Healthcare
Keywords: Systemic Lupus Erythematosus
Systemic Sclerosis
Antiphospholipid Syndrome
Antiphospholipid Syndrome
Rheumatoid Arthritis
Thrombosis
Mixed Connective Tissue Disease
Published in: Rheumatology and Therapy / Issue 1/2021
Print ISSN: 2198-6576
Electronic ISSN: 2198-6584
DOI: https://doi.org/10.1007/s40744-020-00273-w

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2021

Patient Experience With Fatigue and Qualitative Interview-Based Evidence of Content Validation of The FACIT-Fatigue in Systemic Lupus Erythematosus

Revascularization Versus Medical Therapy in Takayasu's Arteritis Patients with Coronary Artery Involvement

Safety and Efficacy of Prefilled Liquid Etanercept-Biosimilar Yisaipu for Active Ankylosing Spondylitis: A Multi-Center Phase III Trial

Frequency of Prescription Claims for Drugs that May Interact with Janus Kinase Inhibitors Among Patients with Rheumatoid Arthritis in the US

Sjögren's Syndrome Associated With Thrombotic Thrombocytopenic Purpura: A Case-Based Review

Serum KL-6, CA19-9, CA125 and CEA are Diagnostic Biomarkers for Rheumatoid Arthritis-Associated Interstitial Lung Disease in the Chinese Population

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials