Restricted accessResearch articleFirst published online 2020-10
Antiphospholipid syndrome (APS) in patients with systemic lupus erythematosus (SLE) implies a more severe disease with more damage accrual and higher mortality
Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in systemic lupus erythematosus(SLE) patients. Our aim was to investigate the differences between SLE patients according to the presence of aPL and/or clinical antiphospholipid syndrome (APS).
Materials and methods
Patients from the RELESSER-T registry were included. RELESSER-T is a Spanish multicenter, hospital-based, retrospective, SLE registry.
Results
We included 2398 SLE patients, 1372 of whom were positive for aPL. Overall 1026 patients were classified as SLE, 555 as SLE-APS and817 as SLE-aPL. Regarding cardiovascular risk factors, SLE-APS patients had higher rates of hypertension, dyslipidemia and diabetes than those with SLE-aPL and SLE (p < 0.001). SLE-APS patients showed higher rates of neuropsychiatric, cardiac, pulmonary, renal and ophthalmological manifestations than the other groups (p < 0.001). SLE-APS patients presented greater damage accrual with higher SLICC values (1.9 ± 2.2 in SLE-APS, 0.9 ± 1.4 in SLE-aPL and 1.1 ± 1.6 in SLE, p < 0.001) and more severe disease as defined by the Katz index (3 ± 1.8 in SLE-APS, 2.7 ± 1.7 in SLE-aPL and 2.6 ± 1.6 in SLE, p < 0.001). SLE-APS patients showed higher mortality rates (p < 0.001).
Conclusions
SLE-APS patients exhibited more severe clinical profiles with higher frequencies of major organ involvement, greater damage accrual and higher mortality than SLE-aPL and SLE patients.
WahlDGGuilleminFDe MaistreEPerretCLecompteTThibautG.Risk for venous thrombosis related to antiphospholipid antibodies in systemic lupus erythematosus – a meta-analysis. Lupus1997;
6: 467–473.
3.
SmythAOliveiraGHLahrBDBaileyKRNorbySMGarovicVD.A systematic review and meta-analysis of pregnancy outcomes in patients with systemic lupus erythematosus and lupus nephritis.Clin J Am Soc Nephrol2010;
5: 2060–2068.
4.
Ruiz-IrastorzaGEgurbideMVUgaldeJAguirreC.High impact of antiphospholipid syndrome on irreversible organ damage and survival of patients with systemic lupus erythematosus. Arch Intern Med2004;
164: 77–82.
5.
Ruiz-IrastorzaGEgurbideMVMartinez-BerriotxoaAUgaldeJAguirreC.Antiphospholipid antibodies predict early damage in patients with systemic lupus erythematosus.Lupus2004;
13: 900–905.
6.
UnluOZuilySErkanD.The clinical significance of antiphospholipid antibodies in systemic lupus erythematosus.Eur J Rheumatol2016;
3: 75–84.
7.
ZuilySRegnaultVSelton-SutyC, et al.
Increased risk for heart valve disease associated with antiphospholipid antibodies in patients with systemic lupus erythematosus: meta-analysis of echocardiographic studies.Circulation2011;
124: 215–224.
8.
CoinMAVilar-LopezRPeralta-RamirezI, et al.
The role of antiphospholipid autoantibodies in the cognitive deficits of patients with systemic lupus erythematosus.Lupus2015;
24: 875–879.
9.
TaraborelliMCavazzanaIMartinazziN, et al.
Organ damage accrual and distribution in systemic lupus erythematosus patients followed-up for more than 10 years.Lupus2017;
26: 1197–1204.
10.
ParodisIArnaudLGerhardssonJ, et al.
Antiphospholipid antibodies in lupus nephritis. PLoS One2016;
11: e0158076.
11.
HochbergMC.Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus.Arthritis Rheum1997;
40: 1725.
12.
Rua-FigueroaILopez-LongoFJCalvo-AlenJ, et al.
National registry of patients with systemic lupus erythematosus of the Spanish Society of Rheumatology: objectives and methodology. Reumatol Clin2014;
10: 17–24.
13.
Pego-ReigosaJMRua-FigueroaILopez-LongoFJ, et al.
Analysis of disease activity and response to treatment in a large Spanish cohort of patients with systemic lupus erythematosus.Lupus2015;
24: 720–729.
14.
Galindo-IzquierdoMRodriguez-AlmarazEPego-ReigosaJM, et al.
Characterization of patients with lupus nephritis included in a large cohort from the Spanish Society of Rheumatology Registry of Patients With Systemic Lupus Erythematosus (RELESSER). Medicine (Baltimore)2016;
95: e2891.
15.
NarvaezJBorrellHSanchez-AlonsoF, et al.
Primary respiratory disease in patients with systemic lupus erythematosus: data from the Spanish Rheumatology Society Lupus Registry (RELESSER) cohort. Arthritis Res Ther2018;
20: 280.
16.
Torrente-SegarraVSalman MonteTCRua-FigueroaI, et al.
Relationship between damage and mortality in juvenile-onset systemic lupus erythematosus: Cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER).Semin Arthritis Rheum 2019; 48: 1025–1029.
17.
Gomez-ReinoJJRodriguez-LozanoCCampos-FernandezCMontoroMDescalzoMACarmonaL.Change in the discontinuation pattern of tumour necrosis factor antagonists in rheumatoid arthritis over 10 years: data from the Spanish registry BIOBADASER 2.0. Ann Rheum Dis2012;
71: 382–385.
18.
Rua-FigueroaIFernandezCMAndreuJL, et al.
Comorbidities in patients with primary Sjogren’s syndrome and systemic lupus erythematosus: a comparative registries-based study. Arthritis Care Res (Hoboken)2017;
69: 38–45.
19.
MiyakisSLockshinMDAtsumiT, et al.
International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).J Thromb Haemost2006;
4: 295–306.
20.
HawkerGGabrielSBombardierCGoldsmithCCaronDGladmanD.A reliability study of SLEDAI: a disease activity index for systemic lupus erythematosus. J Rheumatol1993;
20: 657–660.
21.
PetriMKimMYKalunianKC, et al.
Combined oral contraceptives in women with systemic lupus erythematosus.N Engl J Med2005;
353: 2550–2558.
22.
GladmanDGinzlerEGoldsmithC, et al.
The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus.Arthritis Rheum1996;
39: 363–369.
23.
KatzJDSenecalJLRivestCGouletJRRothfieldN.A simple severity of disease index for systemic lupus erythematosus.Lupus1993;
2: 119–123.
24.
PengoVTripodiAReberG, et al.
Update of the guidelines for lupus anticoagulant detection. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis.J Thromb Haemost2009;
7: 1737–1740.
25.
DeakMBocskaiMBurcsarSDanyiOFeketeZKovacsL.Non-thromboembolic risk in systemic lupus erythematosus associated with antiphospholipid syndrome. Lupus2014;
23: 913–918.
26.
TaraborelliMLazzaroniMGMartinazziN, et al.
The role of clinically significant antiphospholipid antibodies in systemic lupus erythematosus.Reumatismo2016;
68: 137–143.
27.
ZuilySDominguesVSuty-SeltonC, et al.
Antiphospholipid antibodies can identify lupus patients at risk of pulmonary hypertension: a systematic review and meta-analysis.Autoimmun Rev2017;
16: 576–586.
28.
IlgenUYaylaMEAtesA, et al.
Antiphospholipid antibodies and non-thrombotic manifestations of systemic lupus erythematosus.Lupus2018;
27: 665–669.
29.
HughesG.Hughes syndrome (antiphospholipid syndrome) and the nervous system.Lupus2018;
27: 15–17.
30.
ToCHPetriM.Is antibody clustering predictive of clinical subsets and damage in systemic lupus erythematosus?Arthritis Rheum2005;
52: 4003–4010.
31.
Artim-EsenBCeneESahinkayaY, et al.
Cluster analysis of autoantibodies in 852 patients with systemic lupus erythematosus from a single center.J Rheumatol2014;
41: 1304–1310.
32.
IdborgHZandianASandbergAS, et al.
Two subgroups in systemic lupus erythematosus with features of antiphospholipid or Sjogren’s syndrome differ in molecular signatures and treatment perspectives.Arthritis Res Ther2019;
21: 62.
33.
BundhunPKSoogundMZSHuangF.Arterial/venous thrombosis, fetal loss and stillbirth in pregnant women with systemic lupus erythematosus versus primary and secondary antiphospholipid syndrome: a systematic review and meta-analysis.BMC Pregnancy Childbirth2018;
18: 212.
34.
Lopez-SotoACerveraRFontJ, et al.
Isotype distribution and clinical significance of antibodies to cardiolipin, phosphatidic acid, phosphatidylinositol and phosphatidylserine in systemic lupus erythematosus: prospective analysis of a series of 92 patients. Clin Exp Rheumatol1997;
15: 143–149.
35.
TeixidoMFontJReverterJC, et al.
Anti-beta 2-glycoprotein I antibodies: a useful marker for the antiphospholipid syndrome. Br J Rheumatol1997;
36: 113–116.
36.
LovePESantoroSA.Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders. Prevalence and clinical significance.Ann Intern Med1990;
112: 682–698.
37.
DenburgSDCarbotteRMGinsbergJSDenburgJA.The relationship of antiphospholipid antibodies to cognitive function in patients with systemic lupus erythematosus. J Int Neuropsychol Soc1997;
3: 377–386.
38.
TomiettoPAnneseVD'agostiniS, et al.
General and specific factors associated with severity of cognitive impairment in systemic lupus erythematosus. Arthritis Rheum2007;
57: 1461–1472.
39.
MurraySGYazdanyJKaiserR, et al.
Cardiovascular disease and cognitive dysfunction in systemic lupus erythematosus.Arthritis Care Res (Hoboken)2012;
64: 1328–1333.
40.
SahinMDuzgunNTuncSETutkakH.Clinical manifestations and antiphosphatidylserine antibodies in patients with systemic lupus erythematosus: is there an association?Clin Rheumatol2007;
26: 154–160.
41.
HawroTMaurerMSysa-JedrzejowskaAWozniackaA.Prevalence of nonspecific cutaneous vascular lesions and association with antiphospholipid antibodies in patients with systemic lupus erythematosus.Br J Dermatol2013;
168: 213–215.
42.
TaraborelliMLeuenbergerLLazzaroniMG, et al.
The contribution of antiphospholipid antibodies to organ damage in systemic lupus erythematosus.Lupus2016;
25: 1365–1368.
43.
DrenkardCVillaARAlarcon-SegoviaDPerez-Vazquez ME.
Influence of the antiphospholipid syndrome in the survival of patients with systemic lupus erythematosus.J Rheumatol1994;
21: 1067–1072.
44.
Alarcon-SegoviaDPerez-RuizAVillaAR.Long-term prognosis of antiphospholipid syndrome in patients with systemic lupus erythematosus.J Autoimmun2000;
15: 157–161.
45.
Rua-FigueroaIRichiPLopez-LongoFJ, et al.
Comprehensive description of clinical characteristics of a large systemic lupus erythematosus cohort from the Spanish Rheumatology Society Lupus Registry (RELESSER) with emphasis on complete versus incomplete lupus differences.Medicine (Baltimore)2015;
94: e267.
46.
Fernandez-NebroARua-FigueroaILopez-LongoFJ, et al.
Cardiovascular events in systemic lupus erythematosus: a nationwide study in Spain from the RELESSER Registry.Medicine (Baltimore)2015;
94: e1183.
47.
Riveros Frutos ACasasIRua-FigueroaI, et al.
Systemic lupus erythematosus in Spanish males: a study of the Spanish Rheumatology Society Lupus Registry (RELESSER) cohort. Lupus2017;
26: 698–706.
48.
Rua-FigueroaILopez-LongoJGalindo-IzquierdoM, et al.
Incidence, associated factors and clinical impact of severe infections in a large, multicentric cohort of patients with systemic lupus erythematosus. Semin Arthritis Rheum2017;
47: 38–45.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
