Abstract
Background: Avascular necrosis is a common complication in patients with SLE.
Objective: This study aimed to investigate the risk factors for the occurrence of avascular necrosis among SLE patients receiving steroid therapy at various doses in combination with immunosuppressants.
Methods: In this retrospective study, the medical records of all SLE patients under follow-up at the outpatient clinics of Cairo and Kafr Elsheikh University hospitals through the period from November 2014 to August 2019 were included. Avascular necrosis was diagnosed by the findings of different imaging modalities.
Results: We retrieved the medical records of 770 SLE patients during the study period; of them, 55 patients (7.1%) had avascular necrosis. There was significant higher usage of cyclophosphamide (p = 0.003), total cumulative dose of steroids 15-35g plus immunosuppressants (p < 0.001), and steroids >35g plus immunosuppressants (p = 0.016) in the avascular necrosis cohort. Based on the univariate analysis, disease duration of more than five years and cumulative use of steroids were statistically significant predictors for the evolvement of avascular necrosis. Multivariate logistic regression analysis revealed that a disease duration of more than five years was associated independently with avascular necrosis.
Conclusion: Our data seem to show a role of the association of immunosuppressants plus steroids in the risk of developing avascular necrosis.
Keywords: Predictors, avascular necrosis, systemic lupus erythematosus, egyptian, immunosuppressants, corticosteroid.
[1]
Gurevitz SL, Snyder JA, Wessel EK, Frey J, Williamson BA. Systemic lupus erythematosus: a review of the disease and treatment options. Consult Pharm 2013; 28(2): 110-21.
[http://dx.doi.org/10.4140/TCP.n.2013.110] [PMID: 23395811]
[http://dx.doi.org/10.4140/TCP.n.2013.110] [PMID: 23395811]
[2]
Rees F, Doherty M, Grainge MJ, Lanyon P, Zhang W. The worldwide incidence and prevalence of systemic lupus erythematosus: a systematic review of epidemiological studies. Rheumatology (Oxford) 2017; 56(11): 1945-61.
[http://dx.doi.org/10.1093/rheumatology/kex260] [PMID: 28968809]
[http://dx.doi.org/10.1093/rheumatology/kex260] [PMID: 28968809]
[3]
Carter EE, Barr SG, Clarke AE. The global burden of SLE: Prevalence, health disparities and socioeconomic impact. Nat Rev Rheumatol 2016; 605-20.
[4]
Bijl M, Reefman E, Horst G, Limburg PC, Kallenberg CGM. Reduced uptake of apoptotic cells by macrophages in systemic lupus erythematosus: correlates with decreased serum levels of complement. Ann Rheum Dis 2006; 65(1): 57-63.
[http://dx.doi.org/10.1136/ard.2005.035733] [PMID: 15919679]
[http://dx.doi.org/10.1136/ard.2005.035733] [PMID: 15919679]
[5]
Cervera R, Khamashta MA, Font J, et al. Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. Medicine (Baltimore) 1993; 72(2): 113-24.
[http://dx.doi.org/10.1097/00005792-199303000-00005] [PMID: 8479324]
[http://dx.doi.org/10.1097/00005792-199303000-00005] [PMID: 8479324]
[6]
Pons-Estel BA, Catoggio LJ, Cardiel MH, et al. The GLADEL multinational Latin American prospective inception cohort of 1,214 patients with systemic lupus erythematosus: ethnic and disease heterogeneity among “Hispanics”. Medicine (Baltimore) 2004; 83(1): 1-17.
[http://dx.doi.org/10.1097/01.md.0000104742.42401.e2] [PMID: 14747764]
[http://dx.doi.org/10.1097/01.md.0000104742.42401.e2] [PMID: 14747764]
[7]
Boumpas DT, Fessler BJ, Austin HA III, Balow JE, Klippel JH, Lockshin MD. Systemic lupus erythematosus: emerging concepts. Part 2: Dermatologic and joint disease, the antiphospholipid antibody syndrome, pregnancy and hormonal therapy, morbidity and mortality, and pathogenesis. Ann Intern Med 1995; 123(1): 42-53.
[http://dx.doi.org/10.7326/0003-4819-123-1-199507010-00007] [PMID: 7762914]
[http://dx.doi.org/10.7326/0003-4819-123-1-199507010-00007] [PMID: 7762914]
[8]
Boumpas DT, Austin HA III, Fessler BJ, Balow JE, Klippel JH, Lockshin MD. Systemic lupus erythematosus: emerging concepts. Part 1: Renal, neuropsychiatric, cardiovascular, pulmonary, and hematologic disease. Ann Intern Med 1995; 122(12): 940-50.
[http://dx.doi.org/10.7326/0003-4819-122-12-199506150-00009] [PMID: 7755231]
[http://dx.doi.org/10.7326/0003-4819-122-12-199506150-00009] [PMID: 7755231]
[9]
Maidhof W, Hilas O. Lupus: an overview of the disease and management options. P&T 2012; 37(4): 240-9. [Internet].
[PMID: 22593636]
[PMID: 22593636]
[10]
Petri M. Musculoskeletal complications of systemic lupus erythematosus in the Hopkins Lupus Cohort: an update. Arthritis Care Res 1995; 8(3): 137-45.
[http://dx.doi.org/10.1002/art.1790080305] [PMID: 7654797]
[http://dx.doi.org/10.1002/art.1790080305] [PMID: 7654797]
[11]
Gladman DD, Chaudhry-Ahluwalia V, Ibañez D, Bogoch E, Urowitz MB. Outcomes of symptomatic osteonecrosis in 95 patients with systemic lupus erythematosus. J Rheumatol 2001; 28(10): 2226-9.
[PMID: 11669161]
[PMID: 11669161]
[12]
Yang Y, Kumar S, Lim LSH, Silverman ED, Levy DM. Risk factors for symptomatic avascular necrosis in childhood-onset systemic lupus erythematosus. J Rheumatol 2015; 42(12): 2304-9.
[http://dx.doi.org/10.3899/jrheum.150464] [PMID: 26568601]
[http://dx.doi.org/10.3899/jrheum.150464] [PMID: 26568601]
[13]
Assouline-Dayan Y, Chang C, Greenspan A, Shoenfeld Y, Gershwin ME. Pathogenesis and natural history of osteonecrosis. Semin Arthritis Rheum 2002; 32(2): 94-124.
[http://dx.doi.org/10.1053/sarh.2002.33724b] [PMID: 12430099]
[http://dx.doi.org/10.1053/sarh.2002.33724b] [PMID: 12430099]
[14]
Gontero RP, Bedoya ME, Benavente E, Roverano SG, Paira SO. Osteonecrosis in Systemic Lupus Erythematosus. Reumatol Clínica 2015; 11: 151-5.
[http://dx.doi.org/10.1016/j.reumae.2014.05.006]
[http://dx.doi.org/10.1016/j.reumae.2014.05.006]
[15]
Ghaleb RM, Omar GM, Ibrahim MA. Avascular necrosis of bone in systemic lupus erythematosus. Egypt Rheumatol Elsevier 2011; 33: 27-33.
[http://dx.doi.org/10.1016/j.ejr.2010.09.002]
[http://dx.doi.org/10.1016/j.ejr.2010.09.002]
[16]
Prasad R, Ibanez D, Gladman D, Urowitz M. The role of non-corticosteroid related factors in osteonecrosis (ON) in systemic lupus erythematosus: a nested case-control study of inception patients. Lupus 2007; 16(3): 157-62.
[http://dx.doi.org/10.1177/0961203306075771] [PMID: 17432099]
[http://dx.doi.org/10.1177/0961203306075771] [PMID: 17432099]
[17]
Cozen L, Wallace DJ. Risk factors for avascular necrosis in systemic lupus erythematosus. J Rheumatol 1998; 25(1): 188.
[PMID: 9458231]
[PMID: 9458231]
[18]
JAVA. Declaration of Helsinki World Medical Association Declaration of Helsinki. Bull world Heal Organ 2013; 79: 373-4.
[19]
Elm E, Von , Altman DG, et al. The Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) Statement : Guidelines for reporting observational studies. Int J Surg 2014; 12: 1495-9.
[20]
Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012; 64(8): 2677-86.
[http://dx.doi.org/10.1002/art.34473] [PMID: 22553077]
[http://dx.doi.org/10.1002/art.34473] [PMID: 22553077]
[21]
Hawker G, Gabriel S, Bombardier C, Goldsmith C, Caron D, Gladman D. A reliability study of SLEDAI: a disease activity index for systemic lupus erythematosus. J Rheumatol 1993; 20(4): 657-60. [Internet].
[PMID: 8496860]
[PMID: 8496860]
[22]
Gladman DD, Urowitz MB, Goldsmith CH, et al. The reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in patients with systemic lupus erythematosus. Arthritis Rheum 1997; 40(5): 809-13.
[http://dx.doi.org/10.1002/art.1780400506] [PMID: 9153540]
[http://dx.doi.org/10.1002/art.1780400506] [PMID: 9153540]
[23]
Lee J, Kwok SK, Jung SM, et al. Osteonecrosis of the hip in Korean patients with systemic lupus erythematosus: risk factors and clinical outcome. Lupus 2014; 23(1): 39-45.
[http://dx.doi.org/10.1177/0961203313512880] [PMID: 24335586]
[http://dx.doi.org/10.1177/0961203313512880] [PMID: 24335586]
[24]
Tse SM, Mok CC. Time trend and risk factors of avascular bone necrosis in patients with systemic lupus erythematosus. Lupus 2017; 26(7): 715-22.
[http://dx.doi.org/10.1177/0961203316676384] [PMID: 27831540]
[http://dx.doi.org/10.1177/0961203316676384] [PMID: 27831540]
[25]
Kwon HH, Bang SY, Won S, et al. Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus. Lupus 2018; 27(10): 1644-51.
[http://dx.doi.org/10.1177/0961203318784648] [PMID: 29950160]
[http://dx.doi.org/10.1177/0961203318784648] [PMID: 29950160]
[26]
Joo YB, Bae SC. Assessment of clinical manifestations, disease activity and organ damage in 996 Korean patients with systemic lupus erythematosus: comparison with other Asian populations. Int J Rheum Dis 2015; 18(2): 117-28.
[http://dx.doi.org/10.1111/1756-185X.12462] [PMID: 25524656]
[http://dx.doi.org/10.1111/1756-185X.12462] [PMID: 25524656]
[27]
Mankin HJ, Mankin HJ. Nontraumatic necrosis of bone (osteonecrosis). N Engl J Med 1992; 326(22): 1473-9.
[http://dx.doi.org/10.1056/NEJM199205283262206] [PMID: 1574093]
[http://dx.doi.org/10.1056/NEJM199205283262206] [PMID: 1574093]
[28]
Wang GJ, Sweet DE, Reger SI, Thompson RC. Fat-cell changes as a mechanism of avascular necrosis of the femoral head in cortisone-treated rabbits. J Bone Jt Surg - Ser A 1977; 59: 729-35.
[29]
Kabata T, Kubo T, Matsumoto T, et al. Apoptotic cell death in steroid induced osteonecrosis: an experimental study in rabbits. J Rheumatol 2000; 27(9): 2166-71.
[PMID: 10990229]
[PMID: 10990229]
[30]
Chan KL, Mok CC. Glucocorticoid-induced avascular bone necrosis: diagnosis and management. Open Orthop J 2012; 6: 449-57. [Internet].
[http://dx.doi.org/10.2174/1874325001206010449] [PMID: 23115605]
[http://dx.doi.org/10.2174/1874325001206010449] [PMID: 23115605]
[31]
Drescher W, Schlieper G, Floege J, Eitner F. Steroid-related osteonecrosis--an update. Nephrol Dial Transplant 2011; 26(9): 2728-31.
[http://dx.doi.org/10.1093/ndt/gfr212] [PMID: 21602181]
[http://dx.doi.org/10.1093/ndt/gfr212] [PMID: 21602181]
[32]
McAvoy S, Baker KS, Mulrooney D, et al. Corticosteroid dose as a risk factor for avascular necrosis of the bone after hematopoietic cell transplantation. Biol Blood Marrow Transplant 2010; 16(9): 1231-6.
[http://dx.doi.org/10.1016/j.bbmt.2010.03.008] [PMID: 20302963]
[http://dx.doi.org/10.1016/j.bbmt.2010.03.008] [PMID: 20302963]
[33]
Nagasawa K, Tada Y, Koarada S, et al. Very early development of steroid-associated osteonecrosis of femoral head in systemic lupus erythematosus: prospective study by MRI. Lupus 2005; 14(5): 385-90.
[http://dx.doi.org/10.1191/0961203305lu2103oa] [PMID: 15934439]
[http://dx.doi.org/10.1191/0961203305lu2103oa] [PMID: 15934439]
[34]
Abbott KC, Koff J, Bohen EM, et al. Maintenance immunosuppression use and the associated risk of avascular necrosis after kidney transplantation in the United States. Transplantation 2005; 79(3): 330-6. [Internet].
[http://dx.doi.org/10.1097/01.TP.0000149894.95435.7F] [PMID: 15699764]
[http://dx.doi.org/10.1097/01.TP.0000149894.95435.7F] [PMID: 15699764]
[35]
Campbell S, Sun CL, Kurian S, et al. Predictors of avascular necrosis of bone in long-term survivors of hematopoietic cell transplantation. Cancer 2009; 115(18): 4127-35. [Internet].
[http://dx.doi.org/10.1002/cncr.24474] [PMID: 19536905]
[http://dx.doi.org/10.1002/cncr.24474] [PMID: 19536905]
[36]
Petri M, Bechtel B, Dennis G, et al. Burden of corticosteroid use in patients with systemic lupus erythematosus: results from a Delphi panel. Lupus 2014; 23(10): 1006-13.
[http://dx.doi.org/10.1177/0961203314532699] [PMID: 24786783]
[http://dx.doi.org/10.1177/0961203314532699] [PMID: 24786783]
[37]
Zhu KK, Xu WD, Pan HF, et al. The risk factors of avascular necrosis in patients with systemic lupus erythematosus: a meta-analysis. Inflammation 2014; 37(5): 1852-64.
[http://dx.doi.org/10.1007/s10753-014-9917-y] [PMID: 24862229]
[http://dx.doi.org/10.1007/s10753-014-9917-y] [PMID: 24862229]
[38]
Gladman DD, Urowitz MB, Chaudhry-Ahluwalia V, Hallet DC, Cook RJ. Predictive factors for symptomatic osteonecrosis in patients with systemic lupus erythematosus. J Rheumatol 2001; 28(4): 761-5.
[PMID: 11327247]
[PMID: 11327247]
Article Metrics
29
1
