Irreversible organ damages in a cohort of patients with systemic lupus erythematosus (RENAISSANCE)

Objective: to reveal irreversible organ damages and to establish factors that influence their development in a RENAISSANCE cohort of patients with systemic lupus erythematosus (SLE) admitted to the clinic of the V.A. Nasonova Research Institute of Rheumatology in the period 2012 to 2014.

Subjects and methods. The investigation enrolled 231 young (mean age, 34.91±11.10 years) patients (209 women and 22 men) with a mean SLE duration of 107.65±97.36 months. On admission of the patients, the investigators collected history data (disease duration, the number of exacerbations and hospitalizations during the follow-up period), assessed current disease activity by SLEDAI-2K, irreversible organ damages by SLICC damage index (DI), and the therapy performed.

Results and discussion. Irreversible organ damages were absent in 95 (41%) patients; one or more damages associated with both disease itself and the therapy were observed in the other (59%) patients. There were low (1), mean (2–4), and high (>4) SLICC DI values in 64 (28%), 62 (27%), and 11 (5%) patients, respectively. Ocular lesions were most common (35%); a significant proportion of patients were found to have damages to the cardiovascular (22%), musculoskeletal (19%), and nervous (10%) systems. Lung disease, diabetes mellitus, and cancer were less prevalent (6.0, 3.4, and 1.3%, respectively). The patients with damages were significantly older (p = 0.02), had a longer disease duration (p = 0.0005) and more frequent SLE exacerbations and hospitalizations (p = 0.0003 and p = 0.001, respectively). The patients with DI ≥1 received glucocorticoids (GCs) longer (p = 0.001). At the onset of SLE they had significantly higher doses of GCs (mean 44.06±18.97 mg) than those without damages (35.91±20.12 mg; р = 0.002). DI correlated with GC doses at the onset of the disease, duration of GC use, number of hospitalizations and exacerbations. There was also a statistically significant correlation of overall SLICC DI with the duration of disease (r = 0.23) and the total dose of cyclophosphamide (CP) (r = 0.19).

Conclusion. Irreversible organ damages are present in 59 patients in the RENAISSANCE cohort. Older individuals develop a larger number of dam￾ages, with higher frequency of exacerbations and hospitalizations, longer use of GCs, and higher cumulative dose of CP. DI correlates with the dose of GC and does not depend on the activity and clinical manifestations of SLE at its onset. 

1. Насонова ВА. Системная красная волчанка. Москва: Медицина; 1972. 193 c. [Nasonova VA. Sistemnaya krasnaya volchanka [Systemic lupus erythematosus]. Moscow: Meditsina; 1972. 193 p.].

2. Petri M, Purvey S, Fang H, Magder LS. Predictors of organ damage in systemic lupus erythematosus: the Hopkins Lupus Cohort. Arthritis Rheum. 2012 Dec;64(12):4021-8. doi: 10.1002/art.34672

3. Urowitz MB, Gladman DD, Tom BDM, et al. Changing patterns in mortality and disease outcomes for patients with systemic lupus erythematosus. J Rheumatol. 2008;35:2152-8. doi: 10.3899/jrheum.080214

4. Rahman P, Gladman DD, Urowitz MB, et al. Early damage as measured by the SLICC/ACR Damage Index is a predictor of mortality in SLE. Lupus. 2001;10:93-6. doi: 10.1191/096120301670679959

5. Gladman DD, Ginzler E, Goldsmith C, 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 Rheum. 1996;39(3):363-9. doi: 10.1002/art.1780390303

6. 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. doi: 10.1002/art.1780400506

7. Gladman DD, Goldsmith CH, Urowitz MB, et al. The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index for systemic lupus erythema-tosus inter-national comparison. J Rheumatol. 2000;27(2):373-6.

8. Alarcon GS, McGwin G Jr, Bastian HM, et al. Systemic lupus erythematosus in three ethnic groups. VII [correction of VIII]. Predictors of early mortality in the LUMINA cohort .LUMINA Study Group. Arthritis Rheum. 2001;45(2):191-202. doi: 10.1002/1529-0131(200104)45:23.0.CO;2-2

9. Jonsen A, Clarke AE, Joseph L, et al. Association of the Charlson comorbidity index with mortality in systemic lupus erythematosus. Arthritis Care Res. 2011;63(9):1233-7. doi: 10.1002/acr.20506

10. Chen Y, Chen GL, Zhu CQ, et al. Severe systemic lupus erythematosus in emergency department: a retrospective single-center study from China. Clin Rheumatol. 2011;30(11):1463-9. doi: 10.1007/s10067-011-1826-y

11. Becker-Merok A, Nossent HC. Damage accumulation in systemic lupus erythematosus and its relation to disease activity and mortality. J Rheumatol. 2006;33(8):1570-7.

12. Gladman DD, Urowitz MB, Rahman P, et al. Accrual of organ damage over time in patients with systemic lupus erythematosus. J Rheumatol. 2003;30(9):1955-9.

13. Sutton EJ, Davidson JE, Bruce IN. The systemic lupus international collaborating clinics (SLICC) damage index: a systematic literature review. Semin Arthritis Rheum. 2013 Dec;43(3):352-61. doi: 10.1016/j.semarthrit.2013.05.003

14. Ravelli A, Duarte-Salazar C, Buratti S, et al. Assessment of damage in juvenile-onset systemic lupus erythematosus: a multicenter cohort study. Arthritis Rheum. 2003;49(4):501-7. doi: 10.1002/art.11205

15. Андрианова ИА, Иванова ММ. Ранний индекс повреждения у больных системной красной волчанкой. Научно- практическая ревматология. 2005;43(5):19-22 [Andrianova IA, Ivanova MM. Early damage index in systemic lupus erythematosus. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2005;43(5):19-22 (In Russ.)]. doi: 10.14412/1995-4484-2005-35

16. Тарасова ИА. Значение индекса повреждения в прогнозировании исхода системной красной волчанки. Дисс. … канд. мед. наук. Москва; 2003. 140 c. [Tarasova IA. Znachenie indeksa povrezhdeniya v prognozirovanii iskhoda sistemnoi krasnoi volchanki. Diss. … kand. med. nauk [The value of damage index in predicting the outcome of systemic lupus erythemato￾sus. Diss. ... Cand. Med. Sci.]. Moscow; 2003. 140 p.].

17. Попкова ТВ, Лисицына ТА. Рекомендации по ведению больных СКВ в клинической практике (по материалам рекомендаций Европейской антиревматической лиги – EULAR). Современная ревматология. 2011;5(1):4-12 [Popkova TV, Lisitsyna TA. Recommendations for the management of patients with SLE in clinical practice (based on the recommendations of the European League Against Rheumatism – EULAR). Sovremennaya Revmatologiya = Modern Rheumatology Journal. 2011;5(1):4-12. (In Russ.)]. doi: 10.14412/1996-7012- 2011-645

18. Асеева ЕА, Соловьев СК, Насонов ЕЛ. Современные методы оценки активности системной красной волчанки. Научно-практическая ревматология. 2013;51(2):186-200 [Aseeva EA, Solovyev SK, Nasonov EL. Current methods for evaluating the activity of systemic lupus erythematosus. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2013;51(2):186-200 (In Russ.)]. doi: 10.14412/1995-4484-2013-648

19. Асеева ЕА, Амирджанова ВН, Лисицына ТА, Завальская МВ. Качество жизни у больных системной красной волчанкой. Научно-практическая ревматология. 2013;51(3):324-31 [Aseeva EA, Amirdzhanova VN, Lisitsyna TA, Zaval’skaya MV. Quality of life in patients with systemic lupus erythematosus. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2013;51(3):324-31 (In Russ.)]. doi: 10.14412/1995- 4484-2013-1508

20. Соловьев СК, Асеева ЕА, Попкова ТВ и др. Стратегия лечения системной красной волчанки «до достижения цели» (Treat-to-Target SLE). Pекомендации международной рабочей группы и комментарии российских экспертов. Научно-практическая ревматология. 2015;53(1):9-16 [Soloviev SK, Aseeva EA, Popkova TV, et al. Treat-to-target SLE recommendations from the International Task Force and Russian experts’ commentaries. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2015;53(1):9-16 (In Russ.)]. doi: 10.14412/1995-4484-2015-9-16

21. Клюквина НГ. Системная красная волчанка у мужчин: клиника, течение, исходы. Дисс. … дoкт. мед. наук. Москва; 2010 [Klyukvina NG. Sistemnaya krasnaya volchanka u muzhchin: klinika, techenie, iskhody. Diss. … dokt. med. nauk [Systemic lupus erythematosus in men: clinical, during, outcomes. Diss. ... Doct. Med. Sci.]. Moscow; 2010].

22. Maddison P, Farewell V, Isenberg D, et al. The rate and pattern of organ damage in late onset systemic lupus erythematosus. J Rheumatol. 2002;29(5):913-7.

23. Chambers SA, Allen E, Rahman A, Isenberg D. Damage and mortality in a group of British patients with systemic lupus erythematosus followed up for over 10 years. Rheumatology. 2009;48(6):673-5. doi: 10.1093/rheumatology/kep062

24. Vila L, Alarcon G, McGwin Jr, et al. Early clinical manifestations, disease activity and damage of systemic lupus erythematosus among two distinct US Hispanic subpopulations. Rheumatology. 2004;43:358-63. doi: 10.1093/rheumatology/keh048

25. Nossent J, Kiss E, Rozman B, et al. Disease activity and damage accrual during the early disease course in a multinational inception cohort of patients with systemic lupus erythematosus. Lupus. 2010;19(8):949-56. doi: 10.1177/0961203310366572

26. Conti F, Ceccarelli F, Perricone C. The chronic damage in systemic lupus erythematosus is driven by flares, glucocorticoids and antiphospholipid antibodies: results from a monocentric cohort. Lupus. 2016;25(7):719-26. doi: 10.1177/0961203315627199

27. Sawah S, Zhang X, Zhu B. Effect of corticosteroid use by dose on the risk of developing organ damage over time in systemic lupus erythematosus-the Hopkins Lupus Cohort. Lupus Sci Med. 2015 Mar 11;2(1):e000066. doi: 10.1136/lupus-2014-000066