- Email: [email protected]
Sleep disturbance in female patients with systemic lupus erythematosus and its relation to disease parameters
The Egyptian Rheumatologist (2013) 35, 127–132
Egyptian Society for Joint Diseases and Arthritis
The Egyptian Rheumatologist www.rheumatology.eg.net www.sciencedirect.com
ORIGINAL ARTICLE
Sleep disturbance in female patients with systemic lupus erythematosus and its relation to disease parameters Hanan A. kotb a, Hanaa M. Rady a b
a,*
, Doaa H. Ghanim
b
Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University, Egypt Students Hospital, Cairo University, Egypt
Received 11 February 2013; accepted 14 February 2013 Available online 22 March 2013
KEYWORDS Sleep disturbance; Lupus; PSQI
Abstract Aim of the work: To assess the prevalence of sleep disturbance in female patients with systemic lupus erythematosus (SLE) and to evaluate the correlation between sleep disturbance and some disease parameters. Patients and Methods: The Pittsburgh Sleep Quality Index (PSQI) was used to investigate the sleeping habits of 30 female patients with SLE and of 30 healthy age and sex-matched controls. Depressed mood was assessed using the Center for Epidemiological Studies Depression scale (CES-D), functional disability was assessed with the Health Assessment Questionnaire (HAQ) and pain severity was assessed using the visual analogue scale (VAS). Disease activity was measured using the SLE disease activity index (SLEDAI). Disease severity and cumulative damage were measured using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage (SLICC/ACR DI). Results: The mean global scores for the PSQI were significantly different between cases and controls (8.47 ± 3.53 versus 5.10 ± 3.66, p = 0.000) indicating poor sleep quality for these patients compared to healthy controls, and 76.7% (23 patients) were poor sleepers. Sleep disturbances were correlated with disease duration (p = 0.001), functional disability (p = 0.001), SLEDAI (p = 0.000), pain severity (p = 0.002), organ damage (p = 0.000) and depressed mood (p = 0.000). However, with multivariate linear regression analysis SLEDAI and SLICC/ACR were the only significant predictors associated with higher level of PSQI.
* Corresponding author. Address: Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University, Post Office Box 109, Cairo, 11559, Egypt. Tel.: +2 01005268101. E-mail address: [email protected] (H.M. Rady). Peer review under responsibility of Egyptian Society for Joint Diseases and Arthritis.
Production and hosting by Elsevier 1110-1164 Ó 2013 Egyptian Society for Joint Diseases and Arthritis. Production and hosting by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ejr.2013.02.003
128
H.A. kotb et al. Conclusion: Sleep disturbances are prevalent among female SLE patients, with multiple factors contributing to it, but disease activity and cumulative disease damage were the only predictors of sleep quality. Assessment and management of sleep disturbances should be part of the routine care of SLE patients. Ó 2013 Egyptian Society for Joint Diseases and Arthritis. Production and hosting by Elsevier B.V. All rights reserved.
1. Introduction Sleep is a basic biological process possibly related to restorative activity. Difficulty initiating sleep, maintaining sleep, and/or early morning awakenings are all components of sleep disturbance. Sleep disturbance is relatively common in women, in older persons, and in individuals with fewer socioeconomic resources [1,2]. Sleep disturbance is often seen in rheumatic diseases and may contribute to the fatigue that is part of many rheumatic conditions, including SLE. The prevalence of sleep impairment and the factors contributing to sleep quality in patients with SLE remain poorly understood [3]. Poor sleep quality in association with depressed mood, disease activity, prednisone use, lack of exercise and inflammatory cytokines have been reported to contribute to decreased overall sleep quality [4–7]. Sleep problems can complicate the management of SLE by impairing patient’s quality of life [8], increasing fatigue [6], triggering or worsening of depression [9], increasing work absenteeism [10], and increasing healthcare costs [11]. Moreover and in particular relevance to SLE, experimental studies inducing a partial night sleep deprivation typical to what patients with chronic medical diseases experience show alternations in immune function, which may negatively influence inflammatory disease progression and cardiovascular risk [12–14]. Also, symptoms of sleeping problems have been repeatedly reported as being one of the under recognized needs of SLE patients [15,16]. Therefore, the present study was conducted to assess the prevalence of sleep disturbances among a group of Egyptian female SLE patients and to find its correlation to some disease parameters. 2. Patients and methods Thirty-eight consecutive female SLE patients fulfilling the 1982-revised criteria for the classification of systemic lupus erythematosus [17] were screened. They were followed up in the outpatient clinic and the inpatient section of the Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University. Eight patients were excluded from the study for having one or more of the following exclusion criteria: cognitive dysfunction, fulfillment of the ACR criteria for fibromyalgia [18] or other conditions that can lead to sleep disturbances (obesity, sinusitis and obstructive sleep apnea). Thirty age-matched healthy females served as controls. Informed consents were taken from the patients and the study was approved by the local ethics committee. Sociodemographic data, including age, education, occupation, disease duration and marital status, were recorded. Full history taking, thorough clinical examination and laboratory investigations were done. Prescribed medications at the time of inclusion in the study were also recorded.
The disease activity level was evaluated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) [19]. A mini mental status examination (MMSE) was performed in all patients to rule out cognitive dysfunction, especially in those with central nervous system (CNS) involvement [20]. It is a brief 30-point questionnaire test that is used to screen for cognitive impairment. In about ten minutes it samples functions including memory and orientation. Any score greater than or equal to 25 points (out of 30) indicates a normal cognition. Systemic lupus cumulative damage was measured using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) [21]. Depressed mood was assessed using the Center for Epidemiological Studies Depression scale (CES-D). CES-D is a selfreported 20-item scale. Each of the items is rated on a 4-point scale, with a minimum score of zero and a maximum score of 60. It is designed to assess depressive symptoms in non-psychiatric populations. Scores of 16 or greater on the CES-D are interpreted as being suggestive of clinically significant depression [22]. Functional disability was measured by the Health Assessment Questionnaire (HAQ) and pain severity was assessed by the HAQ 15 cm VAS, with 0 denoting no pain and 100 indicating very severe pain. Pain scores were then rescaled from 0 to 3, using pain severity coding translations, with 0 representing no pain and three severe pain [23]. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). The PSQI is a self-report measure that assesses sleep quality and disturbances over a 1-month interval. It includes 19 items, generating seven component scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. A global score is obtained by summing the seven component scores and has a possible range of 0–21 points, a higher score indicating poorer sleep quality. The scale has good psychometric properties with a global score P6 yielding a diagnostic sensitivity of 89.6% and specificity of 86.5% in differentiating good and poor sleepers [24]. Statistical Package for Social Science (SPSS) program version 15 was used for analysis of data. Data were summarized as mean ± SD. Mann–Whitney test was used for comparing and analysis of two quantitative data. Spearman’s correlation was used for detection of the relation between two variables. A series of hierarchical multiple regression analyses were performed to test the importance of disease-related and psychosocial factors to sleep quality after controlling for demographic factors [25]. Each hierarchical regression analysis computed whether the variance explained by the specific set contributed significantly to the total variance in sleep quality after controlling for the demographic set. A full model analysis was then computed with all the variables entered simultaneously into the model to determine the relative contributions of these
Sleep disturbance in female patients with systemic lupus erythematosus and its relation to disease parameters variables to sleep quality. The p-value was considered significant if < 0.05. 3. Results The demographic and clinical characteristics of the SLE patients and controls are shown in Table 1. The mean SLEDAI score was 12.17 ± 5.41; 13 patients (43.3%) had mild disease activity, 14 (46.7%) had moderate and 3 (10%) had severe disease activity. All patients were on corticosteroids, 12 (40%) were taking <7.5 mg/day and 18 (60%) >7.5 mg/day of prednisolone while 70% of them did not use any sleep medication. The mean SLICC/ACR DI score was 0.97 ± 0.93. The mean HAQ-DI was 1.34 ± 0.95 and the pain-VAS was 1.37 ± 0.58. The mean score of the CES-D was 20.8 ± 6.98, with 22 patients (73.3%) scoring at or above the standard cutoff score (P16) for clinically significant levels of depression. Patients with SLE had higher mean PSQI scores, indicating poorer sleep quality compared to healthy controls (8.47 ± 3.53 versus 5.1 ± 3.66, p = 0.000). Twenty-three (76.7%) patients were poor sleepers with a PSQI global score of P6 compared to nine of the control group (30%), p = 0.000. There were statistical significant differences between patients and control group (p < 0.05) in most of the component scores of PSQI
Table 1 Demographic and clinical characteristics of the SLE patients and controls. Characteristic mean ± SD
Controls (n = 30)
SLE patients (n = 30)
Age in years Disease duration in years Education in years Unmarried: married: divorced: widow CES-D SLEDAI SLICC/ACR HAQ-pain HAQ-DI
26.57 ± 6.82 – 13.67 ± 2.31 13:15:1:1
26.17 ± 6.75 4.12 ± 2.46 7.60 ± 6.15 11:17:1:1
13.13 ± 2.83 – – – –
20.80 ± 6.98 12.17 ± 5.41 0.97 ± 0.93 1.37 ± 0.58 1.34 ± 0.95
CES-D = Center for Epidemiological Studies Depression scale, SLEDAI = Systemic Lupus Erythematosus Disease Activity Index, SLICC/ACR = Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, HAQ-DI = Health Assessment Questionnaire Disability Index, HAQ-pain = Pain index of the HAQ.
Table 2
129
except sleep latency, sleep duration and use of sleep medications, which showed no statistically significant difference between both groups (Table 2). Spearman’s coefficients were done to identify the correlates of sleep quality in SLE patients. As shown in Table 3, disease duration (p = 0.001), disease activity (p = 0.000), functional disability (p = 0.001), organ damage index (p = 0.000), pain severity (p = 0.002) and depressed mood (p = 0.000) were significantly correlated with poorer sleep quality. The correlation of the PSQI with the SLEDAI and SLICC is graphically presented in figs. 1 and 2. The dose of corticosteroids did not significantly correlate with poorer sleep quality (p = 0.290). The SLEDAI significantly correlated with the CES-D (r = 0.713, p = 0.000) and with the HAQ-DI (r = 0.713, p = 0.000). Furthermore, the SLICC/ACR DI significantly correlated with SLEDAI (r = 0.510, p = 0.004), CES-D (r = 0.446, p = 0.014) and HAQ-DI (r = 0.527, p = 0.003). Among SLE patients, when demographic and clinical parameters of good (PSQI <6) and poor (PSQI P6) sleepers were compared; disease duration (2 ± 1.55 versus 4.76 ± 2.33, p = 0.006), disease activity (6.29 ± 2.14 versus 13.96 ± 4.7, p = 0.001), functional disability (0.34 ± 0.38 versus 1.3 ± 0.73, p = 0.003), pain severity (0.73 ± 0.54 versus 1.57 ± 0.43, p = 0.003) depressed mood (12.14 ± 2.27 versus 23.43 ± 5.64, p = 0.000) and damage index (0.14 ± 0.38 versus 1.22 ± 0.90, p = 0.006) were found to be significantly different (Table 4). The results of the hierarchical multiple regression analyses are shown in Table 5. Model 1 (demographic model) tests the contribution of demographic variables (age and education years) to disturbed sleep and was not found to be statistically significant (R2 = 0.073). Model 2 (disease-related model) tests the contributions of disease activity, disease severity and damage, functional disability and pain severity to poor sleep quality after controlling for the demographic variables. The addition of disease-related variables resulted in a significant increase in the R2 value (R2 = 0.658). In this disease-related model, disease activity (p = 0.027), contributed significantly to poor sleep quality. Model 3 (psychosocial model) describes the extent to which depression contributes to sleep disturbance after controlling for the demographic variables. Inclusion of depressed mood (CES-D) also significantly added to the demographic set (R2 = 0.474) and contributed significantly (p = 0.000). Models 1–3 are the results of hierarchical regression analyses, which are done to determine the importance of predictor variables. Model 4 is the standard regression analysis where
Comparison of the components of PSQI in SLE patients and control.
PSQI components mean ± SD
SLE patients (n = 30)
Controls (n = 30)
p value
Subjective sleep quality Sleep latency Sleep duration Habitual sleep efficiency Sleep disturbance Use of sleep medication Daytime dysfunction Global PSQI
1.40 ± 1.07 2.03 ± 0.89 0.70 ± 0.99 1.03 ± 0.89 1.47 ± 0.63 0.60 ± 1.07 1.23 ± 0.77 8.47 ± 3.53
0.70 ± 1.09 1.47 ± 0.94 1.03 ± 0.96 0.53 ± 0.78 0.93 ± 0.37 0.07 ± 0.25 0.37 ± 0.56 5.10 ± 3.66
0.016* 0.141 0.162 0.041* 0.003* 0.083 0.000* 0.000*
PSQI = The Pittsburgh Sleep Quality Index. * Significant.
130
H.A. kotb et al.
Table 3 Correlation of the sleep quality with demographic, clinical and psychosocial variables.
Table 4 Comparison between good and poor sleepers in SLE patients.
Variables
r
p
Variables
PSQI
Age Disease duration Years of education CES-D HAQ-DI HAQ-pain SLEDAI SLICC/ACR Corticosteroid dose
0.228 0.558 0.253 0.681 0.568 0.543 0.695 0.658 0.200
0.225 0.001* 0.177 0.000* 0.001* 0.002* 0.000* 0.000* 0.290
Mean ± SD
<6 (n = 7)
>6 (n = 23)
p value
Disease duration Years of education CES-D HAQ-DI HAQ-pain SLEDAI SLICC/ACR
2 ± 1.55 11.86 ± 3.8 12.14 ± 2.27 0.4 ± 0.5 0.73 ± 0. 54 6.29 ± 2.14 0.14 ± 0.38
4.76 ± 2.33 6.30 ± 6.20 23.43 ± 5.64 1.6 ± 0.9 1.57 ± 0.43 13.96 ± 4.79 1.22 ± 0.90
0.006* 0.05 0.000* 0.003* 0.003* 0.001* 0.006*
CES-D = Center for Epidemiological Studies Depression scale, SLEDAI = Systemic Lupus Erythematosus Disease Activity Index, SLICC/ACR = Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, HAQ-DI = Health Assessment Questionnaire Disability Index, HAQ-pain = Pain index of the HAQ. * Significant.
PSQI = The Pittsburgh Sleep Quality Index, CES-D = Center for Epidemiological Studies Depression scale, SLEDAI = Systemic Lupus Erythematosus Disease Activity Index, SLICC/ ACR = Systemic Lupus International Collaborating Clinics/ American College of Rheumatology Damage Index, HAQDI = Health Assessment Questionnaire Disability Index, HAQpain = Pain index of the HAQ. * Significant.
all of the variables were simultaneously considered to assess their relative contributions to sleep quality. This model takes into account the interrelations between predictor variables as well as the effects of predictor variables on the outcome variable (PSQI). In the final full model (standard multiple regression analysis), only disease activity (p = 0.002) and organ damage index (p = 0.007) were the significant determinants of sleep quality. 4. Discussion
Figure 1 The relationship between sleep disturbance (PSQI) and disease activity (SLEDAI).
Figure 2 The relationship between sleep disturbance (PSQI) and disease severity and cumulative damage index (SLICC/ACR-DI).
Patients with SLE reported significantly greater sleep disturbance in comparison with control subjects with their PSQI scores indicating clinical sleep impairment and 76.7% of them had poor sleep quality. Similarly, Greenwood and colleagues reported a prevalence of 80.5% [26] while other studies [3,6,27] reported a lower prevalence using PSQI in their cohorts of SLE patents (52%, 60%, and 62% respectively). In these three studies, the patient sample was recruited from outpatient clinics with no inpatients included, which could explain the higher prevalence of sleep disturbances in the present study. Patients with SLE had poor sleep quality as compared to the control group with higher mean global PSQI score. Among the seven components of PSQI, the most prominent component of sleep disturbance was daytime dysfunction. Despite the high prevalence of sleep complaints among patients, 70% of them did not use any sleep medication, which indicates underestimation of the problem among this patient population. In the present study, poor sleep was associated with longer disease duration and higher SLEDAI. Valencia-Flores et al., in their small cohort of SLE patients (n = 14), found that those with active disease reported significantly poorer sleep efficiency, longer stage 1 sleep, shorter slow-wave sleep and more number of arousals compared to patients with inactive disease [4]. In another study, it has been found that sleep complaints were more frequently reported by SLE patients who had more active disease, especially those with central nervous system involvements, compared to those with less active disease [7].
Sleep disturbance in female patients with systemic lupus erythematosus and its relation to disease parameters Table 5
131
Regression models predicting sleep quality in SLE patients.
Predictors
Model 1 Beta
Age Education (years) Disease duration SLICC/ACR SLEDAI HAQ-DI VAS Prednisone use CES-D R2 Adjusted R2
0.061 0.104
0.073 0.004
Model 2 p 0.619 0.444
Beta 0.073 0.030 0.121 1.407 0.305 0.039 0.791 0.008
Model 3 p 0.451 0.781 0.689 0.104 0.027 0.688 0.521 0.166
0.658 0.528
Beta
Model 4 p
0.028 0.036
0.765 0.733
0.331 0.474 0.413
0.000
Beta 0.061 0.013 0.006 1.357 0.191 0.042 1.139 0.006 0.144 0.690 0.551
p 0.520 0.901 0.983 0.007 0.002 0.657 0.357 0.316 0.165
CES-D = Center for Epidemiological Studies Depression scale, SLEDAI = Systemic Lupus Erythematosus Disease Activity Index, SLICC/ ACR = Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, HAQ-DI = Health Assessment Questionnaire Disability Index, HAQ-pain = Pain index of the HAQ. Bold values are significant.
In contrast, a weak correlation between disease activity and sleep quality in SLE has been reported [6]. Da Costa and colleagues, when using bivariate analyses, also found an association between disease activity and sleep quality assessed with the PSQI [3]. However, this association did not remain significant in the multivariate analysis, suggesting that the relationship between sleep and disease activity may be weak and nonlinear. In our study as well as that of Chandrasekhara and coworkers, [27] this association remained significant in the multivariate analysis. In autoimmune diseases, the elevated levels of proinflammatory cytokines may influence daytime sleepiness and disrupt nocturnal sleep [28]. This pathway remains to be explored in SLE. Importantly the relationship between cytokines and sleep has been found to be bidirectional, with altered sleep also influencing cytokine levels in other populations [29–31]. Our study showed also a significant correlation between poor sleep quality, functional disability as measured by HAQ-DI and depression as assessed by CES-D. However unlike disease activity, these associations did not remain significant in the final full model of standard multiple regression analysis. This could be explained by the significant correlation found between disease activity (by SLEDAI), presence of depressive symptoms (by CES-D) and functional disability (by HAQ-DI). The relationship between disease activity, functional disability and depression has been previously documented. Disease activity is a potential risk factor for the presence and severity of major depression in patients with SLE [32]. On the other hand, depression can in turn contribute to increased disease activity and may be an important cause of medication adherence problems that contributes to higher disease activity [33]. Depression severity has also been shown to correlate with functional disability [34]. In addition to depression, disease activity has been documented as contributing to functional disability in patients with SLE [35]. Again, functional disability significantly contributes to depressed mood [36]. Finally, the role of depression in producing sleep disturbance is also well documented [3]. The relationship between pain intensity and sleep problems has been firmly documented in some rheumatic diseases as rheumatoid arthritis and fibromyalgia [37]. In our study, there
was a positive correlation between PSQI score and pain severity as measured by VAS. Among SLE patients, Tench and associates [6] reported a moderate correlation between pain and poor sleep quality. Another study found that SLE patients reported significantly more pain when trying to fall asleep and during the night compared with age-matched controls [7]. Using multivariate analyses, a very weak relationship between pain and sleep disturbance was found [3,4]. In the present study, despite the low organ damage score SLICC/ACR-DI, it significantly correlated with sleep disturbances and this association remained significant in the multivariate analysis as an independent determinant of poor sleep quality in SLE patients. The statistically significant correlation between SLICC/ACR DI and the SLEDAI, the CES-D and the HAQ-DI in the current study could explain this finding. Corticosteroids, at least in high doses, may give rise to sleep problems and some psychiatric symptoms [37]. However, our study as well as some other previous studies have not shown a relationship between use and dose of corticosteroids and sleep disturbance in SLE [4,6,7]. In conclusion, our study shows a high prevalence of sleep disturbances among studied Egyptian female SLE patients. Several factors contribute to poor sleep quality in these patients including disease activity, functional disability, depression and cumulative damage. However, disease activity and cumulative disease damage were the only predictors of sleep quality. Assessment and management of sleep problems should be part of the management of patients with SLE. Conflict of interest None. References [1] Ohayon MM. Epidemiology of insomnia: what we know and what we still need to learn. Sleep Med Rev 2002;6:97–111. [2] Ancoli-Israel S, Roth T. Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. I. Sleep 1999;22(Suppl. 2):S347–53. [3] DaCosta D, Bernatsky S, Drista M, Clarke AE, Dasgupta K, Keshani A, et al. Determinants of sleep quality in women with systemic lupus erythematosus. Arthritis Rheum 2005;53:272–8.
132 [4] Valencia-Flores M, Resendiz M, Castano VA, Santiago V, Campos RM, Sandino S, et al. Objective and subjective sleep disturbances in patients with SLE. Arthritis Rheum 1999;42: 2189–93. [5] McKinely PS, Ouellette SC, Winkel GH. The contributions of disease activity sleep patterns, and depression to fatigue in SLE. Arthritis Rheum 1995;38:826–34. [6] Tench CM, Mc Curdie I, White PD, D’Cruz DP. The prevalence and associations of fatigue in systemic lupus erythematosus. Rheumatol 2000;39:1249–54. [7] Gudbjornsson B, Hetta J. Sleep disturbances in patients with systemic lupus erythematosus: a questionnaire based study. Clin Exp Rheumatol 2001;19:509–14. [8] Breslau N, Roth T, Rosenthal L, Andreski P. Sleep disturbances and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry 1996;39:411–8. [9] Katz DA, McHorney AC. The relationship between insomnia and health-related quality of life in patients with chronic illness. J Fam Pract 2002;51:229–35. [10] Hatoum H, Kong S, Kania C, Wong J, Mendelson W. Insomnia, health-related quality of life and healthcare resource consumption: a study of managed-care organization enrollees. Pharmacoeconomics 1998;14:629–37. [11] Simon G, VonKorff M. Prevalence, burden, and treatment of insomnia in primary care. Am J Psychiatry 1997;154:1417–23. [12] Everson CA. Sustained sleep deprivation impairs host defense. Am J Physiol 1993;265:R1148–54. [13] Crofford LJ, Kalogeras KT, Mastorakos G, Magiakou MA, Wells J, Kanik KS, et al. Circadian relationships between interleukin (IL)-6 and hypothalamic pituitary-adrenal axis hormones: failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis. J Clin Endocrinol Metab 1997;82:1279–83. [14] Vgontzas AN, Papanicolaou DA, Bixler EO, Lotsikas A, Zachman K, Kales A, et al. Circadian interleukin-6 secretion and quantity and depth of sleep. J Clin Endocrinol Metab 1999;86: 2603–7. [15] Moses N, Wiggers J, Nicholas C, Cockburn J. Prevalence and correlates of perceived unmet needs of people with systemic lupus erythematosus. Patient Educ Couns 2005;57:30–8. [16] Danoff-Burg S, Friedberg F. Unmet needs of patients with systemic lupus erythematosus. Behav Med 2009;35(1):5–13. [17] Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271–7. [18] Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the multicenter criteria committee. Arthritis Rheum 1990;33:160–72. [19] Bombardier C, Gladman D, Urowitz M, Caron D, Chang C. Derivation of the SLEDAI A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 1992;35:630–40. [20] Folstein MF, Folstein SE, McHugh PR. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–98. [21] Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz M, et al. The development and initial validation of the Systemic
H.A. kotb et al.
[22]
[23] [24]
[25]
[26] [27]
[28]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
[36]
[37]
Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for systemic lupus erythematosus. Arthritis Rheum 1996;39:363–9. Radloff LS. The CES-D scale: a self report depression scale for research in general population. Appl Psychol Meas 1977;1: 385–401. Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. Arthritis Rheum 1980;23:137–45. Buysse DJ, Reynolds 3rd CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989;28: 193–213. Cohen J, Cohen P, West SG. Applied multiple regression/ correlation analysis for the behavioral sciences. 3rd ed. Mahwah, NJ: Lawrence Erblaum; 2003. Greenwood KM, Lederman L, Linder HD. Self reported sleep in systemic lupus erythematosus. Clin Rheumatol 2008;27:1147–51. Chandrasekhara PK, Jayachandran NV, Rajasekhar L, Thomas J, Narsimulu G. The prevalence and associations of sleep disturbances in patients with systemic lupus erythematosus. Mod Rheumatol 2009;19:407–15. Bourguignon C, Labyak SE, Taibi D. Investigating sleep disturbance in adults with rheumatoid arthritis. Holist Nurs Pract 2003;17:241–9. von Kanel R, Dimsdale JE, Ancoli-Israel S, Mills PJ, Patterson TL. Poor sleep is associated with higher plasma proinflammatory cytokine interleukin-6 and procoagulant marker fibrin D-dimer in older caregivers of people with Alzheimer’s disease. J Am Geriatr Soc 2006;54:431–7. Redwine L, Hauger RL, Gillin C, Irwin M. Effects of sleep deprivation on interleukin-6, growth hormone, cortisol and melatonin levels in humans. J Clin Endocrinol Metab 2000;85: 3597–603. Irwin M, Mascovich A, Gillin JC, Willoughby R, Pike J, Smith TL. Partial sleep deprivation reduces natural killer cell activity in humans. Psychosom Med 1994;56:493–8. Nery FG, Borba EF, Hatch JP, Soares JC, Bonfa E, Neto FL. Major depressive disorder and disease activity in systemic lupus erythematosus. Compr Psychiatry 2007;48:14–9. Julian LJ, Yelin E, Yazdany J, Panopalis P, Trupin L, Criswell LA, et al. Depression, medication adherence, and service utilization in systemic lupus erythematosus. Arthritis Rheum 2009;61: 240–6. Da Cost D, Dobkin PL, Pinard L, Fortin PR, Danoff DS, Esdaile JM, et al. The role of stress in functional disability among women with systemic lupus erythematosus: a prospective study. Arthritis Care Res 1999;12:112–9. Benitha R, Tikly M. Functional disability and health related quality of life in South Africans with rheumatoid arthritis and systemic lupus erythematosus. Clin Rheumatol 2007;26:24–9. Lowe B, Willand L, Eich W, Zipfel S, Anthony D, Herzong W, et al. Psychiatric comorbidity and work disability in patients with inflammatory rheumatic diseases. Psychosom Med 2004;66: 395–402. Warrington TP, Bostwick JM. Psychiatric adverse effects of corticosteroids. Mayo Clin Proc 2006;81:1361–7.
Egyptian Society for Joint Diseases and Arthritis
The Egyptian Rheumatologist www.rheumatology.eg.net www.sciencedirect.com
ORIGINAL ARTICLE
Sleep disturbance in female patients with systemic lupus erythematosus and its relation to disease parameters Hanan A. kotb a, Hanaa M. Rady a b
a,*
, Doaa H. Ghanim
b
Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University, Egypt Students Hospital, Cairo University, Egypt
Received 11 February 2013; accepted 14 February 2013 Available online 22 March 2013
KEYWORDS Sleep disturbance; Lupus; PSQI
Abstract Aim of the work: To assess the prevalence of sleep disturbance in female patients with systemic lupus erythematosus (SLE) and to evaluate the correlation between sleep disturbance and some disease parameters. Patients and Methods: The Pittsburgh Sleep Quality Index (PSQI) was used to investigate the sleeping habits of 30 female patients with SLE and of 30 healthy age and sex-matched controls. Depressed mood was assessed using the Center for Epidemiological Studies Depression scale (CES-D), functional disability was assessed with the Health Assessment Questionnaire (HAQ) and pain severity was assessed using the visual analogue scale (VAS). Disease activity was measured using the SLE disease activity index (SLEDAI). Disease severity and cumulative damage were measured using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage (SLICC/ACR DI). Results: The mean global scores for the PSQI were significantly different between cases and controls (8.47 ± 3.53 versus 5.10 ± 3.66, p = 0.000) indicating poor sleep quality for these patients compared to healthy controls, and 76.7% (23 patients) were poor sleepers. Sleep disturbances were correlated with disease duration (p = 0.001), functional disability (p = 0.001), SLEDAI (p = 0.000), pain severity (p = 0.002), organ damage (p = 0.000) and depressed mood (p = 0.000). However, with multivariate linear regression analysis SLEDAI and SLICC/ACR were the only significant predictors associated with higher level of PSQI.
* Corresponding author. Address: Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University, Post Office Box 109, Cairo, 11559, Egypt. Tel.: +2 01005268101. E-mail address: [email protected] (H.M. Rady). Peer review under responsibility of Egyptian Society for Joint Diseases and Arthritis.
Production and hosting by Elsevier 1110-1164 Ó 2013 Egyptian Society for Joint Diseases and Arthritis. Production and hosting by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ejr.2013.02.003
128
H.A. kotb et al. Conclusion: Sleep disturbances are prevalent among female SLE patients, with multiple factors contributing to it, but disease activity and cumulative disease damage were the only predictors of sleep quality. Assessment and management of sleep disturbances should be part of the routine care of SLE patients. Ó 2013 Egyptian Society for Joint Diseases and Arthritis. Production and hosting by Elsevier B.V. All rights reserved.
1. Introduction Sleep is a basic biological process possibly related to restorative activity. Difficulty initiating sleep, maintaining sleep, and/or early morning awakenings are all components of sleep disturbance. Sleep disturbance is relatively common in women, in older persons, and in individuals with fewer socioeconomic resources [1,2]. Sleep disturbance is often seen in rheumatic diseases and may contribute to the fatigue that is part of many rheumatic conditions, including SLE. The prevalence of sleep impairment and the factors contributing to sleep quality in patients with SLE remain poorly understood [3]. Poor sleep quality in association with depressed mood, disease activity, prednisone use, lack of exercise and inflammatory cytokines have been reported to contribute to decreased overall sleep quality [4–7]. Sleep problems can complicate the management of SLE by impairing patient’s quality of life [8], increasing fatigue [6], triggering or worsening of depression [9], increasing work absenteeism [10], and increasing healthcare costs [11]. Moreover and in particular relevance to SLE, experimental studies inducing a partial night sleep deprivation typical to what patients with chronic medical diseases experience show alternations in immune function, which may negatively influence inflammatory disease progression and cardiovascular risk [12–14]. Also, symptoms of sleeping problems have been repeatedly reported as being one of the under recognized needs of SLE patients [15,16]. Therefore, the present study was conducted to assess the prevalence of sleep disturbances among a group of Egyptian female SLE patients and to find its correlation to some disease parameters. 2. Patients and methods Thirty-eight consecutive female SLE patients fulfilling the 1982-revised criteria for the classification of systemic lupus erythematosus [17] were screened. They were followed up in the outpatient clinic and the inpatient section of the Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University. Eight patients were excluded from the study for having one or more of the following exclusion criteria: cognitive dysfunction, fulfillment of the ACR criteria for fibromyalgia [18] or other conditions that can lead to sleep disturbances (obesity, sinusitis and obstructive sleep apnea). Thirty age-matched healthy females served as controls. Informed consents were taken from the patients and the study was approved by the local ethics committee. Sociodemographic data, including age, education, occupation, disease duration and marital status, were recorded. Full history taking, thorough clinical examination and laboratory investigations were done. Prescribed medications at the time of inclusion in the study were also recorded.
The disease activity level was evaluated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) [19]. A mini mental status examination (MMSE) was performed in all patients to rule out cognitive dysfunction, especially in those with central nervous system (CNS) involvement [20]. It is a brief 30-point questionnaire test that is used to screen for cognitive impairment. In about ten minutes it samples functions including memory and orientation. Any score greater than or equal to 25 points (out of 30) indicates a normal cognition. Systemic lupus cumulative damage was measured using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) [21]. Depressed mood was assessed using the Center for Epidemiological Studies Depression scale (CES-D). CES-D is a selfreported 20-item scale. Each of the items is rated on a 4-point scale, with a minimum score of zero and a maximum score of 60. It is designed to assess depressive symptoms in non-psychiatric populations. Scores of 16 or greater on the CES-D are interpreted as being suggestive of clinically significant depression [22]. Functional disability was measured by the Health Assessment Questionnaire (HAQ) and pain severity was assessed by the HAQ 15 cm VAS, with 0 denoting no pain and 100 indicating very severe pain. Pain scores were then rescaled from 0 to 3, using pain severity coding translations, with 0 representing no pain and three severe pain [23]. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). The PSQI is a self-report measure that assesses sleep quality and disturbances over a 1-month interval. It includes 19 items, generating seven component scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. A global score is obtained by summing the seven component scores and has a possible range of 0–21 points, a higher score indicating poorer sleep quality. The scale has good psychometric properties with a global score P6 yielding a diagnostic sensitivity of 89.6% and specificity of 86.5% in differentiating good and poor sleepers [24]. Statistical Package for Social Science (SPSS) program version 15 was used for analysis of data. Data were summarized as mean ± SD. Mann–Whitney test was used for comparing and analysis of two quantitative data. Spearman’s correlation was used for detection of the relation between two variables. A series of hierarchical multiple regression analyses were performed to test the importance of disease-related and psychosocial factors to sleep quality after controlling for demographic factors [25]. Each hierarchical regression analysis computed whether the variance explained by the specific set contributed significantly to the total variance in sleep quality after controlling for the demographic set. A full model analysis was then computed with all the variables entered simultaneously into the model to determine the relative contributions of these
Sleep disturbance in female patients with systemic lupus erythematosus and its relation to disease parameters variables to sleep quality. The p-value was considered significant if < 0.05. 3. Results The demographic and clinical characteristics of the SLE patients and controls are shown in Table 1. The mean SLEDAI score was 12.17 ± 5.41; 13 patients (43.3%) had mild disease activity, 14 (46.7%) had moderate and 3 (10%) had severe disease activity. All patients were on corticosteroids, 12 (40%) were taking <7.5 mg/day and 18 (60%) >7.5 mg/day of prednisolone while 70% of them did not use any sleep medication. The mean SLICC/ACR DI score was 0.97 ± 0.93. The mean HAQ-DI was 1.34 ± 0.95 and the pain-VAS was 1.37 ± 0.58. The mean score of the CES-D was 20.8 ± 6.98, with 22 patients (73.3%) scoring at or above the standard cutoff score (P16) for clinically significant levels of depression. Patients with SLE had higher mean PSQI scores, indicating poorer sleep quality compared to healthy controls (8.47 ± 3.53 versus 5.1 ± 3.66, p = 0.000). Twenty-three (76.7%) patients were poor sleepers with a PSQI global score of P6 compared to nine of the control group (30%), p = 0.000. There were statistical significant differences between patients and control group (p < 0.05) in most of the component scores of PSQI
Table 1 Demographic and clinical characteristics of the SLE patients and controls. Characteristic mean ± SD
Controls (n = 30)
SLE patients (n = 30)
Age in years Disease duration in years Education in years Unmarried: married: divorced: widow CES-D SLEDAI SLICC/ACR HAQ-pain HAQ-DI
26.57 ± 6.82 – 13.67 ± 2.31 13:15:1:1
26.17 ± 6.75 4.12 ± 2.46 7.60 ± 6.15 11:17:1:1
13.13 ± 2.83 – – – –
20.80 ± 6.98 12.17 ± 5.41 0.97 ± 0.93 1.37 ± 0.58 1.34 ± 0.95
CES-D = Center for Epidemiological Studies Depression scale, SLEDAI = Systemic Lupus Erythematosus Disease Activity Index, SLICC/ACR = Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, HAQ-DI = Health Assessment Questionnaire Disability Index, HAQ-pain = Pain index of the HAQ.
Table 2
129
except sleep latency, sleep duration and use of sleep medications, which showed no statistically significant difference between both groups (Table 2). Spearman’s coefficients were done to identify the correlates of sleep quality in SLE patients. As shown in Table 3, disease duration (p = 0.001), disease activity (p = 0.000), functional disability (p = 0.001), organ damage index (p = 0.000), pain severity (p = 0.002) and depressed mood (p = 0.000) were significantly correlated with poorer sleep quality. The correlation of the PSQI with the SLEDAI and SLICC is graphically presented in figs. 1 and 2. The dose of corticosteroids did not significantly correlate with poorer sleep quality (p = 0.290). The SLEDAI significantly correlated with the CES-D (r = 0.713, p = 0.000) and with the HAQ-DI (r = 0.713, p = 0.000). Furthermore, the SLICC/ACR DI significantly correlated with SLEDAI (r = 0.510, p = 0.004), CES-D (r = 0.446, p = 0.014) and HAQ-DI (r = 0.527, p = 0.003). Among SLE patients, when demographic and clinical parameters of good (PSQI <6) and poor (PSQI P6) sleepers were compared; disease duration (2 ± 1.55 versus 4.76 ± 2.33, p = 0.006), disease activity (6.29 ± 2.14 versus 13.96 ± 4.7, p = 0.001), functional disability (0.34 ± 0.38 versus 1.3 ± 0.73, p = 0.003), pain severity (0.73 ± 0.54 versus 1.57 ± 0.43, p = 0.003) depressed mood (12.14 ± 2.27 versus 23.43 ± 5.64, p = 0.000) and damage index (0.14 ± 0.38 versus 1.22 ± 0.90, p = 0.006) were found to be significantly different (Table 4). The results of the hierarchical multiple regression analyses are shown in Table 5. Model 1 (demographic model) tests the contribution of demographic variables (age and education years) to disturbed sleep and was not found to be statistically significant (R2 = 0.073). Model 2 (disease-related model) tests the contributions of disease activity, disease severity and damage, functional disability and pain severity to poor sleep quality after controlling for the demographic variables. The addition of disease-related variables resulted in a significant increase in the R2 value (R2 = 0.658). In this disease-related model, disease activity (p = 0.027), contributed significantly to poor sleep quality. Model 3 (psychosocial model) describes the extent to which depression contributes to sleep disturbance after controlling for the demographic variables. Inclusion of depressed mood (CES-D) also significantly added to the demographic set (R2 = 0.474) and contributed significantly (p = 0.000). Models 1–3 are the results of hierarchical regression analyses, which are done to determine the importance of predictor variables. Model 4 is the standard regression analysis where
Comparison of the components of PSQI in SLE patients and control.
PSQI components mean ± SD
SLE patients (n = 30)
Controls (n = 30)
p value
Subjective sleep quality Sleep latency Sleep duration Habitual sleep efficiency Sleep disturbance Use of sleep medication Daytime dysfunction Global PSQI
1.40 ± 1.07 2.03 ± 0.89 0.70 ± 0.99 1.03 ± 0.89 1.47 ± 0.63 0.60 ± 1.07 1.23 ± 0.77 8.47 ± 3.53
0.70 ± 1.09 1.47 ± 0.94 1.03 ± 0.96 0.53 ± 0.78 0.93 ± 0.37 0.07 ± 0.25 0.37 ± 0.56 5.10 ± 3.66
0.016* 0.141 0.162 0.041* 0.003* 0.083 0.000* 0.000*
PSQI = The Pittsburgh Sleep Quality Index. * Significant.
130
H.A. kotb et al.
Table 3 Correlation of the sleep quality with demographic, clinical and psychosocial variables.
Table 4 Comparison between good and poor sleepers in SLE patients.
Variables
r
p
Variables
PSQI
Age Disease duration Years of education CES-D HAQ-DI HAQ-pain SLEDAI SLICC/ACR Corticosteroid dose
0.228 0.558 0.253 0.681 0.568 0.543 0.695 0.658 0.200
0.225 0.001* 0.177 0.000* 0.001* 0.002* 0.000* 0.000* 0.290
Mean ± SD
<6 (n = 7)
>6 (n = 23)
p value
Disease duration Years of education CES-D HAQ-DI HAQ-pain SLEDAI SLICC/ACR
2 ± 1.55 11.86 ± 3.8 12.14 ± 2.27 0.4 ± 0.5 0.73 ± 0. 54 6.29 ± 2.14 0.14 ± 0.38
4.76 ± 2.33 6.30 ± 6.20 23.43 ± 5.64 1.6 ± 0.9 1.57 ± 0.43 13.96 ± 4.79 1.22 ± 0.90
0.006* 0.05 0.000* 0.003* 0.003* 0.001* 0.006*
CES-D = Center for Epidemiological Studies Depression scale, SLEDAI = Systemic Lupus Erythematosus Disease Activity Index, SLICC/ACR = Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, HAQ-DI = Health Assessment Questionnaire Disability Index, HAQ-pain = Pain index of the HAQ. * Significant.
PSQI = The Pittsburgh Sleep Quality Index, CES-D = Center for Epidemiological Studies Depression scale, SLEDAI = Systemic Lupus Erythematosus Disease Activity Index, SLICC/ ACR = Systemic Lupus International Collaborating Clinics/ American College of Rheumatology Damage Index, HAQDI = Health Assessment Questionnaire Disability Index, HAQpain = Pain index of the HAQ. * Significant.
all of the variables were simultaneously considered to assess their relative contributions to sleep quality. This model takes into account the interrelations between predictor variables as well as the effects of predictor variables on the outcome variable (PSQI). In the final full model (standard multiple regression analysis), only disease activity (p = 0.002) and organ damage index (p = 0.007) were the significant determinants of sleep quality. 4. Discussion
Figure 1 The relationship between sleep disturbance (PSQI) and disease activity (SLEDAI).
Figure 2 The relationship between sleep disturbance (PSQI) and disease severity and cumulative damage index (SLICC/ACR-DI).
Patients with SLE reported significantly greater sleep disturbance in comparison with control subjects with their PSQI scores indicating clinical sleep impairment and 76.7% of them had poor sleep quality. Similarly, Greenwood and colleagues reported a prevalence of 80.5% [26] while other studies [3,6,27] reported a lower prevalence using PSQI in their cohorts of SLE patents (52%, 60%, and 62% respectively). In these three studies, the patient sample was recruited from outpatient clinics with no inpatients included, which could explain the higher prevalence of sleep disturbances in the present study. Patients with SLE had poor sleep quality as compared to the control group with higher mean global PSQI score. Among the seven components of PSQI, the most prominent component of sleep disturbance was daytime dysfunction. Despite the high prevalence of sleep complaints among patients, 70% of them did not use any sleep medication, which indicates underestimation of the problem among this patient population. In the present study, poor sleep was associated with longer disease duration and higher SLEDAI. Valencia-Flores et al., in their small cohort of SLE patients (n = 14), found that those with active disease reported significantly poorer sleep efficiency, longer stage 1 sleep, shorter slow-wave sleep and more number of arousals compared to patients with inactive disease [4]. In another study, it has been found that sleep complaints were more frequently reported by SLE patients who had more active disease, especially those with central nervous system involvements, compared to those with less active disease [7].
Sleep disturbance in female patients with systemic lupus erythematosus and its relation to disease parameters Table 5
131
Regression models predicting sleep quality in SLE patients.
Predictors
Model 1 Beta
Age Education (years) Disease duration SLICC/ACR SLEDAI HAQ-DI VAS Prednisone use CES-D R2 Adjusted R2
0.061 0.104
0.073 0.004
Model 2 p 0.619 0.444
Beta 0.073 0.030 0.121 1.407 0.305 0.039 0.791 0.008
Model 3 p 0.451 0.781 0.689 0.104 0.027 0.688 0.521 0.166
0.658 0.528
Beta
Model 4 p
0.028 0.036
0.765 0.733
0.331 0.474 0.413
0.000
Beta 0.061 0.013 0.006 1.357 0.191 0.042 1.139 0.006 0.144 0.690 0.551
p 0.520 0.901 0.983 0.007 0.002 0.657 0.357 0.316 0.165
CES-D = Center for Epidemiological Studies Depression scale, SLEDAI = Systemic Lupus Erythematosus Disease Activity Index, SLICC/ ACR = Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, HAQ-DI = Health Assessment Questionnaire Disability Index, HAQ-pain = Pain index of the HAQ. Bold values are significant.
In contrast, a weak correlation between disease activity and sleep quality in SLE has been reported [6]. Da Costa and colleagues, when using bivariate analyses, also found an association between disease activity and sleep quality assessed with the PSQI [3]. However, this association did not remain significant in the multivariate analysis, suggesting that the relationship between sleep and disease activity may be weak and nonlinear. In our study as well as that of Chandrasekhara and coworkers, [27] this association remained significant in the multivariate analysis. In autoimmune diseases, the elevated levels of proinflammatory cytokines may influence daytime sleepiness and disrupt nocturnal sleep [28]. This pathway remains to be explored in SLE. Importantly the relationship between cytokines and sleep has been found to be bidirectional, with altered sleep also influencing cytokine levels in other populations [29–31]. Our study showed also a significant correlation between poor sleep quality, functional disability as measured by HAQ-DI and depression as assessed by CES-D. However unlike disease activity, these associations did not remain significant in the final full model of standard multiple regression analysis. This could be explained by the significant correlation found between disease activity (by SLEDAI), presence of depressive symptoms (by CES-D) and functional disability (by HAQ-DI). The relationship between disease activity, functional disability and depression has been previously documented. Disease activity is a potential risk factor for the presence and severity of major depression in patients with SLE [32]. On the other hand, depression can in turn contribute to increased disease activity and may be an important cause of medication adherence problems that contributes to higher disease activity [33]. Depression severity has also been shown to correlate with functional disability [34]. In addition to depression, disease activity has been documented as contributing to functional disability in patients with SLE [35]. Again, functional disability significantly contributes to depressed mood [36]. Finally, the role of depression in producing sleep disturbance is also well documented [3]. The relationship between pain intensity and sleep problems has been firmly documented in some rheumatic diseases as rheumatoid arthritis and fibromyalgia [37]. In our study, there
was a positive correlation between PSQI score and pain severity as measured by VAS. Among SLE patients, Tench and associates [6] reported a moderate correlation between pain and poor sleep quality. Another study found that SLE patients reported significantly more pain when trying to fall asleep and during the night compared with age-matched controls [7]. Using multivariate analyses, a very weak relationship between pain and sleep disturbance was found [3,4]. In the present study, despite the low organ damage score SLICC/ACR-DI, it significantly correlated with sleep disturbances and this association remained significant in the multivariate analysis as an independent determinant of poor sleep quality in SLE patients. The statistically significant correlation between SLICC/ACR DI and the SLEDAI, the CES-D and the HAQ-DI in the current study could explain this finding. Corticosteroids, at least in high doses, may give rise to sleep problems and some psychiatric symptoms [37]. However, our study as well as some other previous studies have not shown a relationship between use and dose of corticosteroids and sleep disturbance in SLE [4,6,7]. In conclusion, our study shows a high prevalence of sleep disturbances among studied Egyptian female SLE patients. Several factors contribute to poor sleep quality in these patients including disease activity, functional disability, depression and cumulative damage. However, disease activity and cumulative disease damage were the only predictors of sleep quality. Assessment and management of sleep problems should be part of the management of patients with SLE. Conflict of interest None. References [1] Ohayon MM. Epidemiology of insomnia: what we know and what we still need to learn. Sleep Med Rev 2002;6:97–111. [2] Ancoli-Israel S, Roth T. Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. I. Sleep 1999;22(Suppl. 2):S347–53. [3] DaCosta D, Bernatsky S, Drista M, Clarke AE, Dasgupta K, Keshani A, et al. Determinants of sleep quality in women with systemic lupus erythematosus. Arthritis Rheum 2005;53:272–8.
132 [4] Valencia-Flores M, Resendiz M, Castano VA, Santiago V, Campos RM, Sandino S, et al. Objective and subjective sleep disturbances in patients with SLE. Arthritis Rheum 1999;42: 2189–93. [5] McKinely PS, Ouellette SC, Winkel GH. The contributions of disease activity sleep patterns, and depression to fatigue in SLE. Arthritis Rheum 1995;38:826–34. [6] Tench CM, Mc Curdie I, White PD, D’Cruz DP. The prevalence and associations of fatigue in systemic lupus erythematosus. Rheumatol 2000;39:1249–54. [7] Gudbjornsson B, Hetta J. Sleep disturbances in patients with systemic lupus erythematosus: a questionnaire based study. Clin Exp Rheumatol 2001;19:509–14. [8] Breslau N, Roth T, Rosenthal L, Andreski P. Sleep disturbances and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry 1996;39:411–8. [9] Katz DA, McHorney AC. The relationship between insomnia and health-related quality of life in patients with chronic illness. J Fam Pract 2002;51:229–35. [10] Hatoum H, Kong S, Kania C, Wong J, Mendelson W. Insomnia, health-related quality of life and healthcare resource consumption: a study of managed-care organization enrollees. Pharmacoeconomics 1998;14:629–37. [11] Simon G, VonKorff M. Prevalence, burden, and treatment of insomnia in primary care. Am J Psychiatry 1997;154:1417–23. [12] Everson CA. Sustained sleep deprivation impairs host defense. Am J Physiol 1993;265:R1148–54. [13] Crofford LJ, Kalogeras KT, Mastorakos G, Magiakou MA, Wells J, Kanik KS, et al. Circadian relationships between interleukin (IL)-6 and hypothalamic pituitary-adrenal axis hormones: failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis. J Clin Endocrinol Metab 1997;82:1279–83. [14] Vgontzas AN, Papanicolaou DA, Bixler EO, Lotsikas A, Zachman K, Kales A, et al. Circadian interleukin-6 secretion and quantity and depth of sleep. J Clin Endocrinol Metab 1999;86: 2603–7. [15] Moses N, Wiggers J, Nicholas C, Cockburn J. Prevalence and correlates of perceived unmet needs of people with systemic lupus erythematosus. Patient Educ Couns 2005;57:30–8. [16] Danoff-Burg S, Friedberg F. Unmet needs of patients with systemic lupus erythematosus. Behav Med 2009;35(1):5–13. [17] Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271–7. [18] Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the multicenter criteria committee. Arthritis Rheum 1990;33:160–72. [19] Bombardier C, Gladman D, Urowitz M, Caron D, Chang C. Derivation of the SLEDAI A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 1992;35:630–40. [20] Folstein MF, Folstein SE, McHugh PR. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–98. [21] Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz M, et al. The development and initial validation of the Systemic
H.A. kotb et al.
[22]
[23] [24]
[25]
[26] [27]
[28]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
[36]
[37]
Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for systemic lupus erythematosus. Arthritis Rheum 1996;39:363–9. Radloff LS. The CES-D scale: a self report depression scale for research in general population. Appl Psychol Meas 1977;1: 385–401. Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. Arthritis Rheum 1980;23:137–45. Buysse DJ, Reynolds 3rd CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989;28: 193–213. Cohen J, Cohen P, West SG. Applied multiple regression/ correlation analysis for the behavioral sciences. 3rd ed. Mahwah, NJ: Lawrence Erblaum; 2003. Greenwood KM, Lederman L, Linder HD. Self reported sleep in systemic lupus erythematosus. Clin Rheumatol 2008;27:1147–51. Chandrasekhara PK, Jayachandran NV, Rajasekhar L, Thomas J, Narsimulu G. The prevalence and associations of sleep disturbances in patients with systemic lupus erythematosus. Mod Rheumatol 2009;19:407–15. Bourguignon C, Labyak SE, Taibi D. Investigating sleep disturbance in adults with rheumatoid arthritis. Holist Nurs Pract 2003;17:241–9. von Kanel R, Dimsdale JE, Ancoli-Israel S, Mills PJ, Patterson TL. Poor sleep is associated with higher plasma proinflammatory cytokine interleukin-6 and procoagulant marker fibrin D-dimer in older caregivers of people with Alzheimer’s disease. J Am Geriatr Soc 2006;54:431–7. Redwine L, Hauger RL, Gillin C, Irwin M. Effects of sleep deprivation on interleukin-6, growth hormone, cortisol and melatonin levels in humans. J Clin Endocrinol Metab 2000;85: 3597–603. Irwin M, Mascovich A, Gillin JC, Willoughby R, Pike J, Smith TL. Partial sleep deprivation reduces natural killer cell activity in humans. Psychosom Med 1994;56:493–8. Nery FG, Borba EF, Hatch JP, Soares JC, Bonfa E, Neto FL. Major depressive disorder and disease activity in systemic lupus erythematosus. Compr Psychiatry 2007;48:14–9. Julian LJ, Yelin E, Yazdany J, Panopalis P, Trupin L, Criswell LA, et al. Depression, medication adherence, and service utilization in systemic lupus erythematosus. Arthritis Rheum 2009;61: 240–6. Da Cost D, Dobkin PL, Pinard L, Fortin PR, Danoff DS, Esdaile JM, et al. The role of stress in functional disability among women with systemic lupus erythematosus: a prospective study. Arthritis Care Res 1999;12:112–9. Benitha R, Tikly M. Functional disability and health related quality of life in South Africans with rheumatoid arthritis and systemic lupus erythematosus. Clin Rheumatol 2007;26:24–9. Lowe B, Willand L, Eich W, Zipfel S, Anthony D, Herzong W, et al. Psychiatric comorbidity and work disability in patients with inflammatory rheumatic diseases. Psychosom Med 2004;66: 395–402. Warrington TP, Bostwick JM. Psychiatric adverse effects of corticosteroids. Mayo Clin Proc 2006;81:1361–7.