Division of Rheumatology, Department of Medical and Surgical Sciences, 1 Department of Neuroscience, University of Padua and 2 Department of Rheumatology, University of Ancona, Italy.
Correspondence to: A. Doria, Cattedra e Divisione di Reumatologia, Dipartimento di Scienze Mediche e Chirurgiche, Via Giustiniani, 2, 35128 Padova, Italy. E-mail: adoria{at}unipd.it
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Abstract |
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Methods. The Medical Outcomes Study Short Form-36 was applied in a cohort of 126 SLE patients. At the time of HRQOL testing all patients underwent a clinical and laboratory evaluation, together with the measure of disease activity, severity and damage. In addition, a battery of psychological tests including the Hamilton Anxiety Scale (HAS) and the Hamilton Depression Rating scale (HAM-D) was applied.
Results. The parameters which seemed to greatly influence the impairment of HRQOL were older age, arthralgiaarthritis and higher HAS scores as well as HAM-D. In multivariate analysis (adjusted for age), arthralgiaarthritis and a higher HAM-D score were associated with HRQOL impairment. No relationship between HRQOL and SLE activity, severity or damage were found. However, a relationship between HAS or HAM-D scores and damage or arthralgiaarthritis was noted.
Conclusion. Anxiety, depression and joint pain seem to be the major determinants of HRQOL impairment in SLE patients. Damage seems to influence HRQOL mostly through depression.
KEY WORDS: SF-36, Health-related quality of life, Systemic lupus erythematosus, Anxiety, Depression
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Introduction |
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Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, characterized by alternate phases of remission and exacerbation of the clinical symptoms. During the disease course all the organs and tissues can be potentially involved, sometimes irreversibly. For these reasons, SLE can affect different aspects of the patient's life, leading to an impairment of HRQOL.
The term quality of life or HRQOL [1] refers to the physical, psychological, mental and social aspects of the concept of health, which are in turn influenced by life experiences and expectations of the patient.
As the concept of health and the capacity of coping with possible limitations and disabilities can vary from subject to subject, the same type of physical damage may influence the HRQOL of different persons in a different way. For this reason it is important to be able to integrate the objective evaluation of the patient's health, which is up to the clinician, with the subjective perception which the patient has of his/her own health state [2].
Moreover, during the course of SLE, psychological distress is a common event: depression, anxiety and psychosis are the most commonly reported symptoms [3, 4]. Their prevalence ranges between 17 and 75% as reported in different studies [3, 4]. This wide range can be due to the different tests used to detect psychological distress and to the characteristics of the populations studied. Psychological distress could be a contributing factor to impairment of HRQOL in SLE patients.
The aim of our study was to evaluate the relationship between HRQOL and the clinical as well as immunological aspects of the disease in Italian patients with SLE. Moreover, we wanted to evaluate the possible influence of psychological factors such as depression and anxiety both on HRQOL and disease course.
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Patients and methods |
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The study was approved by the relevant medical ethics committee and all patients gave written consent.
The methods used for disease classification, definition of organ involvement, nuclear and antiphospholipid antibody detection, disease activity, damage and quality of life assessment have been detailed elsewhere [5]. Briefly, disease was classified according to the American College of Rheumatology (ACR) Classification Criteria for SLE [6], disease activity was measured by the European Consensus Lupus Activity Measure (ECLAM) score [7], cumulative damage using the Systemic Lupus International Collaborating Clinic/American College of Rheumatology (SLICC/ACR) damage index [8], and quality of life using the Medical Outcomes Study Short Form-36 (SF-36) [9, 10]. An ECLAM score of >2 was considered indicative of active disease.
Moreover, patients were split into two groups: mild and severe SLE [11]. Patients with skin, joint and haematological involvement (apart from haemolytic anaemia) and serositis were subclassified as mild SLE, whereas those with central nervous system (CNS) and renal involvement, lung and heart parenchymal manifestations and haemolytic anaemia were subclassified as severe SLE. As specified elsewhere [5], for term definition of SLE-specific features we used those included in the ACR criteria [6]. However, for the purpose of this study, we considered arthralgiaarthritis as variable, including arthritis defined according to the ACR criteria and/or persistent arthralgia.
SLE relapse was defined as an event characterized by the appearance of clinical and/or haematological abnormalities or by the worsening of pre-existing manifestations which requested an increment of corticosteroid dosage and/or the introduction of an immunosuppressive agent.
In addition, we applied a battery of tests for the evaluation of psychological performance (that included anxiety and depression). The same examiner evaluated all the patients during a 30-min session and calculated the test score.
Evaluation of anxiety and depression
The Hamilton Anxiety Scale (HAS) includes 14 items, each scoring from 0 to 4. The evaluation of the presence and intensity of different items is based on the patient's condition in the last 37 days. The total score ranges between 0 and 56. A score 5 indicates lack of anxiety, between 6 and 14 mild anxiety and
15 a clinically significant level of anxiety [12].
The Hamilton Depression Rating scale (HAM-D) is a scale for recording and measuring the prevalence and the intensity of specific symptoms of depression. It includes 21 items; the first 17 are considered for the score calculation. The cut-off scores, established on the basis of many clinical studies, are as follows: 07 no depression, 815 mild depression, 16 moderate to severe depression. The scale has been validated and has shown good correlation with the other main indices for measuring the intensity of depressive symptoms [13].
Statistical analysis
Scores are variables measured by an ordinal scale and their distributions showed a significant deviation from normality (KolmogorovSmirnov test for normal distribution): consequently a non-parametric statistic was used. The MannWhitney U-test was used for independent samples. Linear correlation between variables was checked using Spearman's coefficient. Dichotomous variables were analysed using Pearson's
2 or the Fisher exact test. Significance of age was evaluated using the Student's t-test for independent samples. Multivariate analysis was performed using the logistic regression model. Statistical significance was set at P<0.05. All analysis was performed using the statistical software package Statistica (Statsoft Inc.).
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Results |
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Thirty-one patients (24.6%) were affected with severe SLE and 95 (75.4%) with mild SLE. Patients with severe SLE were younger than those with mild SLE: mean age (±S.D.) 31.4±7.7 vs 41.5±12 yr (P<0.0001), whereas the mean disease duration (±S.D.) was not significantly different in the two groups 94.8±54.7 vs 126.7±79.5 months.
Anxiety and depression
The mean values (±S.D.) of HAS and HAM-D scores observed in 126 patients were 10.2±5.8 (median 11; range 025) and 6.7±4.5 (median 6; range 022), respectively. A weak linear relationship between HAS or HAM-D scores and SLICC damage index score ( = 0.26, P<0.004 and
= 0.30, P<0.001, respectively) was found. The mean HAM-D score was higher in patients with arthralgiaarthritis then in those without such manifestation: 8.7±4.7 vs 6.04±4.2, P<0.005.
HAS and HAM-D were converted into ordinal type scales, using the following clinical score: anxiety (absent 5, mild = 614, clinically significant
15), depression (absent
7, mild = 815, clinically significant
16). According to these clinical definitions (Table 1), 94 patients (74.6%) demonstrated mild or clinically significant anxiety and 51 patients (40.5%) mild or clinically significant depression. All depressed patients were also anxious.
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Quality of life
The scores of HRQOL, including overall score as well as the Physical Component Summary (PCS) and Mental Component Summary (MCS), were lower in SLE patients than in controls (P<0.00001, P<0.00001 and P<0.0001, respectively). The scores of all SF-36 subscales but two, rolephysical (RP) and social function (SF), were also lower in patients than in controls. All HRQOL scores are detailed elsewhere [5].
The mean (µ) and standard deviation () subscale values of the control group were used in order to subdivide SLE population into two groups of subjects with respect to each scale: patients with high or low HRQOL score. Patients with values of less than µ 3
with respect to the specific subscale were considered to have a low score. It is worth noting that high and low scores do not correspond to normal or pathological values, since they represent ordinal variables. According to this definition, among the 126 SLE patients 58 (46%) had a low overall score, 42 (33.3%) by MCS and 55 (43.7%) by PCS.
The sub-classification of the patients according to the established cut-off for each HRQOL subscale and the relationships between HRQOL categories and major disease parameters are reported in Tables 2 and 3.
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The negative correlations between HRQOL scales and HAM-D or HAS scores (Table 4) further confirm the great impact of anxiety and depression on HRQOL in SLE patients. The coefficients are negative since, differently from HRQOL score, HAM-D and HAS worsen with increasing score.
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Discussion |
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Only 20% of our patients had permanent damage, a percentage lower than that observed in other studies [1520]. This difference could probably be due to the fact that our patients were all Caucasians and that the majority of them (25%) had mild disease. However, other studies observed a low prevalence of damage in Caucasian patients [19].
In our patients, permanent damage was not correlated with disease duration or disease activity, in keeping with other authors [16, 19, 20]. The lack of correlation between damage and disease duration could be due to the low extent of damage as well as to the relatively short duration of disease in our patients.
However, the characteristics of our cohort exactly represent the subjects to whom we want to address our study, i.e. a group of out-patients, thus excluding in-patients with high disease activity and/or severity, whose lifestyle is certainly modified.
In this cohort of SLE patients, we observed a compromise of HRQOL, as reported in many other studies [16, 18, 2125]. It is worth noting that a previous study [5] showed that in SLE both PCS and MCS contribute to the decrease of HRQOL and that, different from the case in healthy subjects, in SLE there is a close mutual interaction between these two scales. Moreover, a greater than expected worsening of HRQOL related to the increase of age classes has been observed.
In agreement with data reported elsewhere [5], age was one of the major determinants of HRQOL reduction in our cohort. Interestingly, HRQOL was not influenced by moderate damage nor by disease severity in our patients. The relationship between HRQOL and disease activity was more conflicting. We did not find any correlations between SF-36 overall score, MCS or PCS and disease activity. This could be due to the fact that disease activity was substantially low in our patients. In fact, in keeping with some authors [18, 21, 22, 24], it is expected that patients with a more active disease have an impairment of daily life activities which leads, in turn, to a reduction of HRQOL. We found a correlation between GH and disease activity or the number of disease relapses experienced by the patients (Table 3). We also noted a positive correlation between GH and the time elapsed from the last disease flare and the HRQOL assessment. As expected, RP was also related to disease activity (Table 3). Therefore it is possible that SLE activity could influence some HRQOL subscales, but in patients with low disease activity the effect on the overall HRQOL scores could be masked by other determinants.
GH is the subscale which shows the patient's perception of his/her own general health status. It is worth noting that GH is one of the most compromised subscales in SLE patients compared with healthy subjects, as we have shown elsewhere [5]. Therefore, one could wonder why this subscale is compromised in patients with active disease but not in patients with permanent damage or severe disease. Our results, particularly the relationships between GH and the number of SLE flares or the time to the last relapse, suggest that disease activity, more than disease severity or damage, represents a rapid change in the health status of patients. In addition, changes in SLE activity are often unpredictable in terms of flare duration as well as of possible future consequences.
It is also worth noting that arthralgiaarthritis was the unique clinical manifestation able to influence the HRQOL of our patients. Joint pain, with or without a true arthritis, worsens HRQOL either because of the large amount of energy and attention required by the patient to cope with it or because it represents a persistent signal of the disease itself.
In the light of these results we can assume that many SLE out-patients with mild disease manifestations, including arthralgiaarthritis, low disease activity and limited extent of damageand who are therefore able to live quite a normal lifehave a compromised HRQOL, comparable to that found in severe chronic obstructive pulmonary disease (COPD) and in cardiovascular disease [9, 17], i.e. in patients who are much more compromised on a physical level.
Thus, the parameters which allow us to define the level of physical health of the patient, including disease severity, activity and permanent damage, supply us with an incomplete representation of the well-being of the patient. It therefore becomes necessary to evaluate other aspects [17]. For this reason we submitted our patients to a psychopathological investigation in order to find out about the prevalence of complaints related to depression and anxiety. Our results, in agreement with those reported by others [26, 27], showed a high prevalence of anxious and depressive manifestations in SLE patients. The overall score of SF-36 was inversely correlated to both HAS and HAM-D scores (Table 4). These results are similar to those obtained by other authors [2, 2830].
HAS and HAM-D scores did not correlate with disease duration or with disease activity, in keeping with other reports [31], whereas both were correlated with permanent damage. Moreover, in keeping with other authors [32], we found a relationship between arthralgiaarthritis and depression. It has been shown that pain, especially chronic pain, can lead to the development of depressive symptoms which, in turn, can worsen the pain itself [33]. It is interesting that in our sample arthralgiaarthritis worsens the majority of psychosocial indices, indicating a crucial role for pain in modulating mood and well-being. However, in our sample depression and arthralgiaarthritis were independent variables in modulating HRQOL, suggesting the presence of a more complex model in which pain and depression, when present concurrently, have a magnifying effect on HRQOL, but they also contribute significantly to lowering HRQOL when present separately.
We can therefore put forward the hypothesis that permanent physical damage and/or chronic joint pain could lead, in some people, to the development of anxious and/or depressive symptoms (mostly depressive) which, in turn, could influence the person's perception of HRQOL, determining a worsening of it.
In conclusion, the compromising of HRQOL does not seem to depend directly on SLE activity, severity or permanent damage due to the disease itself, but it is probably mostly related to joint pain and depression, which are influenced, at least in part, by progressive cumulative damage. Whether depression simply reveals a psychological reaction to the disease or represents a neurobiological phenomenon still remains to be addressed.
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The authors have declared no conflicts of interest.
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References |
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