Abstract
Objective
This chapter aims to evaluate current knowledge of the burden of systemic lupus erythematosus (SLE) on individual patients, with a particular focus on health-related quality of life (HRQoL), activities of daily living (ADLs), individual symptoms, such as fatigue and pain, work disability and employment.
Methodology
A literature search was performed in Medline (PubMed) and a qualitative analysis was done of all publications relating to the burden of SLE (January 2000 to May 2010, updated in June 2013) matching the following inclusion criteria: prospective studies involving ≥100 patients with SLE; studies focussing on QoL, ADL, function/disability, patient perceptions/experience of their illness, physical/psychological/social impact, unmet needs, work disability/employment status or specific signs/symptoms expected to impact on HRQoL/ADL; studies predominantly involving patients of Caucasian ethnicity; and studies based in Europe, North America or Australia. Studies in juvenile patients; studies of the impact of obesity; studies of non-pharmacological interventions, dietary supplements or alternative medicines; and health-economic analyses were excluded.
Results/conclusions
The present literature analysis showed that SLE has a considerable impact on the HRQoL of patients and their ability to carry out normal daily activities, resulting in a high prevalence of disability. The HRQoL of patients with SLE is consistently lower than that of matched healthy control subjects or patients with other chronic diseases. Predictors of poor HRQoL in patients with SLE include older age, fatigue and the presence of co-morbid neurological or psychiatric disorders, particularly depression or anxiety. Conversely, clinical measures of disease activity and organ damage are poor indicators of patients’ HRQoL. Even though current evidence gives an insight into the HRQoL in patients with SLE, there are still many areas where results need to be confirmed or clarified and therefore there is the need to conduct further studies including trials with HRQoL as a primary objective.
More sensitive diagnostic tests, earlier diagnosis and optimised therapeutic strategies have changed the overall prognosis of patients suffering from systemic lupus erythematosus (SLE). In addition, new medications which are already licenced or in the pipeline will hopefully further improve the life expectations. Major reasons for mortality are infections and damage, especially accelerated arteriosclerosis. Therefore, the therapeutic aim in SLE is to control disease activity and to prevent progressive damage, which should be regularly documented by validated scores .
In addition, the European League against Rheumatism (EULAR) recommends evaluating the health-related quality of life (HRQoL) at every visit, because HRQoL is finally the domain that reflects the burden of SLE on individual patients. Physicians’ focus on disease activity and damage as their primary therapeutic goal does not detect the patients’ perspective on their disease, which can be seen in symptoms such as fatigue and other patient-reported outcomes (PROs) which may cause interruptions in treatment and misunderstandings in communication between both.
With this in mind, a literature analysis was undertaken to evaluate current knowledge of the burden of SLE on individual patients, with a particular focus on:
- •
patient HRQoL and activities of daily living (ADLs);
- •
individual symptoms, such as fatigue, pain, sleep disturbance and neuropsychiatric symptoms; and
- •
work disability and employment.
Methodology
A search of all publications relating to the burden of SLE (January 2000 to March 2010) was performed using the Medline (PubMed) database. The following search terms were used to identify potentially relevant publications: SLE plus QoL, patient perspective, patient burden of illness/disease, family impact/burden, prognosis, self, employment/work impact, psychological impact, patient(s) and psychological impact/physical impact/daily living or functionality/fatigue/functioning and impact on social life; these were compared with rheumatoid arthritis (RA). This search retrieved a total of 4250 results.
The abstracts of these papers were then reviewed manually to identify primary studies pertaining to the burden of SLE ( n = 58 studies). An update of the same search in June 2013 listed 15 additional studies. The inclusion criteria were as follows: prospective studies involving ≥100 patients with SLE; studies focussing on QoL, ADL, function/disability, patient perceptions/experience of their illness, physical/psychological/social impact, unmet needs, work disability/employment status or specific signs/symptoms expected to impact on HRQoL/ADL; studies predominantly involving patients of Caucasian ethnicity; and studies based in Europe, North America or Australia. Studies of multiple rheumatic diseases were included only if they were comparative studies with an equal focus on all conditions. However, studies of multiple diseases were excluded if the main focus was a different disease and SLE was only described as part of a control arm. Multi-ethnic studies were included if a large proportion of the patients were Caucasian. Studies primarily relating to the development or evaluation of QoL tools were excluded, as were: studies in juvenile patients; studies of the impact of obesity; studies of non-pharmacological interventions (e.g., support groups, psychotherapy and exercise), dietary supplements or alternative medicines; and health-economic analyses (except when pertinent ‘end’ points were reported in the abstract, as the economic burden of SLE was beyond the scope of this analysis). A qualitative analysis of the identified publications is presented.
Results: SLE and QoL from a patient perspective
Assessment of HRQoL in patients with SLE
Twenty-four studies that evaluated HRQoL in patients with SLE used Short Form 36-Item Health Survey (SF-36) . Other generic instruments, such as the EuroQoL utility index (EuroQoL-5D), EuroQoL visual analogue scale (EuroQoL VAS) and shortened QoL instruments derived from SF-36 (SF-8, SF-6D and SF-12), were occasionally used, but much less commonly than SF-36 . The general reliance on generic questionnaires to assess health status in patients with SLE presumably reflects the lack of an accepted SLE-specific HRQoL instrument, although there are now at least four instruments (LupusQoL, L-QOL, SLEQOL and LupusPRO) developed . Nonetheless, the use of generic instruments does allow comparisons to be made between SLE and other diseases.
The impact of SLE on HRQoL in patients with SLE
The results of eight studies showed that the HRQoL of patients with SLE (assessed using the SF-36 in the majority of cases) was consistently lower than that of matched healthy control subjects or the population norm . In addition to impacting on physical function, the disease also had an effect on patients’ psychological and emotional states, vitality, general health and social lives . In the four studies in which absolute numbers were specified, reductions in the physical component summary (PCS) scores of the SF-36 in patients with SLE were clinically significant compared with control values , according to the criteria published by Colangelo and colleagues . Two of these studies also reported clinically significant reductions in the mental component summary scores of the SF-36, although the absolute changes were less than in the PCS scores and not always statistically significant .
One study reported a high prevalence of hand problems (including reduced grip force and activity-induced pain) affecting ADLs in patients with SLE . In this Swedish study, 73% of 109 patients reported hand problems and 42% reported consequent interference with the performance of daily activities (including household tasks, work at home, work/study and child care).
Even though additional information on the impact of SLE on a specific ADL was scarce, there is evidence that SLE leads to disability in 25–57% of patients . Among 892 members of the German lupus patient association, 57% were registered as ‘disabled’ and 83% had an average grade of disability of >50% (as appraised by the German welfare system) . In a similar study conducted in the Netherlands, approximately two-thirds of 114 patients with SLE reported either a temporary or a permanent inability to perform daily activities at home and/or at work and 25% were receiving disability benefits .
According to the German lupus patient association study, factors that may predict worse disability in patients with SLE include prolonged disease duration, concomitant osteoarthritis, cerebral insults and poor functional capacity . The results of another study suggest that the presence of a neuropsychiatric SLE (NPSLE) syndrome may also lead to increased disability .
Factors influencing HRQoL in patients with SLE
Various factors were reported to adversely influence HRQoL in patients with SLE. These factors included:
- •
older age,
- •
younger age at enrolment,
- •
female gender,
- •
ethnicity: Caucasian , African American,
- •
a high number of diagnostic criteria,
- •
erythrocyte sedimentation rate,
- •
poor initial HRQoL,
- •
low educational attainment,
- •
poverty or low household income,
- •
lack of social support,
- •
unemployment,
- •
disease duration,
- •
overall cumulative medication use,
- •
co-morbid osteoarthritis/arthralgia,
- •
vertebral fractures,
- •
carotid plaques,
- •
overall self-reported co-morbidity,
- •
lack of exercise,
- •
smoking,
- •
body mass index,
- •
corticosteroid dose,
- •
NPSLE syndromes,
- •
co-morbid fibromyalgia,
- •
depression and/or anxiety,
- •
fatigue,
- •
abnormal illness-related behaviours and
- •
feeling of helplessness.
Overall, these factors address a wide variety of domains, some of which may be caused by other reasons or reflecting consequences of suffering from SLE. Across all these studies, the most commonly implicated factors affecting HRQoL in patients with SLE (by number of citations) were older age, fatigue, the presence of co-morbid neurological or psychiatric disorders (particularly depression or anxiety), low educational attainment and poverty/low household income.
Factors identified as independent predictors of HRQoL (by multivariate analysis) are shown in Table 1 .
| Study | No. of patients | Mean (SD) age, years | Mean (SD) disease duration, years | HRQoL instrument(s) | Independent predictors of HRQoL (by multivariate regression analysis) |
|---|---|---|---|---|---|
| Alarcón et al., 2004 | 346 | 37.7 (13.0) | 1.5 (1.3) | SF-36 | PCS: poor initial HRQoL (−), older age (−), fibromyalgia (−) MCS: poor initial HRQoL (−), fibromyalgia (−), low educational attainment (−), abnormal illness-related behaviours (−) |
| Doria et al., 2004 | 126 | 38.9 (11.9) | 9.9 (6.3) | SF-36 | PCS and MCS: older age (−), arthralgia/arthritis (−), high scores on depression inventory (−) |
| Sanchez et al., 2009 | 588 | 36.6 (12.4) | 1.6 (1.4) | SF-36 SF-6D | PCS: older age (−), lack of exercise (−), smoking (−), poverty (−), high number of diagnostic criteria (−), high disease activity (−), organ damage (−), fatigue (−), feeling of helplessness (−), abnormal illness-related behaviours (−) MCS: high disease activity (−), fatigue (−), feeling of helplessness (−), abnormal illness-related behaviours (−), high number of diagnostic criteria (+), social support (+) SF-6D: older age (−), poverty (−), high disease activity (−), fatigue (−), feeling of helplessness (−), abnormal illness-related behaviours (−), social support (+) |
| Almehed et al., 2010 | 163 | 48.5 (13.6) | 13.7 (9.6) | SF-36 | PCS: older age (−), working ability (−), corticosteroid dose (−), body mass index (−), disease activity (−) |
| Hanly et al., 2010 | 1206 | 34.5 (13.2) | 0.5 (0.4) | SF-36 | PCS: NPSLE events (−), female gender (−), lack of college education (−), high disease activity (−), high organ damage (−) MCS: NPSLE events (−), diffuse NPSLE events (−), high disease activity (−), high organ damage (−) |
| Hanly et al., 2009 | 209 | 43.7 (13.8) | 8.4 (8.9) | SF-36 | PCS: NPSLE events (−), lack of college education (−), older age (−), high disease activity, excluding neuropsychiatric variables (−), overall cumulative medication use (−) MCS: NPSLE events (−), Caucasian ethnicity (−), younger age (−), overall cumulative medication use (−) |
| Friedman et al., 2003 | 266 | – | 4.7 (2.8) | SF-36 | PCS: fibromyalgia/fibromyalgia-like manifestations (−) |
| Choi et al., 2012 | 108 | 37.4 (11.1) | 7.2 (5.9) | FACIT | Total QoL: depression and daily glucocorticoid dose, physical well-being: depression (−), fatigue (−), and daily glucocorticoid (−) Emotional well-being: depression (−) Functional well-being: depression (−) |
| Tamayo et al., 2010 | 274 | 45 (12.2) | 9.6 (7.8) | SF-12 | PCS: Impairment last 7 days (−), previous PCS (−), actual MCS (−), Lupus flare-up last 3 months (−), married or marriage-like partnership (−), PRO disease activity (−), type of medication (−), age at baseline (−) MCS: Impairment last 7 days (−), previous MCS (−), actual PCS (−), married or marriage-like partnership (−), PRO disease activity (−) |
The relationship between HRQoL and disease activity or organ damage in patients with SLE
There is much controversy over whether disease activity and/or organ damage are associated with change in HRQoL in patients with SLE. Although six studies reported that physician-documented disease activity and/or organ damage were linked with overall change in HRQoL , seven other studies failed to make such an association .
One reason for this unclear situation might be the fact that there are discrepancies between patient and physician assessments of disease activity in SLE . While patients focussed more on self-perceived function, physicians were more concerned with laboratory features. These findings demonstrate the importance of including patient-orientated or even PRO measures in clinical studies and of overcoming this discrepancy and improving treatment results.
Thus, it appears that actually used clinical measures of disease activity and organ damage are poor indicators of patients’ actual health status. In support of this conclusion, there is evidence that renal damage by itself does not influence patients’ HRQoL . Active renal disease, on the other hand, may lead to a slight reduction in HRQoL; however, these results require confirmation, as the confidence intervals were too wide to allow definitive conclusions to be made .
Patients’ perceptions of impact of SLE on health status
Patients generally perceive their health to be suboptimal, with 50% of 1033 patients within the German Lupus Self-Help Organisation completing the LULA survey rating their health as ‘not so good’ or ‘poor’ . Very similar findings were reported in two North American studies and one further German study, in which 35–47% of patients rated their health as ‘fair/not so good’ or ‘poor’ .
In terms of coping skills, a Canadian study of 120 women with SLE found that most patients coped adequately with their disease over the 15-month study period despite fluctuations in disease activity . However, approximately 40% of patients remained distressed and unable to cope.
Across two surveys based on a version of the SLE Needs Questionnaire (SLENQ), 94–100% of patients with SLE reported at least one unmet need relating to their illness and its management . In an Australian survey of 386 patients with SLE, tiredness (81%), pain (73%), not being able to do the things one used to (72%), fear of exacerbation (72%), sleeping problems (70%), anxiety/stress (69%) and feeling down/depressed (68%) were all rated highly as unmet needs . Similarly, in a US survey of 112 patients with SLE, tiredness (90%), pain (80%), not sleeping well (75%), feeling worse after physical activity (71%), dealing with anxiety/stress (79%), not being able to do the things one used to (77%), fears about SLE getting worse (80%) and fears about physical disability (74%) rated highly as unmet needs . These findings suggest that patients’ physical, psychological and practical concerns are not being managed adequately. In addition, they also indicate that patients place a great deal of importance on their physical well-being, valued life activities (VLAs) and mental health. This contrasts with the traditional physician-based focus on clinical and laboratory measures.
Symptomatic burden of SLE
The literature searches identified a number of common symptoms that contribute towards the burden of SLE in individual patients. These symptoms include fatigue, pain, sleep disturbance and neurological/psychiatric findings, particularly anxiety and depression. Co-morbidities can further add to the burden of disease.
Fatigue
Fatigue was found to be a very common symptom in SLE, affecting 50–92% of patients . This is an important observation as this symptom was shown to have a significant adverse influence on the HRQoL of patients, impacting on both the physical and the mental health domains of the SF-36 . In one study of 127 US women with SLE, patients rated fatigue worse than pain, depression or anxiety , which highlights the severity of this symptom.
Several studies showed that fatigue is very closely associated with sleep disturbance and depressed mood in patients with SLE , with both factors predicting increased fatigue. Depressed mood, in particular, appears to predict an increase in both physical and mental fatigue .
Independent predictors of fatigue (by multivariate analysis) are shown in Table 2 .
| Study | No. of patients | Mean (SD) age, years | Mean (SD) disease duration, years | Fatigue instrument | Independent predictors of increased fatigue (by multivariate regression analysis) |
|---|---|---|---|---|---|
| Da Costa et al., 2006 | 130 | 45.4 (14.0) | 13.8 (10.1) | MFI-20 | Physical fatigue: organ damage, disease activity, fibromyalgia, depression, sleep quality, level of exercise participation Mental fatigue: depression, sleep quality, social support |
| Jump et al., 2005 | 127 | 40.6 (12.2) | 9.0 (7.7) | Fatigue VAS | Pain, depression, social support |
| Burgos et al., 2009 | 515 | 37.2 (12.6) | 4.7 (3.2) | Short FSS | Caucasian ethnicity, constitutional symptoms (fever, weight loss), pain, abnormal illness-related behaviours, feeling of helplessness |
| Dobkin et al., 2001 | 120 | 42.5 (10.8) | 10.8 (8.7) | Vitality subscale of SF-36 | Depression, stress |
The association between fatigue and disease activity or organ damage was equivocal in the five studies that examined this association. Four studies reported a direct – albeit generally weak – correlation between increasing disease activity and higher levels of fatigue , while a fifth study failed to show such an association . Similarly, a relationship between fatigue and organ damage was observed in one study , but not in three others . These findings suggest that clinical measures of disease activity and damage are poor indicators of fatigue.
Sleep disturbance
Similarly to fatigue, disturbed sleep was reported in 56–88% of patients with SLE .
With regard to related factors, poor sleep quality was linked with pain , a depressed/anxious mood , fatigue , lack of exercise, high disease activity , cumulative organ damage and poor functional ability .
Pain
Pain is commonly suffered by patients with SLE. In the three studies in which it was reported, 71–89% of patients with SLE experienced some degree of pain . This finding was supported by SF-36 data showing that patients with SLE scored significantly worse on the bodily pain subscale of SF-36 than matched healthy controls or the population norms .
Psychiatric and neurological symptoms
In patients with SLE, both psychiatric and neurological manifestations can occur within the context of an NPSLE syndrome (such as headaches, cerebrovascular disease, motor/sensory deficits, cognitive dysfunction, seizures and psychiatric disorders) . Importantly, patients with NPSLE syndromes were shown to have a reduced HRQoL (in both the physical and the mental domains of the SF-36) and a higher degree of fatigue , compared with non-NPSLE patients. These findings suggest that NPSLE syndromes have a major impact on patients.
In terms of its impact on patients, the presence of co-morbid depression and/or anxiety was linked with reduced HRQoL in two studies . In one of these studies, it was suggested that anxiety and/or depression may have a more important role in determining patient HRQoL than disease activity or organ damage . However, this is difficult to determine as depression and anxiety are also linked with these clinical measures . Other factors that may increase the odds of developing depression in patients with SLE include co-morbid osteoarthritis/arthralgia and concomitant cardiovascular disease (CVD) .
Cognitive impairment is commonly reported in patients with SLE and has a great influence on daily life and activities . Already newly diagnosed patients score significantly worse than control subjects on cognitive tests evaluating cognitive processing speed and efficiency . Factors associated with poor cognitive performance in this study included depressive symptoms, organ damage and a high erythrocyte sedimentation rate . Data from a separate study also supported the (independent) association between depressive symptoms and declining cognitive function in patients with SLE . Other independent factors associated with declining cognitive function (by general linear mixed modelling) included positive antiphospholipid antibody levels, positive anti-β2-glycoprotein 1 immunoglobulin G (IgG) levels, consistent prednisone use, the presence of diabetes and low educational attainment .
With regard to their impact on patients, various co-morbidities have been shown to impact adversely on the HRQoL of patients with SLE . Specific concomitant conditions associated with deteriorating HRQoL include osteoarthritis/arthralgia , fibromyalgia , CVD (carotid plaques) and osteoporosis (vertebral fractures) .
Results: SLE and QoL from a patient perspective
Assessment of HRQoL in patients with SLE
Twenty-four studies that evaluated HRQoL in patients with SLE used Short Form 36-Item Health Survey (SF-36) . Other generic instruments, such as the EuroQoL utility index (EuroQoL-5D), EuroQoL visual analogue scale (EuroQoL VAS) and shortened QoL instruments derived from SF-36 (SF-8, SF-6D and SF-12), were occasionally used, but much less commonly than SF-36 . The general reliance on generic questionnaires to assess health status in patients with SLE presumably reflects the lack of an accepted SLE-specific HRQoL instrument, although there are now at least four instruments (LupusQoL, L-QOL, SLEQOL and LupusPRO) developed . Nonetheless, the use of generic instruments does allow comparisons to be made between SLE and other diseases.
The impact of SLE on HRQoL in patients with SLE
The results of eight studies showed that the HRQoL of patients with SLE (assessed using the SF-36 in the majority of cases) was consistently lower than that of matched healthy control subjects or the population norm . In addition to impacting on physical function, the disease also had an effect on patients’ psychological and emotional states, vitality, general health and social lives . In the four studies in which absolute numbers were specified, reductions in the physical component summary (PCS) scores of the SF-36 in patients with SLE were clinically significant compared with control values , according to the criteria published by Colangelo and colleagues . Two of these studies also reported clinically significant reductions in the mental component summary scores of the SF-36, although the absolute changes were less than in the PCS scores and not always statistically significant .
One study reported a high prevalence of hand problems (including reduced grip force and activity-induced pain) affecting ADLs in patients with SLE . In this Swedish study, 73% of 109 patients reported hand problems and 42% reported consequent interference with the performance of daily activities (including household tasks, work at home, work/study and child care).
Even though additional information on the impact of SLE on a specific ADL was scarce, there is evidence that SLE leads to disability in 25–57% of patients . Among 892 members of the German lupus patient association, 57% were registered as ‘disabled’ and 83% had an average grade of disability of >50% (as appraised by the German welfare system) . In a similar study conducted in the Netherlands, approximately two-thirds of 114 patients with SLE reported either a temporary or a permanent inability to perform daily activities at home and/or at work and 25% were receiving disability benefits .
According to the German lupus patient association study, factors that may predict worse disability in patients with SLE include prolonged disease duration, concomitant osteoarthritis, cerebral insults and poor functional capacity . The results of another study suggest that the presence of a neuropsychiatric SLE (NPSLE) syndrome may also lead to increased disability .
Factors influencing HRQoL in patients with SLE
Various factors were reported to adversely influence HRQoL in patients with SLE. These factors included:
- •
older age,
- •
younger age at enrolment,
- •
female gender,
- •
ethnicity: Caucasian , African American,
- •
a high number of diagnostic criteria,
- •
erythrocyte sedimentation rate,
- •
poor initial HRQoL,
- •
low educational attainment,
- •
poverty or low household income,
- •
lack of social support,
- •
unemployment,
- •
disease duration,
- •
overall cumulative medication use,
- •
co-morbid osteoarthritis/arthralgia,
- •
vertebral fractures,
- •
carotid plaques,
- •
overall self-reported co-morbidity,
- •
lack of exercise,
- •
smoking,
- •
body mass index,
- •
corticosteroid dose,
- •
NPSLE syndromes,
- •
co-morbid fibromyalgia,
- •
depression and/or anxiety,
- •
fatigue,
- •
abnormal illness-related behaviours and
- •
feeling of helplessness.
Overall, these factors address a wide variety of domains, some of which may be caused by other reasons or reflecting consequences of suffering from SLE. Across all these studies, the most commonly implicated factors affecting HRQoL in patients with SLE (by number of citations) were older age, fatigue, the presence of co-morbid neurological or psychiatric disorders (particularly depression or anxiety), low educational attainment and poverty/low household income.
Factors identified as independent predictors of HRQoL (by multivariate analysis) are shown in Table 1 .
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Paediatric-onset systemic lupus erythematosus
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Pulmonary hypertension in systemic lupus erythematosus
Managing lupus patients during pregnancy
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