Definition

Quality of life is an ill-defined term that means different things to different people. The concept is vague and multidimensional, and research in this area spans a wide range of disciplines. Of particular concern in the health sciences are those areas that are affected by disease and its treatment, and so to distinguish between QoL in its more general sense and to emphasize its relevance within the context of health, the term health-related quality of life (HRQOL) is frequently used. The concept of HRQOL parallels the World Health Organization’s 1948 definition of health: “Health is a state of complete physical, mental and social well-being and not merely the absence of disease and infirmity.” Measures of the physiologic processes of disease alone cannot adequately capture the many dimensions of health embodied within this broad definition. Traditionally, health status assessments relied on a “disease” model, in which abnormalities are indicated by objective signs and symptoms. In contrast, the “illness” model relies on subjective feelings of pain and discomfort that may not necessarily result from a pathologic abnormality. Both of these concepts of health—disease and illness—must be taken into account in order to make comprehensive assessments of health status. Health-related quality of life comprises those parts of QoL that directly relate to a person’s health, and may be defined as a measure of a person’s sense of physical, emotional, and social well-being associated with a disease or its treatment. This definition may be broadened to include indirect consequences of disease such as unemployment or financial difficulties.¹

Why Measure Quality of Life?

Increasingly, HRQOL is being recognized as an important aspect of chronic diseases such as SLE and is being recognized as a relevant measure of efficacy in clinical trials. OMERACT (Outcomes Measures in Rheumatology Clinical Trials), an international network of experts and opinion leaders, has recommended the inclusion of three outcome measures in SLE clinical trials: (1) a disease activity score, (2) a damage index, and (3) a patient-assessed measure of health status, disability, and HRQOL.² The importance of QoL assessment in health has been underscored by the need to assess the relative effectiveness and appropriateness of rival medical treatments in a context of increasing pressure on healthcare resources. Increased questioning of the use of various medical treatments and methods of organizing health services has led to a paradigm shift in the approach to measurement of health outcomes.³ Furthermore, measurement of QoL in addition to more objective clinical indicators of disease allows for a more comprehensive assessment of the impact of disease and clinical therapies. Information about broader patient outcomes empowers physicians and patients when making decisions about the most appropriate health care. The challenge remains to identify instruments that will accurately and reliably assess these disease outcomes.

Measuring Quality of Life

Although it has been debated whether QoL assessments should be made by the patient or by a health professional, there is now a general agreement among researchers that patients should complete questionnaires about their QoL themselves. Questionnaires may be administered to patients by trained interviewers in certain situations, such as when the patient is unable to read or write.³ The goal of QoL research is to determine health outcomes from the perspective of the patient, and numerous studies have shown that patients’ opinions may vary considerably from those of both healthcare professionals and patients’ relatives.¹ Although one important criticism of patient self-assessment is the occurrence of subjectivity, this subjectivity should, in fact, be viewed as a strength, as it reflects the patient’s point of view.

A plethora of instruments exist that aim to measure aspects of QoL regarded as pertinent to health status, such as life satisfaction, mental health, relationships, fatigue, energy, and vitality.⁴ Given its multidimensional nature, instruments developed for measuring HRQOL will likely be more accurate if they evaluate a number of dimensions. Most authors agree on the existence of four major domains of QoL: (1) physical status and functional abilities, (2) psychological status and well-being, (3) social interactions, and (4) economic and/or vocational status and factors.⁵ Tools that measure only one or two of these domains may fail to comprehensively assess an individual’s well-being. Two basic approaches have been used in the measurement of HRQOL: generic instruments and disease-specific instruments.

Generic Instruments

The SF-36, developed by Ware and Sherbourne,⁸ is the most commonly used generic health status questionnaire. It has become the standard health status questionnaire in U.S. health policy research and it is increasingly being used worldwide.⁹ It is a concise 36-item questionnaire that was designed to be a short, psychometrically sound, generic measure of subjective health status applicable in a wide range of settings.¹⁰ It can either be self-assessed or administered by a trained interviewer. Eight domains are measured: physical functioning, social functioning, role limitations due to physical problems, role limitations due to emotional problems, mental health, energy/vitality, pain, and general health perception. These subscales can be summarized into two component scores: the Physical Component Summary score (PCS) and the Mental Component Summary score (MCS), allowing for easier comparisons and reducing the probability of chance findings.¹¹ The SF-36 has been translated into numerous languages and cultures, and has been found to be valid and reliable in various conditions.

The SF-36 has been shown to be a valid and reliable questionnaire in SLE.¹² Patients with SLE have been shown to have a poorer QoL than people without chronic illness with respect to all aspects of health.^12,13 In a British study of 150 patients with SLE, Stoll and colleagues¹² showed that all of the QoL domains assessed by the SF-36, except for emotional role limitations, were significantly lower in patients with SLE than in a British control population of normal adults of working age. In another study, SF-36 results of 120 Canadian SLE patients were compared to normative data from Canadian women of the same age. The authors found that SLE has a negative influence on patients’ QoL, especially with regard to physical health status.¹⁴

Disease-Specific Instruments

Disease Activity

Health-related QoL questionnaires, such as the SF-36, have allowed the study of predictors and associations of impaired QoL in SLE.⁹ SLE disease activity, as evaluated by various measures, has been assessed in SLE and correlated with QoL. Stoll and colleagues,¹² using the British Isles Lupus Assessment Group (BILAG) disease activity instrument, showed that disease activity was closely and significantly correlated with each domain of the SF-36. In fact, the authors of this study noted that even patients with minimal disease activity had significantly impaired QoL. In another study, Sutcliffe and colleagues,¹³ using the Systemic Lupus Activity measure (SLAM)³² to measure disease activity, showed that a higher SLAM score (i.e., increased disease activity) was an important determinant of health status. Higher disease activity was associated with significantly poorer scores in the SF-36 domains of physical functioning, role limitations (physical), pain, general health, vitality, and social functioning. Fortin and colleagues ³³ evaluated the association of two measures of disease activity, the Systemic Lupus Disease Activity Index (SLEDAI)³⁴ and the SLAM-R, with health status as expressed on the SF-36. The SLAM-R was correlated with several aspects of the SF-36 while the SLEDAI was not. Gladman and colleagues³⁵ have shown a similar lack of correlation between the SLEDAI and the SF-36. These findings suggest that important differences exist between these disease activity indices, possibly related to the SLAM-R capturing more patient-derived information on lupus activity.

Damage

Damage, whether resulting from the disease process itself or as a result of treatment, is recognized as an important outcome in SLE. Studies that have assessed associations between disease damage and QoL have shown that the major effects in health status result from decreases in physical functioning. Fortin and colleagues,³³ in a prospective study of 96 patients, measured disease damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI), and correlated it with QoL assessed using the SF-36. Not surprisingly, as stated by the authors, the SLICC/ACR DI correlated with the SF-36 domain physical function at baseline and with its mean value over time. It appears that permanent damage will continue to interfere with physical performance and functioning, whereas other areas of health status such as emotional well-being and social functioning may, with time, adapt to a physical deficit. Other studies have shown no significant correlation between disease damage and health status. In one longitudinal observational study of 87 SLE patients, Gilboe and colleagues³⁶ showed that the best predictors of SF-36 PCS and MCS scores were the respective baseline scores and no significant relationship was found between SLICC/ACR DI score and health status. Gladman and colleagues,³⁵ in an earlier study, also showed no such correlation.

Psychosocial Aspects

Psychological disorders occur frequently in SLE patients. Up to 40% of patients with SLE have diagnosable psychological disorders, most commonly anxiety disorders and depression.³⁷ The importance of psychological functioning in QoL was underscored in a study by Burckhardt and colleagues²⁷ which showed that psychological distress alone was the best predictor of QoL among patients with SLE. Nevertheless, studies on the prevalence of psychological disorders in SLE and physically healthy controls have shown conflicting results, with one study showing higher rates of psychological disorders among patients than among controls,³⁸ and another showing rates that were similar between patients and controls.³⁹

Psychological functioning appears to worsen with increased disease activity and damage, particularly when the disease causes greater pain, helplessness, and physical disability.^37,40,41 Given the pervasive nature of SLE and its course, its impact on mental health is not surprising. Moreover, poor baseline psychological functioning may, in turn, contribute to worse physiologic outcomes in SLE, as has been seen in a number of other diseases.^42,43 The effect of psychological function on SLE outcomes requires further investigation.

Social support has also been found to be an important determinant of health status. A cross-sectional study by Sutcliffe and colleagues¹³ showed that social support, as measured by the Interpersonal Support Evaluation List (ISEL), was one of the most consistent determinants of health status in their study of 195 patients with SLE. Their study showed that increasing total social support had a positive effect on all of the SF-36 subscales. The authors, therefore, suggest that increasing social support may have the potential to improve overall functioning. A study by Bae and colleagues⁴⁴ also showed that higher social support influenced health status. However, the patients found to benefit most from social support were those who already possessed social, economic, and health advantages: white patients above poverty level who had health insurance and low premorbid disease activity.

Fibromyalgia/Fatigue

Fibromyalgia is a common rheumatologic disorder that is characterized by widespread pain and fatigue, and may be an important potential confounder in measurement of health status. The prevalence of fibromyalgia in the general population is approximately 2%⁴⁵; in SLE it has been reported to be much more common, with estimates as high as 23%.⁴⁶ A recent study of patients with SLE showed a strong association between the number of fibromyalgia tender points and health status as assessed by the HAQ.⁴⁷ They noted that the number of tender points, and not just the absence or presence of fibromyalgia, was associated with health status in SLE. In a cross-sectional study of 119 outpatients with SLE, Gladman and colleagues showed that SF-36 scores reflected the presence of fibromyalgia, rather than disease activity or damage.⁴⁸ Fibromyalgia, therefore, is likely a very important determinant of health status in SLE.

An important and common symptom in SLE is fatigue. One study of fatigue in SLE found that 80% to 90% of patients surveyed reported abnormal fatigue⁴⁹; similar findings have been reported in other studies.⁵⁰ Fatigue is a symptom that may result from many different processes: active lupus, mood disorders, fibromyalgia, and other comorbid illnesses. It is often difficult to determine the etiology of fatigue in any given case and just as difficult to quantify. Nevertheless, there is evidence that conditions commonly co-expressed in SLE, such as fibromyalgia and depression, may be more important in the development of fatigue than active lupus. In one study of 81 patients with SLE, fatigue was found to correlate moderately or strongly with all components of the SF-36; increased fatigue scores were associated with worse SF-36 scores. Fatigue did not correlate with disease activity or disease damage.⁵¹ In another study by Wang and colleagues,⁵² fatigue was found to be highly correlated with the presence of fibromyalgia and depression. There was no correlation between fatigue and disease activity. The authors of this study conclude that fatigue may reflect a decreased overall coping ability in these patients, rather than active disease itself.

Studies of interventions aimed at improving disease activity may not have the desired effect on QoL indices if a significant number of patients have comorbid conditions such as fibromyalgia. Specific assessments for such conditions may need to be included in studies of QoL in order to better help understand the associations between lupus manifestations and health status.