A Transcultural Perspective of Systemic Lupus Erythematosus–Related Fatigue: Systematic Review and Narrative Synthesis

Background Fatigue is one of the most common symptoms of systemic lupus erythematosus (SLE) worldwide, yet it remains poorly assessed and managed. The lack of universal definition and standard measurement of fatigue may add to the continued limitations in its understanding across cultures. Objective The psycho-sociocultural underpinnings of fatigue are understudied; therefore, in this paper, we conducted a systematic review to understand a transcultural perspective of SLE-related fatigue. Methods Following PRISMA (Preferred Reporting items for Systematic Reviews and Meta-Analysis) systematic review guidelines, we searched CINAHL Complete, Scopus, and PubMed databases for all published articles covered until the search date. Search was expanded using citation and web search. A 3-step process was used to identify articles meeting the inclusion criteria. The results were analyzed using narrative synthesis. Results From a total of 370 (n=364, 98.4% scientific databases; n=6, 1.6% web and citation search) articles searched, 18 (4.9%) studies met the inclusion and exclusion criteria and were included in this review. All (18/18, 100%) studies enrolled primarily female participants, and half (9/18, 50%) had cross-sectional designs. Although race was not reported in all studies, most studies had White racial background as the largest proportion of their samples. A majority (7/18, 39%) of the studies were conducted in the United States. Using a narrative synthesis, the prominent themes drawn based on the domains of the culture care theory (CCT) and the sunrise enabler were as follows: SLE-related fatigue (1) as an integral component of the disease process, (2) as a personal challenge, and (3) as a psychosocial dimension. Conclusions CCT and sunrise enabler by Leininger guided this review. There are still gaps on how other domains of the CCT and sunrise enabler might influence SLE-related fatigue experience, assessment, and evaluation. The findings from this review showed that SLE-related fatigue has disease, personal, and psychosocial components. Thus, a purely subjective assessment of fatigue in SLE and even other conditions may limit a more accurate assessment and management. The inclusion of disease, personal, and psychosocial indicators is warranted and essential. A culturally sensitive and congruent assessment as well as evaluation models and measurement tools should be developed to capture fatigue experiences accurately. In addition, since global migration is inevitable, advancement in symptom management strategies should coincide with the understanding that fatigue has subjective and objective indicators present across cultures.


Introduction
Due to the increase in global migration, health care organizations are caring for more culturally diverse individuals and families. This culturally diverse setup is likewise expanding in the health care workforce, especially in countries recruiting foreign-educated and trained health professionals. These inevitable changes in the current landscape may influence the accurate assessment of symptoms and provision of culturally congruent care, especially in fatigue, which has robust psycho-sociocultural underpinnings but is currently without universal definition or standard of measurement. Given this situation, a better understanding of fatigue across cultures is needed.
Although there is no universal standard measurement of fatigue [1], it can be defined as an overwhelming, uncommon, extreme tiredness [2]. In patients with systemic lupus erythematosus (SLE), fatigue is the most common and most prevalent symptom. Fatigue is present even with mild and inactive cases of SLE disease [3]. Although numerous studies and reviews highlighted SLE-related fatigue as the most burdensome and often the most reported symptom in SLE, it remains poorly assessed and managed across cultures. Since there is no cure for SLE, quality of life may be improved with accurate assessment, evaluation, and management of SLE-related fatigue. SLE-related fatigue is commonly associated with other symptoms that may compound limitations to individuals with SLE. This article aimed to conduct a systematic review to develop a transcultural perspective of SLE-related fatigue.
A transcultural perspective integrates similarities and differences of certain cultures to provide culturally congruent health care [4]. Thus, an integrated transcultural perspective of SLE-related fatigue from empirical studies may facilitate a more accurate and culturally congruent symptom assessment, evaluation, and management. Although fatigue severity can be validly and reliably measured in SLE [5,6], a transcultural perspective provides a better understanding because the social and cultural factors (eg, health beliefs) may also determine the threshold for the symptom's normality and pathology [7], especially when caring for individuals across cultures. The social and cultural structures identified in the culture care theory (CCT) and the sunrise enabler influence health patterns and well-being [8].
This article presents a transcultural (nursing) perspective. This perspective aims to provide culturally congruent care and practice based on the domains of the CCT and sunrise enabler, such as "technology, religion, family and kinship, politics, cultural beliefs and practices, economics, physical conditions, and biological factors" [8].

Search Strategy
A search strategy was developed in consultation with subject matter experts using Medical Subject Headings (MeSH) terms relevant to SLE-associated fatigue and cultural perspectives of fatigue (Textbox 1). We searched for all published articles meeting inclusion criteria in scientific databases such as CINAHL Complete, Scopus, and PubMed until the search date (October 14, 2021). Table 1 presents the search strategy used. We used the same terms in our web search; however, no search terms were used for the citation-based search. Citation-based search means finding articles based on what a related article has referenced. • "systemic lupus erythematosus" OR "lupus erythematosus disseminatus" OR "libman-sacks disease" OR "libman sacks disease" OR "disease, libman-sacks" OR "lupus" AND fatigue OR exhaust* OR tired* OR lethargy OR "muscle weak*" AND cultur* OR transcultur* OR "cross-cultural comparison" OR belief* OR value* OR attitude* • Limiters -Peer Reviewed 174 (47.8) Scopus • "systemic lupus erythematosus" OR "lupus erythematosus disseminatus" OR "libman-sacks disease" OR "libman sacks disease" OR "disease, libman-sacks" OR "lupus" AND fatigue OR exhaust* OR tired* OR lethargy OR "muscle weak*" AND cultur* OR transcultur* OR "cross-cultural comparison" OR belief* OR value* OR attitude*

Inclusion and Exclusion Criteria
Articles were included if (1) they were original peer-reviewed research articles, (2) they were published in English, (3) they focused on patients with SLE, and (4) they mentioned fatigue and its derivative terms in the title or abstract. All research designs were included. Articles were excluded (1) if the articles did not describe a cultural perspective based on the CCT and the sunrise enabler or (2) if the articles were commentary, abstracts, theoretical, quality improvement projects, or literature review articles.

Study Selection
Articles were directly downloaded using the comma-separated values format. The downloaded comma-separated values, which is in Microsoft Excel, assisted the authors with organizing and deduplication. We used a three-step screening process, which is as follows: (1) titles were screened for relevance to the research question; (2) abstracts were then screened to determine further if inclusion criteria were met; and (3) full-text screening was completed on all articles accepted in step 2. Additional articles were also included using web and citation searches. Screenings were conducted independently by JBT and LNS. Disagreements were resolved through discussion. The more senior author (LNS) made the final decision if consensus was not reached. Table 1 presents the search outcome.

Data Abstraction
A data charting form was developed based on PRISMA (Preferred Reporting items for Systematic Reviews and Meta-Analysis) guidelines by JBT and calibrated by both JBT and LNS. JBT extracted the data. LNS performed a quality check on data extraction after data extraction was complete. Based on the extracted information, homogeneity could not be established since the findings were not similar, and therefore meta-analysis or quantitative pooling was not feasible. We did not specify to which domains the findings belong because we maintain that a transcultural perspective is always open to interpretation from various cultures. Thus, by understanding the domains of CCT and the sunrise enabler by Leininger, a transcultural perspective from the findings were extracted.

Quality Appraisal
Quality appraisal was conducted using the Joanna Briggs Institute Critical Appraisal Checklists for Analytical Cross-Sectional Studies [9]. The checklist contains 8 items that assess the risk of bias in studies. The 2 authors independently appraised each article. Disagreements were adjudicated by the more senior author (LNS).

Data Synthesis
We synthesized extracted data using a thematic approach. This type of synthesis is useful when the data are varied and when dealing with abstract findings. Specifically, thematic synthesis involves an iterative review of data to identify patterns or themes. The authors used a narrative approach of thematic type for the following reasons: (1) meta-analysis was not feasible; (2) the main topic dealt with an abstract topic (transcultural perspective); and (3) data extracted from the included studies contained more textual data rather than numerical data.

Study Selection
A total of 364 articles were initially identified. After deduplication of these 364 articles, 290 (79.7%) underwent title and abstract screening; of these, 27 (9.3%) were eligible for full-text screening. In step 3, of the 27 eligible articles, 14 (52%) were excluded ( Figure 1). Moreover, we identified 6 additional articles during the citation and web search; of these 6 articles, 1 (17%) was excluded (Figure 1), resulting in a final sample of 18 articles. *Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). **If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools.
Participants expressed a lack of understanding of their experience of fatigue. However, attendance to the fatigue management program validated through others in the group helped them accept their experience of fatigue. Arising from the literature review, some of the health issues identified were fatigue, energy, or vitality (n=8); depression (n=7); pain (n=4); helplessness (n=4); and the inability to cope with the disease (n=4). Impaired concentration (n=3), impaired worklife (n=3), anxiety or distress (n=3), and impaired or compromised personal relationships (n=2).

Risk of Bias
In the quality appraisal of the studies included, there are apparent differences in the methodological scores of studies. The scores ranged between 2 and 8 points, which is justifiable since the methodologies are incomparable. Thus, we did not set a cut-off score for inclusion in the review. Based on our appraisal, all studies included information on the criteria for sample inclusion. There was an incomplete discussion of the confounding variables and strategies for dealing with them. In the quality appraisal, the authors rated studies that employed qualitative methodology with "Not Applicable (N/A)," which was reasonable because some of the items in the quality appraisal checklist were not applicable for studies that employed a qualitative methodology.

Themes
This section presents the narrative synthesis of themes drawn from the studies included. The themes were extracted based on the patterns from the studies following the domains of the culture care theory.

SLE-Related Fatigue as Integral to the Disease Process
Based on the studies included in this review, SLE-related fatigue showed variation in the nature and severity in the course of the disease [15]. Greater disease damage and disease activity contributed to higher physical fatigue scores [17]. SLE-related fatigue is also considered an unstable yet constant characteristic of SLE. Its impact ranges from work, leisure, occupation [21], emotional and cognitive aspects, activities of daily living, as well as social and family activities [15]. The common factors to increase fatigue were stress, physical activity, joint pain [21], higher levels of helplessness, and abnormal illness-related behaviors, although exercise is associated with lower levels of fatigue [25]. Thus, SLE-related fatigue can be considered integral to the disease process because it is a common and distinct characteristic of the disease affecting daily functioning and activities. The factors influencing SLE-related fatigue as provided in the literature above reflect the biological, kinship, social, and cultural values, as well as belief and lifeway factors in the domains of the CCT and sunrise enabler.

SLE-Related Fatigue as a Personal Challenge
In this review, SLE-related fatigue has been shown to be contributing to the daily challenges of patients with SLE. SLE-related fatigue was considered a controlling factor in the everyday life of women with SLE [24]. It has also been associated with poor Quality of Life (QoL). Patients with SLE had lower 36-Item Short Form Survey (SF-36) scores on all subscales compared with controls [20]. SF-36 is a tool to assess health-related quality of life and is a frequently cited general tool to measure fatigue [28]. In a cross-sectional study, poorer health-related QoL was significantly predicted by higher depressive and fatigue symptoms during the initial visit [10]. SLE-related fatigue, along with pain, influenced the everyday life of patients with SLE [19].
Moreover, SLE-related fatigue is commonly misunderstood, which negatively affects activities of daily living, work, and sexual well-being [27]. Fatigue severity scores were also significantly worse in formal work disability subjects compared with never-disabled subjects [16]. In addition, fatigue and the feeling of being a burden to others had the greatest influence on patients' health-related QoL [23]. Overall, SLE-related fatigue can be considered a personal challenge because it is associated with a reduced health-related quality of life and daily functioning and has contributed to the daily challenges of individuals with SLE. QoL, as the commonly identified findings associated with SLE-related fatigue, may be related to all the domains of the CCT and sunrise enabler since QoL is a holistic aspect that may influence the domains of the CCT and the sunrise enabler.

SLE-Related Fatigue as a Psychosocial Dimension
The psychosocial dimension has influenced SLE-related fatigue's nature and severity levels. Higher levels of social support were associated with lower fatigue levels [25]. Social support from family, friends, and neighbors of individuals with SLE was considered valuable help while managing their fatigue [21]. There was an inverse relationship between perceived social support and fatigue [11]. Attendance to the fatigue management program of individuals with SLE validated their fatigue experience through others in the group. The program provided a statistically significant improvement in the depression and categories of "burden to others" and "fatigue" using the LupusQoL [22]. Fatigue impacted the participants' physical functioning (9/15, 60%); it had emotional (15/15, 100%) and social impacts (14/15, 93%); it had also influenced their work or school-related roles (12/15, 80%) and limited activities of daily living (15/15, 100%), and most of the participants (14/15, 93%) reported that they were unable to perform many activities. In addition, being unable to participate in social events was the most frequently reported social functioning limitation [13]. Focus group findings identified the most frequent health issues such as pain (83%), fatigue (61%), and work or school impairment (48%). On questionnaire responses, the findings were similar. The most common health issue was the inability to perform previous activities (87%), pain (87%), and fatigue (87%) [14].
Stress as a social construct also influenced fatigue levels. Patients were less fatigued when depression and stress were decreased [18]. Some participants associated depression with fatigue [15]. Patients with SLE reported fatigue as the most debilitating symptom, which was being experienced daily (N=121, 79%). They also reported reliance on help from their caregivers and a reduced ability to engage in social activities (N=121, 89%) [23]. Patients with SLE experienced more distress compared with patients with rheumatoid arthritis and healthy controls on all the subscales and in total scores. Patients with SLE had significantly higher Social Withdrawal Subscale scores compared with healthy controls [12]. Results showed that the need for help in relation to tiredness had the highest prevalence (81%) [26]. Strong social support is a significant driver in reducing the severity of SLE-related fatigue, while, on the contrary, stress worsens SLE-related fatigue. The CCT domains and sunrise enabler, which represent the findings in this theme, may be related to kinship, social factors, and economic factors.

Principal Findings
Although SLE-related fatigue is one of the most common symptoms in SLE, there is still an inadequate understanding of it across cultures, which limits providing an accurate assessment, evaluation, and management. Currently, there are no consistent findings on the relationship of SLE-related fatigue and immunologic and inflammatory disease characteristics; however, some psychosocial characteristics are associated with SLE-related fatigue [29]. Following the domains of CCT and the sunrise enabler, this review examined the transcultural perspective of SLE-related fatigue from published empirical studies in identified scientific electronic databases.
The development of the CCT and the sunrise enabler was traced back from Leininger's dissertation in 1970s, which, as she explained, was derived from anthropology. The theory aims to facilitate and explain the interdependence of culture and care by noting differences and similarities across cultures to achieve a culturally congruent care. Along with the theory is the sunrise enabler, which serves to introduce the different aspects of the theory such as the dimensions, facets, and its components [8].
In the theory, cultural and social structures that influence care expression, patterns and practices, as well as holistic health and well-being are as follows: (1) technological factors; (2) religious, spiritual, and philosophical factors; (3) kinship and social factors; (4) cultural beliefs and lifeways; (5) biological factors; (6) political and legal factor; (6) economic factor; and (7) educational factors [8].
The key findings from this review affirm that SLE-related fatigue has underpinnings rooted in (1)  Often, fatigue is understood from biological factors or from a clinical lens; in this review, the clinical attributes of individual with SLE-related fatigue may represent a biological factor. In the CCT and sunrise enabler, biological factors include hereditary, genetic conditions, including those influencing and being influenced by professional and generic care [8].
Fatigue may be associated with disease activity; however, this is not always the case [30]. In a large international observational study with a systematic review of literature, disease activity showed a weak association with fatigue [31]. Hierarchical multiple regression showed that greater disease damage, disease activity, and other factors contributed to higher physical fatigue scores [17]. Although there are a good number of studies separating fatigue and disease activity, a closer assessment and management of fatigue in all cultures or ethnicities are warranted. In fact, in recent updates of the CCT and sunrise enabler, the biological factors covering culture-bound syndromes as well as the role of genetics and heredity were recognized to affect social and cultural factors [8], which may influence how SLE-related fatigue is expressed and managed. The inclusion of biological factors in understanding fatigue supports the idea that even when mood disorders are absent (common associations of fatigue), fatigue still exists in autoimmune and inflammatory diseases, including SLE [32].
The culture, value, belief, and lifeway factors influencing SLE-related fatigue were the QoL and individual functioning, whereas in terms of kinship and social factors, stress and social support should be taken into consideration. QoL, functioning, social support, and stress are intertwined in a social and cultural setting because they exist in the day-to-day living conditions of individuals with SLE. These findings support those of a prior study that there were significant associations among changes in fatigue scores, SF-36 physical subscale, mood, and some domains of LupusQOL [33], which included pain and burden to others [34]. All LupusQoL domains had low scores with fatigue and being a burden to others as the most affected [35].
A seminal Integrated Fatigue Management Model supports the findings of this review. The dimensions of fatigue, such as subjective, physiological, biochemical and metabolic, and behavioral aspects, are surrounded by social factors such as cultural and ethnic practices, significant life event patterns, environmental patterns, psychological, activity and rest, race, and genetic makeup, among others. The surrounding factors are thought to modulate fatigue [2]. The theory of symptom management also supported the multidimensional aspect of symptoms such as fatigue. The interdependent circles of symptom experience, management strategies, and symptom status outcome interact with the 3 domains of nursing, which include the person domain (demographic, psychological, physiological, sociological, and developmental), environment domain (physical, social, and cultural), and health and illness domain (risk factors, health status and disease, and injury) [36]. Finally, in a concept analysis of fatigue, some of the identified critical attributes of fatigue encompassed physical, cognitive, and emotional dimensions; accordingly, fatigue causes distress and chronic or unrelenting symptoms, and it is dependent on the individual's perception [37]. Recent developments in symptom clusters also pointed out that symptoms occurring in clusters have strong psycho-sociocultural underpinnings. The psycho-sociocultural factors may mediate or modulate fatigue symptom severity or intensity. Fatigue commonly co-occurs with other symptoms such as in SLE. Although fatigue remains challenging to conceptualize across cultures, this review highlighted the expanding multidimensionality of SLE-related fatigue.

Limitations
Some of the limitations of this review should be considered. First, a meta-analysis was not feasible due to the variations in methodologies used. With this variation, a narrative summary was deemed more appropriate, and only 3 databases were considered and expanded to citation and web searches. Since only 3 databases were considered, articles from other countries may have been missed. Third, only 1 author (JBT) conducted the synthesis, and it was ascertained by the second author (LNS), which may pose limitations to the breadth of the review. The review may also be limited to the countries where the studies were conducted. For instance, there was no study conducted in an Asian country in this review. An additional limitation of the review may also be pointed to the predominantly female sample and White ethnicity of the study participants enrolled. The name of the research designs was based on what the authors have indicated in their respective articles. Since this review used a thematic approach in presenting the data, this may limit the presentation in terms of the heterogeneity of the studies included. The conclusion may also be biased since the themes were based on a single theoretical framework. There was also an incomplete discussion of the confounding variables in the studies included. Future research or review should also include more male individuals and participants from other racial and ethnic backgrounds and use other theoretical frameworks to comprehensively assess the transcultural aspect of SLE-related fatigue.

Implications and Conclusions
This systematic review, focusing on SLE-related fatigue, draws evidence that SLE-related fatigue experience has both disease-related, personal, and psychosocial components. Applying culture care theory and sunrise enabler by Leininger, there are still gaps in the literature on how technological advances, individuals' religion and philosophy, political climate, economic and educational factors, and the worldviews of particular geographic locations might influence SLE-related fatigue experience across cultures. More culturally congruent fatigue symptom assessment and treatment may also be derived by applying the findings of this review. The CCT and the sunrise enabler may be used in different conditions to capture the holistic components of different aspects of the disease. Cultural and contextual considerations are also warranted to improve the assessment and evaluation of the outcomes of SLE-related fatigue. Pure symptom assessment based on subjective data may narrow the potential or actual factors contributing to SLE-related fatigue. Adding the disease, personal and psychosocial indicators of fatigue should be considered. Future research should be conducted on the following areas: (1) large-scale cross-cultural study focusing on contributing factors for SLE-related fatigue; (2) employment impact of SLE-related fatigue; (3) increasing male participants in empirical studies conducted; and (4) transcultural perspective of fatigue in other conditions.