Quality of life, pain, depression, fatigue and sleep in patients with remission or mild fibromyalgia: a comparison with remission or low disease activity rheumatoid arthritis and healthy controls

Background

Fibromyalgia is a chronic condition marked by widespread pain and various accompanying symptoms. Compared to healthy individuals and other rheumatic disease patients, it leads to more severe symptoms and a lower quality of life. Whether fibromyalgia patients in a mild activity or remission stage still experience core symptoms remains unclear.

Objective

To compare the severity of clinical symptoms and quality of life (QOL) in patients with remission or mild fibromyalgia (RFM) and remission or low disease activity in rheumatoid arthritis (RRA) patients and healthy controls (HCs) to investigate whether fibromyalgia in a stable stage can be disease-free.

Methods

This cross-sectional study evaluated a total of 266 RFM and 252 RRA patients and 50 HCs using Revised Fibromyalgia Impact Questionnaire (FIQR), Widespread Pain Index (WPI), Pain Visual Analogue Scale (VAS), Numerical Rating Scale, Multidimensional Fatigue Inventory (MFI-20), Pittsburgh Sleep Quality Index (PSQI), and Beck Depression Inventory (BDI), and Short Form-36 Health Status Questionnaire (SF-36).

Results

The FIQR total score and pain VAS, MFI, and PSQI scores were higher in RFM and RRA patients compared to HCs (P < 0.001). RFM patients had higher BDI and WPI scores than RRA patients (P < 0.001). The majority of RFM patients (97.4%) had more than two pain sites, with moderate-to-severe pain (78.2%), sleep disorders (85.0%), and depression (53.4%), all of which were significantly higher than those in RRA patients (P < 0.001). RFM patients also had lower scores in SF-36 physical and mental component summaries and subscores for role physical, pain index, general health perception, vitality, and mental health index, but a higher social functioning score than RRA patients (P < 0.001).

Conclusion

Despite being in a mild activity or remission stage, RFM patients experience more severe symptoms and poorer QOL than RRA patients. Therefore, individualized evaluation and intensive management are required.

Trial registration

ClinicalTrials.gov Identifier: NCT02449395, registered on May 20, 2015.

Fibromyalgia syndrome (fibromyalgia) is a chronic condition characterized by widespread pain, tenderness, and other related symptoms, including fatigue, reduced sleep quality, physical impairment, and negative emotions. This significantly impacts the physical and mental well-being and quality of life (QOL) of the affected individuals [1]. The estimated occurrence of fibromyalgia ranges from 0.7% to 9.3%, with a higher prevalence among female patients, resulting in a male-to-female ratio of 1:3 [2]. The diagnostic criteria for fibromyalgia have evolved as understanding of the condition has deepened. In 1990, the American College of Rheumatology (ACR) developed fibromyalgia classification criteria that required generalized pain lasting at least 3 months and tenderness at 11 of 18 specific tender points [3]. In 2010, the criteria were updated to replace tender points with an assessment of the number of painful body parts and the severity of clinical symptoms, along with a self-report questionnaire introduced in 2011 [4]. By 2016, the criteria required pain in at least 4 of 5 body regions, helping distinguish fibromyalgia from localized pain conditions [5]. Currently, the established pathogenesis of fibromyalgia involves the dysfunctional central nervous system and its over excitation, leading to central sensitization resulting in widespread pain and accompanying symptoms [6]. Pain is the primary symptom in fibromyalgia patients and is also an independent risk factor for somatic dysfunction [7]. Furthermore, fatigue, insomnia, and poor mood are common accompanying symptoms of the disease, which significantly affect the daily life and work of patients [8]. Traditional methods of evaluation focus solely on the locomotor system and measures of impairment [7]. However, they are inadequate in capturing the accompanying symptoms of fibromyalgia and cannot provide a comprehensive representation of the overall condition of fibromyalgia and its impact on patients' lives.

Chronic pain is prevalent in rheumatic diseases and affects various aspects, including sleep, somatic functioning, and mood, resulting in overlapping clinical symptoms [9]. This contributes to the high rate of misdiagnosis (13.3%–22.7%) of fibromyalgia. Although fibromyalgia is often misdiagnosed as rheumatoid arthritis (20.6%–22.8%), spondyloarthritis (12.7%–28.1%), and connective tissue diseases (6.3%–26.3%) [10,11,12], fibromyalgia patients experience a lower QOL and present more severe clinical symptoms than patients with other rheumatic diseases, such as rheumatoid arthritis [9]. This phenomenon is attributed to the distinct pathogenesis and treatment approaches between the two disease types. Rheumatoid arthritis (RA) is a prototypical arthritic condition characterized by synovial inflammation, joint pain, swelling, and the possibility of deformation as the primary clinical presentation [13]. With the continuous optimization of the anti-rheumatic drug regimen and introduction of novel biologics, significant progress has been made in treating RA using western medicine. The pain mechanism of fibromyalgia is primarily classified as nociplastic pain [14], linked to central sensitization, which amplifies nociceptive signaling and lowers pain thresholds in the central nervous system. This results in persistent pain and hypersensitivity to touch, pressure, movement, or temperature changes. Previous comparative studies have shown that fibromyalgia patients exhibit more severe and diverse clinical symptoms, along with a lower QOL compared to healthy individuals and patients with heumatoid arthritis, spondyloarthritis, and Sjögren's syndrome [7, 9]. However, it remains unclear whether remission or mild fibromyalgia patients continue to experience the core symptoms.

Therefore, this study aims to compare the severity of clinical symptoms and QOL in patients with remission or mild fibromyalgia (RFM) and remission or low disease activity in rheumatoid arthritis (RRA) patients and healthy controls (HCs) to investigate whether fibromyalgia in a stable stage can be disease-free.

Study design and setting

A cross-sectional survey was conducted to select individuals diagnosed with fibromyalgia and RA who were receiving treatment at the outpatient clinic of the Department of Rheumatology, Guang'anmen Hospital, China Academy of Traditional Chinese Medicine, during the period from October 2018 to December 2021.

Sample size

The G*Power 3.1.7 program calculated the required sample size. Prior studies on clinical symptoms in FMS and RA showed effect sizes (Cohen's d) of 0.35–0.60 [7, 9]. Assuming an effect size of 0.44, with alpha at 0.01 and power at 95%, 224 participants per group were needed. Convenience sampling recruited 266 RFM and 252 RRA patients to improve robustness and generalizability.

Participants

The diagnosis of fibromyalgia was determined using the diagnostic/classification criteria established by the American College of Rheumatology (ACR) in 1990 [3], 2011 [4], and 2016 [5]. In patients with secondary fibromyalgia, the severity of the primary condition may directly impact the fibromyalgia symptoms [15]. So this study excluded patients with secondary fibromyalgia to ensure the homogeneity of the study population and reduce the impact of confounding factors. The activity of fibromyalgia was assessed using the Revised Fibromyalgia Impact Questionnaire (FIQR), with remission defined as a total FIQR score of ≤ 30, and mild severity defined as an FIQR total score of ≤ 45. RA diagnosis was made using the ACR 2010 classification criteria [16]. All RA patients were also evaluated using the fibromyalgia ACR 1990, 2011, and 2016 diagnostic criteria, and cases with concomitant fibromyalgia were excluded. The activity of RA was evaluated using the recognized disease activity score-28 (DAS28) assessment tool, with remission defined as DAS28-CRP of ≤ 2.6 and low disease activity defined as DAS28-CRP of ≤ 3.2. Simultaneously, 50 age- and sex-matched healthy volunteers were recruited from our medical examination center to participate in the survey. All participants provided informed consent and received instructions from a trained physician during the questionnaire completion process. The study adhered to the Declaration of Helsinki and was reviewed by the Clinical Research Ethics Committee of Guang'anmen Hospital, China Academy of Traditional Chinese Medicine (No. 2018–059-KY).

Variables and study procedure

A semi-structured interview design was used. First, the participants were informed of the purpose of the study, after which they underwent an examination of tender point count (TPC), recorded in all groups by trained physicians [3]. Finally, the participants were asked to complete a comprehensive package of questionnaires in two parts. The first part included the participants' demographic data, such as age, sex, weight, height, marital status, employment, education, and household income. The second part focused on disease variables, including the duration of fibromyalgia symptoms, severity of key symptoms assessed through questionnaires, QOL, and overall impact of fibromyalgia.

Measurement

Pain evaluation: 1) Severity of pain: The pain Visual Analog Scale (VAS) and the Numerical Rating Scale (NRS) were used to evaluate the average pain level experienced by patients in the past week. The pain VAS score ranges from 0 to 10, with higher scores indicating more severe pain [17]. The NRS employs a 0–10 point scale, with 0 indicating no pain, 1–3 indicating mild pain, 4–6 indicating moderate pain, 7–9 indicating severe pain, and 10 indicating intolerable pain [18]. 2) Range of pain: The widespread pain index (WPI) measures pain or tenderness in 19 different body parts (from the chin to the leg) over a period of 7 days preceding the assessment, with scores ranging from 0 to 19 [4].

Fatigue evaluation: The multidimensional fatigue inventory (MFI) was employed to determine the fatigue status of patients over the past week. The MFI comprises 20 items, each scored on a 5-point Likert scale, with a total score ranging from 20 to 100 points. A higher score indicates more severe fatigue [19]. This scale has been locally validated in China [20].

Sleep quality evaluation: The Pittsburgh sleep quality index (PSQI) was used to assess sleep quality over the previous month, with scores ranging from 0 to 21 points. A cutoff point of 7 is used, with scores exceeding 7 indicating the presence of sleep disorders and higher scores suggesting poorer sleep quality [21]. The Chinese version of the PSQI demonstrated good internal consistency, test–retest reliability, and high conceptual validity in 1996 [22].

Depression evaluation: The Beck Depression Inventory (BDI) was used to evaluate depression. This inventory consists of 13 items, with a score range of 0–39 points. Scores between 0 and 4 represent the absence of depression, while scores between 5 and 39 indicate the presence of depression [23]. The reliability and effectiveness of the Chinese version of the BDI were confirmed in 2011 [24].

Overall fibromyalgia impact evaluation: The overall impact of fibromyalgia was assessed using the revised fibromyalgia impact questionnaire (FIQR). The questionnaire includes 21 items, with a score range of 0–100 points. Higher scores indicate a greater severity of fibromyalgia-related symptoms and their impact on daily life. The cutoff scores are as follows: 0–30 for remission, 31–45 for mild severity, 46–65 for moderate severity, and 65–100 for high severity [25]. The reliability and effectiveness of the Chinese version of the FIQR have been verified [26].

QOL evaluation: The QOL was evaluated using the Short Form-36 Health Status Questionnaire (SF-36). The SF-36 assesses eight domains of health-related QOL, namely, physical functioning, role physical, pain index, general health perception, vitality, social functioning, role emotional, and mental health index. Two summary measures—the physical component summary (PCS) and mental component summary (MCS)—are derived from distinct component scores. All dimensions range from 0 to 100, with higher scores indicating better health-related QOL [27]. The Chinese version of the SF-36 was tested and validated in 2002 [28].

Statistical methods

Statistical analysis was conducted using SPSS 25 software (IBM Corporation, Armonk, New York, USA). Measurements are presented as mean and standard deviation (SD) if they followed a normal distribution, and as median and quartile deviation (IQR) if they did not. The RFM, RRA, and HC groups were compared using the one-way analysis of variance (ANOVA) test for homogeneous variances and least-significant difference (LSD) test for two-way comparisons. For non-homogeneous variances, the Welch test was employed for two-way comparisons. The progression of RFM and RRA was compared using Tambane's T2 test and Mann–Whitney U rank sum test, respectively. Count data were expressed as percentages, and comparisons among the three groups were conducted using either the χ² test or Fisher's exact probability method. A p-value of < 0.05 was considered to indicate a statistically significant difference.

A total of 450 patients diagnosed with fibromyalgia participated in the survey, with 266 (59.1%) identified as RFM patients. Additionally, 252 were RRA patients and 50 were healthy individuals. Among the 266 RFM patients, 126 (47.4%) met the ACR criteria for all three diagnostic classifications: 1990, 2011, and 2016. Forty-seven patients (17.7%) fulfilled the diagnostic criteria for ACR 1990 and 2011, while 53 met the criteria for 2011 and 2016 (19.9%). Twenty-two patients (8.3%) were classified using only the ACR 1990 criteria, while 14 (5.2%) met only the 2011 diagnostic criteria. Finally, four patients (1.5%) met only the 2016 diagnostic criteria.

Comparison of demographic indicators of RFM, RRA and HC

Table 1 demonstrates that there were no statistically significant differences among the three groups in terms of age, sex, and other demographic indicators. RFM patients had a median disease duration of 24 months (P25/P75: 6.0/60.0), which was significantly shorter than that of RRA patients (48 months; P25/P75: 12/144.0, P < 0.001). TPC was significantly higher in RFM patients than in RRA patients and HCs (P < 0.001).

Comparison of fibromyalgia core symptom severity among RFM and RRA patients and HCs

Table 2 presents the impact of fibromyalgia symptoms on pain range and severity, fatigue, depression, and sleep quality. Table 3 illustrates the comparison of symptom severity. RFM patients exhibited more severe pain than HCs and RRA patients (P < 0.001), with 78.2% of RFM patients experiencing moderate-to-severe pain, in contrast to only 30.2% of RRA patients (76/252) and 2% of HCs. None of the HCs reported severe pain. Moreover, 85% (226/266) of RFM patients experienced sleep disorders, and 53.4% (142/266) had depression, both significantly higher than in RRA patients and HCs (P < 0.001). RFM patients also scored higher on sleep, fatigue, and depression scales (P < 0.001), indicating poorer sleep quality and more severe depression and fatigue levels (P < 0.001). In contrast, RRA patients demonstrated more severe symptoms in the aforementioned areas than HCs (P < 0.001).

Comparison of QOL

Comparison of the QOL among the three groups is given in Table 4. The MCS and PCS total scores, along with the scores of all dimensions except social functioning, were significantly lower in the SF-36 of RFM patients than in HCs (P ≤ 0.01). Additionally, the scores of these dimensions were significantly lower in RRA patients, indicating that both the physical and mental QOL were significantly impaired in RFM and RRA patients (P ≤ 0.01). Furthermore, the social functioning scores of the SF-36 in RFM patients were notably higher than those in RRA patients. However, the total scores of MCS and PCS, as well as the scores of the dimensions of role physical, pain index, general health perception, vitality, and mental health index, were significantly more impaired (P < 0.001) in RFM patients.

This study reveals that RFM patients continued to experience more significant pain, fatigue, sleep disturbances, and depression and had 6.4 times more painful sites and a higher proportion of patients experiencing moderate-to-severe pain (78.2% vs. 30.2%), sleep disturbances (85% vs. 59.5%), and depressed mood (53.4% vs. 23.4%) than RRA patients. These findings suggest that achieving overall remission or disease relief does not necessarily entail the elimination or relief of common fibromyalgia symptoms simultaneously. Individualized assessment of these common symptoms, along with intensive management and treatment, is still crucial. Additionally, there is a need to re-evaluate the validated severity cutoffs of the FIQR scale or develop tools that more accurately reflect the severity of fibromyalgia.

The results of this study suggest that RFM patients continued to exhibit numerous tender points, a wide range of pain, and more severe pain. Compared with RRA patients, this is attributed to several factors; first, RFM patients demonstrated a greater number of tender points and higher WPI scores, likely due to lower pain thresholds caused by central sensitization in fibromyalgia, resulting in reduced tolerance to tenderness [29]. Second, RFM patients experienced more severe somatic pain, which aligns with the findings of scholars from Italy and Turkey who studied the overall patient population [30, 31]. Scholars such as Piarulli from Italy [30] discovered that the pain level evaluated by the pain VAS, with a score of 4.2, was higher in fibromyalgia patients than in RA patients with a score of 3.5. Similarly, Turkish scholars such as Tander [31] found that fibromyalgia patients (average FIQ: 51.7) reported more pain (pain VAS: fibromyalgia 7.1 vs. RA 4.8) than RA patients (average DAS-28: 4.3).

Furthermore, the results of this study indicate that fatigue, sleep disturbances, and depressed moods remained more severe in RFM patients. Fatigue, a common symptom of chronic pain disorders, demonstrated a significant positive correlation with the degree of pain [32]. As suggested by Zautra [32] and other scholars, a decrease in positive affect also amplifies fatigue, which reflects the negative impact of depressed mood on the experience of fatigue among patients with fibromyalgia in this study. Additionally, a significant bidirectional causal relationship exists between pain and depression in fibromyalgia patients, with pain exacerbating the level of depression and negative emotions such as depression intensifying the experienced pain among patients [33, 34]. Moreover, the absence of specific laboratory diagnostic indicators for fibromyalgia leads to common instances of underdiagnosis or misdiagnosis [35], consequently delaying treatment and potentially exacerbating the psychological burden on patients, which may lead to lower mood, depression, and anxiety [36]. Regarding sleep, Ulus et al. [37] confirmed that sleep disturbances in fibromyalgia were associated with pain, fatigue, depression, and disease activity. However, unlike the findings of the present study, the sleep quality of fibromyalgia (average FIQ: 61.0) and RA patients (average DAS-28: 4.0) in their study was comparable (average PSQI total score: fibromyalgia 9.7 vs. RA 9.5). This discrepancy may be attributed to the more severe pain levels observed in both groups in that study (average pain VAS: fibromyalgia 8.0 vs. RA 6.6) than in our study, where all RA patients were in mild disease activity or clinical remission, unlike the majority of RA patients in that study who were in moderate disease activity [37].

This study also discovered that RFM patients continued to experience a lower level of QOL, with a more pronounced decline in physical health (average SF-36 PCS: 44.5) than in mental health (average SF-36 MCS: 55.1). Notably, limitations in somatic functions due to impaired physiological health (SF-36 role physical subscale: fibromyalgia 25.3 vs. RA 45.2) and lack of energy (SF-36 vitality subscale: fibromyalgia 46.6 vs. RA 79.6) were the most significantly impaired in RRA patients. These findings are consistent with previous findings indicating poorer physical roles in fibromyalgia patients (SF-36 role physical subscale: fibromyalgia 19.2 vs. RA 47.5), but contradict the findings regarding comparable energy levels (SF-36 vitality subscale: fibromyalgia 46.8 vs. RA 53.5), which were based on the comparison of a moderate severity fibromyalgia group (average FIQ: 51.7) and a moderate activity RA control group (average DAS-28: 4.3) [31]. Conversely, contrasting results were found by Salaffi et al. [7], who discovered that the mental health of fibromyalgia patients declined more significantly than that of RA patients (SF-36 MCS: fibromyalgia 32.8 vs. RA 40.2), while the physical health of RA patients declined more significantly than that of fibromyalgia patients (SF-36 PSC: fibromyalgia 38.6 vs. RA 33.5). The application of different fibromyalgia diagnostic/classification criteria in this study may have contributed to these different findings. Previous studies have shown that the patient populations covered by the fibromyalgia ACR 1990, 2011, and 2016 classification criteria differ from each other [38, 39]. To maximize the inclusion of fibromyalgia patient groups with different characteristics, this study chose to use all three criteria simultaneously. In contrast to Salaffi et al., who used only the ACR 1990 criteria, this study also included 26.7% (71/266) of fibromyalgia patients who met only the ACR 2011 and/or 2016 criteria, potentially impacting the assessment results of fatigue, insomnia, mood, etc., in fibromyalgia patients, thereby affecting the evaluation of physiological well-being. Similarly, findings from surveys of fibromyalgia patients who met both 1990 and 2011 ACR criteria, as conducted by scholars such as Carmen [40], revealed lower levels of physiological well-being in fibromyalgia patients than in RA patients.

The core symptoms of fibromyalgia, including pain, fatigue, insomnia, and negative mood, can significantly impact the QOL for individuals with this condition. Previous research has demonstrated a significant negative correlation between pain levels and both the SF-36 role physical and vitality dimensions [31], indicating that higher pain levels correspond to lower scores in the SF-36 role physical and vitality dimensions. Galvez-Sánchez et al. [41] have similarly found that elevated depression levels contribute to decreased physical health among fibromyalgia patients, leading to increased levels of disability. Carmen et al. [40] also identified that depression and fatigue serve as the primary predictors of QOL, with depressed mood substantially reducing the physical and mental well-being of fibromyalgia patients, and fatigue exerting an even greater impact on physical health. Moreover, this study observed that the level of the SF-36 subscale social functioning score was lower in RRA patients than in RFM patients. This discrepancy may be attributed to the fact that disability also affects the social activities of RA patients with their families, friends, and neighbors.

Several reasons could account for the more severe core clinical manifestations and lower QOL among RFM patients. First, distinct pathogenic mechanisms may lead to differences in clinical symptoms. RA, as a chronic autoimmune arthritic disease, represents peripheral pain, with its pathogenesis involving various immune cells such as T-cells, primarily characterized by inflammation of the synovial tissue in the joints. On the other hand, fibromyalgia represents a chronic central sensitizing pain disorder, and its pathogenesis is widely accepted to involve abnormal central nervous system functioning, resulting in heightened generalized pain sensitivity manifested by diffuse nociceptive sensitization (increased pain from normal painful stimuli) and ectopic nociceptive sensitization (pain from normal nonpainful stimuli), as well as symptoms such as fatigue, sleep disturbances, reduced somatic functioning, and negative mood [42]. Second, a lower pain threshold in patients with fibromyalgia leads to a lower QOL score. Furthermore, the widespread pain characteristic of this disease significantly impacts daily activities and societal participation [43]. Third, there are mutual adverse effects between symptoms that further diminish QOL. The relationship between pain and sleep disorders is reciprocal, with sleep deprivation indicating increased pain intensity, while heightened pain indicates poorer sleep quality. Fatigue shows a positive correlation with pain, sleep disturbances, and depression and a negative correlation with positive mood. Additionally, depressive symptoms have the potential to influence all the core symptoms of fibromyalgia, including pain, fatigue, sleep quality, and overall symptom severity [44].

In this study, the FIQR scale served as an assessment tool to evaluate and categorize the overall condition and degree of fibromyalgia in patients, demonstrating its superior specificity for fibromyalgia. However, despite the classification of patients as RFM according to the FIQR scale, they continued to experience symptoms such as pain, depression, and sleep disturbances, significantly impacting their QOL. This suggests that the cutoffs proposed by the FIQR do not correspond directly to the severity of a specific symptom in a patient, warranting further exploration of methodologies utilizing the current cutoff points of the FIQR scale for classifying the condition severity of fibromyalgia. The FIQR scale is specially designed to assess the severity of symptoms associated with fibromyalgia and their overall impact on a patient's life. Designed to evaluate the severity of symptoms associated with fibromyalgia and the overall impact on life, the FIQR scale is the most widely used disease-specific questionnaire for evaluating the health status of patients with fibromyalgia [45]. It has been utilized in studies such as Giorgi's prospective study [46], encompassing patients undergoing stable (≥ 3 months) standard analgesic treatment and medical cannabis treatment, where no patient achieved a FIQR score of ≤ 30 even after 6 months of treatment. Furthermore, Salaffi et al. [47] attempted to redefine the FIQR cutoff points through a multicenter cohort study involving 2339 fibromyalgia patients (remission: ≤ 23; mild: > 23 and ≤ 40; moderate: > 40 and ≤ 63; severe: > 63 and ≤ 82; very severe: > 82). This study also reveals that even under the conduction of existing guidelines [48], patients with fibromyalgia in remission or classified as having mild symptoms based on the FIQR still experience significant disease burden. Notably, 78.2% reported moderate-to-severe pain, alongside poor physical and mental health, highlighting the limitations and inadequacies of current treatment approaches. In summary, the current cutoff points of the FIQR scale are insufficiently sensitive for comprehensive assessment of fibromyalgia severity and evaluation of treatment effectiveness.

This study has some limitations. First, the questionnaires were completed by patients during their clinic visits, and the noisy outpatient clinic environment in China may have heightened patients' psychological pressure, impacting their concentration during the questionnaire completion process. Second, patient participation in this study was voluntary, resulting in incomplete data from some participants. Finally, being a single-center, cross-sectional study, the results may not be fully representative, necessitating validation through similar multicenter studies in the future.

In conclusion, despite sharing a state of low disease activity or remission, fibromyalgia patients experience more severe pain, exacerbated core symptoms, and a diminished QOL than RA patients. Therefore, clinical treatment should involve targeted evaluation and active management of the core symptoms in fibromyalgia patients to enhance their overall well-being and QOL. Moreover, the FIQR scale may not comprehensively and accurately evaluate the disease status of patients, suggesting the necessity of redefining more sensitive cutoff points for the comprehensive assessment of fibromyalgia severity or the development of new assessment tools or methods.

Despite being in a mild activity or remission stage, RFM patients experience more severe symptoms and poorer QOL than RRA patients. Therefore, individualized evaluation and intensive management are required.

The data that support the findings of this study are available from the Ethical Committees of Guang’anmen Hospital and the corresponding author on reasonable request.

ACR:

American College of Rheumatology

ANOVA:

Analysis of variance

BDI:

Beck Depression Inventory

HC:

Healthy controls

LSD:

Least-significant difference

MCS:

Mental component summary

MFI:

Multidimensional Fatigue Inventory

NRS:

Numerical Rating Scale

PCS:

Physical component summary

PSQI:

Pittsburgh Sleep Quality Index

QOL:

Quality of life

RA:

Rheumatoid arthritis

SD:

Standard deviation

TPC:

Tender point count

VAS:

Visual Analogue Scale

WPI:

Widespread Pain Index

Not applicable.

Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences (CI2021B007).

1. Yidan Wang and Pengxiao Liu contributed equally to this work.

Authors and Affiliations

1. Rheumatology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, 5 Beixiange Street, Xicheng District, Beijing, China

   Yidan Wang, Zihao Li, Shiya Wu, Meijuan Long, Yang Li & Juan Jiao

2. Rheumatology Department, Guang’anmen Hospital Baoding, China Academy of Chinese Medical Sciences, Hebei, China

   Pengxiao Liu

3. Geriatrics Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, 5 Beixiange Street, Xicheng District, Beijing, China

   Zheng Xie

Contributions

Y.W., Z.L., S.W., M.L., and Y.L. participated in the investigation work. Y.W. and P.L. conducted formal analysis and wrote the original draft, with P.L. also responsible for validation. Z.X. was responsible for data curation and methodology. J.J. handled conceptualization, methodology, validation, resources, writing the original draft, review, editing, supervision, and project administration. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Juan Jiao or Zheng Xie.

Ethics approval and consent to participate

This study was reviewed and approved by the Clinical Research Ethics Committee of Guang'anmen Hospital, China Academy of Traditional Chinese Medicine under reference number No. 2018–059-KY. All participants provided informed consent prior to their inclusion in the study. Participants were informed of the study's objectives, procedures, potential risks, and their right to withdraw at any point without any repercussions. Moreover, the researchers adhered to the Declaration of Helsinki of 2008.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

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