Do functionality, strength, vascularization, inflammatory and biopsychosocial status improve by biopsychosocial model-based exercise in SSc?

Abstract

Objectives

This study aimed to investigation of the effects of the Cognitive Exercise Therapy Approach [Bilişsel Egzersiz Terapi Yaklaşımı (BETY)], a supervised biopsychosocial model-based exercise intervention, on functionality, muscle strength, vascularization, anti-inflammatory and biopsychosocial status in SSc patients.

Methods

Thirty-seven SSc patients were included. Twenty of them were recruited into the study group (SG) undergoing BETY group exercise sessions three times a week for 3 months and seventeen were in the control group (CG) following a home exercise program. Assessment tools were the Modified Rodnan Skin Score (mRSS), Scleroderma HAQ (SHAQ), Modified Hand Mobility in Scleroderma (mHAMIS), Duruoz Hand Index (DHI), Six-Min Walk Test (6-MWT), skeletal muscle strength measurements using an isokinetic dynamometer (Biodex System 3 Pro), Shear Wave Elastography, ELISA kits (for tumour necrosis factor-alpha, Interleukin-6, IL-10, serum irisin level), BETY-Biopsychosocial Questionnaire (BETY-BQ), Hospital Anxiety and Depression Scale (HADS) and Short Form-36 (SF-36).

Results

The SG demonstrated improvements in SHAQ, mHAMIS, 6-MWT, BETY-BQ, HADS and SF-36 values, excluding the DHI scores (P < 0.05). In contrast, CG showed worsening in SHAQ-general scleroderma symptoms and HADS scores compared with SG (P < 0.05). IL-10 and TNF-alpha increased in both groups, also various vascular parameters were significantly different changed in SG than CG (P < 0.05). Muscle strength values improved in the SG but decreased in the CG, however, this was statistically not significant (P > 0.05).

Conclusion

BETY can be recommended as a non-pharmacological approach to the disease management of SSc patients.

Introduction

SSc is a rheumatic connective tissue disease with a broad systemic impact, featuring fibrosis, vascular issues and immunologic abnormalities in the skin and internal organs. SSc is classified as a rare disease and has a high morbidity and mortality rate [1]. The disease has two primary subtypes: diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc), with dcSSc notably demonstrating rapid progression and early organ involvement [2].

In addition to multiple organ involvement, musculoskeletal system involvement is reported with a prevalence of 24–97% in SSc patients. These damages may result from both the inflammatory nature of the disease and the side effects of some medications used [3]. Studies also focus on cytokines like IL-6, IL-10 and TNF-alpha in SSc pathogenesis, emphasizing their roles in pathological processes such as vascular damage, inflammation and fibrosis [4, 5]. This process may result in decreased functional capacity and muscle strength, and increased pain, fatigue and mood disturbances in the patient.

Although increasing studies showing the positive effects of regular physical activity and exercise practices on all these parameters, it has been reported that individuals with SSc have lower physical activity levels than the general population [6]. Considering all these comprehensive potential problems, it is clear that both evaluations and treatments in this disease group may be benefited from a biopsychosocial treatment approach.

According to EULAR recommendations, optimal disease management in SSc requires a combination of pharmacological and non-pharmacological treatments [7]. However, with the COVID-19 pandemic, these recommendations were expanded. They emphasized the importance of telerehabilitation in non-pharmacological approaches such as patient education, exercise practices, self-management strategies and psychosocial interventions. However, in addition to these recommendations, EULAR also mentioned the challenges associated with implementing an exercise approach based on the biopsychosocial model through telerehabilitation [8].

Cognitive Exercise Therapy Approach [Bilişsel Egzersiz Terapi Yaklaşımı (BETY)], an exercise approach based on a biopsychosocial model developed for individuals with rheumatism, has been presented in the literature with its positive effects in clinic-based practice. Previously, the effectiveness of BETY in individuals diagnosed with ankylosing spondylitis was assessed through 3-month follow-ups. The findings revealed improvements in biopsychosocial characteristics alongside anti-inflammatory conditions [9, 10]. Considering the biopsychosocial affected of SSc patients, it was necessary to investigate the potential effects of BETY on this population. However, there has not been any research conducted on SSc patients regarding the use of BETY. This study investigated the effects of BETY on functionality, muscle strength, vascularization, anti-inflammatory and biopsychosocial status in SSc patients.

Methods

Study design

Patients with SSc who attended routine rheumatologist appointments during the study were consecutively included. The study group (SG) comprised city residents, while the control group (CG) included those outside the city. Measurements were conducted initially and after the 3-months later.

Participants

Individuals with diagnosed SSc according to 2013 ACR/EULAR criteria [11], between the ages of 18 and 65 years, who attended the Hacettepe University rheumatology outpatient clinic, and who had no medication changes in the last 3 months were included in the study. Individuals with a severe musculoskeletal disability, pulmonary hypertension, Forced Vital Capacity below 50%, history of active infection, symptomatic cardiac involvement, psychiatric illness, pregnancy, history of active myositis, renal failure and illiteracy were excluded.

Ethical approval

This study was approved by the Non-Interventional Clinical Research Ethics Committee of the Hacettepe University (approval number: GO 19/191). The participants signed informed consent form. This study was registered on ClinicalTrials.gov (NCT number: NCT05453071).

Measurement

Demographic data

Demographic and medical information such as gender, age, height, weight and disease duration were recorded. Individuals were assessed with relevant tests and completed the scales randomized.

Modified Rodnan skin score

The Modified Rodnan skin score (mRSS) assesses skin stiffness in 17 body areas, graded from 0 (normal) to 3 (severe skin thickness). The total score ranges from 0 to 51, indicating increased skin thickness [12].

Functionality

Scleroderma health assessment questionnaire

The scleroderma health assessment questionnaire (SHAQ) was developed by adding five questions to the HAQ about Raynaud’s phenomenon, digital ulcers, gastrointestinal, pulmonary and general scleroderma symptoms. The SHAQ global score is between 0 and 3. A high score shows low functionality [13].

Modified hand mobility in scleroderma

The modified hand mobility in scleroderma (mHAMIS) is a functional test that assesses four specific movements of the hand (finger flexion, finger extension, finger abduction and dorsal extension). Scores range from 0 (normal) to 3 (complete failure) for each movement, with a total score of 0–12 [14].

Duruoz hand index

It was used to assess hand functions. Eighteen items assess dexterity in the kitchen, dressing, maintaining personal hygiene, doing office tasks and other general issues. Each item is scored from 0 (without difficulty) to 5 (impossible). The total score is between 0 and 90 [15].

Six-Min walk test

Patients were instructed to walk as fast as possible in a 30 m-long corridor following American Thoracic Society guidelines [16]. The total distance was recorded in metres.

Muscle Strength

Assessment of muscle strength with Biodex System 3 pro

Muscle strength was assessed using a Biodex System 3 Pro^® isokinetic device (Biodex Medical Systems Inc., Shirley, NY, USA). Before the initial assessment, participants underwent a familiarization session and followed the manufacturer’s recommendations for knee flexion-extension movements. A 10-min warm-up walk preceded each assessment, and participants performed knee flexor and extensor maximal concentric isokinetic muscle strength tests at angular velocities of 180°/s (10 repetitions) and 60°/s (5 repetitions), with a 30-s rest interval. Peak torque (PT) and average power (AP) were recorded in Newton per metre (Nm) and watts (W). Participants received prior instruction in maximal strength training, and verbal encouragement was provided during the tests.

Vascularization

Evaluation of vascular structure

Spectral Doppler ultrasonography (US) and shear wave elastography (SWE) measurements were performed with ultrasound equipment, Siemens Acuson S2000, using a linear probe with 9 MHz frequency (Siemens AG, Erlangen, Germany) [17]. Doppler US measurements were performed on radial and posterior tibial arteries. Resistive index (RI) values (peak systolic velocity—end diastolic velocity/peak systolic velocity) of these vessels were obtained. The average values of three measurements of RI values were determined. SWE measurements were made on bilateral deltoid and rectus femoris muscles. The average of the SWE values of three measurements from the lateral and medial areas of each muscle was obtained. After the patients rested for at least 30 min, SWE values of muscles were obtained while the probe was motionless on the muscles for at least 5 seconds. Since the SWE technique is a method that assumes that the tissues are homogeneous, isotropic and elastic, measurements were made by holding the transducer in a parallel orientation to the muscle fibres to reduce this effect in the anisotropic muscle tissue [18, 19]. SWE values of muscles were obtained as kilopascal (kPa) units.

Anti-inflammatory status

The cytokine profiles were analysed before and after the intervention for the SG and at the initial and final evaluations for the CG. On the clinical interview day, blood was collected via venipuncture, centrifuged at 2000 × g for 10 min, and stored at −80°C until assay. Serum cytokines (TNF-α, IL-6, IL-10) were measured using ELISA kits (DIAsource ImmunoAssays S.A., Belgium), and Serum irisin levels were determined with a human ELISA kit (USCN Life Science, Wuhan, China).

Biopsychosocial status

BETY-Biopsychosocial questionnaire

It assessed the individual’s biopsychosocial status regarding pain, functionality, mood, sociability, sexuality and sleep using a scoring system: ‘0 (never), 1 (yes rarely), 2 (yes sometimes), 3 (yes often), 4 (yes always)’ across 30 items. Total scores range from 0 to 120, with higher scores indicating a poorer biopsychosocial status [20].

Hospital anxiety and depression scale

The hospital anxiety and depression scale (HADS) comprises 14 items, with seven each for anxiety and depression, scored between 0 and 3. Total scores range from 0 to 21, and cut-off values are set at 10 for anxiety and 7 for depression. Higher scores signify elevated anxiety and depression levels [21].

Short form-36

It is a 36-item generic scale that assesses the quality of life with eight parameters [physical functioning (PF), social functioning, role limitations due to physical complaints (PR), role limitations due to emotional problems (ER), mental health (MH), energy-vitality (EV), bodily pain (BP), general health perception (GH)], each scored between 0 and 100. A high score indicates a good quality of life [22].

Intervention

SSc patients in the SG were included in the supervised group exercise therapy based on the biopsychosocial model named BETY. For years, BETY has been applied face-to-face to patients with rheumatism in a clinical setting, under the supervision of a physiotherapist, in the form of individual or group training. During the COVID-19 pandemic, telerehabilitation was implemented, and patients continued their exercise routines in real time under the supervision of a physiotherapist via a WhatsApp group [23].

In this study, patients involved in SG first participated in the clinic for an initial session and went through the BETY stages under the supervision of experts (Supplementary Table S1, available at Rheumatology online). Patient education was provided to the participants under the headings of function-oriented core stabilization exercises, dance therapy-authentic movement, chronic pain management and sexual information management [10]. Then, individualized function-oriented core stabilization exercises were taught to address the patients’ main complaints. In addition, all exercises were given in a brochure to increase patients’ compliance with the BETY sessions they would attend SG (Supplementary Table S2, available at Rheumatology online). After the face-to-face training sessions, patients in SG were added to the existing WhatsApp group and attended 1-h online BETY sessions three times a week for 3 months. Patients in the CG were given only a home exercise program, and the same brochure with exercise visuals was provided to the participants. Participants were asked to perform the given exercises for three months. Patients in both groups continued their pharmacological treatments prescribed by their rheumatologists.

Statistical analysis

The sample size was calculated using G∗Power software (Kiel University, Kiel, Germany) with an effect size (f2 = 1.32) for changes over time, α level of 0.05, and power (1–β) of 0.95 [10, 24]. Sample size calculations revealed that 32 (SG: 16; CG: 16) participants were required. Accounting for potential dropouts, 40 (SG: 20; CG: 20) participants were recruited according to Karaca et al. [10].

Data were analysed using IBM^® SPSS© 23 software. The normal distribution assumption of the variables was determined by Shapiro Wilk test. Descriptive statistics were expressed as mean (s.d.) or median and interquartile range (IQR) for numerical data and number and percentage (%) for categorical data. The χ² Test or Fisher’s exact test was used to determine whether there was a difference in the baseline status of categorical data. Between-group and within-group comparisons for the relationship between normally distributed data were performed by repeated measures analysis of variance (repeated measures ANOVA), and if not normally distributed, by Mann–Whitney U test and Wilcoxon signed ranks test, respectively. Missing values were input with a median value of each variable. The significance level was accepted as P < 0.05 for all analyses.

Results

Demographic and clinical characteristics of the participants

About 49 SSc patients were assessed for eligibility criteria, of which 40 were recruited. Following the research, three patients from the CG were lost to follow-up. The study was completed with 37 diffuse cutaneous SSc patients, 20 (19 women) in SG and 17 (14 women) in CG (Supplementary Fig. S1, available at Rheumatology online). The initial and main disease characteristics of patients in SG and CG were similar (Tables 1–4). All patients had a disease duration of ∼10 years or more. Individuals in both groups showed low disease activity and high depression according to the cut-off values of mRSS and HADS.

In CG, 4 missing values were input in the initial and 1 in the final isokinetic measurement. In SG, 1 missing value was input in the initial blood analysis.

Effectiveness of BETY group sessions

Tables 2–4 displays the initial and 3-month changes in the groups. Within- and between-group improvements were found in BETY-Biopsychosocial questionnaire (BETY-BQ), 6-MWT, and short form-36 (SF-36) parameters (P < 0.05) (Table 2). In Table 3, where mRSS, mHAMIS, Duruoz hand index (DHI), SHAQ, HADS and SF-36 parameters are shown, within and between groups, changes were observed in favour of SG in all values except mRSS and DHI scores (P < 0.05). In addition, general scleroderma symptoms, which are SHAQ parameters, and anxiety and depression scores of HADS were found to worsen in CG (P < 0.05). Table 4 presents isokinetic (Fig. 1), blood (Fig. 2), and ultrasound measurements and indicates no change in IL-6 and irisin (P > 0.05). At the same time, IL-10 and TNF-alpha increased in both groups, RI values of the right and left tibialis posterior arteries were significantly higher in final assessment in SG group while average RI value of the left radial artery was significantly lower in final assessment compared with initial assessment in SG (P < 0.05). Muscle strength values were generally similar, increased in SG but decreased in CG (P > 0.05).

Discussion

This study investigated the effect of BETY, a biopsychosocial-based exercise approach in systemic sclerosis; positive effects on functionality, muscle strength, vascularization, anti-inflammatory and biopsychosocial status were found in SSc patients who participated in BETY group sessions for three months compared with the CG.

A review by Piga et al. it was reported that telemedicine in rheumatological diseases has positive aspects such as high patient satisfaction, time-space independence, and cost savings were reported in rheumatologic diseases compared with face-to-face methods [25]. This study presented BETY as an exercise approach suitable for telerehabilitation in SSc patients.

Kisacik et al. examined the effects of BETY sessions on inflammatory markers in patients with ankylosing spondylitis who did not receive anti-TNF treatment in a 3-month follow-up and revealed anti-inflammatory effects [9]. Karaca et al. reported that BETY sessions started simultaneously with anti-TNF treatment in patients with active ankylosing spondylitis and showed improvement in the participants’ biopsychosocial characteristics and all other measurement parameters of the participants [10]. Thus, BETY was presented in the literature as a biopsychosocial exercise model in rheumatic disease. This study investigated the effectiveness of BETY sessions with patient-reported outcome measures and objective assessments in SSc patients. Our findings, as in these other studies, showed improvements indicating the effectiveness of BETY in many aspects.

The demographic characteristics of the study and CGs were similar. Although the mRSS, reported as the gold standard for evaluating skin involvement reflecting the disease activity of SSc patients [12], showed progressive worsening [26], it did not change between the groups at the end of 3 months compared with the initial values after BETY sessions. However, a decrease in mRSS was observed in the SG, although it was not statistically significant. Additionally, considering the limited information about the reflections of exercise effects on disease activity and progression in SSc patients [27], this study is remarkable in exploring the effects of a 3-month group exercise approach with a biopsychosocial model, especially regarding disease activity.

Functionality

While significant within and between groups improvements were found in SHAQ and mHAMIS scores of SSc patients, this was not reflected in DHI scores, assessing activities of daily living [15], which was attributed to the fact that this score was already good at the beginning. Our SG participating in the BETY sessions showed a significant improvement of 31 m (initial: 420.07 (54.57; final: 451.87 (64.95) in the 6-MWT, and the assessment results were consistent with the findings of Vandecasteele et al. [28]. Unlike the 12-week multidisciplinary team care program compared with outpatient clinic care [29], the improvement in the mHAMIS score at three months is linked to BETY’s chronic pain management strategy of isolated hand-wrist exercises. In addition, the improvement in the SHAQ global score developed to measure disease-specific functionality was remarkable. Our study introduced a biopsychosocial-based exercise approach in SSc, limiting direct comparisons with existing literature.

Muscle strength

Justo et al. [3] found reduced strength and endurance in female SSc patients using the Biodex System 4 Pro dynamometer. Our study, utilizing the Biodex System 3 Pro, revealed significant post-intervention differences in muscle strength compared with the CG. This difference may be due to the emphasis in the SG on function-oriented core stabilization exercises related to the main complaints of the patients and the progression of the exercises over time under the supervision of a physiotherapist. Since we only used strength from isokinetic dynamometer measurement features when evaluating the muscle strength of the SG participating in BETY sessions, we could not examine changes in other parameters reported [30], such as an increase in muscle fibre size, endurance and fatigue resistance, which may be other measurement features. On the other hand, to the best of our knowledge, this is the first study to demonstrate the effectiveness of the exercise approach based on the biopsychosocial model in individuals with SSc using the Biodex System 3 Pro device by showing that muscle strength is preserved. Moreover, our study aligns with the literature linking quadriceps strength to quality of life and physical disability [3].

Vascularization

Our study assessed muscle stiffness and blood flow velocity of SSc patients via SWE; no statistically reflected change in muscle stiffness was observed. BETY uses core stabilization in the basic exercise model to create a base for arm and leg movements. During the movement, exhaling requests transversus abdominis muscle activation in the neutral spine position. Thus, isolated movement aims to create a muscular corset in the core. Therefore, this may explain the sustained effects of SSc patients with proximal and core involvement who have low levels of mRSS at baseline with participation in BETY sessions.

On the other hand, the significant increase in the Resistive Index values of the right and left tibial posterior arteries was interpreted as a result of the closed kinetic functional structuring of the trunk with the upper extremity. However, the differences between these individuals and the SG could not be analysed since ultrasound measurements could not be performed in CG because they were out-of-city patients. This original study that assesses the effect of a biopsychosocial model-based exercise approach in SSc patients. Moreover, SSc patients with changes reflected in muscle stiffness and blood flow velocity increased the value of our study.

Anti-inflammatory status

Our study, evaluating blood analyses in SSc patients, ESR and CRP values decreased in the SG, while IL-10 and TNF-alpha values increased in both groups (Table 4). However, no significant differences between groups were observed in these increased values. The anti-inflammatory role of IL-6 and irisin [31] remained unchanged by exercise in both SSc groups. SSc patients treated with medication did not experience any negative effects from exercise sessions on anti-inflammatory properties. In the study by Kisacik et al. [9] the anti-inflammatory effect seen with BETY in AS patients was similarly interpreted in SSc patients. Our study is the first to assess the effects of a 3-month biopsychosocial-based exercise approach on IL-6, IL-10, TNF-alpha and irisin in individuals with SSc. While not evident in blood analysis, improvements in other measurement tools indicate that BETY sessions may alleviate inflammation-related symptoms. A face-to-face without telerehabilitation BETY study with SSc individuals might further clarify group differences.

Biopsychosocial status

BETY sessions, providing group support and cognitive restructuring statements, contributed to the biopsychosocial improvement in SSc patients. The improvement of anxiety and depression scores in the SG, contrasted with the worsening in the CG, emphasizes the necessity of employing biopsychosocial approaches for patients with SSc. BETY’s positive impact on mood can be attributed to integrating slow and controlled function-oriented core stabilization exercises and breathing control. This combination enhances patients’ physical and cognitive awareness, complemented by group support. Utilizing BETY, a biopsychosocial-based approach, to manage the biopsychosocial status of SSc patients aligns with the literature [32], which reports the need for comprehensive assessments and approaches in rheumatologic rehabilitation.

Strengths and limitations

While SSc is categorized as a rare disease, our study’s strength lies in implementing a controlled examination through group sessions, employing a biopsychosocial model-based exercise approach. Additionally, the uniqueness of BETY lies in its potential to illuminate forthcoming studies, offering a biopsychosocial approach, as it is applied for the first time in SSc patients within this study. Since all of the patients who attended to us when we conducted this study fall under the category of dcSSc, we could not include patients with lcSSc. We recognize this as a limitation, particularly in terms of generalizability. Another limitation in our study is the inability to execute randomization due to the unavailability of out-of-city SSc patients during the measurement and BETY training sessions. Furthermore, the exclusion of participants in the CG from certain comparisons in terms of vascularization occurred because the scheduled appointments for SWE did not align with the control visits of out-of-city participants. This challenge resulted in a limitation for our study, impacting the comprehensive analysis of vascularization in the CG.

In conclusion, this study is original as it is the first to comprehensively assess functionality, muscle strength, vascularization, anti-inflammatory effects and biopsychosocial status together in SSc patients. It also demonstrates the effectiveness of a biopsychosocial model-based exercise approach in improving these parameters. Based on these positive results, BETY, which aligns with EULAR recommendations, can be recommended as a standardized and named biopsychosocial-based exercise approach in the disease management of SSc patients. For future studies exploring nonpharmacological treatments in SSc patients, we suggest that comparing BETY with different biopsychosocial model-based exercise approaches will enhance the efficiency of the research.

Supplementary material

Supplementary material is available at Rheumatology online.

Data availability

The data underlying this article cannot be shared publicly for the privacy of individuals that participated in the study and for ethical reasons. The data will be shared on reasonable request to the corresponding author.

Contribution statement

O.T., EÜ., B.E.A., A.A.T., I.H.Ç., E.K., A.P., F.K., M.R.O., S.K. and A.A. were part of the multidisciplinary expert team. O.T., E.Ü. and A.A. designed the study; A.A. referred patients; O.T., B.E.A., A.A.T. and İ.H.Ç. evaluated the patients and collected data; O.T. and E.K. analysed the data; O.T. and E.Ü. wrote the final manuscript. All authors critically revised and approved the final version of the submitted manuscript.

Funding

This study received support from the Hacettepe University Scientific Research Committee (Project number: H.U.B.A.B. THD-2022–19983). No additional financial support or benefits from commercial sources were involved in the research reported in the manuscript. The authors declare no other financial interests related to the study.

Disclosure statement: The authors have declared no competing interests. The authors declare no conflict of interest and no funding.

Acknowledgement

We express our sincere gratitude to the patients who participated in our study.

References