
==== Front
Rheumatol Adv Pract
Rheumatol Adv Pract
rheumap
Rheumatology Advances in Practice
2514-1775
Oxford University Press

10.1093/rap/rkae107
rkae107
Systematic Review and Meta-Analysis
Clinical Science
AcademicSubjects/MED00010
High-quality research on physical therapy in psoriatic arthritis is needed: a systematic review
https://orcid.org/0000-0002-7149-9852
Kaerts Marlies Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium

https://orcid.org/0000-0002-5289-1023
Swinnen Thijs W Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium
Department of Rehabilitation Sciences, Research Group for Musculoskeletal Rehabilitation, KU Leuven, Leuven, Belgium
Division of Rheumatology, University Hospitals Leuven, Leuven, Belgium

https://orcid.org/0000-0001-6616-9341
Dankaerts Wim Department of Rehabilitation Sciences, Research Group for Musculoskeletal Rehabilitation, KU Leuven, Leuven, Belgium

https://orcid.org/0000-0003-3848-5122
de Vlam Kurt Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium
Division of Rheumatology, University Hospitals Leuven, Leuven, Belgium

https://orcid.org/0000-0001-9220-9466
Neerinckx Barbara Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium
Division of Rheumatology, University Hospitals Leuven, Leuven, Belgium

Correspondence to: Marlies Kaerts, Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Herestraat 49 3000 Leuven, Belgium. E-mail: marlies.kaerts@kuleuven.be
M.K. and T.W.S. shared first authorship.

2024
27 8 2024
27 8 2024
8 3 rkae10725 4 2024
22 8 2024
06 9 2024
© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Abstract

Objectives

Although physical therapy is recommended as part of the non-pharmacological management of patients with psoriatic arthritis (PsA), the evidence is still unclear. Therefore, this study aimed to systematically review and appraise the quality of research on physical therapy in the management of patients with PsA.

Methods

In June 2024, a systematic literature search using four different databases (Medline, Embase, Web of Science and the Cochrane Library) was performed to include interventional and observational studies examining physical therapy in patients with PsA (PROSPERO ID 255501). A risk of bias assessment was conducted. Due to the wide variety of interventions and outcomes, a narrative synthesis was used.

Results

Of 9442 abstracts, 15 papers examining physical therapy uptake in clinical practice (N = 2) and different physical therapy interventions (N = 13) were included: cardiorespiratory exercises (N = 5), resistance exercises (N = 2), therapeutic modalities (N = 4) and mixed rehabilitation programs (N = 2). A low risk of bias was scored in only one RCT assessing cardiorespiratory exercises. The well-tolerated 11-week high-intensity interval training resulted in a long-term increase in peak oxygen uptake and a short-term decrease in truncal fat percentage in patients with low disease activity. Resistance training in patients with active disease did not increase muscle strength, but improved functional capacity, disease activity, pain and general health after the intervention. Evidence for other modalities was inconclusive.

Conclusion

High-quality evidence on physical therapy in PsA was scarce. Cardiorespiratory and resistance exercises demonstrated promising results to positively influence cardiometabolic risk as well as disease-related outcomes. Future research on physical therapy in PsA with adequate methodological quality is needed.

physical therapy
psoriatic arthritis
PsA
systematic review
rehabilitation
spondyloarthropathies
non-pharmacological management
comorbidity
Fonds voor Wetenschappelijk ReumaOnderzoek/Fonds pour la Recherche Scientifique en Rhumatologie
==== Body
pmcKey messages High-quality evidence on physical therapy in patients with psoriatic arthritis is scarce.

Cardiorespiratory and resistance exercises demonstrate promising results in patients with psoriatic arthritis.

More research, with adequate methodology quality, on physical therapy in the management of psoriatic arthritis is needed.

Introduction

PsA is a heterogeneous chronic inflammatory joint disease affecting 20% of the patients with psoriasis [1–3]. It is characterized by inflammation in the synovium and enthesis as well as skeletal structural damage. PsA presenting symptoms are pain and stiffness often leading to loss of functioning and fatigue [1, 2]. The last decades, there is more insight in the high comorbidity burden including cardiometabolic risk factors and diseases as well as psychological comorbidities [4–7]. Moreover, cardiometabolic risk factors are impacting disease management, worsening the patients’ clinical status and might be associated with the onset of PsA [8–17]. Together, PsA with its associated conditions is negatively influencing health-related quality of life [11, 18, 19].

PsA management consists of both a pharmacological and non-pharmacological approach. For longtime, most attention and importance were given to research on pharmacological treatment options for PsA resulting in multiple new pharmacological options nowadays. In contrast, only limited research is focusing on non-pharmacological aspects such as regular exercise and physical therapy, despite the fact that these treatment options are largely recommended by leading professional societies in rheumatology (e.g. EULAR, Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and ACR) [13–15]. The World Confederation for Physical Therapy defines physical therapy as follows ‘services provided by physical therapists to develop, maintain and restore maximum movement and functional ability throughout the lifespan’ [20]. In addition, scientific cardiology societies from all over the world are highlighting the importance of a non-pharmacological approach to tackle cardiometabolic risk factors in the general population [21, 22]. Education, regular physical activity, smoking cessation, a healthy diet, mental healthcare and bodyweight management are crucial to lower cardiometabolic risk [21, 22].

At present, recommendations for the non-pharmacological management of rheumatic and musculoskeletal diseases (RMDs) are limited to management principles and the evidence base for physical therapy treatment in PsA is unclear [13–15, 23–29]. Hence, a summary of the available evidence on physical therapy in the management of patients with PsA is needed. Therefore, this study aims to systematically review and appraise the quality of research on physical therapy in patients with PsA.

Methods

This systematic review was conducted in accordance with the methods of the Cochrane Handbook for Systematic Reviews of Interventions where appropriate and was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist [30–32]. The protocol was prospectively registered at the PROSPERO database (ID 255501).

Eligibility criteria

Papers examining physical therapy (according to the definition of the World Confederation for Physical Therapy) in patients with PsA with a minimum age of 18 years were included [20]. Diagnosis of PsA was mandatory confirmed by a physician or by classification criteria. All eligible quantitative studies, interventional and observational, with a full-text paper written in English or Dutch were included without restrictions regarding the publication year. The outcomes of interest were disease activity, physical fitness, pain, function, symptoms, physical activity and quality of life.

Search strategy and study selection

A systematic literature search was performed from inception to June 2024 using four different electronic databases: Medline, Embase, Web of Science and the Cochrane Library. A search string was developed using Mesh Terms for PubMed and Cochrane and Emtree terms for Embase completed with free-text entries. ‘Psoriatic arthritis’ and synonyms were combined with ‘physical therapy’ OR ‘physical activity’ OR ‘physical fitness’ supplemented with related topics of these concepts. The PICO search strategy and full search string are available in Supplementary Data S3, available at Rheumatology Advances in Practice online. During the search, no filters or limits were used to make sure no eligible titles were left out.

The search results of the four online databases were imported in biographic software (EndNote 20, Clarivate, UK), where a deduplication process was performed. After deduplication, the eligible papers were exported to Rayyan QCRI, an online collaborative tool to review papers [33]. First, title and abstract were screened for eligibility by two blinded reviewers (M.K. and T.W.S.). Conflicts were discussed until consensus was reached and involvement of a third rater was not needed. Thereafter, a full-text analysis was performed by two reviewers (M.K. and T.W.S.). Additional eligible studies were added from screening references of screened articles.

Due to the extensiveness of the search, the research group decided to report only studies discussing a physical therapy approach in PsA in this review article. The other topics, physical activity and fitness in PsA, will be reported in a separate review article to allow sufficient in-depth discussions of all three topics.

Risk of bias assessment

Risk of bias of the quantitative studies was independently assessed by reviewers (M.K. and T.W.S.). The Revised Cochrane risk-of-bias tool for randomized trials (RoB2) was used to appraise the quality of randomized controlled trials (RCTs) [34]. The Newcastle-Ottawa Scale (NOS) was used to assess risk of bias in cross-sectional studies [35]. There is no exact cut-off to determine whether a study is of low or high quality, as all items of the NOS are weighted the same. However, a study with a score of seven or more is generally considered to have low risk of bias [36]. For single-group intervention studies, the NOS was supplemented by a modified RoB2 consisting of domain two and the first question of domain four.

Data extraction and synthesis methods

Data of the included articles were extracted into a spreadsheet (Excel version, Microsoft, USA) by two reviewers (M.K. and T.W.S.). The following parameters were gathered in the table: study characteristics (author, publication year, study design, and risk of bias (RoB)), the intervention, patient characteristics (recruitment method, diagnostic criteria, number of patients, age, proportion of female patients, disease activity and disease duration), outcome parameters and effect of the studied intervention on these parameters (disease activity, physical fitness, pain, function, symptoms, physical activity and quality of life).

A meta-analysis was not possible due to the wide variety of interventions and outcomes. Therefore, a narrative synthesis was performed according to the following topics: physical therapy interventions (cardiorespiratory exercises, resistance exercises, physiotherapeutic modalities and mixed rehabilitation programs) and physical therapy uptake in clinical practice. Due to extensiveness of data, for RCTs, only significant between-group statistics were presented in the table. For single-group intervention studies, significant within-group statistics were extracted into the table. For cross-sectional studies, the descriptive statistics presenting physical therapy uptake in clinical practice were collected in the table. Overall, quantitative data were presented as mean (standard deviation), except when specifically indicated as mean (95% confidence interval) or median (interquartile range). In the main text, significant quantitative data of the primary study outcome(s), if specified, were described. Significant quantitative data of secondary outcome measures were presented in the table in Supplementary Data S1, available at Rheumatology Advances in Practice online.

Results

Study selection

The systematic literature search resulted in 12 472 records (Fig. 1). After deduplication, a total of 9442 abstracts were retrieved, of which 511 abstracts were selected for full-text analysis. Ultimately, 59 papers published between 1994 and 2024 were identified, of which four papers were added from screening references. Fifteen papers discussing physical therapy as part of the management of PsA were included in this review.

Figure 1. PRISMA flow diagram of the study selection process

Study characteristics and risk of bias assessment

A summary of study characteristics and findings is presented in Table 1 and a complete data overview of the individual studies is available in Supplementary Data S1, available at Rheumatology Advances in Practice online. Physical therapy interventions were examined in 13 studies of which ten were RCTs and three were single-group intervention studies. The reported physical therapy interventions were cardiorespiratory exercises (N = 5), resistance exercises (N = 2), physiotherapeutic modalities (N = 4) and mixed rehabilitation programs (N = 2) [37–49]. The intervention studies had a median sample size of 41 patients with PsA (Min-Max: 9–166). Two studies with a cross-sectional design evaluated physical therapy uptake in clinical practice [50, 51].

Table 1. Summary of physical therapy interventions in PsA

Study design	Risk of bias	Patient characteristics	Study results	
N
Disease activity (baseline)	Disease activity	Physical fitness	Pain	Function	Symptoms	Physical activity	Quality of life	
Cardiorespiratory exercises	
Thomsen (2018) [37]: HIIT vs control group	
RCT	Low	IG: 30

CG: 31

Low

	NI	↑: VO2max (3M and 9M)

↓: truncal fat% (3M)

ns: truncal fat% (9M), HR, total fat%, BMI, lean muscle mass

	NI	NI	NI	NI	NI	
Thomsen (2019) [38]: HIIT vs control group	
RCT	High	IG: 32

CG: 35

Low

	ns: PGA (VAS), DAS-44, ASDAS-CRP, hsCRP	NI	ns: pain intensity (VAS)	NI	ns: fatigue-VAS	NI	NI	
Thomsen (2023) [41]: HIIT vs control group	
RCT	High	IG: 32

CG: 35

Low

	ns: US joint, US entheses, MRI BME SIJ, MRI BME spine	NI	NI	NI	NI	NI	NI	
Chronaiou (2022) [40]: HIIT vs control group	
RCT	High	IG: 19

CG: 20

Low

	ns: MRI BME spine, MRI SPARCC scoring	NI	NI	NI	NI	NI	NI	
Chimenti (2014) [39]: home-based aerobic exercises	
Single-group intervention study	High	30

Low

	ns: PGA	NI	↓: SF-36 bodily pain

ns: Pain VAS

	ns: SpA-HAQ	NI	Correlation: PA-level with SpA-HAQ and subdomains SF-36	ns: global health, SF-36	
Resistance exercises	
Roger-Silva (2018) [42]: resistance exercises vs waiting list control group	
RCT	High	IG: 20

CG: 21

Active disease

	↓: BASDAI

ns: DAS28

	↑: 1RM leg extension R

ns: other 1RM

	↑: SF-36 bodily pain	↓: HAQS

ns: BASFI

	NI	NI	↑: SF-36 general health

ns: SF-36 other domains

	
Roger-Silva (2023) [43]: functional vs resistance exercises	
RCT	Some concerns	IG: 20

CG: 21

Active disease

	ns: BASDAI, DAS28	ns: 1-RM	ns: SF-36 bodily pain	ns: HAQS, BASFI	NI	NI	ns: SF-36	
Physiotherapeutic modalities: physical agents, electrotherapeutic, and mechanical modalities	
Cozzi (2015) [44]: mud-bath therapy vs control group	
RCT	High	IG: 18

CG: 18

Low to moderate

	↓: PASI, DAS28, SJC, TJC, VAS, CEUS synovial washout rate

↑: CEUS synovial appearance time

ns: CRP, other CEUS (peri)synovial

	NI	NI	↓: HAQ	NI	NI	↑: SF-36 PCS, SF-36 MCS	
Sukenik (1994) [45]: balneotherapy (IG) + sun exposure and bathing in the Dead Sea (IG and CG)	
RCT	High	IG: 146

CG: 20

NI

	No between-group analysis	
Walker (2006) [46]: interferential current treatment	
Single-group intervention study	High	9

Moderate

	↓: physician global, morning stiffness, TJC

ns: PGA, SJC, ESR, CRP, radiographs, MRI, bone scan

	NI	↑: SF-36 body pain

ns: VAS

	NI	NI	NI	ns: SF-36 MCS, SF-36 PCS	
Elkayam (2000) [47]: balneotherapy (IG) + sun exposure and bathing in the Dead Sea (IG and CG)	
RCT	High	IG: 23

CG: 19

Moderate

	↓: TJC, SJC

ns: morning stiffness, PGA, PASI, ESR

	ns: grip strengths	↓: presence of neck and back pain	ns: Schober test, bending forward	NI	NI	NI	
Mixed rehabilitation exercises	
Patrascu (2018) [48]: standard therapy + physical therapy vs standard therapy	
RCT	High	IG: 60

CG: 60

NI

	NI	NI	NI	↓: HAQ-DI (24 W)	↑: FACIT-fatigue (vitality) (16 W-24W)	NI	↓: DLQI-physical pain (16 W-24W)

↑: SF-36 PCS (16 W)

ns: SF-36 MCS

	
Bilberg (2022) [49]: weight-loss treatment with very low energy diet + individual physical activity counselling	
Single-group intervention study	High	Cases: 41

Controls: 42 (non-PsA)

Low to moderate

	NI	↓: timed stand test; body weight; BMI; waist circumference; total fat mass; total, arm, and leg lean mass

↑: VO2 (ml/kg/min)

ns: hand grip strength, VO2 (l/min)

	ns: hand pain	NI	NI	↑: Saltin-Grimby physical activity scale	↑: SF-36 PCS	
Summary of outcome measures: significant increase (↑), significant decrease (↓) or non-significant difference (ns) of parameters according between-group analysis for RCTs or within-group analysis for single-group intervention studies. Primary outcome measures are presented in bold.

%: percentage; 1 RM: one repetition maximum; ASDAS-CRP: AS Disease Activity Score with CRP; BME: bone marrow oedema; CEUS: contrast-enhanced ultrasound; CG: control group; DAS28: Disease Activity Score 28; DAS-44: Disease Activity Score 44; DLQI: Dermatology Life Quality Index; ESR: erythrocyte sedimentation rate; FACIT-fatigue: Functional Assessment of Chronic Illness Therapy—Fatigue Scale; HIIT: high intensity interval training; HR: heart rate; hsCRP: high sensitivity CRP; IG: intervention group; kg: kilogram; l: litres; M: months; min: minutes; ml: millilitres; N: number; NI: no information; PA: physical activity; PASI: Psoriasis Area Severity Index; PGA: patient global assessment; R: right; RCT: randomized controlled trial; SF-36 MCS: 36-item Short Form Health Survey mental component summary; SF-36 PCS: 36-item Short Form Health Survey physical component summary; SF-36: 36-item Short Form Health Survey; SIJ: sacro-iliacal joint; SJC: swollen joint count; SPARCC scoring: Spondyloarthritis Research Consortium of Canada; TJC: tender joint count; US: ultrasound; VAS: visual global assessment; VO2max: maximal oxygen uptake; W: weeks.

Overall, risk of bias was high in the physical therapy intervention studies, except in one RCT that scored low risk of bias and one RCT that had some concerns (Fig. 2). The risk of bias scores of the individual studies are presented in Supplementary Data S2, available at Rheumatology Advances in Practice online. Risk of bias was mainly increased due to selection bias or insufficient described recruitment process, an insufficient randomization process, the lack of blinding possibilities of the physical therapy interventions, and the use of non-validated and/or patient-reported outcomes [37–48].

Figure 2. Risk of bias assessment using the RoB2-tool of the included RCTs (N = 10). Domain 1: randomization process; domain 2: deviations from intended interventions; domain 3: missing outcome data; domain 4: measurement of the outcome; domain 5: selection of the reported result; domain 6: overall bias

Physical therapy intervention

Cardiorespiratory exercises (N = 5)

The effect of 11-week high-intensity interval training (HIIT) in PsA-patients with low disease activity (N = 30) versus a control group (N = 31) was studied by one Norwegian research group and reported in four different papers [37, 38, 40, 41]. Eleven-week HIIT was associated with a substantial increase in the primary outcome peak oxygen uptake (baseline mean both groups: 29.51 ml/kg/min (95% CI 27.97–31.05)) with a mean between-group difference of 3.72 ml/kg/min (95% CI 2.38–5.06, P < 0.001) and, secondary, a reduction in truncal fat percentage at 3 months (RCT, RoB: low, data presented in Supplementary Data S1, available at Rheumatology Advances in Practice online) [37]. In addition, a long-term effect on the increase of peak oxygen uptake at 9 months with a mean between-group difference of 3.08 ml/kg/min (95% CI 1.63–4.53, P < 0.001) was reported [37]. The authors conclude that HIIT was well tolerated in patients with PsA with no deleterious effect on peripheral and axial disease activity evaluated by patient global assessment, clinical examination as well as by ultrasound and magnetic resonance imaging (RCT, RoB: high). An Italian study assessing a 12-week home-based aerobic exercise program (circuit training, twice a week) in PsA-patients with minimal disease activity (N = 30) reported high adherence rate of 76.6% [39]. No significant effects on the main study outcomes, disease activity and quality of life, were noted, but SF-36 bodily pain was reduced after the exercise program (see Supplementary Data S1, available at Rheumatology Advances in Practice online) [39].

Resistance exercises (N = 2)

The effect of a 12-week resistance training program using weight machines for upper limbs, lower limbs, and trunk according to the American College of Sports Medicine (ACSM) training guidelines was examined in PsA-patients with active disease (N = 20) versus a waitlist control group (N = 21) [42]. The resistance program was effective in improving the primary outcome functional capacity (HAQS: IG-baseline 0.72 (0.45), IG-week12 0.45 (0.43), between-P = 0.048). Secondary, significant beneficial effects on disease activity, pain, and general health were observed after 12 weeks training (RCT, RoB: high). By contrast, no overall significant improvement in muscle strength was observed, except for leg extension of the right leg [42]. A similar study comparing programs using elastic bands (N = 20) to weight machines (N = 21) with the same exercise repertoire and sets showed equal results for both groups (RCT, RoB: some concerns) [43]. Adherence was high for both programs with a frequency of 83.4% for the functional training and 91.7% for the resistance training [43]. Both training programs were equally effective in improving functional capacity, disease activity, pain, muscle strength, and quality of life after 12 weeks of training [43].

Physiotherapeutic modalities: physical agents, electrotherapeutic, and mechanical modalities (N = 4)

Physiotherapeutic modalities, i.e. application of physical agents, electrotherapeutic, and mechanical modalities, were examined in four studies [44–47]. All studies had a high risk of bias, analysed a small number of patients (except one study), and reported a wide range of outcomes without specifying the primary outcome (data presented in Supplementary Data S1, available at Rheumatology Advances in Practice online). Two-week mud-bath therapy (N = 18) in addition to anti-TNF therapy (control group N = 18) was examined in patients with low to moderate disease activity (RCT, RoB: high) [44]. At 45 days, this therapy resulted in a significant improvement of musculoskeletal and skin disease activity, residual synovial inflammation on contrast-enhanced ultrasound, patient global, physical function, and quality of life (data presented in Supplementary Data S1, available at Rheumatology Advances in Practice online). Next, a 3-week add-on balneotherapy program (N = 146) in addition to sun exposure and bathing in the Dead Sea (control group N = 20) improved musculoskeletal and skin disease activity, hand grip strength, presence of pain in the cervical, thoracic and lumbar spine, mobility of the lumbar spine, and ADL (RCT, RoB: high, data presented in Supplementary Data S1, available at Rheumatology Advances in Practice online) [45]. Although inclusion of a small control group, between-group analysis was not performed. Another add-on balneotherapy program during 4 weeks (N = 23) in addition to sun exposure and bathing in the Dead Sea (control group N = 19), examined in patients with moderate disease activity, resulted in a significant improvement in tender and swollen joint count, and presence of neck and back pain (original quantitative data only presented in graphs, RCT, RoB: high) [47]. Lastly, a 16-week interferential current treatment in nine patients with moderate disease activity suggested beneficial effects on physician assessed disease activity, duration of morning stiffness, tender joint count, and pain (data presented in Supplementary Data S1, available at Rheumatology Advances in Practice online) [46]. A control group was not included in the study protocol (single-group intervention, RoB: high).

Mixed rehabilitation programs (N = 2)

Physical therapy combined with pharmacological TNFα-inhibition treatment (adalimumab, N = 60) had beneficial short-term effects (<6 months) on physical function, pain, and fatigue in patients with PsA compared with TNFα-inhibition treatment (adalimumab) alone (control group N = 60, original quantitative data was only presented in graphs, RCT, RoB: high) [48]. However, the content of the physical therapy treatment was not specified. The effect of a weight-loss treatment of 12 months with very low-energy diet combined with individual physical activity counselling in obese patients with PsA with low to moderate disease activity (N = 41) was examined (single-group intervention, RoB: high) [49]. The program resulted in significant beneficial effects on the timed stand test as the main outcome measure (median (IQR): PsA-baseline 26.9 (22.1, 35.4), PsA-M12 23.2 (19.4, 30.4), P < 0.001), but no significant change in the second main outcome handgrip strength was observed. Secondary, after the diet and physical activity intervention, significant improvements on body composition, VO2 divided by body weight, physical activity level, and quality of life were noted (see Supplementary Data S1, available at Rheumatology Advances in Practice online). The outcomes were not compared to a PsA control group, but to an obese non-PsA control group who received the same intervention.

Physical therapy uptake in real clinical practice (N = 2)

Physical therapy uptake in clinical practice has only been examined in two studies (for details, see Supplementary Data S1, available at Rheumatology Advances in Practice online) [50, 51]. In India, a cross-sectional survey carried out in multiple rheumatology centres revealed that only 14% of the patients with PsA (total: N = 262) had seen a physical therapist in the last 12 months and 64% had never seen a physical therapist (RoB: high) [50]. In Serbia, a retrospective analysis concluded that 100% of the studied PsA population (total: N = 162) followed physical therapy as part of their PsA treatment (RoB: high) [51].

Discussion

This study aimed to systematically review the effect and quality of physical therapy in the management of PsA. Despite physical therapy is largely recommended, only 15 studies fulfilled our inclusion criteria. Thirteen studies investigated different physical therapy interventions and two studies described physical therapy uptake in clinical practice. The studies have various study designs, heterogeneous outcome measures, and a high overall risk of bias, except one RCT assessing cardiorespiratory exercises [37]. A second RCT examining functional versus resistance training had minor concerns according to the RoB2-tool [43]. Consequently, conclusions about physical therapy management in PsA must be interpreted with caution.

Training programs consisting of HIIT, resistance and functional training hint on promising and clinically interesting results in patients with PsA. First of all, these training programs were safe and well tolerated, as there was no deleterious effects on peripheral and axial disease activity [37, 38, 40–43]. Good tolerance of moderate to high intense aerobic and resistance exercise programs was already demonstrated in patients with RA and axial spondylarthritis (axSpA) [52–56]. In PsA-patients with low disease activity, the increase in peak oxygen uptake after 11-week HIIT training was comparable and slightly higher compared with the ExeHeart trial and ESPA-study assessing HIIT in patients with RMDs and axSpA, respectively [54, 56]. The ExeHeart trial, in which HIIT was performed in primary care setting, also evaluated a long-term increase on VO2peak, but no effects on pain, fatigue, and body composition [56]. The ESPA study, combining HIIT with high intense resistance training, reported estimated VO2peak values, which were higher at baseline, and did not include a long-term evaluation [54]. Similar to the short-term decrease in truncal fat percentage observed in the HIIT-study of Thomsen et al., the ESPA-study showed a significant decrease in waist circumference [37, 54]. Moreover, a short-term significant improvement in fatigue was noted in the ESPA study, which was not confirmed in the HIIT-study of Thomsen et al. [38, 57]. However, the threshold for clinical relevance was reached [38].

Despite design peculiarities, resistance and functional training programs showed promising results with improvement of functional capacity, disease activity, pain, and quality of life after 12 weeks training [42, 43]. No significant effects were observed for the secondary outcome muscle strength, but the chosen resistance of 60% of one repetition maximum (due to inclusion of a sedentary population) might have been insufficient to increase muscle strength [42]. The interesting finding that using elastic bands was equally effective as weight machines facilitates the implementation of resistance training in clinical practice [43]. Compared with RA, a meta-analysis of moderate to high intense resistance exercise programs with a duration ranging between 3 and 104 weeks concluded reduction of disease activity, while no difference was observed in physical function assessed by HAQ [55]. The effect on muscle strength was not evaluated in this meta-analysis. Lastly, low methodological study quality hinders firm conclusions about physiotherapeutic modalities interventions and mixed rehabilitation programs in PsA.

This low methodological study quality was an important first concern. First of all, the recruitment process often facilitated the selection of motivated patients by using local advertisements or was left unreported. Secondly, due to the nature of rehabilitation programs, where blinding to group allocation is almost impossible, it is remarkable that few studies included a blinded assessor and the majority focused on patient-reported outcomes only. According to the principles of exercise physiology, it is unlikely that interventions with a duration of maximum 3 months and no boost session to support the maintenance phase can actually result in meaningful long-term clinical outcomes [58]. Last, trial design aspects such as appropriate sample sizes, inclusion of trustworthy control groups, and adherence to reporting guidelines (e.g. disease-related information) would improve generalizability of future results.

Another concern is the content of the studied physical therapy interventions. Today, the improved pharmacological treatment options are targeting disease activity more effectively which results in better control of symptoms, less severe structural damage and less disability in ADL [59]. However, residual (non-inflammatory) pain and remaining cardiometabolic risk factors in patients with PsA are still an unmet need in PsA and were not addressed in the reviewed interventions [6, 9–17, 60]. Despite the high prevalence of psychological comorbidities in PsA, limited attention was given to mental health comorbidities and outcomes in the included studies. For example, previous research in RMDs has already highlighted the importance of targeting fear of movement, injury beliefs and widespread pain to optimize patient outcomes [61–67]. We propose that future physical therapy research in PsA will further include physical activity and exercise programs, because of their known beneficial effects on cardiometabolic risk factors as well as on musculoskeletal pain in the general population and in RMDs [21, 54, 56, 68–70]. Furthermore, incorporating the biopsychosocial model of care is needed to address unmet needs in PsA, e.g. residual pain, mental health and cardiometabolic risk.

Two included studies reported real-life data of the uptake of physical therapy in the management of PsA with various numbers of physical therapy use and without description of the goals and content [50, 51]. EULAR, ACR and Group for Research and Assessment of Psoriasis and Psoriatic Arthritis treatment recommendations encompass several statements about non-pharmacological interventions [13–15]. Physical therapy is particularly advised to manage axial disease and enthesitis, but the exact content of the recommended treatment is not provided. Since high-quality evidence in patients with PsA is scarce, recommendations are mainly supported by evidence in patients with osteoarthritis, RA, and axSpA, or based on expert opinion. Occasionally, patients with PsA are part of the included mixed RMD-population, but the published results do not distinguish between different RMDs [71–74]. Distinction between the results of different RMDs is recommended. After all, PsA is a heterogeneous disease with specific disease characteristics that might impact the feasibility, safety, and outcomes of physical therapy interventions: e.g. skin lesions and inflammation; cardiometabolic risk profile already present in early disease or even before disease onset; presentation of enthesitis, peripheral and axial disease; and potential impact of mechanical loading in the pathogenesis of spondylarthritis [1, 2, 6, 8, 10, 12, 75, 76]. Further research should clarify if evidence in patients with other RMDs might be extended to patients with PsA. Additionally, future research on identification of patient profiles in PsA based on their dominant disease type, musculoskeletal and skin disease activity level, the presence and type of comorbidities, and the presence of psychosocial factors might be necessary. It will enhance the design of targeted interventions to address the management needs of each patient profile.

Some strengths and limitations of this systematic review should be discussed. We performed a broad search examining physical therapy, physical activity, and physical fitness in PsA to create a complete overview of the available literature. To discuss each topic thoroughly, only papers examining physical therapy in PsA were reported in this systematic review. Papers examining physical activity and fitness will be discussed in a separate review article. The broad search contributed to heterogeneous outcomes and interventions which complicated analysis and synthesis of the results. With a great interest in the management of patients with PsA, we have only included papers reporting results of PsA-patients separately. Consequently, interesting physical therapy studies might have been missed as study populations often consist of mixed RMD-populations. Nevertheless, we have strengthened the methodological quality of this systematic review by conducting and reporting according to the recommended guidelines and by prospectively registering the protocol at the PROSPERO database.

To conclude, high-quality evidence on physical therapy in PsA was scarce. Cardiorespiratory, resistance and functional exercises demonstrated promising results to positively influence cardiometabolic risk factors as well as disease-related outcomes in patients with PsA. Evidence for other physical therapy modalities was inconclusive. Future physical therapy research in PsA with adequate methodological quality is needed to support clinical guidelines for PsA management.

Supplementary Material

rkae107_Supplementary_Data

Acknowledgements

This review was performed in collaboration with master students of Rehabilitation and Movement Sciences of KU Leuven. We acknowledge the contribution of Julie Eelen, Naomi Plancke, Astrid Liekens and Floor Van Loock.

Supplementary material

Supplementary material is available at Rheumatology Advances in Practice online.

Data availability

Data are available on reasonable request to the corresponding author.

Funding

This study was supported by a grant from the Fonds voor Wetenschappelijk ReumaOnderzoek/Fonds pour la Recherche Scientifique en Rhumatologie.

Disclosure statement: The authors have declared no conflicts of interest.
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References

1 Gladman DD , AntoniC, MeaseP, CleggDO, NashP. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis 2005;64 :ii14–7.15708927
2 Ritchlin CT , ColbertRA, GladmanDD. Psoriatic arthritis. N Engl J Med 2017;376 :957–70. Review).28273019
3 Alinaghi F , CalovM, KristensenLE et al Prevalence of psoriatic arthritis in patients with psoriasis: a systematic review and meta-analysis of observational and clinical studies. J Am Acad Dermatol 2019;80 :251–65.e19.29928910
4 Gupta S , SyrimiZ, HughesDM, ZhaoSS. Comorbidities in psoriatic arthritis: a systematic review and meta-analysis. Rheumatol Int 2021;41 :275–84.33423070
5 Gezer HH , Acer KasmanS, DuruözMT. Autonomic dysfunction and cardiovascular risk in psoriatic arthritis. Clin Rheumatol 2023;42 :2635–49.36542174
6 Ishchenko A , PazminoS, NeerinckxB, LoriesR, de VlamK. Comorbidities in early psoriatic arthritis: data from the metabolic disturbances in psoriatic arthritis cohort study. Arthritis Care Res (Hoboken) 2024;76 :231–40.37667975
7 Zhao SS , MillerN, HarrisonN et al Systematic review of mental health comorbidities in psoriatic arthritis. Clin Rheumatol 2020;39 :217–25.31486931
8 Xie W , HuangH, DengX, GaoD, ZhangZ. Modifiable lifestyle and environmental factors associated with onset of psoriatic arthritis in patients with psoriasis: a systematic review and meta-analysis of observational studies. J Am Acad Dermatol 2021;84 :701–11.32827608
9 Stober C , YeW, GuruparanT et al Prevalence and predictors of tumour necrosis factor inhibitor persistence in psoriatic arthritis. Rheumatology (Oxford) 2018;57 :158–63.29077973
10 Ballegaard C , SkougaardM, Guldberg-MøllerJ et al Comorbidities, pain and fatigue in psoriatic arthritis, psoriasis and healthy controls: a clinical cohort study. Rheumatology (Oxford) 2021;60 :3289–300.33325531
11 Freites Nuñez D , Madrid-GarcíaA, LeonL et al Factors associated with health-related quality of life in psoriatic arthritis patients: a longitudinal analysis. Rheumatol Ther 2021;8 :1341–54.34287811
12 Fernández-Carballido C , Martín-MartínezMA, García-GómezC et al ; Cardiovascular in Rheumatology Project Collaborative Group. Impact of comorbidity on physical function in patients with ankylosing spondylitis and psoriatic arthritis attending rheumatology clinics: results from a cross-sectional study. Arthritis Care Res (Hoboken) 2020;72 :822–8.31033231
13 Coates LC , SorianoER, CorpN et al ; GRAPPA Treatment Recommendations Domain Subcommittees. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA): updated treatment recommendations for psoriatic arthritis 2021. Nat Rev Rheumatol 2022;18 :465–79.35761070
14 Singh JA , GuyattG, OgdieA et al Special article: 2018 American College of Rheumatology/National Psoriasis Foundation guideline for the treatment of psoriatic arthritis. Arthritis Care Res 2019;71 :2–29.
15 Gossec L , BaraliakosX, KerschbaumerA et al EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update. Ann Rheum Dis 2020;79 :700–12.32434812
16 Gialouri CG , PappaM, EvangelatosG, NikiphorouE, FragoulisGE. Effect of body mass index on treatment response of biologic/targeted-synthetic DMARDs in patients with rheumatoid arthritis, psoriatic arthritis or axial spondyloarthritis. A systematic review. Autoimmun Rev 2023;22 :103357.37150489
17 Campanholo CB , MaharajAB, CorpN et al Management of psoriatic arthritis in patients with comorbidities: an updated literature review informing the 2021 GRAPPA treatment recommendations. J Rheumatol 2023;50 :426–32.36319003
18 Cañete JD , TasendeJAP, LasernaFJR, CastroSG, QueiroR. The impact of comorbidity on patient-reported outcomes in psoriatic arthritis: a systematic literature review. Rheumatol Ther 2020;7 :237–57.32270447
19 Torre-Alonso JC , QueiroR, ComellasM, LizánL, BlanchC. Patient-reported outcomes in European spondyloarthritis patients: a systematic review of the literature. Patient Prefer Adherence 2018;12 :733–47.29780239
20 World Confederation for Physical Therapy. Description of physical therapy—policy statement. United Kingdom: World Confederation for Physical Therapy, 2019.
21 Visseren FLJ , MachF, SmuldersYM et al ; ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice: developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies With the special contribution of the European Association of Preventive Cardiology (EAPC). Eur Heart J 2021;42 :3227–337.34458905
22 Arnett DK , BlumenthalRS, AlbertMA et al 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task force on clinical practice guidelines. Circulation 2019;140 :e596–646.30879355
23 Adams J , WilsonN, HurkmansE et al 2019 EULAR points to consider for non-physician health professionals to prevent and manage fragility fractures in adults 50 years or older. Ann Rheum Dis 2021;80 :57–64.32332077
24 Agca R , HeslingaSC, RollefstadS et al EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis 2017;76 :17–28.27697765
25 Geenen R , OvermanCL, ChristensenR et al EULAR recommendations for the health professional’s approach to pain management in inflammatory arthritis and osteoarthritis. Ann Rheum Dis 2018;77 :797–807.29724726
26 Rausch Osthoff AK , NiedermannK, BraunJ et al 2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis. Ann Rheum Dis 2018;77 :1251–60.29997112
27 Zangi HA , NdosiM, AdamsJ et al ; European League Against Rheumatism (EULAR). EULAR recommendations for patient education for people with inflammatory arthritis. Ann Rheum Dis 2015;74 :954–62.25735643
28 Nikiphorou E , SantosEJF, MarquesA et al 2021 EULAR recommendations for the implementation of self-management strategies in patients with inflammatory arthritis. Ann Rheum Dis 2021;80 :1278–85.33962964
29 Gwinnutt JM , WieczorekM, BalanescuA et al 2021 EULAR recommendations regarding lifestyle behaviours and work participation to prevent progression of rheumatic and musculoskeletal diseases. Ann Rheum Dis 2023;82 :48–56.35260387
30 Higgins JPT , ThomasJ, ChandlerJ et al Cochrane handbook for systematic reviews of interventions version 6.3 (updated February 2022). https://training.cochrane.org/handbook (July 2024, date last accessed).
31 Page MJ , McKenzieJE, BossuytPM et al The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372 :n71.33782057
32 Page MJ , MoherD, BossuytPM et al PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ 2021;372 :n160.33781993
33 Ouzzani M , HammadyH, FedorowiczZ, ElmagarmidA. Rayyan—a web and mobile app for systematic reviews. System Rev 2016;5 :210.27919275
34 Sterne JAC , SavovićJ, PageMJ et al RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019;366 :l4898.31462531
35 Wells G , SheaB, O’ConnellD et al The Newcastle–Ottawa Scale (NOS) for assessing the quality of non-randomized studies in meta-analysis, 2000.
36 Noll L , MithamK, MoranJ, MallowsA. Identifying current uses of return to work screening tests and their effectiveness of reducing the risk of reinjury in athletic occupations—a systematic review. Phys Ther Sport 2022;58 :141–50.
37 Thomsen RS , NilsenTIL, HaugebergG et al Effect of high-intensity interval training on cardiovascular disease risk factors and body composition in psoriatic arthritis: a randomised controlled trial. RMD Open 2018;4 :e000729.30402265
38 Thomsen RS , NilsenTIL, HaugebergG et al Impact of high-intensity interval training on disease activity and disease in patients with psoriatic arthritis: a randomized controlled trial. Arthritis Care Res (Hoboken) 2019;71 :530–7.29882634
39 Chimenti MS , TriggianeseP, ConigliaroP et al Self-reported adherence to a home-based exercise program among patients affected by psoriatic arthritis with minimal disease activity. Drug Develop Res 2014;75 :S57–9.
40 Chronaiou I , GiskeødegårdGF, NeubertA et al Evaluating the impact of high intensity interval training on axial psoriatic arthritis based on MR images. Diagnostics (Basel) 2022;12 :1420.35741229
41 Thomsen RS , NilsenTIL, HaugebergG et al Changes of inflammation in patients with psoriatic arthritis after high intensity interval training assessed by ultrasound and MRI, a randomized controlled trial. BMC Musculoskelet Disord 2023;24 :743.37726677
42 Roger-Silva D , NatourJ, MoreiraE, JenningsF. A resistance exercise program improves functional capacity of patients with psoriatic arthritis: a randomized controlled trial. Clin Rheumatol 2018;37 :389–95.29185133
43 Silva DR , MeirelesSM, BruminiC, NatourJ. Effectiveness of functional training versus resistance exercise in patients with psoriatic arthritis: randomized controlled trial. Adv Rheumatol 2023;63 :58.38093394
44 Cozzi F , RaffeinerB, BeltrameV et al Effects of mud-bath therapy in psoriatic arthritis patients treated with TNF inhibitors. Clinical evaluation and assessment of synovial inflammation by contrast-enhanced ultrasound (CEUS). Joint Bone Spine 2015;82 :104–8.25623520
45 Sukenik S , GiryesH, HalevyS et al Treatment of psoriatic arthritis at the Dead Sea. J Rheumatol 1994;21 :1305–9.7966074
46 Walker UA , UhlM, WeinerSM et al Analgesic and disease modifying effects of interferential current in psoriatic arthritis. Rheumatol Int 2006;26 :904–7.16432686
47 Elkayam O , OphirJ, BrenerS et al Immediate and delayed effects of treatment at the Dead Sea in patients with psoriatic arthritis. Rheumatol Int 2000;19 :77–82.10776684
48 Patrascu V , OchianaLC, DelceaF, AlexeO. Secondary kinetoprophylaxis in psoriatic arthropathy. Exp Dermatol 2018;27 :23.
49 Bilberg A , LarssonI, BjörkmanS, EliassonB, KlingbergE. The impact of a structured weight-loss treatment on physical fitness in patients with psoriatic arthritis and obesity compared to matched controls: a prospective interventional study. Clin Rheumatol 2022;41 :2745–54.35648298
50 Pathak H , GoyalM, DasP et al Awareness, perspectives and satisfaction levels among patients with psoriatic arthritis: a multicentric cross-sectional survey. Rheumatol Int 2023;43 :1531–9.37173547
51 Pavlica L , Perić-HajzlerZ, JovelićA, SeklerB, DamjanovićM. Psoriatic arthritis: a retrospective study of 162 patients. Vojnosanitetski Pregled Military-Med Pharm Rev 2005;62 :613–20.
52 Andonian BJ , JohannemannA, HubalMJ et al Altered skeletal muscle metabolic pathways, age, systemic inflammation, and low cardiorespiratory fitness associate with improvements in disease activity following high-intensity interval training in persons with rheumatoid arthritis. Arthritis Res Ther 2021;23 :187.34246305
53 Lange E , KucharskiD, SvedlundS et al Effects of aerobic and resistance exercise in older adults with rheumatoid arthritis: a randomized controlled trial. Arthritis Care Res (Hoboken) 2019;71 :61–70.29696812
54 Sveaas SH , BilbergA, BergIJ et al High intensity exercise for 3 months reduces disease activity in axial spondyloarthritis (axSpA): a multicentre randomised trial of 100 patients. Br J Sports Med 2020;54 :292–7.30745314
55 Wen Z , ChaiY. Effectiveness of resistance exercises in the treatment of rheumatoid arthritis: a meta-analysis. Medicine (Baltimore) 2021;100 :e25019.33787585
56 Nordén KR , SembAG, DagfinrudH et al Effect of high-intensity interval training in physiotherapy primary care for patients with inflammatory arthritis: the ExeHeart randomised controlled trial. RMD Open 2024;10 :e003440.
57 Sveaas SH , DagfinrudH, BergIJ et al High-intensity exercise improves fatigue, sleep, and mood in patients with axial spondyloarthritis: secondary analysis of a randomized controlled trial. Physical Therapy 2020;100 :1323–32.32367124
58 McArdle WD , KatchFI, KatchVL. Exercise physiology: nutrition, energy and human performance, 9th edn. Philadelphia: Lippincott Williams & Wilkins, 2022.
59 Kerschbaumer A , SmolenJS, DougadosM et al Pharmacological treatment of psoriatic arthritis: a systematic literature research for the 2019 update of the EULAR recommendations for the management of psoriatic arthritis. Ann Rheum Dis 2020;79 :778–86.32381564
60 Roseman C , WallmanJK, JöudA et al Persistent pain and its predictors after starting anti-tumour necrosis factor therapy in psoriatic arthritis: what is the role of inflammation control? Scand J Rheumatol 2024;53 :94–103.38031733
61 Dures E , BowenC, BrookeM et al Diagnosis and initial management in psoriatic arthritis: a qualitative study with patients. Rheumatol Adv Pract 2019;3 :rkz022.31528844
62 Lubrano E , HelliwellP, ParsonsW, EmeryP, VealeD. Patient education in psoriatic arthritis: a cross sectional study on knowledge by a validated self-administered questionnaire. J Rheumatol 1998;25 :1560–5.9712101
63 Swinnen TW , VlaeyenJWS, DankaertsW, WesthovensR, de VlamK. Activity limitations in patients with axial spondyloarthritis: a role for fear of movement and (re)injury beliefs. J Rheumatol 2018;45 :357–66.29142031
64 Lööf H , JohanssonUB. “A body in transformation”—an empirical phenomenological study about fear-avoidance beliefs towards physical activity among persons experiencing moderate-to-severe rheumatic pain. J Clin Nurs 2019;28 :321–9.29971848
65 Demmelmaier I , BjörkA, DufourAB, NordgrenB, OpavaCH. Trajectories of fear-avoidance beliefs on physical activity over two years in people with rheumatoid arthritis. Arthritis Care Res (Hoboken) 2018;70 :695–702.28941003
66 Davergne T , MoeRH, FautrelB, GossecL. Development and initial validation of a questionnaire to assess facilitators and barriers to physical activity for patients with rheumatoid arthritis, axial spondyloarthritis and/or psoriatic arthritis. Rheumatol Int 2020;40 :2085–95.32862307
67 Swinnen TW , WesthovensR, DankaertsW, de VlamK. Widespread pain in axial spondyloarthritis: clinical importance and gender differences. Arthritis Res Ther 2018;20 :156.30053895
68 Leemans L , PolliA, NijsJ et al It hurts to move! intervention effects and assessment methods for movement-evoked pain in patients with musculoskeletal pain: a systematic review with meta-analysis. J Orthop Sports Phys Ther 2022;52 :345–74.35128943
69 Kraus WE , PowellKE, HaskellWL et al ; 2018 Physical Activity Guidelines Advisory Committee. Physical activity, all-cause and cardiovascular mortality, and cardiovascular disease. Med Sci Sports Exerc 2019;51 :1270–81.31095084
70 Liu Y , LeeDC, LiY et al Associations of resistance exercise with cardiovascular disease morbidity and mortality. Med Sci Sports Exerc 2019;51 :499–508.30376511
71 Nilssen IR , KoksvikHS, GrønningK, SteinsbekkA. Rehabilitation in warm climate for young adults with inflammatory arthritis: a 12-month randomized controlled trial. J Rehabil Med 2020;52 :jrm00040.32179929
72 Leung YY , KwanJ, ChanP et al A pilot evaluation of arthritis self-management program by lay leaders in patients with chronic inflammatory arthritis in Hong Kong. Clin Rheumatol 2016;35 :935–41.25294300
73 Klemm P , PreuslerP, HudowenzO et al Multimodal rheumatologic complex treatment in patients with spondyloarthritis—a prospective study. Eur J Internal Med 2021;93 :42–9.34344550
74 Hagel S , LindqvistE, BremanderA, PeterssonIF. Team-based rehabilitation improves long-term aerobic capacity and health-related quality of life in patients with chronic inflammatory arthritis. Disability Rehabil 2010;32 :1686–96.
75 Gracey E , BurssensA, CambréI et al Tendon and ligament mechanical loading in the pathogenesis of inflammatory arthritis. Nat Rev Rheumatol 2020;16 :193–207.32080619
76 Enos C , AlgrniK, Van VoorheesA, WilsonP. Physical activity engagement and responses to exercise in plaque psoriasis: a multifactorial investigation of influential factors. J Dermatolog Treat 2022;33 :805–11.32522068
