Clinical significance and usefulness of rehabilitation for systemic sclerosis

Abstract

Systemic sclerosis is a multisystem connective tissue disorder characterized by excessive fibrosis of the skin and internal organs. Impairments in skin, the musculoskeletal system, and respiratory system require rehabilitation therapy because they may lead to disabilities and reduce the quality of life in daily activities. Rehabilitation for systemic sclerosis mainly comprises two distinct approaches that include local and global rehabilitation. Local rehabilitation is applied to maintain and/or improve hand and face functions, while global rehabilitation includes aerobic and resistance exercises. Although few high-quality randomized clinical trials have been conducted to date, previous studies indicated the effectiveness of rehabilitation therapy for decreasing local and systemic disabilities, resulting in improved quality of life. Rehabilitation for systemic sclerosis needs to be regularly and constantly performed at home as well as in hospitals. Physicians involved in the treatment of systemic sclerosis need to consider rehabilitation, and skilled physiotherapists and occupational therapists also play a crucial role in evaluating and treating systemic sclerosis patients.

Systemic sclerosis (SSc) is a multisystem connective tissue disorder characterized by excessive fibrosis of the skin and internal organs and microvascular damage with an autoimmune background. Fibrosis affects various physical activities that include not only hand and face functions but also breathing and postural maintenance due to the involvement of skin, subcutaneous tissues, and the musculoskeletal system. Although extensive efforts have been made to develop therapeutic agents for SSc, satisfactory results have yet to be achieved. Since the pathophysiology of SSc is complex, its management requires a multidisciplinary team of physicians, such as rheumatologists, pulmonologists, cardiologists, and dermatologists. Similarly, the impairment of skin, musculoskeletal system, and respiratory system requires a rehabilitation therapy to be carried out by multidisciplinary team composed of physicians, physiotherapists, podiatrists, and occupational therapists (1). Physicians who are knowledgeable of the symptoms, complications, and clinical course of SSc play a central role in the management of patients, even in rehabilitation. Rheumatologists are generally in charge of the treatment of patients with SSc; however, other physicians including dermatologists and pulmonologists are also involved. Rehabilitation for SSc may prevent and reduce local disabilities, resulting in the amelioration of global disabilities and impaired quality of life (QoL). Although most physicians recognize the importance of rehabilitation for SSc, limited information is currently available and rehabilitation therapy for SSc is not widespread (2). Moreover, the European League Against Rheumatism (EULAR) recommendations for SSc management do not include rehabilitation therapy. In daily practice, adequate rehabilitation is not fully conducted by physiotherapists and occupational therapists with specific skills in the treatment of SSc patients (3). This review describes local and global rehabilitation currently applied for SSc.

Evaluation indices for rehabilitation for SSc

Appropriate evaluation indices are needed in order to assess the effects and usefulness of rehabilitation for SSc (4). Tab. I summarizes evaluation indices that are clinically used for rehabilitation for SSc. Assessments of general health-related QoL (HRQoL) include the Health Assessment Questionnaire Disability Index (HAQ-DI), Scleroderma HAQ (SHAQ), UK Scleroderma Functional Score (UKFS), EuroQol 5-Domain (EQ-5D), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Medical Outcomes Short Form 36 (SF-36). HAQ-DI is a self-reported questionnaire in eight domains and directly correlates with skin involvement, hand deformities, muscle strength, and cardiac or renal impairments in patients with SSc (5, 6). SHAQ consists of HAQ (eight domains) and also includes the following scales: Raynaud’s phenomenon, digital ulcers, lung involvement, gastrointestinal involvement, pain, and overall disease severity (5). UKFS has been developed to focus on disabilities caused by skin tightness in the upper limbs and proximal muscle weakness (7). A comparative study on UKFS and HAQ-DI revealed a strong correlation between assessment methods, and when used in combination, these tools assess general and organ-specific symptoms as well as functional limitations (8). EQ-5D is a self-reported measure of HRQoL (9). It is a short, rapidly completed questionnaire that provides information on pain, mobility, self-care, activity, and anxiety in addition to a patient global assessment. Gualtierotti et al. (23) reported good correlations between the conceptually equivalent domains of EQ-5D and HAQ-DI in 33 Italian SSc patients. FACIT-F is a 13-item questionnaire that assesses self-reported fatigue and its impact on daily activities and function. FACIT-F was initially developed to assess fatigue associated with anemia in patients with cancer, but has since been used and validated for many other conditions, including rheumatoid arthritis (12) and SSc (10). SHAQ scores correlated with FACIT-F and EQ-5D scores (10). SF-36 is a self-administered survey that assesses HRQoL (24). It consists of four physical health domains (physical functioning, body pain, role limitations due to physical health, and general health perceptions), four mental health domains (mental health, role limitations due to emotional issues, vitality, and social functioning), and a health transition domain. The four physical health domains may be compiled as a physical component summary (PCS) score and the four mental health domains as a mental component summary (MCS) score. Summary physical index (SPI) and summary mental index (SMI) of SF-36 are widely utilized in assessments of physical and mental conditions in SSc patients (11).

Table I.

Evaluation indices for rehabilitation for systemic sclerosis

	Reference
Quality of life
Health Assessment of Questionnaire Disability Index (HAQ-DI)	Steen and Medsger (5) and Kuwana et al. (6)
Scleroderma HAQ (SHAQ)	Steen and Medsger (5)
UK Scleroderma Functional Score (UKFS)	Silman et al. (7) and Smyth et al. (8)
EuroQol 5 Dimension (EQ-5D)	EuroQol Group (9) and Strickland et al. (10)
Summary Physical Index and Summary Mental Index of Short Form 36 (SPI and SMI of SF-36)	Khanna et al. (11)
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)	Strickland et al. (10) and Cella et al. (12)
Oral
Oral Health Impact Profile (OHIP)	Baron et al. (13)
Mouth Handicap in SSc scale (MHISS)	Mouthon et al. (14) and Maddali-Bongi et al. (15)
Hand
Cochin Hand Function Disability Scale (CHFDS)/Duruoz’s Hand Index (HDI)	Silman et al. (7) and Brower and Poole (16)
Hand Mobility in Scleroderma Scale (HAMIS)	Sandqvist and Eklund (17)
Duruöz Hand Index (DHI)	Silman et al. (7) and Bro wer and Poole (16)
Respiratory
Saint George’s Respiratory Questionnaire (SGRQ)	Beretta et al. (18)
COPD Assessment Test (CAT)	Jones et al. (19)
Baseline dyspnea Index (BDI) and transition dyspnea index (TDI)	Khanna et al. (20)
6-min walk test (6MWT)	Villalba et al. (21)
Exercise-induced oxygen desaturation	Someya et al. (22)

Severe skin thickness may result in flexion deformities of the fingers, and the loss of hand function represents a serious issue under various conditions. In order to evaluate hand function, the Cochin Hand Function Disability Scale (CHFDS), also called the Duruoz’s Hand Index (DHI), and Hand Mobility in Scleroderma (HAMIS) are representative measures for SSc. CHFDS was developed to measure the functional ability of the hand among patients with rheumatic diseases and has been validated (25). CHFDS consists of 18 items that, when completed by the patient or clinician, assess the ability to perform daily hand-related activities and is used extensively for SSc (26, 27). HAMIS is a hand function test for SSc patients, and its purpose is to obtain an estimation of hand mobility that is sufficiently precise to detect limitations in motion while indicating the ability to use the hand in daily occupations (17). HAMIS has a demonstrated concurrent validity compared with range of motion (ROM) and skin scores and exhibits the ability to discriminate between healthy individuals and SSc patients.

The Oral Health Impact Profile (OHIP) and Mouth Handicap in Systemic Sclerosis (MHISS) scale are representative tools to evaluate oral function. OHIP is a questionnaire that assesses the functional, social, and psychological impacts of the disease on oral health. Baron et al. (13) found that SSc patients had worse oral conditions and oral health quality of life (OHQoL) than healthy controls. MHISS is a specific tool that quantifies the handicaps associated with mouth disabilities and OHQoL examines issues not assessed by HAQ or SF-36 (14). The validity and reliability of OHQoL were confirmed in Italian SSc patients (15).

Pulmonary rehabilitation is also clinically important because interstitial lung disease (ILD) is a leading cause of mortality in SSc patients. A respiratory-related QoL index specifically designed for SSc-related ILD has not yet been developed. Several evaluation indices that were developed for other chronic respiratory diseases, such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), have been applied to SSc-related ILD. The Saint George’s Respiratory Questionnaire (SGRQ) has been successfully evaluated in patients with IPF (28) and others with ILD (29, 30). SGRQ is a valid respiratory-specific questionnaire for the evaluation of HRQoL in patients with SSc-related ILD. SGRQ performs better in relation to exercise capacity and lung imaging than other non-respiratory-specific questionnaires widely used in SSc studies (18). The COPD Assessment Test (CAT) was originally developed to evaluate HRQoL in patients with COPD (19). CAT was introduced to evaluate patients with ILD, and a very strong correlation was observed between CAT scores and SGRQ total scores (31). The basal dyspnea index (BDI) and transition dyspnea index (TDI) measure dyspnea at one point in time and also how it changes at another time point (32). A change (improvement/deterioration) of 1.5 U in the TDI is the minimally important difference for SSc-related ILD, and this change may contribute to the interpretation of clinically important changes in breathlessness in SSc-related ILD (20). The 6-min walk test (6MWT) is a representative and well-validated exercise test and is preferred over treadmill testing (33, 34) 6MWT has been shown to correlate variably with measures of SSc-related ILD severity (21, 35). Exercise-induced oxygen desaturation in patients with SSc-related ILD may be one of the crucial factors in exercise limitations (21, 36). A decrease in SpO₂ to ≤88% during 6MWT predicts a high-mortality risk in patients with IPF (37). A factor underlying exercise-induced oxygen desaturation may be reduced as %DLco, which was found to be useful as a predictor in more than 80% of subjects (22).

Hand and face changes and disabilities

Skin involvement affects the hands and face in the early stages. In SSc, the clinical course of skin involvement consists of three phases: edematous, sclerotic, and atrophic. Hand disabilities develop from the edematous phase, in which edema reduces finger movement and hand function. In the sclerotic phase, skin becomes fibrotic and increases its consistency. Skin also becomes inelastic, shiny, and taut. In the later atrophic stage, skin is thinner due to reductions in the thickness of the dermis (1).

In the sclerotic phase, SSc patients exhibit many characteristic changes in the face, such as microstomia, microcheilia, radial wrinkles around the mouth, nose sharpening, the smoothing of wrinkles, and amimia (the loss of facial movements reflecting emotions). These alterations cause disabilities in the chewing of food, slurred speech, difficulties with the maintenance of oral hygiene and dental treatments, and esthetic issues and consequently reduce OHQoL and overall QoL (38). Bone resorption of the temporomandibular joint (TMJ) may cause osteolysis of the condyles, branches, and angles of the mandible. Resulting TMJ impairments may lead to severe dysfunctions in jaw movements and mouth opening.

Changes in the hands and face in the course of SSc cause severe disabilities. A longitudinal observational survey performed on 745 Canadian SSc patients showed that SSc respiratory issues and the diffuse cutaneous SSc subset were major predictors of the severity of disabilities (39). In a series of 1250 SSc patients, disability assessed by HAQ directly correlated with skin involvement, hand deformities, muscle strength, and cardiac or renal impairments (5). Changes in the skin of the hands and face impair interpersonal relationships, self-esteem, and psychosocial functions; therefore, skin modifications in SSc may be among the factors leading to image dissatisfaction (40). SSc patients consider thin lips, mouth furrows, facies amimica, and a small mouth to be the major causes of face dissatisfaction and express greater concerns over face than hand changes (41).

In SSc patients, local disabilities in the hands and face measured by specific scales (CHFDS, HAMIS, and MHISS) are related to global disability (HAQ) (15, 42). Sandqvist et al. (43) showed that difficulties in the Activities of Daily Living (ADL) were mainly related to functional impairments in the hands, particularly stiffness and reduced grip strength and dexterity. The same group reported that women with limited cutaneous SSc had a reduced work capacity of 50% (44), and pain, fatigue, and impaired hand function were confirmed to have a marked impact on work (45).

Changes in the hands and face of SSc patients are often undervalued and not thoroughly investigated and treated (3). Therefore, SSc patients need to be treated carefully and with different techniques in order to tailor treatments to personal needs.

Hand rehabilitation

Severe skin thickness in the hands may result in flexion deformity of the fingers, leading to the loss of flexion at the metacarpophalangeal (MP) joints, the loss of extension of the proximal interphalangeal (PIP) joints, and the loss of thumb abduction. The distal interphalangeal (DIP) joint may also become fixed in midrange flexion. These changes cause a claw-type deformity of MP extension, PIP flexion, and thumb adduction. Finger flexion and extension are the most impaired aspects of hand mobility in SSc patients (43). The loss of hand-grasp ability and hand impairments influence the ADL of SSc patients (46). Therefore, the development of deformities and disabilities needs to be prevented. In order to maintain hand function, hand exercises that focus on flexion/extension and abduction of the fingers and thumb and/or rehabilitation are useful.

A Japanese open study showed that a program of self-administered stretching exercises of the fingers in 45 SSc patients for 1 month improved the function of the fingers, and these improvements were maintained for 1 year (47). Previous studies used finger mobilization exercises preceded by the application of paraffin. Sandqvist et al. conducted a randomized controlled trial (RCT) on 17 SSc patients over 1 month. In that study, one hand was treated daily with a paraffin bath in combination with hand exercises and the other hand was treated with exercises only as a control. Finger exercises and paraffin significantly improved the mobility of the hands, stiffness, and skin elasticity, while the hands treated with exercises only showed improved mobility (48). These findings indicated that exercises of finger stretching and mobility, particularly if preceded by a paraffin bath, promote vasodilation and joint flexibility and reduce skin stiffness. Furthermore, hand exercises need to be performed regularly by SSc patients in order to maintain and improve hand function.

The efficacy of manual lymphatic drainage (MLD) by the Vodder method for 5 weeks was evaluated on the edematous hands of 20 SSc patients in the early stage and compared to a control group with observations only (15 SSc patients). In the treatment group, MLD significantly reduced hand volume and improved function (assessed by HAMIS), pain, and the perception of edema and their interference in ADL (assessed by the visual analog scale (VAS)). Global disability (HAQ) and QoL (SPI and SMI of SF-36) significantly improved, with all results (except for SMI) being maintained at a 9-week follow-up (49).

In order to treat the hands in the later sclerotic phase, a 9-week rehabilitative program that was specifically designed for SSc and tailored to individual patients was conducted (26). Connective tissue massage, Mc Mennell manipulation, and daily home exercises were compared to home exercises only. In all, 20 SSc patients treated with the combined protocol showed significant improvements in fist closure, hand function (evaluated by HAMIS and CHFDS), global disability (HAQ-DI), and QoL (SPI and SMI of SF-36) over the control group. All results, except for SPI and SMI, were maintained at a 9-week follow-up. In the control group, the home exercise program improved fist closing only (26). These findings indicate that rehabilitation techniques need to be integrated, selected, and tailored to SSc patients individually according to the phase of their disease.

Face rehabilitation

In SSc, face rehabilitation aims to improve mouth function (mouth opening, chewing, and swallowing) and disabilities, movements, and alignment of the cervical spine. Exercises include the exaggeration of usual facial movements and oral augmentation exercises (manual stretching of the mouth, executed by thumbs and tongue depressors). Two studies conducted on small cohorts of patients showed the significant impact of these exercises on mouth opening (50, 51). However, a more recent RCT evaluating daily manual mouth-stretching and oral augmentation exercises in 13 SSc patients versus a control group (15 patients) showed that exercises significantly improved mouth opening at a 3-month, but not 6-month evaluation (52). These findings may have been due to the low adherence rate to the program and the insufficient frequency, repetition, and duration of the exercises (50, 51). Another RCT was conducted to examine the efficacy of a 9-week program combining connective tissue massage, the Kabat’s technique (method of proprioceptive neuromuscular facilitation), physiotherapy, and daily home exercises in 20 SSc patients in the sclerotic phase and 20 patients performing home exercises only as a control group. The combined program significantly ameliorated mouth opening, facial skin scores, and oral disabilities (measured by MHISS). Improvements in mouth opening and skin scores were maintained at a 9-week follow-up. The control group reported a significant improvement in mouth opening only, but lost it at the follow-up (53). These findings indicate that facial rehabilitation is useful for improving mouth function and may ameliorate OHRQoL.

Global rehabilitation

In SSc patients, as well as in patients affected by other chronic systemic rheumatic diseases, rehabilitation needs to include a global rehabilitation program in order to improve posture, breathing, muscle strength, and overall QoL. The musculoskeletal system needs to be treated in its entirety in order to prevent or reduce impairments in all other areas and prevent damage due to postural adjustments. A careful clinical assessment including local and global evaluations provides important information for a comprehensive rehabilitation program that needs to be tailored and centered on the physical, psychological, and social conditions of the patient (54).

De Oliveira et al. (55) reviewed aerobic and resistance exercises for SSc. Most studies included a small number of SSc patients comprising those with and without pulmonary involvement. The presence of pulmonary involvement needs to be considered in global rehabilitation because SSc patients without pulmonary involvement have the ability to perform and benefit from aerobic exercises of at least moderate intensity. Exercise tolerance, aerobic capacity, walking distance, muscle strength, and muscle function as well as HRQoL improved after participation in programs including aerobic exercise and aerobic exercise combined with resistance exercise (55).

Alexanderson et al. enrolled four SSc patients (two with lung fibrosis) in a 6-week non-interventional baseline period program and 8-week exercise intervention period program. Patients completed aerobic exercise corresponding to 15 on the Borg scale and muscular endurance training three times/week. Physical capacity (6MWT), aerobic capacity (submaximal treadmill test), and muscle endurance in shoulder and hip flexion (Functional Index 2) were assessed every other week throughout the 14-week study. Muscular endurance significantly improved in three patients, while aerobic capacity showed significantly or clinically relevant improvements in two patients, suggesting that an 8-week exercise program was largely successful with positive effects on aerobic capacity and muscle endurance (56). Antonioli et al. enrolled 16 SSc patients (7 with ILD) who received 10 individual 30 min sessions of interventional therapy (including a warm up, cool down, motor function training, respiratory exercises, walking, finger stretching, and occupational therapy) and 17 SSc patients (9 with ILD) who received standard care. The 16 SSc patients receiving interventional therapy were also instructed to exercise at home. After 4 months, patients receiving interventional therapy had significantly better hand mobility, exercise tolerance, and HRQoL. QoL significantly improved after the period of observation in most patients (57). In another study, a large-scale RCT was conducted on 220 SSc patients with a 12-month follow-up. The experimental intervention group included 112 SSc patients who received a 1 month personalized supervised physical therapy program provided by trained care providers followed by home sessions. The control group consisted of 108 SSc patients who underwent usual care that included ambulatory physical therapy. The primary outcome was the HAQ-DI score. Disabilities were reduced at 1 month in SSc patients in the physical therapy group. Significant differences were observed in hand mobility and function as well as pain at 1 month. Microstomia was reduced in the physical therapy group at 1, 6, and 12 months. However, no significant differences were noted in disabilities at 12 months. They concluded that a personalized physical therapy program did not reduce disabilities at 12 months, but had short-term benefits for SSc patients (58).

Pulmonary rehabilitation

ILD is a group of lung disorders affecting the tissue and spaces around the air sacs and is an important manifestation of SSc. Although the severity of ILD in SSc varies from mild to very severe, it is a leading cause of death in patients with SSc (59). Depending on exercise intensity, SSc patients with ILD develop hypoxia, shortness of breath, and coughing, which limit daily living behaviors.

The basic concept of pulmonary rehabilitation is to “reduce breathing difficulties” and “increase physical strength.” In order to achieve this, pulmonary rehabilitation involves the following: (1) maintaining the flexibility of the rib cage, (2) maintaining the flexibility of breathing-related muscles, (3) improving breathing-related muscle strength, (4) strengthening lower body muscles, (5) performing aerobic exercise, (6) understanding proper breathing methods, and (7) learning self-care and self-training. The actual training session is mainly tolerance exercise that sets the lowest SpO₂ during exercise training as 90% and muscle training for the extremities. Walking, an ergometer, and/or treadmill are frequently used for tolerance exercise. Training programs need to be designed and monitored for each patient by an experienced physiotherapist. Nishiyama et al. (60) evaluated the effects of pulmonary rehabilitation on patients with IPF. The program involved a twice-a-week outpatient program of exercise training integrated with peripheral muscle training. In the first week, a baseline assessment was performed that included the 6MWT and evaluations of BDI and SGRQ scores. Between the second and ninth week, exercise training was performed on a treadmill at 80% of the patient’s maximal walking speed assessed at baseline 6MWT or at 80% of the initial maximum workload evaluated by a cycle ergometer. Supplemental oxygen was given to maintain oxygen saturation at greater than 90% if desaturation was observed. Strength training for the limbs was conducted using elastic bands; exercises included arm raising and knee extensions for approximately 20 min. Few studies have investigated rehabilitation for SSc-related ILD, which applies the methods used for IPF and COPD.

A 43-year-old male SSc patient with decreasing oxygen saturation (SpO₂) because of severe ILD completed a 27-week walking exercise program (walking training and training for leg muscle strengthening) with SpO₂ monitoring. The continuous walking distance without severe hypoxia (SpO₂ > 90%) increased from 60 to 300 m after this program; however, his 6-min walking distance remained unchanged (61). Someya et al. reported that 16 SSc patients in a stable condition completed exercise training for 55 days on average. Mean 6MWT significantly improved from 467 to 502 m. The improvement in distance was negatively related to the baseline distance, but not to parameters from pulmonary function tests or echocardiograms. Oxygen saturation was normal at rest, but decreased in 15 patients at the end of the test. Exercise-induced oxygen desaturation was positively related to the diffusion capacity of the lungs for carbon monoxide at the baseline. Out of 16 patients, 7 showed ameliorated exercise-induced oxygen desaturation or no oxygen desaturation after exercise training. These findings indicated that exercise training was beneficial for improving exercise tolerance (62). Shoemaker et al. (63) described a patient with SSc and pulmonary arterial hypertension (PAH) with a forced vital capacity (FVC) of 85% who performed a 6-week cycle ergometer program three times per week at workloads progressing from 50% to 80% of the peak workload; maximal oxygen uptake improved by 4% and 6MWT by 101 m and the exercise program was tolerated well.

SSc patients without pulmonary involvement may be as physically active as the general population. Patients with mild pulmonary involvement may become physically active by engaging in moderate intensity exercises and participating in moderate-load resistance exercises. Pulmonary rehabilitation programs need to be carefully tailored for each patient in order to avoid unrecoverable damage because exercise tolerance largely varies among SSc patients due to the severity of pulmonary and cardiac involvement (Tab. II).

Table II.

Summary of rehabilitation studies on SSc patients

Domain	Study design	Intervention	Number of patients enrolled	Control group	Outcome parameters	Study outcomes	Reference
Hand	Pretest–post-test	Self-administrated exercises for finger stretching	Tx: 45 SSc	N/A	• Hand function (finger passive ROM) • Global disability (HAQ) • Skin score	Significant improvement in finger passive ROM (maintained at the 12-month follow-up) and hand function (HAQ)	Mugii et al. (47)
Hand	RCT	One hand treated with paraffin bath once a day. After the paraffin bath, hand exercises performed daily	Tx: 17 SSc Ctl: 17 SSc	Other hand treated with hand exercises only	• Hand function (ROM, HAMIS, and grip force) • Pain (VAS pain) • Skin concerns (VAS stiffness and VAS skin elasticity)	Significant increase in finger ROM and improvements in stiffness and skin elasticity	Sandqvist et al. (48)
Hand	RCT	Manual lymph drainage of the hand (1/week)	Tx: 19 SSc Ctl: 15 SSc	Observation (no manual lymph drainage)	• Hand function (hand volumetry, HAMIS, VAS hand edema, VAS hand pain, VAS interference edema, and VAS interference pain) • Global disability (HAQ) • Quality of life (SF-36)	Significant reduction in hand volume and improvements in HAMIS, VAS pain, VAS edema, VAS interference edema, VAS interference pain, HAQ, and SF-36	Maddali-Bongi et al. (49)
Hand	RCT	Connective tissue massage plus Mc Mennell joint manipulation (2/week)	Tx: 20 SSc Ctl: 20 SSc	Home daily ROM exercises	• Hand function (HAMIS, CHSF, hand opening, and fist closure) Global disability (HAQ) Quality of life (SF-36)	Tx: improved significantly for fist closure and hand function (HAMIS, CHSF, HAQ, and SF-36) Ctl: improved significantly for fist closure only	Maddali-Bongi et al. (26)
Face	Pretest–post test	Home daily mouth-stretching exercises	Tx: 10 SSc	N/A	• Mouth opening	Significant increase in mouth opening (improvements in eating, speaking, and ability to perform oral hygiene)	Pizzo et al. (51)
Face	RCT	Home daily mouth-stretching exercises plus oral augmentation exercises	Tx: 13 SSc Ctl: 15 SSc	Usual dental care	• Mouth opening	In Tx, significant increase in mouth opening from Ctl at 3 months, but not at 6 months	Yuen et al. (52)
Face	RCT	Connective tissue massage, Kabat’s method, and kinesiotherapy (2/week for 9 weeks) daily Mouth-stretching and oral augmentation exercises (for 18 weeks)	Tx: 13 SSc Ctl: 15 SSc	Mouth-stretching and oral augmentation exercises for 18 weeks	• Mouth function (MHISS, mouth opening) Facial skin score Global disability (HAQ) Quality of life (SF-36)	In Tx, significant improvement in mouth opening, facial skin scores, and MHISS. In Ctl, significant improvement in mouth opening only	Maddali-Bongi et al. (53)
Global	Pretest–post-test	Aerobic, resistance, and stretching exercises (3/week)	Tx: 4 SSc	N/A	• Physical capacity (6-min walk test), aerobic capacity (submaximal treadmill test), and muscle endurance (Functional Index 2) • Global disability (HAQ) • Quality of life (SF-36) • VAS Raynaud, VAS fatigue, and VAS global health	Three patients showed significantly improved muscle endurance, while two had significantly improved aerobic capacity	Alexanderson et al. (56)
Global	Pretest-post-test	Diaphragmatic breathing and controlled coughing exercises (5/week) Treadmill land free-walking Finger stretching and occupational therapy	Tx: 16 SSc Ctl: 17 SSc	No rehabilitation intervention	• Hand function (HAMIS) • Skin score • Global disability (HAQ) • Quality of life (SF-36) • 6-min walk test • Lung function test	In Tx, significant increase in hand function (HAMIS), decrease in heart rate and dyspnea (6-min walk test), and improvement in SF-36 In Ctl, no significant improvement in any parameter measured	Antonioli et al. (57)
Global	RCT	Personalized supervised physical therapy by trained care providers	Tx: 112 SSc Ctl: 108 SSc	Usual care (ambulatory physical therapy)	• Hand function (CHSF and MACTAR) • Microstomia • Skin score • Global disability (HAQ and SHAQ) • Quality of life (SF-36) • Aerobic capacity (FEV1.0)	No significant difference in disability (HAQ) at 12 months In Tx, significant decrease in disability (HAQ) at 1 and 6 months, increase in hand mobility and function, and pain at 1 month. In Tx, microstomia was lower at 1, 6, and 12 months	Rannou et al. (58)
Pulmonary	Pretest-post-test	Walking exercise training (5/week)	Tx: 16 SSc	N/A	• Exercise-induced oxygen desaturation after the 6-min walk test	6-min walk distance significantly improved; 7 out of 16 showed ameliorated exercise-induced oxygen desaturation	Someya et al. (62)

Tx = treatment group; Ctl = control group; N/A = not available; ROM = range of motion; HAQ = Health Assessment of Questionnaire; RCT = randomized controlled study; HAMIS = Hand Mobility in Scleroderma Scale; VAS = visual analog scale; SF-36 = Short Form 36; CHSF = Cochin Hand Function Scale; MHISS = Mouth Handicap in SSc scale; MACTAR = McMaster Toronto Arthritis; SHAQ = Scleroderma HAQ; FEV = forced expiratory volume.

Limitations and adverse effects of SSc rehabilitation

Appropriate rehabilitation may be useful for improving QoL in SSc patients and is often underappreciated in the management of SSc. However, there is currently limited evidence to support the efficacy and safety of rehabilitation for SSc because most studies on rehabilitation for SSc examined a small number of patients, adverse effects are rarely valuated, and the control group was often insufficient or absent. Therefore, direct evidence has not yet been obtained to demonstrate that rehabilitation stops or reduces the progression of this disease. Well-organized RCTs using a sufficient number of SSc patients and an adequate control group are needed in order to confirm the efficacy of rehabilitation. However, large rehabilitation RCTs are difficult to conduct for the following reasons: (1) the lack of information on rehabilitation for physicians, (2) difficulties associated with the recruitment of SSc patients, (3) limited institutions that provide professional rehabilitation programs, and (4) the lack of skilled physiotherapists and occupational therapists to evaluate and treat SSc patients.

Rehabilitation for SSc is safe and does not cause significant adverse effects when instructed by experienced physiotherapists and occupational therapists. However, safety needs to be carefully considered in order to avoid injury and severe damage. For example, in pulmonary rehabilitation, exercise desaturation of ≥4 predicts mortality (37) and is a prognostic sign (64) in patients with IPF.

Conclusion

The clinical characteristics and course of SSc are largely heterogeneous. Although rehabilitation is considered to be a part of the management of SSc patients, it may influence different aspects of the disease (e.g. skin and the musculoskeletal and respiratory systems). The following points are of importance: (1) the careful selection of patients for specific forms of rehabilitation, which need to consider the potential benefit-to-risk ratio; (2) individually designed and tailored rehabilitation programs; (3) careful monitoring of SSc patients undergoing rehabilitation, particularly those with life-threatening internal organ complications; and (4) the role of a multidisciplinary team (including not only experienced physiotherapists and occupational therapists, but also other specialists such as rheumatologists, pulmonologists, cardiologists, and dermatologists in the planning and supervision of rehabilitation for SSc patients).