EULAR recommendations for the non-pharmacological management of systemic lupus erythematosus and systemic sclerosis

Objective To develop evidence-based recommendations for the non-pharmacological management of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Methods A task force comprising 7 rheumatologists, 15 other healthcare professionals and 3 patients was established. Following a systematic literature review performed to inform the recommendations, statements were formulated, discussed during online meetings and graded based on risk of bias assessment, level of evidence (LoE) and strength of recommendation (SoR; scale AD , A comprising consistent LoE 1 studies, D comprising LoE 4 or inconsistent studies), following the European Alliance of Associations for Rheumatology standard operating procedure. Level of agreement (LoA; scale 0-10, 0 denoting complete disagreement, 10 denoting complete agreement) was determined for each statement through online voting. Results Four overarching principles and 12 recommendations were developed. These concerned common and disease-specific aspects of non-pharmacological management. SoR ranged from A to D. The mean LoA with the overarching principles and recommendations ranged from 8.4 to 9.7. Briefly, non-pharmacological management of SLE and SSc should be tailored, person-centred and participatory. It is not intended to preclude but rather complement pharmacotherapy. Patients should be offered education and support for physical exercise, smoking cessation and avoidance of cold exposure. Photoprotection and psychosocial interventions are important for SLE patients, while mouth and hand exercises are important in SSc. Conclusions The recommendations will guide healthcare professionals and patients towards a holistic and personalised management of SLE and SSc. Research and educational agendas were developed to address needs towards a higher evidence level, enhancement of clinician-patient communication and improved outcomes

The nature and impact of oral disease of systemic sclerosis

Systemic Sclerosis (SSc) is a multisystem immune-mediated disorder that by virtue of its many possible orofacial features has the potential to adversely affect oral function, impact on oral health care and lessen the quality of life. This thesis has sought to determine the oral and dental consequences of SSc upon a substantial group of affected individuals in the UK. A retrospective analysis of 138 patients with SSc found that the most frequent extra-oral feature was facial skin fibrosis followed by perioral skin tightening, 37% and 35% respectively. Intra-oral features were common, as 73% of patients had microstomia and 47% had xerostomia and generalised chronic periodontitis. An assessment of the online information regarding the treatment of the oral manifestations of SSc found that there are general scarcity of websites providing relevant content with most sites being of poor quality and difficult to read. A cross-sectional observational questionnaire study of the implications of SSc upon the access to dental care services and oral health-related quality of life (OHRQoL) indicated that SSc has a negative impact on general and OHRQoL with a high level of psychological disability that included pain, anxiety and depression. A detailed study of the psychometric properties of the only specific patient-reported outcome measure Mouth Handicap in Systemic Sclerosis (MHISS) in a large group of patients with SSc found that this instrument had good levels of validity and reliability with respect to patients resident in the UK. The results of this thesis indicate that many patients with SSc may have oral manifestations that can potentially impact adversely upon their oral function, ability to maintain good oral health and lessen OHRQoL. They will not be able to obtain reliable, understandable information from the world wide web concerning oral aspects of SSc – although their OHRQoL can be assessed well using the MHISS

Elaboration and administration of new measures of disease course and outcome in patients with systemic sclerosis and idiopathic inflammatory myopathies

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The Effects of Exercise on Vascular Physiology in Systemic Sclerosis Patients

The original research in this thesis aimed to investigate the efficacy and feasibility of exercise in people with systemic sclerosis (SSc). The heralding symptom in the pathophysiology of SSc is vascular dysfunction in the digital area which is the primary cause of Raynaud's phenomenon (RP). Digital disfiguration, ulcers and RP affect the quality of life (QoL) in people with SSc. Medical treatment does not have dramatic improvements and is also accompanied by short- and long-term side effects leading to further health complications. Exercise could be considered as a safe and cost-effective adjunct therapy that could potentially reduce the use of medication. The primary outcomes in study 1 were the physiological differences between the arm crank (ACE) and cycler ergometer (CE) protocols in sedentary adults. Study 2 investigated the microvascular function, quality of life, cardiorespiratory fitness, functional capacity and body composition in people with SSc. Study 3 explored the feasibility of exercise in people with SSc with primary outcomes being the recruitment and attrition rates as well as the adherence rates to exercise. The novel findings of this research were: Study's 1 novelty was 1) the predictive equation for the cycle ergometer peak oxygen uptake (CEV̇ O2peak) trough the physiological responses of ACE and body composition features (Study 1). The equation estimated with this model is: CEV̇ O2peak = 11.776 + 1.418 X arm crank ergometer peak oxygen uptake (ACEV̇ O2peak) (ml·kg-1·min-) – 1.454 x total lean body mass (TLBM) + 3.967 X lower limb lean body mass (LLLBM). This predictive equation was later used in study 2 to compare ACE to CE V̇ O2peak as a correlation between the improvement of microcirculation (laser-Doppler fluximetry) and V̇ O2peak has been demonstrated in rheumatoid arthritis patients before (Metsios et al., 2014). Study's 2 novelties were 2) ACE seems more potent to improve the microcirculation in the digital area in people with SSc compared to CE, 3) the exercise programme that consisted of a high intensity interval training (HIIT) protocol that was performed for 12 weeks twice per week seems capable to prevent the formation of digital ulcers in people with SSc and the concomitant hospitalisations and/or in some occasions digital amputations, 4) QoL in people with SSc significantly improved after the exercise intervention. Study's 3 novelties were that 5) the exercise programme (12 weeks, twice/week) was feasible in people with SSc with very high recruitment and adherence rates, 6) our combined exercise protocol (HIIT and resistance training) was enjoyable and fairly easy to be performed by our participants, 7) individuals experiences confirmed the feasibility of our intervention and exercise protocol and highlighting the importance of applying supervised exercise programmes. Study 2 acted as a guiding study as to which mode of exercise could induce better results in the microcirculation in the digital area. Afterwards, study 3 utilised the upper limb exercise with weight training to assess its feasibility in people with systemic sclerosis. These findings contribute to the growing evidence base for the effects of exercise in people with SSc. Our study is the first to investigate the effects of HIIT on digital microcirculation in people with SSc and the first to explore the feasibility of a combined exercise protocol in this clinical population. Future research should explore the effects of exercise in people with SSc in larger clinical trials

THE EFFECT OF SOCIO-ECONOMIC STATUS AS MEASURED BY EDUCATION ON OUTCOMES IN SCLERODERMA (SYSTEMIC SCLEROSIS)

The goal of this study was to assess socioeconomic status (SES) as a social determinant of outcomes in patients with systemic sclerosis (SSc). In systemic lupus erythematosus, SES has a large effect on outcomes. It is unknown what the effect of SES is on outcomes in SSc. SES is often measured by income, occupation and education. In SSc, highest education would be attained decades prior to disease onset whereas current income and occupation could be low due to SSc and thus would confound interpretation of effect of SES on SSc. Therefore, education was used as a measure of SES in this study. Bivariate, regression and survival analyses were used to study the effect of education on SSc outcome. Education had a very limited role as a risk factor of poor outcome in SSc. It had a significant statistical association with forced vital capacity in case of limited SSc only

Psychological Factors in Symptom Severity and Quality of Life in Raynaud’s Phenomenon

Background: Despite emotional stress being recognised as a key trigger for Raynaud’s phenomenon episodes, research in the area is still in its infancy.Aims: This study investigated the role of psychological factors relating to symptom severity and quality of life, and differences between Raynaud’s types (primary and secondary) to further inform the development of intervention in this field.Method: A cross-sectional design was used. Two hundred and ten adults with Raynaud’s completed an online questionnaire measuring stress, anxiety, depression, anxiety sensitivity, beliefs about emotions, symptom severity and quality of life. Results: Primary and secondary Raynaud’s groups differed in anxiety (p < .004), symptom severity (p < .001) and quality of life (p < .001). Stepwise multiple regressions indicated anxiety and Raynaud’s type explained 23% variance in hand symptom severity (p < .001); anxiety, Raynaud’s type and anxiety sensitivity explained 29% variance in symptom severity (global impact, p < .001); depression, Raynaud’s type and anxiety sensitivity explained 32% variance in quality of life (p < .001).Conclusions: Results highlight the importance of psychological factors in Raynaud’s phenomenon, indicating possible targets for treatment. Interventions such as cognitive behavioural therapy, which target both physical and psychological wellbeing, bear some promise as an adjuvant therapy for this group

Clinical trajectories of hand function impairment in systemic sclerosis: an unmet clinical need across disease subsets

Background Hand involvement is an early manifestation of systemic sclerosis (SSc), culprit of diagnosis and classification, and recognised major driver of disability. Impairment of hand function burdens both limited and diffuse cutaneous subsets and therefore could be targeted as ‘basket’ endpoint in SSc. Nevertheless, its natural history in current standard of care is not well characterised, limiting the design of targeted trials. The aim of this study is to describe prevalence, natural history and clinical factors associated with hand function deterioration in a longitudinal, multicentre, observational SSc cohort. Methods Hand function was captured through the validated Cochin Hand Function Scale in patients consecutively enrolled in a multicentre observational study and observed over 24 months. Minimal clinically important differences and patient acceptable symptom state were analysed as previously described. Results Three hundred and ninety-six consecutive patients were enrolled from 10 centres; 201 with complete follow-up data were included in the analysis. Median (IQR) disease duration was 5 (2–11) years. One hundred and five (52.2%) patients reported clinically significant worsening. Accordingly, the proportion of patients reporting unacceptable hand function increased over 2 years from 27.8% to 35.8% (p<0.001). Least absolute shrinkage and selection operator analysis identified male gender, disease subset, Raynaud’s Condition Score, tenosynovitis and pain, as some of the key factors associated with worsening hand involvement. Conclusions Hand function deteriorates over time in more than 50% of SSc patients despite available therapies. The analysis of factors associated with hand function worsening supports the involvement of both inflammation, vascular and fibrotic processes in hand involvement, making it a hallmark clinical manifestation of SSc. Our data are poised to inform the design of intervention studies to target this major driver of disability in SSc

Multifactorial pathways contributing to the development and impact of foot problems in systemic sclerosis (scleroderma)

Systemic sclerosis (SSc) is a heterogeneous connective tissue disease characterised by vasculopathy, immune activation and fibrosis [1-3]. The multisystem nature of the disease has a wide-ranging impact on the patient’s overall health on physical, psychological and psychosocial levels [4] [5-7]. While foot problems in patients with SSc have been previously described and that their presence is associated with disability [8-10], the impact of such problems and its major contributors has yet to be determined. The underpinning hypothesis of this thesis was that the development and impact of foot problems on the Quality of Life (QoL) of patients with SSc is multifactorial; involving a complex inter-relationship between disease, functional impairment, personal factors, environmental factors and psychosocial factors. In order to explore this hypothesis, a multiple methodological approach was employed. First, a literature review and a consultation with clinical experts was undertaken to identify the potential candidate factors that may contribute to foot problems. Second, a case-control, cross-sectional study of 121 patients with SSc and 51 healthy participants was undertaken in order to investigate the impact of factors that contribute to foot problems. Finally, the pathway by which the candidate factors that were identified as contributing to foot pathology impacted on the overall quality of life in people with SSc was explored. Using data from the same 121 patients with SSc, structural equation modelling (SEM) was used to explore the inter-relationships between multifactorial pathways associated with foot pathology and its impact on patients with SSc. The results from this thesis can be summarised as follows: i) patients with SSc have significant foot problems; ii) SSc has both a physical and psychological impact; iii) foot problems are affected by complex interrelations between multiple factors; and iv) foot problems are a significant contributor to the impact on the quality of life of patients with SSc

Patient and healthcare professional eHealth literacy and needs for systemic sclerosis support: a mixed methods study

OBJECTIVES: We engaged patients with systemic sclerosis (SSc) and healthcare professionals to assess electronic health (eHealth) literacy and needs relating to web-based support using internet-based information and communication technologies (ICT). METHODS: We employed an explanatory sequential mixed methods design. First, we conducted a cross-sectional survey in patients (n=101) and professionals (n=47). Next, we conducted three focus groups with patients, family members and professionals (n=17). RESULTS: Of patients, 89.1% used ICT at least weekly for private communication. Patients reported relatively high comprehension of eHealth information ([Formula: see text] =6.7, 95% CI: 6.2 to 7.3, range 1-10), yet were less confident evaluating information reliability ([Formula: see text] =5.8, 95% CI: 5.1 to 6.4) and finding eHealth apps ([Formula: see text] =4.8, 95% CI: 4.2 to 5.4). Patients and professionals reported little experience with web-based self-management support. Focus groups revealed 'considering non-ICT-accessible groups' and 'fitting patients' and professionals' technology' as crucial for acceptability. In relation to understanding/appraising eHealth, participants highlighted that general SSc information is not tailored to individual's disease course. Recommendations included 'providing timely, understandable and safe information' and 'empowering end-users in ICT and health decision-making skills'. Professionals expressed concerns about lacking resources. Patients were concerned about data security and person-centredness. Key eHealth drivers included 'addressing end-user perceptions' and 'putting people at the centre of technology'. CONCLUSIONS: Patients and professionals need education/training to support uptake of eHealth resources. Key elements include guiding patients to timely/reliable information and using eHealth to optimise patient-provider communication. Design that is responsive to end-users' needs and considers individuals with limited eHealth literacy and/or ICT access appears to be critical for acceptability