The efficacy of dietary intervention on gastrointestinal involvement in systemic sclerosis:A systematic literature review

BACKGROUND: Gastrointestinal involvement in systemic sclerosis is common and a major cause of disease-related morbidity. Patients increasingly enquire about dietary modifications that may help with gastrointestinal symptoms. Many clinical practice reviews and treatment guidelines make specific reference to dietary modifications in the management of gastrointestinal involvement in systemic sclerosis. We report the findings of a systematic literature review designed to evaluate the evidence to support dietary modification in the management of gastrointestinal symptoms of systemic sclerosis.METHODS: A systematic literature review protocol was developed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered with the International prospective register of systematic reviews (CRD42018103549). Standardised searches of EMBASE and MEDLINE were undertaken to identify studies reporting the outcome of dietary modification in the management of gastrointestinal symptoms of systemic sclerosis. Wide heterogeneity in study design, interventions and study outcomes necessitated a qualitative data synthesis.RESULTS: Our standardised searches identified 1032 articles, of which 3 were deemed eligible for full data extraction. These studies were small (mean 19 subjects per study), single centre, short-term (mean 6 week duration) open-label non-randomised studies examining the role of probiotics, low-fermentable oligo-saccharides, disaccharides, monosaccharides, and polyol (low-FODMAP) diet and highly individualised medical nutrition therapy counselling, respectively. Improvements in patient-reported outcome assessment of gastrointestinal symptoms were reported after intervention with probiotic therapy and low-FODMAP diet but not following tailored dietary and nutritional counselling. The Risk of Bias Assessment Tool for Nonrandomized Studies identified high risk-of-bias for confounding variables and blinding of assessors in each of the three studies evaluated.CONCLUSIONS: The evidence-base to support dietary modification for gastrointestinal involvement in systemic sclerosis is currently limited and clinical practice guidelines should take a measured approach to such recommendations. The emergence of large patient registries could facilitate the capture of vital practice-based evidence regarding the efficacy of dietary modification in the management of gastrointestinal involvement in systemic sclerosis to inform future clinical practice guidelines.</p

Anti-phospholipid syndrome leading to digital ischaemia and rare organ complications in systemic sclerosis and related disorders

Antiphospholipid syndrome (APS) is an acquired, autoimmune thrombophilia that can occur as a primary disorder (with no associated disease) or secondary to infection, medication usage and autoimmune rheumatic diseases (ARDs). The association between APS and systemic lupus erythematosus (SLE) is well established, and practicing rheumatologists check for APS antibodies in the routine assessment of SLE, particularly if clinical features such as thrombotic events or pregnancy loss are present. APS secondary to systemic sclerosis (SSc)-related disorders is less widely recognised and easily overlooked. We describe 5 cases that highlight the varied breadth of clinical manifestations of APS in the context of SSc and related disorders. These cases range from uncomplicated Raynaud’s phenomenon, digital ulceration/necrosis, critical digital ischaemia/gangrene and rare internal organ complications of APS in SSc-spectrum disorders. To our knowledge, our cases include the first reported case of secondary APS contributing to digital necrosis in the context of RACAND syndrome (Raynaud’s phenomenon, anti-centromere antibodies and necrosis of the digits) and the first reported case of secondary APS in SSc causing posterior reversible encephalopathy syndrome (PRES). The case series is accompanied by a comprehensive review of the literature relevant to each case. Rheumatologists should be alert to the possibility of APS in SSc-spectrum disorders and should routinely check APS antibodies in all patients at diagnosis, and again later in the disease course if new features emerge that could indicate the presence of thrombotic events or other recognised APS manifestations.Key points• APS should be considered in all patients with digital ischaemic symptoms.• APS may be an important driver of SSc-related digital ulceration/necrosis.• Identification of SSc-associated APS opens up new therapeutic options for acute management and secondary prevention.</p

Product state control of bi-alkali chemical reactions

We consider ultracold, chemically reactive scattering collisions of the diatomic molecules KRb. When two such molecules collide in an ultracold gas, we find that they are energetically forbidden from reacting to form the trimer species K$_2$Rb or Rb$_2$K, hence can only react via the bond-swapping reaction 2KRb $\to$ K$_2$ + Rb$_2$. Moreover, the tiny energy released in this reaction can in principle be set to zero by applying electric or microwave fields, implying a means of controlling the available reaction channels in a chemical reaction.Comment: 4 pages double column, 2 figures, 2 table

Pauling and Frech reply

We thank Dr. Hughes for his interest1 in our article2 reporting factors influencing Raynaud phenomenon (RP) symptom reporting in patients with systemic sclerosis (SSc). We presented data demonstrating differences in Raynaud symptom reporting using the Raynaud Condition Score (RCS) diary depending on season of enrollment2.</p

Behaviour change interventions for the management of Raynaud's phenomenon : a systematic review protocol

Introduction Raynaud's phenomenon (RP) describes excessive peripheral vasospasm to cold exposure and/or emotional stress. RP episodes are associated with digital colour changes, pain and reduced quality of life. Pharmacological interventions are of low to moderate efficacy and often result in adverse effects such as facial flushing and headaches. Recommended lifestyle and behavioural interventions have not been evaluated. The objectives of the proposed systematic review are to assess the comparative safety and efficacy of behaviour change interventions for RP and identify what we can learn to inform future interventions. Methods and analysis Studies eligible for inclusion include randomised controlled trials testing behaviour change interventions with a control comparator. A comprehensive search strategy will include peer review and grey literature up until 30 April 2017. Search databases will include Medline, Embase, PsychINFO and Cochrane. Initial sifting, eligibility, data extraction, risk of bias and quality assessment will be subject to review by two independent reviewers with a third reviewer resolving discrepancies. Risk of bias assessment will be performed using Cochrane risk of a bias assessment tool with quality of evidence assessed using Grading of Recommendations Assessment, Development and Evaluation(GRADE). A meta-analysis will be performed if there are sufficient data. Two subgroup analyses are planned: primary versus secondary RP outcomes; comparison of theoretically informed interventions with pragmatic interventions. Ethics and dissemination This review does not require ethical approval as it will summarise published studies with non-identifiable data. This protocol complies with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. Findings will be disseminated in peer-reviewed articles and reported according to PRISMA. This review will make a significant contribution to the management of RP where no review of behaviour-change interventions currently exist. The synopsis and protocol for the proposed systematic review is registered in the International Prospective Register of Systematic Reviews (registration number CRD42017049643)

Behaviour change interventions for the management of Raynaud's Phenomenon: A systematic review

Objectives Raynaud’s phenomenon (RP) is a significant cause of morbidity. Vasodilator medications cause unwanted adverse effects, with behavioural and lifestyle changes forming the mainstay of self-management; this is difficult to implement successfully. The objectives of this study were to evaluate the efficacy of behaviour change interventions for RP and identify learning points for future treatment development.Design Systematic literature review and narrative synthesis of findings.Data sources EMBASE, MEDLINE, Cochrane and PsycINFO were searched for eligible studies on 22 August 2017.Eligibility criteria Randomised controlled trials (RCTs) of behaviour change interventions with at least one control comparator arm.Data extraction and synthesis Study selection, data extraction and risk of bias were assessed independently by two reviewers, reaching consensus with a third when necessary. Primary outcomes of interest included severity/impact, frequency and duration of RP episodes, pain, disability, adverse events and study withdrawal.Results Of 638 articles retrieved, eight studies fulfilled criteria for inclusion. Biofeedback was the active behaviour change treatment arm for seven studies, with one study reporting a behavioural intervention. Studies were published 1978–2002; six were USA-based studies, one German and one Swedish. Using Cochrane Risk of Bias assessment, studies were assessed to be overall at high risk of bias, with the exception of one large RCT. The total sample included 495 participants (study median=29), with a median age of 39.5 years and preponderance towards females (73%). Five studies reported significant effects in primary outcomes of interest; however, due to missing data, relative efficacy of interventions could not be reliably assessed.Conclusions There is no evidence to support or refute claims of the efficacy of behaviour change interventions for the management of RP. There remains a strong case for developing and testing behaviour change interventions that focus on self-management; however, theoretical development and advancement in trial quality is imperative to underpin future work

The challenge of establishing treatment efficacy for cutaneous vascular manifestations of systemic sclerosis

INTRODUCTION: The cutaneous vascular manifestations of systemic sclerosis (SSc) comprise Raynaud's phenomenon, cutaneous ulceration, telangiectasia formation and critical digital ischaemia; each of which are associated with significant disease-related morbidity. Despite the availability of multiple classes of vasodilator therapy, many of which have been the subject of RCTs, a limited number of pharmacological interventions are currently approved for the management of cutaneous vascular manifestations of SSc. Areas covered: A major challenge has been demonstrating treatment efficacy with examples of promising therapies yielding contrasting results in controlled trial settings. Differences between consensus best-practice guidelines, evidence-based recommendations and marketing approvals in different jurisdictions has resulted in geographic variation in clinical practice concerning the management of cutaneous vascular manifestations of SSc. Difficulty demonstrating treatment efficacy risks waning industry engagement for drug development programmes in this field. This article highlights the key challenges in establishing treatment efficacy and barriers that must be overcome to support successful clinical trial programmes across the spectrum of cutaneous vascular manifestations of SSc. Expert commentary: The paucity of approved treatments for cutaneous vascular manifestations of SSc relates as much to challenges in clinical trial design and the need for reliable clinical trial endpoints, as to lack of therapeutic options.</p

Impact of Covid-19 on clinical care and lived experience of systemic sclerosis:An international survey from EURORDIS-Rare Diseases Europe

INTRODUCTION: Outcomes related to Covid-19 in systemic sclerosis patients could be influenced by internal organ involvement and/or immunosuppressive treatment, leading to efforts to shield patients from Covid-19 transmission. We examined the impact of Covid-19 on the lived experience of systemic sclerosis with regards to other aspects of daily living including occupation and emotional well-being. METHOD: Individuals with systemic sclerosis or relatives/carers participated in an online survey, disseminated through international patient associations and social media pages, designed to examine the impact of Covid-19 on living with a rare disease. RESULTS: Responses from 121 individuals (98% were patients with systemic sclerosis) from 14 countries were evaluable. Covid-19 was considered a probable/definite personal threat (93%) or threat for the individual they care for (100%). Approximately two-thirds of responders reported either cancellation or postponement/delay to appointments, diagnostic tests, medical therapies at home (e.g. infusions), surgery or transplant, psychiatry follow-up or rehabilitation services. Twenty-six percent reported at least one systemic sclerosis medicine/treatment had been unavailable, and 6% had to either stop taking usual medications or use an alternative. Most reported online consultations/telemedicine via phone (88%) and online (96%) as being ‘fairly’ or ‘very’ useful. Respondents reported tensions among family members (45%) and difficulty overcoming problems (48%). Restrictions on movement left around two-thirds feeling isolated (61%), unhappy and/or depressed (64%), although the majority (85%) reported a strengthening of the family unit. CONCLUSION: Covid-19 has resulted in significant impact on the clinical-care and emotional well-being of systemic sclerosis patients. Changes to clinical care delivery have been well-received by patients including telemedicine consultations

Factors influencing Raynaud condition score diary outcomes in systemic sclerosis

Objective. Raynaud phenomenon (RP) in systemic sclerosis (SSc) could be influenced by clinical phenotype, environmental factors (e.g., season), and personal factors (e.g., coping strategies and ill-health perceptions). We studied the relative influence of a range of putative factors affecting patient-reported assessment of SSc-RP severity. Methods. SSc patients were enrolled at UK and US sites. Participants completed the 2-week Raynaud Condition Score (RCS) diary alongside collection of patient demographics, clinical phenotype, the Coping Strategies Questionnaire, Pain Catastrophizing Scale, Scleroderma Health Assessment Questionnaire (SHAQ), and both patient/physician visual analog scale (VAS) assessments for RP, digital ulcer disease, and global disease. Environmental temperature data were obtained at each site. A second RCS diary was completed 6 months after enrollment. Results. We enrolled 107 patients (baseline questionnaires returned by 94). There were significant associations between RCS diary variables and both catastrophizing and coping strategies. There were significant associations between RCS diary outcomes and both environmental temperature and season of enrollment. Age, disease duration, sex, disease subtype, smoking, and vasodilator use were not associated with RCS diary outcomes. The best-fitting multivariate model identified the patient RP VAS, SHAQ pain VAS, and SHAQ gastrointestinal VAS subscales as the strongest independent predictors of the RCS. Conclusion. Patient-reported assessment of SSc-RP severity is associated with a number of factors including pain, catastrophizing, and coping strategies. The effects of seasonal variation in environmental temperature on SSc-RP burden has implications for clinical trial design. Treatments targeting SSc-RP pain and the development of behavioral interventions enhancing coping strategies may reduce the burden of SSc-RP.</p