Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX. INTRODUCTION: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD). METHODS: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted ß-coefficients. RESULTS: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination. CONCLUSION: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.

Update of the fracture risk prediction tool FRAX: a systematic review of potential cohorts and analysis plan.

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Patients' and rheumatologists' perspectives on the efficacy and safety of low-dose glucocorticoids in rheumatoid arthritis-an international survey within the GLORIA study.

OBJECTIVE: To evaluate the current perspectives of patients and health professionals regarding the efficacy and safety of low-dose glucocorticoids (GCs) in RA. METHODS: Two online surveys were disseminated to patients and health professionals, in their native language, through national patient organizations and national rheumatology medical societies, respectively. SurveyMonkey®, MediGuard.org and the Glucocorticoid Low-dose Outcome in RA Study (GLORIA) website were used to offer and deliver these surveys. RESULTS: A total of 1221 RA patients with exposure to GCs, and 414 rheumatologists completed the surveys. Patients and rheumatologists reported high levels of agreement regarding the efficacy of low-dose GCs: at least 70% considered that they are very rapid and effective in the control of signs and symptoms of RA. However, half of the patients also reported having suffered serious adverse events with GCs, and 83% described concerns about safety. The majority of rheumatologists estimated that endocrine, ophthalmologic and cutaneous adverse events affect >4% of all patients treated with low-dose GCs for 2 years, based on a heat map. CONCLUSIONS: RA patients with self-reported exposure to GCs express high levels of satisfaction with low-dose GCs efficacy, as do rheumatologists. However, both expressed excessive concerns regarding the safety of GCs (greatly exceeding the published evidence data), which may compromise the optimal use of this medication. This study indicates that there is an unmet need for appropriately designed prospective trials that shed light on the real risk associated with low-dose GCs, as well as a need for renovated educational programs on the real benefits and harms of low-dose GCs, for both patients and physicians.

Multitarget therapy of mycophenolate mofetil and cyclosporine A for induction treatment of refractory lupus nephritis.

Standard induction therapy for lupus nephritis (LN) with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) is often ineffective. Evidence on rescue induction regimens is scarce. We analyzed efficacy and tolerability of multitarget immunosuppression with MMF and cyclosporine A (CsA) as induction treatment for LN (class III/IV/V) refractory to CYC and/or MMF. We included all six refractory LN patients (class IV = 3, class V = 2, class III = 1) from our 400-patient tertiary Lupus Clinic observed between 2012 and 2015. Four patients had previously received pulse CYC. All six received MMF as first or second induction therapy and CsA was added once failure to reach remission was established. Daily dose of MMF was 2-3 g and CsA was dosed up to 2.6-3.7 mg/kg/day. Mean proteinuria was reduced from 2407 mg/24 hours at the start of the MMF+CsA regimen to 544 mg/day after six months. The mean prednisolone dose was reduced from 17.5 to 6 mg/day after six months of MMF+CsA. Four patients achieved a complete renal response, one patient had a partial renal response and one failed to respond. None of the patients presented with adverse events. These data suggest that adding CsA to MMF can induce complete remission of refractory LN and is well tolerated.

The Portuguese Rheumatoid Arthritis Impact of Disease (RAID) score and its measurement equivalence in three countries: validation study using Rasch Models.

PURPOSE: The Rheumatoid Arthritis Impact of Disease (RAID) score assesses seven impact domains of interest for people with RA. This study aimed to test patients' understanding of the Portuguese RAID and evaluate its cross-cultural validity for use in Portugal. METHODS: This was a mixed methods study comprising two phases: (i) cognitive debriefing to determine patient's comprehension of the Portuguese RAID and (ii) cross-cultural validation using Rasch analysis. Construct validity was determined by fit to the model, invariance culture (compared with France and UK datasets) and evidence of convergent and divergent validity. RESULTS: Patients' input (n = 38) led to minor changes in the phrasing of two items to ensure conceptual equivalence between the Portuguese and the original RAID. In Rasch analysis (n = 288), two items 'Sleep' and 'Physical well-being' in the Portuguese dataset did not adequately fit the model specifications, suggesting multidimensionality (sleep-not necessarily associated with RA) and redundancy (physical well-being overlapping with functional disability). Despite the imperfections, the scale had high internal consistency, evidence of convergent and divergent validity and invariance to culture (compared to France n = 195 and UK n = 205 datasets). The scale was well targeted for patients with different levels of disease impact. CONCLUSIONS: The RAID has been successfully adapted into Portuguese and it can be used with confidence in clinical practice. Further research will be required to ensure it captures the full range of sleep problems in RA. Meanwhile, data across the three countries (Portugal, France and the UK) are comparable except for the two items (sleep and physical well-being).

The burden of osteoporotic hip fractures in Portugal: costs, health related quality of life and mortality.

UNLABELLED: The study rationale was to provide a detailed overview of the costs, quality of life and mortality of hip fractures in Portugal. Mean individual fracture-related costs were estimated at €13,434 [12,290; 14,576] for the first year and €5985 [4982; 7045] for the second year following the fracture. INTRODUCTION: Osteoporotic fractures represent a remarkable burden to health care systems and societies worldwide, which will tend to increase as life expectancy expands and lifestyle changes favour osteoporosis. The cost-effectiveness evaluation of intervention strategies demands accurate data on the epidemiological and economical reality to be addressed. METHODS: Information was collected retrospectively on consumption of resources and changes in quality of life attributable to fracture as well as mortality, regarding 186 patients randomly selected to represent the distribution of hip fractures in the Portuguese population, in terms of gender, age and geographical provenience. Data were cross-tabulated with socio-demographic variables and individual resource consumption to estimate the burden of disease. A societal perspective was adopted, including direct and indirect costs. Multivariate analyses were carried out to assess the main determinants of health-related quality of life (HrQoL). RESULTS: Mean individual fracture-related costs were estimated at €13,434 [12,290; 14,576] for the first year and €5985 [4982; 7045] for the second year following the fracture. In 2011 the economic burden attributable to osteoporotic hip fractures in Portugal could be estimated at €216 million. Mean reduction in HrQoL 12 months after fracture was estimated at 0.34. Regression analysis showed that age was associated with a higher loss of HrQoL, whereas education had the opposing effect. We observed 12 % excess mortality in the first year after hip fracture, when compared to the gender and age-matched general population. CONCLUSIONS: Results of this study indicate that osteoporotic hip fractures are, also in Portugal, despite its low incidence of fractures and cost per event, associated with a high societal burden, in terms of costs, loss in HrQoL and mortality. These data provide valuable input to the design and selection of fracture prevention strategies.

Characterization of damage in Portuguese lupus patients: analysis of a national lupus registry.

BACKGROUND: Although the survival rate has considerably improved, many patients with systemic lupus erythematosus (SLE) develop irreversible organ damage. OBJECTIVES: The objectives of this paper are to characterize cumulative damage in SLE patients and identify variables associated with its presence and severity. METHODS: A cross-sectional analysis of SLE patients from the Portuguese Lupus register Reuma.pt/SLE in whom damage assessment using the SLICC/ACR-Disability Index (SDI) was available was performed. Predictor factors for damage, defined as SDI ≥ 1, were determined by logistic regression analyses. A sub-analysis of patients with severe damage (SDI ≥ 3) was also performed. RESULTS: In total, 976 patients were included. SDI was ≥1 in 365 patients, of whom 89 had severe damage. Musculoskeletal (24.4%), neuropsychiatric (24.1%) and ocular (17.2%) domains were the most commonly affected. Older age, longer disease duration, renal involvement, presence of antiphospholipid antibodies and current therapy with steroids were independently associated with SDI ≥ 1. The subpopulation with severe damage had, in addition, a greater interval between the first manifestation attributable to SLE and the clinical diagnosis as well as and more frequently early retirement due to SLE. CONCLUSIONS: This large lupus cohort confirmed that demographic and clinical characteristics as well as medication are independently associated with damage. Additionally, premature retirement occurs more often in patients with SDI ≥ 3. Diagnosis delay might contribute to damage accrual.

Coexisting primary Sjögren's syndrome and sarcoidosis: coincidence, mutually exclusive conditions or syndrome?

Herein, we describe a 44-year-old female diagnosed with histologically proven coexistence of primary Sjögren's syndrome and sarcoidosis with pulmonary and muscular involvement. The differential diagnosis may be difficult, but this is not an exceptional case, which highlights the need to critically revise the consideration of sarcoidosis as an exclusion for primary Sjögren's syndrome, as established in current classification criteria.

EULAR evidence-based and consensus-based recommendations on the management of medium to high-dose glucocorticoid therapy in rheumatic diseases.

To develop recommendations for the management of medium to high-dose (ie, >7.5 mg but ≤100 mg prednisone equivalent daily) systemic glucocorticoid (GC) therapy in rheumatic diseases. A multidisciplinary EULAR task force was formed, including rheumatic patients. After discussing the results of a general initial search on risks of GC therapy, each participant contributed 10 propositions on key clinical topics concerning the safe use of medium to high-dose GCs. The final recommendations were selected via a Delphi consensus approach. A systematic literature search of PubMed, EMBASE and Cochrane Library was used to identify evidence concerning each of the propositions. The strength of recommendation was given according to research evidence, clinical expertise and patient preference. The 10 propositions regarded patient education and informing general practitioners, preventive measures for osteoporosis, optimal GC starting dosages, risk-benefit ratio of GC treatment, GC sparing therapy, screening for comorbidity, and monitoring for adverse effects. In general, evidence supporting the recommendations proved to be surprisingly weak. One of the recommendations was rejected, because of conflicting literature data. Nine final recommendations for the management of medium to high-dose systemic GC therapy in rheumatic diseases were selected and evaluated with their strengths of recommendations. Robust evidence was often lacking; a research agenda was created.

Comparing Prevalence of Sarcopenia Using Twelve Sarcopenia Definitions in a Large Multinational European Population of Community-Dwelling Older Adults.

OBJECTIVES: Multinational prevalence data on sarcopenia among generally healthy older adults is limited. The aim of the study was to assess prevalence of sarcopenia in the DO-HEALTH European trial based on twelve current sarcopenia definitions. SETTING AND PARTICIPANTS: This is an analysis of the DO-HEALTH study including 1495 of 2157 community-dwelling participants age 70+ years from Germany, France, Portugal, and Switzerland with complete measurements of the sarcopenia toolbox including muscle mass by DXA, grip strength, and gait speed. MEASUREMENTS: The twelve sarcopenia definitions applied were Asian Working Group on Sarcopenia (AWGS1), AWGS2, Baumgartner, Delmonico, European Working Group on Sarcopenia in Older People (EWGSOP1), EWGSOP2, EWGSOP2-lower extremities, Foundation for the National Institutes of Health (FNIH1), FNIH2, International Working Group on Sarcopenia in Older People (IWGS), Morley, and Sarcopenia Definitions and Outcomes Consortium (SDOC). RESULTS: Mean age was 74.9 years (SD 4.4); 63.3% were women. Sarcopenia prevalence ranged between 0.7% using the EWGSOP2 or AWGS2 definition, up to 16.8% using the Delmonico definition. Overall, most sarcopenia definitions, including Delmonico (16.8%), Baumgartner (12.8%), FNIH1(10.5%), IWGS (3.6%), EWGSOP1 (3.4%), SDOC (2.0%), Morley (1.3%), and AWGS1 (1.1%) tended to be higher than the prevalence based on EWGSOP2 (0.7%). In contrast, the definitions AWGS2 (0.7%), EWGSOP2-LE (1.1%), FNIH2 (1.0%) - all based on muscle mass and muscle strength - showed similar lower prevalence as EWGSOP2 (0.7%). Moreover, most sarcopenia definitions did not overlap on identifying sarcopenia on an individual participant-level. CONCLUSION: In this multinational European trial of community-dwelling older adults we found major discordances of sarcopenia prevalence both on a population- and on a participant- level between various sarcopenia definitions. Our findings suggest that the concept of sarcopenia may need to be rethought to reliably and validly identify people with impaired muscle health.

European League Against Rheumatism recommendations for the inclusion of patient representatives in scientific projects.

OBJECTIVE: To develop recommendations to enable successful inclusion of the patient perspective in European League Against Rheumatism (EULAR)-funded scientific research projects. METHODS: The EULAR standardised operational procedures for guideline development were followed. A systematic literature review was presented during a first task force meeting, including 3 rheumatologists, 1 rheumatologist/epidemiologist, 2 allied health professionals, 2 representatives of arthritis research organisations and 7 patient representatives, resulting in 38 statements. A Delphi method was carried out to reduce and refine the statements and agree on a set of eight. Next, a survey among a wider group of experts, professionals and patient representatives (n=42), was completed. Feedback from this wider group was discussed at the second meeting and integrated in the final wording of the recommendations. Subsequently, the level of agreement of the group of experts (n=81) was re-evaluated. RESULTS: The project resulted in a definition of patient research partner and agreement on a set of eight recommendations for their involvement in research projects. These recommendations provide practical guidance for organising patient participation, capturing (1) the role of patient research partners, (2) phase of involvement, (3) the recommended number, (4) recruitment, (5) selection, (6) support, (7) training and (8) acknowledgement. CONCLUSION: Collaboration between patients and professionals in research is relatively new. Trials or effectiveness studies are not yet available. Nevertheless, it is possible to define recommendations for the inclusion of patients in research following a solid expert opinion based consensus process.

Safety of glucocorticoids - clinical trials.

Clinical trials published over the last 5 years support the main conclusion of a comprehensive review on glucocorticoid safety published in 2006: there is little if any solid evidence to support the fear that low-dose glucocorticoids are associated with significant toxicity when used appropriately in inflammatory rheumatic diseases. In fact, most of the recent randomised-controlled research underlines the influence of the underlying inflammatory process in the occurrence of 'adverse events' such as osteoporosis, fractures, hypertension and glucose intolerance. This 'confounding by indication' is inherent to the field and questions the validity of the observational data, that seems to drive currently common concepts about low-dose glucocorticoid toxicity. Decisive conclusions cannot, in any case, be achieved at this stage because the clinical trials available are of limited duration and dimension and have not been designed specifically to address toxicity. Toxicity with low-dose glucocorticoids needs to be kept under careful clinical surveillance while we expect such trials to be produced. Meanwhile, the risks of stopping these medications, even on longstanding well controlled disease, need also to be considered, as underlined by withdrawal trials recently published.

Impact of impaired morning function on the lives and well-being of patients with rheumatoid arthritis.

Morning joint stiffness and pain are prominent features in patients suffering from rheumatoid arthritis (RA) and contribute to impaired function. A survey was conducted across 11 European countries to assess the impact of impaired morning function on patients' quality of life. A total of 518 rheumatologists, and 750 patients aged 18-75 years with RA for ≥ 6 months and impaired morning function at least three times a week, completed the structured questionnaires. Impaired morning function was defined as 'stiffness and pain in the joints first thing in the morning that results in difficulty to function or perform tasks'. The mean duration of morning stiffness and pain was 83 min according to patients, slightly longer than that estimated by rheumatologists (70 min). Impaired morning function lasting more than 30 min/day was reported by 75% of patients, with 76% of rheumatologists estimating this duration for their patients. Most respondents (82% of patients and 96% of rheumatologists) considered that impaired morning function had a significant effect on patient quality of life. Around two-thirds of patients reported changes in how they carry out usual morning activities. Patients who were unable to function normally in the morning reported feeling frustrated (58%) and angry (32%). Almost one in five patients in the survey (18%) was unable to work as a direct result of their RA. Of the 274 patients included in the survey who were in paid work, 73% reported that impaired morning function had a significant impact on their job; 40% missed time from work in the past 6 months due to impairment in morning function, resulting in a mean of 4.5 days lost from work/employed person. In conclusion, the survey shows that impaired morning function has a considerable impact on the lives and well-being of patients with RA.

Monitoring adverse events of low-dose glucocorticoid therapy: EULAR recommendations for clinical trials and daily practice.

OBJECTIVE: To develop recommendations on monitoring for adverse events (AEs) of low-dose glucocorticoid (GC) therapy (≤7.5 mg prednisone or equivalent daily) in clinical trials and daily practice. METHODS: Literature was searched for articles containing information on incidence and monitoring of GC-related AEs using PubMed, EMBASE and Cochrane databases. Second, the authors searched for broad accepted guidelines on the monitoring of certain AEs (eg, WHO guidelines on screening for diabetes). Available data were summarised and discussed among experts (rheumatologists and patients) of the EULAR Task Force to decide which potential AEs should be monitored, how and at which interval. RESULTS: Data on monitoring proved to be scarce; most articles were focused on therapeutic effects of GCs, not on occurrence and monitoring of AEs. Most recommendations had to be based on consensus. Those for clinical trials aimed at getting insights into incidence, prevalence and clinical relevance of AEs to create a comprehensive and valid AE-profile of GC therapy. The set of AEs to monitor is therefore more extensive, and often consists of assessments at baseline and at end of trials. Recommendations for daily practice are meant to protect patients from real dangers, which can be prevented or treated. Standard care monitoring needs NOT be extended for patients on low-dose GC therapy, except for osteoporosis (follow national guidelines), and baseline assessments of ankle edema, fasting blood glucose and risk factors for glaucoma. CONCLUSION: Given the incompleteness of literature data, consensus-based recommendations on monitoring for GC-related AEs were created, separately for daily practice and clinical trials.

Patient and rheumatologist perspectives on glucocorticoids: an exercise to improve the implementation of the European League Against Rheumatism (EULAR) recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases.

OBJECTIVE: To explore perspectives among patients and rheumatologists on glucocorticoid (GC) therapy and European League Against Rheumatism (EULAR) recommendations on the management of systemic GC therapy in order to enhance implementation of the recommendations. METHODS: Rheumatologists (from eight countries) and patients (from five countries) acquainted with GCs participated in separate meetings, during which positive and negative aspects of GC therapy were discussed and possible adverse events (AEs) were ranked for importance; in addition participants were asked to evaluate the published EULAR recommendations. The reports from these meetings and themes related to implementation of the recommendations were discussed during an international forum of the experts who had formulated the recommendations and patient participants. RESULTS: In all, 140 patients (78% women; mean age 53 years; 61% patients with rheumatoid arthritis) and 110 rheumatologists (mean work experience 15 years) participated in the meetings. Osteoporosis, diabetes and cardiovascular diseases were ranked among the five most worrisome AEs by patients and rheumatologists. In both groups, there was agreement with most of the recommendations; the recommendations on GC information cards and GC use during pregnancy scored lowest. Ideas to improve implementation of the recommendations and a research agenda were generated. CONCLUSION: The patient and rheumatologist views on GCs corresponded to a large extent, reflected by concerns in both groups about osteoporosis, diabetes and cardiovascular diseases. Specific problems with the EULAR recommendations were identified and addressed to improve their implementation. This exercise shows that patient and rheumatologist perspectives should be included early in the process of formulating recommendations.

Selecting men for bone densitometry: performance of osteoporosis risk assessment tools in Portuguese men.

SUMMARY: Clinicians need tools to identify patients most likely to benefit from bone mineral density (BMD) testing, for which cost-effectiveness does not allow generalized screening. This study supports the utility of osteoporosis risk assessment tools in selecting men for BMD testing. Different cutoff values may be appropriate for different countries and/or ethnic origins. INTRODUCTION: Our aim was to evaluate the utility of three osteoporosis (OP) risk assessment tools in a large group of Portuguese men aged 50 or more and to determine the best cutoff value to be used for selecting men for bone densitometry. METHODS: We assessed the performance of three simple tools in 202 randomly selected men: body weight criterion (BWC), osteoporosis self-assessment tool for Asians (OSTA), and a modified version of the OSTA equation (OST). Previously published cutoff values (validated in postmenopausal women) and three additional cutoff values were tested. Sensitivity (SE), specificity (SP), predictive values, and area under the receiver operating characteristic (AUROC) curve for correctly selecting men with OP (defined by BMD testing) were determined. RESULTS: Mean age of the cohort was 63.8 years. According to the World Health Organization diagnostic categories, 16.8% had osteoporosis. The best performing cutoffs for correctly selecting men with OP for BMD testing were OST < 3 (SE = 75.5%, SP = 50.0%, AUROC = 0.632), OSTA < 3 (SE = 73.5%, SP = 58.3%, AUROC = 0.659), and BWC < 75 kg (SE = 73.5%, SP = 61.3%, AUROC = 0.674). CONCLUSIONS: OP risk assessment tools seem to be useful in men aged 50 or more. Best cutoff values are different from those recommended for postmenopausal women. Different cutoff values may be appropriate for different countries and/or ethnic origins.

How much of skin improvement over time in systemic sclerosis is due to normal ageing? A prospective study with shear-wave elastography.

BACKGROUND: Measurement of skin involvement is essential for the diagnosis and assessment of prognosis and disease progression in systemic sclerosis (SSc). The modified Rodnan skin score (mRSS) is the gold standard measure of skin thickness, but it has been criticised for the lack of objectivity, poor inter-observer reproducibility and lack of sensitivity to change. Recently, shear-wave elastography (SWE) emerged as a promising tool for the objective and quantitative assessment of the skin in SSc patients. However, no studies have evaluated its sensitivity to change over time. OBJECTIVE: To assess changes in skin stiffness in SSc patients using SWE during a 5-year follow-up. METHODS: Skin stiffness [i.e. shear-wave velocity values (SWV) in metres per second] was assessed by SWE ultrasound (using virtual touch image quantification) at the 17 sites of the mRSS, in each participant, at baseline and follow-up. mRSS was performed at both time points. Differences between groups were analysed using the related-samples Wilcoxon signed-rank test and the Mann-Whitney U test. RESULTS: We included 21 patients [85.7% females; mean age 56.3 (10.4) years at baseline, 57.1% with limited SSc] and 15 healthy controls [73.3% females; mean age 53.6 (14.1) years)]. The median follow-up was 4.9 (0.4) years. Skin stiffness decreased significantly at all Rodnan sites (p ≤ 0.001) (except in the fingers), in SSc patients, over time. The same phenomenon occurred in controls, but to a lesser degree, in terms of percentage change. The percentage reduction in skin stiffness varied in the different Rodnan sites and in different phases of the disease. In addition, SWV values also decreased significantly in 15/16 skin sites with local normal Rodnan at baseline, whereas local Rodnan skin score only changed significantly in the upper arm (p = 0.046) and forearm (p = 0.026). CONCLUSION: This study provides first-time evidence suggesting that skin SWV values are more sensitive to change over time than mRSS and reduce significantly over time in SSc and normal controls.

Exuberant calcinosis and acroosteolysis. A diagnostic challenge.

A case of exuberant acroosteolysis and subcutaneous tissue calcinosis in the absence of skin involvement is presented. Different hypotheses are discussed following the clinical unfolding of the case in practice.

Ultrasonography for the Assessment of Skin in Systemic Sclerosis: A Systematic Review.

OBJECTIVE: To identify and synthesize the best available evidence on the use of ultrasound to assess skin involvement in systemic sclerosis (SSc). METHODS: We conducted a systemic review of the literature on PubMed Medline and Embase, using the vocabulary terms ("systemic sclerosis OR scleroderma") AND ("ultrasonography" OR "elasticity imaging techniques") AND ("skin" OR "dermis"). Two independent reviewers selected articles, collected data from studies, and carried out a manual search of the references from the studies included. This search was further enhanced by a review of bibliographic references extrapolated from these studies. The quality of the evidence was assessed by the Effective Public Health Practice Project system. RESULTS: A total of 30 studies were identified, enrolling 1,171 SSc patients, predominantly middle-aged (mean age 55.5 years) females (88.8%). The ultrasound skin measurements that were reported included thickness in 28 studies and/or echogenicity (7 studies), and/or stiffness (6 studies), and/or vascularity (1 study). The main comparator was the global and site-specific modified Rodnan skin thickness score. Reported interrater and intrarater reproducibility appeared to be excellent, but this reproducibility was assessed by a small number of studies. Moreover, there were no published evaluations of construct or criterion validity of skin ultrasound assessment. The responsiveness to change of ultrasound elastography has not been assessed. CONCLUSION: Published reports have strong limitations and are highly heterogeneous, hindering the evidence to support the use of skin ultrasound assessment in clinical practice. Further studies, with modern devices and appropriate methodology, are needed to establish the real value of skin ultrasound assessment in the early diagnosis and monitoring of SSc patients.

EULAR evidence-based recommendations for the management of fibromyalgia syndrome.

OBJECTIVE: To develop evidence-based recommendations for the management of fibromyalgia syndrome. METHODS: A multidisciplinary task force was formed representing 11 European countries. The design of the study, including search strategy, participants, interventions, outcome measures, data collection and analytical method, was defined at the outset. A systematic review was undertaken with the keywords "fibromyalgia", "treatment or management" and "trial". Studies were excluded if they did not utilise the American College of Rheumatology classification criteria, were not clinical trials, or included patients with chronic fatigue syndrome or myalgic encephalomyelitis. Primary outcome measures were change in pain assessed by visual analogue scale and fibromyalgia impact questionnaire. The quality of the studies was categorised based on randomisation, blinding and allocation concealment. Only the highest quality studies were used to base recommendations on. When there was insufficient evidence from the literature, a Delphi process was used to provide basis for recommendation. RESULTS: 146 studies were eligible for the review. 39 pharmacological intervention studies and 59 non-pharmacological were included in the final recommendation summary tables once those of a lower quality or with insufficient data were separated. The categories of treatment identified were antidepressants, analgesics, and "other pharmacological" and exercise, cognitive behavioural therapy, education, dietary interventions and "other non-pharmacological". In many studies sample size was small and the quality of the study was insufficient for strong recommendations to be made. CONCLUSIONS: Nine recommendations for the management of fibromyalgia syndrome were developed using a systematic review and expert consensus.