Characteristics of ScleroID highlighting musculoskeletal and internal organ implications in patients afflicted with systemic sclerosis

BACKGROUND Systemic sclerosis (SSc) is a multi-organ disease with impaired health-related quality of life (HRQoL). The EULAR SSc Impact of Disease (ScleroID) is a newly introduced SSc-specific patient-reported outcome to evaluate HRQoL in SSc. OBJECTIVE To investigate the correlation between the ScleroID and the involvement of organ systems as well as disease activity/damage in a SSc cohort from a large tertiary care centre. PATIENTS AND METHODS The ScleroID and clinical characteristics including internal organ involvement and hand function were investigated in 160 consecutive patients with SSc (median age 46 (43;56) years; diffuse cutaneous SSc 55%). RESULTS A strong correlation was found between the ScleroID and articular disease activity scores (DAS28-CRP, DAS28-ESR, CDAI, SDAI), a hand function performance test, the Hand Anatomy Index and muscle strength tests. Additionally, a strong significant correlation was discovered using instruments representing hand function and musculoskeletal disability including the Cochin Hand Function Scale, the Quick Questionnaire of the Disability of the Hands, Arms and the Shoulders and the Health Assessment Questionnaire Disability Index. A significant negative correlation was found between the ScleroID score and the 6-min walking test (6MWT) (rho - 0.444, p < 0.001). Clinically mild lung/heart disease did not show increased ScleroID values. The Mouth Handicap in the Scleroderma Scale and the University of California Los Angeles Scleroderma Clinical Trials Consortium gastrointestinal tract 2.0 also showed significant positive correlations to the ScleroID score (rho: 0.626, p < 0.001; rho: 0.646, p < 0.001, respectively). Patients experiencing oesophageal difficulties bore a significantly higher score compared to individuals with a normal functioning oesophagus (3.2/1.5;4.5/ vs. 2.2/1.0;3.2/, p = 0.011). Moreover, the ScleroID showed a significant positive correlation to the revised EUSTAR disease activity index and modified activity index. CONCLUSION In a large single-centre cohort, the previously described ScleroID-related findings were confirmed. Furthermore, several organ involvement-related functional and performance tests showed a good correlation to the ScleroID including the 6MWT and gastrointestinal-related complaints. Many aspects of musculoskeletal damage, overall disease activity, pain and fatigue were also well represented in the ScleroID, which efficiently reflects the impact of organ involvement, disease activity and functional damage

Educational needs and preferences of young European clinicians and physician researchers working in the field of rheumatology

Funding Information: CB: Grant BE 5191/1-1 of the Deutsche Forschungsgemeinschaft.Objectives: To understand the educational needs and preferences of young clinicians and physician researchers in the field of rheumatology in Europe. Methods: An international online survey was performed as a joint venture of ESCET and EMEUNET. The survey assessed the acceptance of and the access to the current European League Against Rheumatism (EULAR) educational portfolio, as well as the unmet educational needs and learning preferences among individuals below the age of 40 years working in rheumatology in Europe. Results: Among 568 European clinicians and physician researchers, 65% indicated that the existing EULAR educational portfolio adequately covers their educational needs. Within the EULAR portfolio, the online course on rheumatic diseases and the postgraduate course were the most appreciated. Participants were very much in favour of new educational courses on imaging techniques, and 63% of participants indicated a particular interest in musculoskeletal ultrasound. A strong interest in refresher (60%) and general review (55%) courses was observed. Lack of funding was considered the major obstacle to participating in existing EULAR programmes. Finally, participants showed diverse preferences regarding learning modalities with common interests in live courses and conferences. Conclusions: EULAR's training opportunities are well appreciated among young clinicians and physician researchers in rheumatology. The results from this survey will help to develop EULAR's future educational portfolio.publishersversionPeer reviewe

Personalized medicine in systemic sclerosis: facts and promises

The concept of personalized medicine has led to a paradigm shift in recent years. It integrates multiple clinical and biological levels of investigation aimed at offering the best possible and patient-tailored healthcare. This holds great potential in a rare and heterogeneous disease such as systemic sclerosis (SSc). The development of validated clinical screening algorithms and the identification of predictors for disease outcomes can help in stratifying patients according to their individual risk of progression. The ongoing search for biomarkers and key pathogenic molecules has brought valuable insights into molecular networks operative in SSc. In parallel, genetic and genomic studies have revealed new SSc susceptibility loci and validated gene expression profiles that might identify patients benefiting from specific therapies. In this review, we focus on recent findings relevant for the concept of personalized medicine in patients with SSc

Enrichment Strategy for Systemic Sclerosis Clinical Trials Targeting Skin Fibrosis: A Prospective, Multiethnic Cohort Study

OBJECTIVE The modified Rodnan skin score (mRSS) is often used as a primary outcome measure in systemic sclerosis (SSc) randomized clinical trials (RCTs). Previous cohort studies with predominantly European Caucasian patients showed that setting an upper limit of mRSS as a selection criterion for RCTs leads effectively to enrichment with progressive patients. This study aimed to demonstrate this effect in an ethnically diverse cohort, rich in patients positive for anti-RNA polymerase III antibodies (Pol3). METHODS We selected from the Genetics versus Environment in Scleroderma Outcomes Study (GENISOS) cohort patients with diffuse cutaneous SSc (dcSSc), who had mRSS of 7 or more at inclusion and a documented mRSS after 12 ± 2 months. Progression of skin fibrosis was defined as an increase in mRSS greater than 5 points and 25% or more from baseline. To identify the optimal cutoff for the baseline mRSS yielding the highest sensitivity for progressive skin fibrosis, we developed ROC curves and logistic regression models with "progression" as the outcome variable and a binary variable of baseline mRSS cutoff point as predictor. RESULTS We included 152 patients (age and disease duration [mean ± SD, years]: 48.7 ± 13.0 and 2.4 ± 1.5 respectively, 22.4% males, 34.2% Pol3-positive). Seventeen patients (11.2%) had skin fibrosis progression after 12 ± 2 months. An mRSS cutoff of 27 or less had the highest probability of progression (odds ratio, 9.12; 95% confidence interval: 1.173-70.851; P = 0.035; area under the curve, 0.652; sensitivity, 94%). CONCLUSION We demonstrated in an ethnically diverse cohort of patients with early dcSSc and with a high proportion of patients who are Pol3-positive that setting an upper limit of the mRSS as a selection criterion leads effectively to cohort enrichment with progressors

Performance of the UCLA Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 instrument as a clinical decision aid in the routine clinical care of patients with systemic sclerosis

BACKGROUND AND OBJECTIVES The University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument 2.0 (UCLA GIT 2.0) is validated to capture gastrointestinal (GI) tract morbidity in patients with systemic sclerosis (SSc). The aims of this study were to determine in a large SSc cohort if the UCLA GIT 2.0 is able to discriminate patients for whom a rheumatologist with experience in SSc would recommend an esophago-gastro-duodenoscopy (EGD), and if it could identify patients with endoscopically proven esophagitis or with any pathologic finding on EGD. METHODS We selected patients fulfilling the ACR/EULAR 2013 criteria for SSc from our EUSTAR center having completed at least once the UCLA GIT 2.0 questionnaire, and we collected data on gastrointestinal symptoms and EGD from their medical charts. We analyzed by general linear mixed effect models several parameters, including UCLA GIT 2.0, considered as potentially associated with the indication of EGD, as well as with endoscopic esophagitis and any pathologic finding on EGD. RESULTS We identified 346 patients (82.7% female, median age 63 years, median disease duration 10 years, 23% diffuse cutaneous SSc) satisfying the inclusion criteria, who completed UCLA GIT 2.0 questionnaires at 940 visits. EGD was recommended at 169 visits. In multivariable analysis, UCLA GIT 2.0 and some of its subscales (reflux, distention/bloating, social functioning) were associated with the indication of EGD. In 177 EGD performed in 145 patients, neither the total ULCA GIT 2.0 score nor any of its subscales were associated with endoscopic esophagitis, nor with any pathologic EGD findings. CONCLUSIONS In a real-life setting, the UCLA GIT 2.0 and its reflux subscale were able to discriminate patients with SSc who had an indication for EGD, but did not correlate with findings in EGD. We conclude that, while using the UCLA GIT 2.0 in the routine care of patients with SSc may help the rheumatologist to better understand the burden of GI symptoms in the individual patient, it should not be used as a stand-alone instrument to identify an indication of EGD

Pain chronification and the important role of non-disease-specific symptoms in patients with systemic sclerosis

BACKGROUND Pain is a frequent, yet inadequately explored challenge in patients with systemic sclerosis (SSc). This study aimed to conduct an extensive pain assessment, examining pain chronification and its association with disease manifestations. METHODS Consecutive SSc patients attending their annual assessment were included. SSc-specific features were addressed as defined by the European Scleroderma Trials and Research (EUSTAR) guidelines. Pain analysis included intensity, localization, treatment, chronification grade according to the Mainz Pain Staging System (MPSS), general well-being using the Marburg questionnaire on habitual health findings (MFHW) and symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS). RESULTS One hundred forty-seven SSc patients completed a pain questionnaire, and 118/147 patients reporting pain were included in the analysis. Median pain intensity was 4/10 on a numeric rating scale (NRS). The most frequent major pain localizations were hand and lower back. Low back pain as the main pain manifestation was significantly more frequent in patients with very early SSc (p = 0.01); those patients also showed worse HADS and MFHW scores. Regarding pain chronification, 34.8% were in stage I according to the MPSS, 45.2% in stage II and 20.0% in stage III. There was no significant correlation between chronification grade and disease severity, but advanced chronification was significantly more frequent in patients with low back pain (p = 0.024). It was also significantly associated with pathological HADS scores (p < 0.0001) and linked with decreased well-being and higher use of analgesics. CONCLUSIONS Our study implies that also non-disease-specific symptoms such as low back pain need to be considered in SSc patients, especially in early disease. Since low back pain seems to be associated with higher grades of pain chronification and psychological problems, our study underlines the importance of preventing pain chronification in order to enhance the quality of life

Evaluation of botulinum toxin A injections for the treatment of refractory chronic digital ulcers in patients with systemic sclerosis

OBJECTIVES To evaluate the therapeutic benefit of botulinum toxin A (BTX-A) injections for digital ulcers (DU) in patients with systemic sclerosis (SSc). METHODS A systematic literature review was performed and the identified articles were selected by two reviewers and analysed with respect to date of publication, inclusion and exclusion criteria, number and age of participants, volume of BTX-A, injection sites, outcomes, and adverse events. In addition, in the Zurich cohort, 7 SSc patients were eligible for the study and were assessed for the duration of DU to heal, duration of DU-free periods, changes in frequency and numbers of prescribed vasodilators, pain and blood flow. RESULTS In five articles from the systematic review, at least 48% of DU had healed and up to 100% reduction in VAS for pain was reported. Our 7 patients (median age of 53 (47-82) years) had in median 2.5 (2-4) DU and were injected with a median BTX-A volume of 90 (50-100) units per hand. Of the 31 DU in all patients, 77% (n=24) healed. Time to wound closure was in median 8 (4-12) weeks and the DU-free duration was in median 8 (3-10) months. In 80% of the cases, at least one vasodilator was stopped or could be administered less frequently. An improvement of blood flow and pain was reported in 60% of the cases. CONCLUSIONS BTX-A injections might be of benefit for the treatment of chronic, refractory DU in selected SSc patients, yet a sufficiently powered prospective study will be needed as ultimate proof

Impaired micronutrients and prealbumin in patients with established and very early systemic sclerosis

OBJECTIVES Gastrointestinal involvement and impaired nutritional status are frequent in patients with systemic sclerosis (SSc). Hereby, we hypothesised that micronutrients and/or prealbumin could be deficitary in SSc. METHODS Patients with SSc and very early SSc (veSSc) were prospectively included. Clinical assessment, data recording and quality controls followed EUSTAR standards. The UCLA SCTCGIT 2.0 questionnaire was applied and the serum levels of zinc, selenium, prealbumin, holotranscobalamin, folic acid were measured. RESULTS Half (52.4%) of the 176 patients with established SSc showed a deficiency in at least one of the measured nutrients. The most frequent deficit was seen in folic acid (17.9%), followed closely by selenium, prealbumin and zinc (around 15% each). Nearly a fifth (19%) of these patients had multiple deficiencies. Patients with more severe disease, including advanced skin fibrosis, positive ACR 1980 classification criteria, anemia and elevated serum inflammation markers were more likely to be nutrient deficient. Lower BMI<20kg/m2 was associated with several nutrient deficiencies. Prealbumin deficiency was associated with more frequent stomach symptoms and methotrexate therapy. A third of veSSc patients (27%, 44/74) presented a nutrient deficiency, mostly of zinc (10%). Surprisingly, micronutrient deficiencies were not associated with usual parameters of gastrointestinal involvement. CONCLUSIONS These novel data reveal deficiencies in micronutrients and/or prealbumin are a frequent burden in patients with SSc. Moreover, these correlate with clinical aspects of the disease. Especially patients with advanced disease appear at high risk for an impaired nutrient status, suggesting that screening of micronutrients status should be performed in these patients