This guideline was developed according to the British Society for Rheumatology Guidelines Protocol by a Guideline Development Group comprising healthcare professionals with expertise in SSc and people with lived experience, as well as patient organization representatives. It is an update of the previous 2015 SSc guideline. The recommendations were developed and agreed by the group and are underpinned by published evidence, assessed by systematic literature review and reinforced by collective expert opinion of the group. It considers all aspects of SSc including general management, treatment of organ-based complications, including cardiopulmonary, renal and gastrointestinal tract manifestations, as well as broader impact of disease. Whilst it is focused on adults with SSc we expect that the guideline will be relevant to people of all ages and expert input and review by paediatric rheumatologists and other relevant specialists considered where the guideline was, or may not be, applicable to young people with SSc and juvenile-onset disease. In addition to providing guidance on disease assessment and management the full guideline also considers service organization within the National Health Service and future approaches to audit of the guideline. The lay summary that accompanies this abstract can be found in Supplemental information 1.

Objective: To outline the clinical, histological and prognostic features of systemic sclerosis (SSc) endomyocardial biopsy-proven myocarditis with respect to those of diverse endomyocardial biopsy-proven virus-negative myocarditis (VNM).Methods: We retrospectively analysed data from three cohorts of endomyocardial biopsy-proven myocarditis: SSc-related VNM (SSc-VNM); isolated VNM (i-VNM); and VNM related to other systemic autoimmune diseases (a-VNM). The degree of myocardial fibrosis was expressed as relative percentage and fibrotic score (0–3). Clinical data, cardiac enzymes, echocardiogram, 24 h ECG Holter and cardiac magnetic resonance were obtained at baseline and during follow-up. Non-parametric tests were used.Results: We enrolled 12 SSc-VNM [11 females, mean age 49.3 (14.2) years; seven diffuse-SSc, five early-SSc], 12 i-VNM [12 females, mean age 47.7 (10.8) years] and 10 a-VNM [four females, mean age 48.4 (16.3) years] patients. SSc patients had higher degrees of myocardial fibrosis as assessed by both percentage [SSc-VNM: 44.8 (18.8)%; a-VNM: 28.6 (16.5)%; i-VNM: 24.9 (10.3)%; P = 0.019] and score [SSc-VNM: 2.3 (0.8); a-VNM: 1.4 (1.1); i-VNM: 1.2 (0.7); P = 0.002]. Myocardial fibrosis directly correlated with skin score (r = 0.625, P = 0.03) and number of ventricular ectopic beats on 24 h ECG Holter in SSc patients (r = 0.756, P = 0.01). Dyspnoea class was higher at presentation in SSc-VNM patients (P = 0.041) and we found heart failure only in SSc patients (25%) (P = 0.05). At cardiac magnetic resonance, myocardial oedema was nearly undetectable in SSc-VNM patients compared with others (P = 0.02). All patients received immunosuppressive treatment. The number of patients who died during follow-up due to cardiac complications was significantly higher in SSc-VNM patients (50%), as compared with a-VNM (0%) and i-VNM (8.3%) patients (P = 0.006). Patients who died during follow-up had higher degrees of myocardial fibrosis [52.2 (11.6)% vs 27.5 (12.9)%, P = 0.024; fibrotic score: 2.83 (0.41) vs 1.4 (0.9), P < 0.001].Conclusion: SSc has unique clinical and histological features, as it tends to present more frequently with heart failure and a higher dyspnoea class and to show higher degrees of myocardial fibrosis. These specific features are paralleled by a worse cardiac prognosis.

Introduction Nintedanib (NTD) has been shown to be effective in systemic sclerosis (SSc)-interstitial lung disease (ILD). Here we describe the efficacy and safety of NTD in a real-life setting. Methods Patients with SSc-ILD treated with NTD were retrospectively evaluated at 12 months prior to NTD introduction; at baseline and at 12 months after NTD introduction. The following parameters were recorded: SSc clinical features, NTD tolerability, pulmonary function tests and modified Rodnan skin score (mRSS). Results 90 patients with SSc-ILD (65% female, mean age 57.6±13.4 years, mean disease duration 8.8±7.6 years) were identified. The majority were positive for anti-topoisomerase I (75%) and 77 (85%) patients were on immunosuppressants. A significant decline in %predicted forced vital capacity (%pFVC) in the 12 months prior to NTD introduction was observed in 60%. At 12 months after NTD introduction, follow-up data were available for 40 (44%) patients and they showed a stabilisation in %pFVC (64±14 to 62±19, p=0.416). The percentage of patients with significant lung progression at 12 months was significantly lower compared with the previous 12 months (60% vs 17.5%, p=0.007). No significant mRSS change was observed. Gastrointestinal (GI) side effects were recorded in 35 (39%) patients. After a mean time of 3.6±3.1 months, NTD was maintained after dose adjustment in 23 (25%) patients. In nine (10%) patients, NTD was stopped after a median time of 4.5 (1–6) months. During the follow-up, four patients died. Conclusions In a real-life clinical scenario, NTD, in combination with immunosuppressants, may stabilise lung function. GI side effects are frequent and NTD dose adjustment may be necessary to retain the drug in patients with SSc-ILD.

Objective: To assess the value of serum type I interferon (IFN) score in predicting clinically meaningful progression in limited cutaneous systemic sclerosis (lcSSc) using a novel composite endpoint adopted from the MINIMISE clinical trial. Methods: A retrospective, longitudinal lcSSc cohort was identified within a national, multicenter observational cohort. The MINIMISE trial combined Morbi‐mortality endpoint was used as the clinical outcome for a time to clinical worsening (TTCW) design. The IFN score was calculated from the serum concentration of chemokine C‐C motif ligand (CCL) 2, CCL8, CCL19, C‐X‐C motif chemokine ligand (CXCL) 9, CXCL10, and CXCL11 on patients and age‐ and sex‐matched healthy controls (HCs). A “high” IFN score was defined as 2 SDs above the HC mean. The association of the IFN score with TTCW was assessed using Cox proportional hazard regressions and Kaplan‐Meier curves. The potential improvement in risk stratification when combining IFN score with lcSSc clinical features was explored. Results: A total of 149 patients were included in the analysis: 67 “high” IFN and 82 “low.” High IFN patients presented a shorter TTCW (74.7 months [95% confidence interval (CI) 70.1–79.3] vs 110.6 months [95% CI 107.2–114.0]; P < 0.001) and met the endpoint in higher proportion compared with low IFN (55% vs 12%; P < 0.001). A high IFN score conferred hazard ratio (HR) 5.5 (95% CI 2.7–11.3) for TTCW compared with low IFN, and IFN score as a continuous variable conferred HR 2.38 (95% CI 1.4–4.0) for TTCW independently of clinical variables. Pulmonary arterial hypertension, interstitial lung disease, digital ulcers, and modified Rodnan skin score were associated with TTCW. An exploratory analysis showed that these clinical features improve risk stratification over time in combination with IFN score. Conclusion: Serum assessment of type I IFN activity is a valuable predictor of clinically meaningful outcomes in lcSSc. The combination of serum IFN score with sentinel clinical features can improve stratification strategies in clinical trials and patient management. image

Vascular fibrosis is a key manifestation of systemic sclerosis that leads to the narrowing of small and medium arteries, causing vascular clinical manifestations including digital ulcers and pulmonary arterial hypertension. We investigated the potential of the MRI-based Digital Artery Volume Index (DAVIX) as a surrogate outcome measure of vascular fibrosis by using it to quantify and predict the burden of digital ulcer disease in patients with systemic sclerosis. Two independent cohorts of patients participating in the prospective observational study STRIKE were consecutively enrolled from the Scleroderma Clinic of the Leeds Teaching Hospitals Trust, Leeds, UK. Eligible patients were aged 18 years or older and fulfilled the very early diagnosis of systemic sclerosis (VEDOSS) or the 2013 American College of Rheumatology (ACR)-European Alliance of Associations for Rheumatology (EULAR) systemic sclerosis classification criteria. DAVIX was calculated as the percentage mean of the ratio of digital artery volume to finger volume in the four fingers of the dominant hand. Data were collected at baseline and 12-month follow-up, and the primary outcome was the presence of digital ulcers at 12-month follow-up. Between Feb 7, 2018, and April 11, 2022, we included 85 patients in the exploratory cohort and 150 in the validation cohort. In the exploratory cohort, the mean age was 54·5 years (SD 11·6), 75 (88%) of 85 patients were women, ten (12%) were men, and 69 (82%) were White. In the validation cohort, the mean age was 53·5 years (SD 13·8), 136 (91%) of 150 patients were women, 14 (9%) were men, and 127 (85%) were White. In the exploratory cohort, DAVIX was significantly lower in patients with previous or active digital ulcers (0·34% [IQR 0·16-0·69]) than in those without digital ulcer disease (0·65% [0·42-0·88]; p=0·015); this finding was substantiated in the validation cohort (0·43% [0·20-0·73] vs 0·73% [0·53-0·97]; p<0·0001). Patients who developed new digital ulcers during 12-month follow-up had a lower DAVIX (0·23% [0·10-0·66]) than those who did not (0·65% [0·45-0·91]; p=0·0039). DAVIX was negatively correlated with disease duration (r=-0·415; p<0·0001), the ratio of forced vital capacity to the diffusing capacity of the lungs for carbon monoxide (r=-0·334; p=0·0091), nailfold capillaroscopy pattern (r=-0·447; p<0·0001), and baseline modified Rodnan skin score (r=-0·305; p=0·014) and was positively correlated with the diffusing capacity of carbon monoxide (r=0·368; p=0·0041). DAVIX was negatively correlated with change in score on the Scleroderma Health Assessment Questionnaire-Disability Index (r=-0·308; p=0·024), Visual Analogue Scale (VAS) Raynaud's (r=-0·271; p=0·044), and VAS digital ulcers (r=-0·291; p=0·044). DAVIX is a promising surrogate outcome measure of digital ulcer disease in patients with systemic sclerosis. The ability of DAVIX to non-invasively predict future digital ulcers and worsening of patient-reported outcomes could aid patient enrichment and stratification in clinical trials. Clinically, DAVIX could offer insights into the assessment of vascular activity. The sensitivity of DAVIX to change over time and with treatment will establish its value as an imaging outcome measure of vascular disease. National Institute for Health Research Biomedical Research Centre and University of Leeds Industry Engagement Accelerator Fund.

Multidisciplinary team (MDT) discussion is the gold standard in the management of interstitial lung disease (ILD). The rheumatologist is not routinely involved in MDT, even if up to 20% of ILD are related to systemic autoimmune rheumatic diseases (SARD). The study aims to assess the agreement and its variation over time between rheumatologists and pulmonologists in the screening of SARD and between rheumatologists and an MDT extended to rheumatologists (eMDT) in evaluating the progression of SARD. We computed the agreement between the pulmonologist and rheumatologist in the identification of red flags for SARDs of 81 ILD cases and between the rheumatologist alone and eMDT in the confirmation of 70 suspected SARD-ILD progressions. The agreement between rheumatologists and pulmonologists was moderate for the detection of autoimmunity test positivity (κ = 0.475, p < 0.001) and family history of SARD (κ = 0.491, p < 0.001) and fair for the identification of extrapulmonary symptoms (κ = 0.225, p = 0.064) or routine laboratory abnormalities consistent with SARD. The average agreement between the rheumatologist and eMDT in the identification of ILD progression was moderate (κ = 0.436, p < 0.001). The class of agreement improved from the first to the third semester. The average agreement with the rheumatologist ranged from fair to moderate, suggesting that a shared evaluation of SARD-ILD in eMDT could improve the diagnostic work-up and the evaluation of ILD progression.