Five year risk assessment and treatment patterns in patients with chronic thromboembolic pulmonary hypertension.

AIMS: Repeated risk assessments and treatment patterns over long time are sparsely studied in chronic thromboembolic pulmonary hypertension (CTEPH); thus, we aimed to investigate changes in risk status and treatment patterns in incident patients with CTEPH over a 5 year period. METHODS AND RESULTS: Descriptive and explorative study including 311 patients diagnosed with CTEPH 2008-2019 from the Swedish pulmonary hypertension registry, stratified by pulmonary endarterectomy surgery (PEA). Risk and PH-specific treatment were assessed in surgically treated (PEA) and medically treated (non-PEA) patients at diagnosis and up to 5 years follow-up. Data are presented as median (Q1-Q3), count or per cent. Prior to surgery, 63% in the PEA-group [n = 98, age 64 (51-71) years, 37% female] used PH-specific treatment and 20, 69, and 10% were assessed as low, intermediate or high risk, respectively. After 1 year post-surgery, 34% had no PH-specific treatment or follow-up visit registered despite being alive at 5 years. Of patients with a 5 year visit (n = 23), 46% were at low and 54% at intermediate risk, while 91% used PH-specific treatment. In the non-PEA group [n = 213, age 72 (65-77) years, 56% female], 28% were assessed as low, 61% as intermediate and 11% as high risk. All patients at high risk versus 50% at low risk used PH-specific treatment. The 1 year mortality was 6%, while the risk was unchanged in 57% of the patients; 14% improved from intermediate to low risk, and 1% from high to low risk. At 5 years, 27% had a registered visit and 28% had died. Of patients with a 5 year visit (n = 58), 38% were at low, 59% at intermediate and 1% at high risk, and 86% used PH-specific treatment. CONCLUSIONS: Risk status assessed pre-surgery did not foresee long-term post-PEA risk and pre-surgery PH-specific treatment did not foresee long-term post-PEA treatment. Medically treated CTEPH patients tend to remain at the same risk over time, suggesting a need for improved treatment strategies in this group.

Ultrasound and elastography in the assessment of skin involvement in systemic sclerosis: A systematic literature review focusing on validation and standardization - WSF Skin Ultrasound Group.

OBJECTIVE: To summarize the published evidence in the literature on the role of ultrasound and elastography to assess skin involvement in systemic sclerosis (SSc). METHODS: A systematic literature review (SLR) was performed within the "Skin Ultrasound Working Group" of the World Scleroderma Foundation, according to the Cochrane Handbook. A search was conducted in Pubmed, Cochrane Library and Embase databases from 1/1/1979 to 31/5/2021, using the participants, intervention, comparator and outcomes (PICO) framework. Only full-text articles involving adults, reported in any language, assessing ultrasound to quantify skin pathology in SSc patients. Two reviewers performed the assessment of risk of bias, data extraction and synthesis, independently. RESULTS: Forty-six studies out of 3248 references evaluating skin ultrasound and elastography domains were included. B-mode ultrasound was used in 30 studies (65.2%), elastography in nine (19.6%), and both methods in seven (15.2%). The ultrasound outcome measure domains reported were thickness (57.8%) and echogenicity (17.2%); the elastography domain was stiffness (25%). Methods used for image acquisition and analysis were remarkably heterogeneous and frequently under-reported, precluding data synthesis across studies. The same applies to contextual factors and feasibility. Our data syntheses indicated evidence of good reliability and convergent validity for ultrasound thickness evaluation against mRSS and skin histological findings. Stiffness and echogenicity have limited evidence for validity against histological findings. Evidence for sensitivity to change, test-retest reliability, clinical trial discrimination or thresholds of meaning is limited or absent for reported ultrasound domains. CONCLUSION: Ultrasound is a valid and reliable tool for skin thickness measurement in SSc but there are significant knowledge gaps regarding skin echogenicity assessment by ultrasound and skin stiffness evaluation by elastography in terms of feasibility, validity and discrimination. Standardization of image acquisition and analysis is needed to foster progress.

Early risk prediction in idiopathic versus connective tissue disease-associated pulmonary arterial hypertension: call for a refined assessment.

Despite systematic screening and improved treatment strategies, the prognosis remains worse in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) compared to patients with idiopathic/hereditary pulmonary arterial hypertension (IPAH). We aimed to investigate differences in clinical characteristics, outcome and performance of the European Society of Cardiology (ESC)/ European Respiratory Society (ERS) risk stratification tool in these patient groups. This retrospective analysis included incident patients with CTD-PAH (n=197, of which 64 had interstitial lung disease, ILD) or IPAH (n=305) enrolled in the Swedish PAH Register (SPAHR) 2008-2019. Patients were classified as low, intermediate or high risk at baseline, according to the "SPAHR-equation". One-year survival, stratified by type of PAH, was investigated by Cox proportional regression. At baseline, CTD-PAH patients had lower diffusing capacity for carbon monoxide and lower haemoglobin but, at the same time, lower N-terminal prohormone-brain natriuretic peptide, longer 6 min walk distance, better haemodynamics and more often a low-risk profile. No difference in age, World Health Organisation functional class (WHO-FC) or renal function between groups was found. One-year survival rates were 75, 82 and 83% in patients with CTD-PAH with ILD, CTD-PAH without ILD and IPAH, respectively. The 1-year mortality rates for low-, intermediate- and high-risk groups in the whole cohort were 0, 18 and 34% (p<0.001), respectively. Corresponding percentages for CTD-PAH with ILD, CTD-PAH without ILD and IPAH patients were: 0, 26, 67% (p=0.008); 0, 19, 39% (p=0.004); and 0, 16, 29% (p=0.001), respectively. The ESC/ERS risk assessment tool accurately identified low-risk patients but underestimated the 1-year mortality rate of CTD-PAH and IPAH patients assessed as having intermediate risk at diagnosis.

Identifying unmet needs in SSc-ILD by semi-qualitative in-depth interviews.

OBJECTIVES: Interstitial lung disease is frequent in SSc (SSc-ILD) and associates with significantly reduced quality of life. Here we aimed to analyse patient pathways, and experiences of patients and healthcare providers (HCPs) in order to identify unmet needs in the management of SSc-ILD patients. METHODS: Semi-structured qualitative interviews conducted in eight European countries looked at HCP (n = 95) and patient perspectives (n = 47) using two sets of 70 research questions. Pre-diagnostic, diagnostic and post-diagnostic phases of the patient pathway were systematically explored. RESULTS: (i) In the pre-diagnostic phase several gaps were identified by HCPs and patients in all participating countries: limited disease knowledge among primary care physicians and specialists, lack of accurate patient information, and delayed and/or inappropriate referral. (ii) The diagnostic phase is in most countries coordinated by rheumatologists, who are also the main point of care. Depending on the local health system, organization of multidisciplinary collaboration varies. HCPs issued lack of national guidelines, while patients stated difficulties obtaining disease-related information. (iii) In the post-diagnostic phase, HCPs and patients indicated lack of curative treatment, specialized nurses, and paramedical  and psychological support. Patients and caregivers additionally expressed the need for clear information on SSc-ILD. CONCLUSION: Lack of disease specific knowledge, gaps in national healthcare systems and insufficient information and support for patients and caregivers were identified as unmet needs to ensure timely diagnosis, provide better patient management and to improve quality of life in SSc-ILD patients.

Standardisation of nailfold capillaroscopy for the assessment of patients with Raynaud's phenomenon and systemic sclerosis.

Capillaroscopy is a non-invasive and safe tool which allows the evaluation of the morphology of the microcirculation. Since its recent incorporation in the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for systemic sclerosis together with its assessed role to monitor disease progression, capillaroscopy became a 'mainstream' investigation for rheumatologists. Given its increasing use by a variety of physicians internationally both in daily practice to differentiate primary from secondary Raynaud's phenomenon, as well as in research context to predict disease progression and monitor treatment effects, standardisation in capillaroscopic image acquisition and analysis seems paramount. To step forward to this need, experts in the field of capillaroscopy/microcirculation provide in this very consensus paper their view on image acquisition and analysis, different capillaroscopic techniques, normal and abnormal capillaroscopic characteristics and their meaning, scoring systems and reliability of image acquisition and interpretation.

Gender differences in early systemic sclerosis patients: a report from the EULAR scleroderma trials and research group (EUSTAR) database.

OBJECTIVES: To describe differences in clinical presentation between men and women in a large group of patients with early (<3 years' duration) systemic sclerosis (SSc) according to disease subsets. METHODS: A cross-sectional analysis of the prospective EULAR Scleroderma Trial and Research database (EUSTAR) was performed. Patients fulfilling preliminary ACR 1980 classification criteria for SSc, with less than 3 years from the first non-Raynaud's symptom at first entry, were selected. A group of patients with less than 3 years from the first SSc symptom, including Raynaud's phenomenon, was also analysed. SSc related variables, including antibodies, SSc subsets, disease activity and organ involvement were included. Descriptive and bivariate analyses were performed. RESULTS: A total of 1,027 patients were included, 90% Caucasian, 80% women, and 40% with diffuse cutaneous disease. In early stages of SSc, men showed more frequently than women active disease, diffuse cutaneous subset, anti-Scl-70 antibodies, elevated acute phase reactants, muscular and pulmonary involvement. Differences between men and women were confirmed in the limited, but not in the diffuse SSc subset. The results were similar when 650 patients with less than three years from the first SSc symptom, including Raynaud's phenomenon, were analysed. CONCLUSIONS: In early stages of SSc, men present signs and symptoms of more severe disease. In the limited disease subset, men might appear with clinical features and organ involvement similar to those of the diffuse subgroup. In clinical practice, the identification of such differences might help to select the appropriate management for each particular patient.

Disability, fatigue, pain and their associates in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study.

Objectives: Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features. Methods: Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined. Results: The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (s.d.) HAQ-DI 1.1 (0.83)], with 'grip' and 'activity' being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (ρ = 0.34, P < 0.0001 and ρ = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (ρ = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (ρ = 0.40, P < 0.0001), decreasing hand function (ρ = 0.57, P < 0.0001) and increasing fatigue (ρ = -0.53, P < 0.0001). Conclusion: The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability.

Work Disability in Early Systemic Sclerosis: A Longitudinal Population-based Cohort Study.

OBJECTIVE: To study work disability (WD) with reference to levels of sick leave and disability pension in early systemic sclerosis (SSc). METHODS: Patients with SSc living in the southern part of Sweden with onset of their first non-Raynaud symptom between 2003 and 2009 and with a followup of 36 months were included in a longitudinal study. Thirty-two patients (26 women, 24 with limited SSc) with a median age of 47.5 years (interquartile range 43-53) were identified. WD was calculated in 30-day intervals from 12 months prior to disease onset until 36 months after, presented as the prevalence of WD per year (0-3) and as the period prevalence of mean net days per month (± SD). Comparisons were made between patients with different disease severity and sociodemographic characteristics, and between patients and a reference group (RG) from the general population. RESULTS: Seventy-eight percent had no WD 1 year prior to disease onset, which decreased to 47% after 3 years. The relative risk for WD in patients with SSc compared with RG was 0.95 (95% CI 0.39-2.33) at diagnosis, and increased to 2.41 (1.28-4.55) after 3 years. There were no significant correlations between WD and disease severity, but between WD and years at workplace (rs = -0.72; p = 0.002), education (rs = -0.51; p = 0.004), and sickness absence the month before disease onset (rs = 0.58; p = 0.001), respectively. CONCLUSION: Considerable increase in WD was noted 3 years after disease onset. Limited education, fewer years at workplace, and sickness absence before disease onset may be risk factors for sustained WD.

Assessment of capillary density in systemic sclerosis with three different capillaroscopic methods.

OBJECTIVES: Capillary abnormalities, such as the enlargement and/or disappearance of capillary loops, occur early in the majority of patients with systemic sclerosis (SSc). The aim of this study was to compare three capillaroscopic methods of determining the capillary density in patients with SSc. METHODS: Two of the three methods involved stereo-zoom microscopy at a magnification of 20 times, used either for direct counting, or with a camera and imaging software for determination of the capillary density on coded images. The third method was computerised nailfold video capillaroscopy with 300 x magnification using coded images. The capillary density (loops/mm) was determined on the fourth finger of the non-dominant hand with all three methods in 40 patients, 32 with limited cutaneous SSc (lcSSc) and 8 with diffuse cutaneous SSc (dcSSc), and in 21 healthy control subjects. RESULTS: The median values of capillary density assessed with the three methods were: 4.3, 5.4 and 6.1 loops/mm in lc-SSc patients, 4.5, 5.0 and 6.3 loops/mm in dcSSc patients, and 7.0, 7.0 and 6.9 loops/mm in the controls. Capillary density was thus lower in lcSSc and dcSSc patients than in the controls according to all three methods. Agreement between the three methods was good in the controls. In patients, direct counting resulted in lower values than in the two computer-based methods. CONCLUSIONS: Assessment of capillary density with three different methods showed good agreement between methods. All methods could differentiate between SSc patients and controls.

A multicentre study on the reliability of qualitative and quantitative nail-fold videocapillaroscopy assessment.

OBJECTIVE: To investigate the inter- and intra-observer reliability of both qualitative and quantitative parameters used in the assessment of nail-fold capillaroscopy images. METHODS: Fifty mosaic nail-fold images of healthy controls (n = 10), patients with primary RP (n = 10) and SSc (n = 30) were assessed in random order by two blinded observers on two occasions at centres in Sweden, UK and The Netherlands. Each image was therefore scored by six observers twice. RESULTS: Inter- and intra-observer reliability of quantitative parameters showed substantial to almost perfect agreement [inter- and intra-observer weighted κ's for the number of widened capillaries was 0.75 and 0.87 and giant capillaries was 0.84 and 0.92, intra-class correlation coefficients (ICCs) for capillary density was 0.87 and 0.92 and total loop width was 0.94 and 0.98, respectively]. Qualitative parameters including architecture, avascularity, haemorrhage, crossed, ramified and bushy capillaries showed moderate to substantial inter-observer reproducibility (weighted κ ranging from 0.47 to 0.73), and substantial intra-observer repeatability (weighted κ ranging from 0.71 to 0.80), whereas the scoring of tortuous and bizarre capillaries showed poor inter-observer and substantial intra-observer agreement (inter-observer weighted κ's was 0.39 and 0.21 and intra-observer weighted κ's was 0.68 and 0.76, respectively). CONCLUSION: All quantitative and certain qualitative parameters are highly reliable in terms of inter- and intra-observer agreement. A combination of parameters with the highest reliability should be incorporated into future capillaroscopic scoring systems in studies of prediction and monitoring of SSc spectrum disorders.

Concepts of functioning and health important to people with systemic sclerosis: a qualitative study in four European countries.

OBJECTIVE: To describe the experiences of people with systemic sclerosis (SSc) in different European countries of functioning and health and to link these experiences to the WHO International Classification of Functioning, Disability and Health (ICF) to develop a common understanding from a bio-psycho-social perspective. METHOD: A qualitative multicentre study with focus-group interviews was performed in four European countries: Austria, Romania, Sweden and Switzerland. The qualitative data analysis followed a modified form of 'meaning condensation' and the concepts that emerged in the analysis were linked to the ICF. RESULTS: 63 people with SSc participated in 13 focus groups. In total, 86 concepts were identified. 32 (37%) of these were linked to the ICF component body functions and structures, 21 (24%) to activities and participation, 26 (30%) to environmental factors, 6 (7%) to personal factors and 1 (1%) to the health condition itself. 19 concepts (22%) were identified in all four countries and included impaired hand function, household activities, paid work, drugs, climate and coldness, support from others and experiences with healthcare institutions, non-pharmacological treatment, social security and benefits. CONCLUSION: Concepts identified in all four countries could be used for guiding clinical assessment, as well as interdisciplinary team care and rheumatological rehabilitation for patients with SSc. For a full understanding of the aspects of the disease that were most relevant to people with SSc, people with SSc from multiple countries needed to be involved.