Alessandra Vacca

Background/Objectives: This study aimed to evaluate whether liver stiffness (LS), as assessed by transient elastography (TE), is increased in patients with systemic sclerosis (SSc) and to identify the factors associated with LS. Methods: In this exploratory cross-sectional study, the LS value and the prevalence of LS ≥ 5.3 and LS ≥ 7.5 kPa in 94 SSc patients and 50 healthy controls (HCs) were compared by univariate and multivariate analyses (adjusted for age and sex). TE was performed using FibroScan^® and LS values were expressed in kPa. Clinical and laboratory variables were analysed as factors potentially associated with LS, LS ≥ 5.3 kPa and LS ≥ 7.5 kPa, in exploratory analyses adjusted for a pre-specified set of confounders. Results: Among the 94 SSc patients, 79 (84%) were female; median age was 59 (49–70) years, and median disease duration was 8 (3–13) years. LS was significantly higher in SSc patients than in HCs in both univariate (5.12 ± 1.95 vs. 4.18 ± 0.98 kPa, p < 0.001) and multivariate analyses (β = 0.289, p = 0.001), with a higher prevalence of LS ≥ 5.3 kPa (40.4% vs. 10.0%, adjOR 6.85, p = 0.001) and LS ≥ 7.5 kPa (11.7% vs. 0%, p = 0.009). Only a limited number of factors were associated with LS abnormalities: telangiectasias (β = 0.222, p = 0.044) and glutamic–oxaloacetic transaminase (GOT) (β = 0.278, p = 0.012) for LS, and GOT (adjOR 1.082, p = 0.020) and anti-centromere antibodies (adjOR 4.09, p = 0.017) for LS ≥ 5.3 kPa. In univariate analysis, LS ≥ 7.5 kPa was associated with pulmonary hypertension (p = 0.049), pre-capillary pulmonary hypertension (p = 0.011), and GOT (p = 0.032); no multivariate model was fitted because of the few events. Conclusions: SSc patients show increased LS values and a higher prevalence of both LS ≥ 5.3 kPa and LS ≥ 7.5 kPa than HCs, easily detectable by TE. These findings are exploratory and require confirmation in larger cohorts to determine whether increased LS in SSc reflects hepatic fibrosis and whether it carries clinical and prognostic implications.

Objectives To determine the causes of death and risk factors in systemic sclerosis (SSc). Methods Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. Results We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. Conclusion Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients’ survival.

The multisystem manifestations of SSc can greatly impact patients’ quality of life. The aim of this study was to identify factors associated with disability in SSc. SSc patients from the prospective DeSScipher cohort who had completed the scleroderma health assessment questionnaire (SHAQ), a disability score that combines the health assessment questionnaire and five visual analogue scales, were included in this analysis. The effect of factors possibly associated with disability was analysed with multiple linear regressions. The mean SHAQ and HAQ scores of the 944 patients included were 0.87 (s.d. = 0.66) and 0.92 (s.d. = 0.78); 59% of the patients were in the mild to moderate difficulty SHAQ category (0 ⩽ SHAQ < 1), 34% in the moderate to severe disability category (1 ⩽ SHAQ < 2) and 7% in the severe to very severe disability category (2 ⩽ SHAQ ⩽ 3). The means of the visual analogue scales scores were in order of magnitude: overall disease severity (37 mm), RP (31 mm), pulmonary symptoms (24 mm), gastrointestinal symptoms (20 mm) and digital ulcers (19 mm). In multiple regression, the main factors associated with high SHAQ scores were the presence of dyspnoea [modified New York Heart Association (NYHA) class IV (regression coefficient B = 0.62), modified NYHA class III (B = 0.53) and modified NYHA class II (B = 0.21; all vs modified NYHA class I)], FM (B = 0.37), muscle weakness (B = 0.27), digital ulcers (B = 0.20) and gastrointestinal symptoms (oesophageal symptoms, B = 0.16; stomach symptoms, B = 0.15; intestinal symptoms, B = 0.15). SSc patients perceive dyspnoea, pain, digital ulcers, muscle weakness and gastrointestinal symptoms as the main factors driving their level of disability, unlike physicians who emphasize objective measures of disability.

This study describes clinical characteristics, prognostic factors, and quality of life in patients with newly diagnosed (incident) digital ulcers (DU). Observational cohort study of 189 consecutive SSc patients with incident DU diagnosis identified from the EUSTAR database (22 centres in 10 countries). Data were collected from medical charts and during one prospective visit between 01/2004 and 09/2010. Median age at DU diagnosis was 51 years, majority of patients were female (88%), and limited cutaneous SSc was the most common subtype (61%). At incident DU diagnosis, 41% of patients had one DU and 59% had ≥2 DU; at the prospective visit 52% had DU. Pulmonary arterial hypertension (PAH) and multiple DU at diagnosis were associated with presence of any DU at the prospective visit (odds ratios: 4.34 and 1.32). During the observation period (median follow-up was 2 years) 127 patients had ≥1 hospitalisation. The event rate of new DU per person-year was 0.66, of DU-associated complications was 0.10, and of surgical or diagnostic procedures was 0.12. At the prospective visit, patients with ≥1 DU reported impairment in daily activities by 57%, those with 0 DU by 37%. The mean difference between patients with or without DU in the SF-36 physical component was 2.2, and in the mental component 1.4. DU patients were not routinely prescribed endothelin receptor antagonists or prostanoids. This real world cohort demonstrates that DU require hospital admission, and impair daily activity. PAH and multiple DU at diagnosis were associated with future occurrence of DU.

Postmarketing Phase IV HLA‐B27 (B27) interactions with the killer‐cell immunoglobulin‐like receptors (KIR) have been implicated in the pathogenesis of ankylosing spondylitis (AS), with consistent differences among populations. KIR3DL1 and possibly KIR3DS1 interact with classical B27, whereas KIR3DL2 binds B27 heavy chain dimers. The aim of this review is to summarize data from recent studies performed in our laboratory and from the literature, which provide support for a possible role of KIR3DL2/B27 dimer interactions in the pathogenesis of AS. Recent studies in cells from AS patients and from health controls carrying the predisposing B*2705 and the nonpredisposing B*2709 haplotypes, have shown a higher percentage of positive cells and a higher surface expression of KIR3DL2 receptors on natural killer (NK) and CD4+ T cells in B*2705 AS patients compared with B*2705, B*2709 and B27‐negative healthy controls. Increased expression of HC10‐reactive molecules on AS monocytes was seen, supporting the possible role of the KIR3DL2/B27₂ pair in the pathogenesis of AS. These results underline the importance of NK cells and innate immunity, and of CD4+ T cells in the inflammatory pathogenesis of AS.

Signs and symptoms of arrhythmias or conduction defects are frequently reported in patients with SSc. These rhythm disorders may have several origins (i.e. related to primary heart involvement, pericardial disease, valvular regurgitation or pulmonary arterial hypertension) and may negatively affect the overall prognosis of these patients. It is therefore important to identify patients at high risk for cardiac arrhythmias with a complete cardiological evaluation and to identify the underlying heart disease, including SSc-related myocardial involvement. In addition, some therapeutic options in SSc patients may differ from those recommended in other populations.