Increased incidence of pregnancy complications in women who later develop scleroderma: a case control study

ABSTRACT: INTRODUCTION: Studies have shown that fetal progenitor cells persist in maternal blood or bone marrow for more than 30 years after delivery. Increased trafficking of fetal cells occurs during pregnancy complications, such as hypertension, preeclampsia, miscarriage and intra-uterine growth restriction (IUGR). Women with these pregnancy complications are significantly more often HLA-class II compatible with their spouses. Women who later develop scleroderma also give birth to an HLA-class II child more often. From these prior studies we hypothesized that preeclampsia and other pregnancy complications could be associated with increased levels of fetal cell trafficking, and later be involved in the development of scleroderma. METHODS: This study was a retrospective multi-centre matched case-control study. One-hundred-and-three women with systemic sclerosis (SSc) and 103 women with no history of SSc or other autoimmune disease were given a questionnaire regarding complications during pregnancy, such as hypertension, intra-uterine growth restriction (IUGR) and miscarriage. Conditional logistic regression analysis was used to assess associations. RESULTS: We found a statistically significantly increased incidence of having had a pregnancy history of hypertension or a fetus with IUGR in women who subsequently developed SSc compared to healthy controls. We found an odds ratio of 2.6 (95% confidence interval (CI): 1.1 to 4.6) for hypertensive complications during pregnancy and an odds ratio of 3.9 (95% CI: 1.2 to 12.3) for intra-uterine growth restriction for women with SSc compared to healthy controls. CONCLUSIONS: This is the first study to show an association between hypertensive complications during pregnancy or IUGR and the development of SSc at a later age. We speculate that the pregnancy abnormalities may have resulted in increased fetomaternal trafficking, which may have played a role in the increased incidence of SSc. Further studies are indicated to examine this putative relationship.Pathophysiology and treatment of rheumatic disease

Randomized feasibility trial of the Scleroderma Patient-centered Intervention Network hand exercise program (SPIN-HAND): study protocol

Background: Significant functional impairment of the hands is nearly universal in systemic sclerosis (SSc, scleroderma). Hand exercises may improve hand function, but developing, testing and disseminating rehabilitation interventions in SSc is challenging. The Scleroderma Patient-centered Intervention Network (SPIN) was established to address this issue and has developed an online hand exercise program to improve hand function for SSc patients (SPIN-HAND). The aim of the proposed feasibility trial is to evaluate the feasibility of conducting a full-scale randomized controlled trial (RCT) of the SPIN-HAND intervention. Design and methods: The SPIN-HAND feasibility trial will be conducted via the SPIN Cohort. The SPIN Cohort was developed as a framework for embedded pragmatic trials using the cohort multiple RCT design. In total, 40 English-speaking SPIN Cohort participants with at least mild hand function limitations (Cochin Hand Function Scale ≥3) and an indicated interest in using an online hand-exercise intervention will be randomized with a 1:1 ratio to be offered to use the SPIN-HAND program or usual care for 3 months. The primary aim is to evaluate the trial implementation processes, required resources and management, scientific aspects, and participant acceptability and usage of the SPIN-HAND program. Discussion: The SPIN-HAND exercise program is a self-help tool that may improve hand function in patients with SSc. The SPIN-HAND feasibility trial will ensure that trial methodology is robust, feasible, and consistent with trial participant expectations. The results will guide adjustments that need to be implemented before undertaking a full-scale RCT of the SPIN-HAND program. Trial registration: ClinicalTrials.gov Identifier: NCT03092024.Canadian Institutes of Health Research(undefined

Feasibility of tailored treatment based on risk stratification in patients with early rheumatoid arthritis

Introduction: Personalized medicine is the holy grail of medicine. The EULAR recommendations for the management of rheumatoid arthritis (RA) support differential treatment between patients with baseline characteristics suggestive of a non-poor prognosis (non-PP) or poor prognosis (PP) (presence of autoantibodies, a high inflammatory activity and damage on radiographs). We aimed to determine which prognostic risk groups benefit more from initial monotherapy or initial combination therapy. Methods: 508 patients were randomized t

The Natural Sequence in Which Subclinical Inflamed Joint Tissues Subside or Progress to Rheumatoid Arthritis:A Study of Serial MRIs in the TREAT EARLIER Trial

Objective: The natural trajectory of clinical arthritis progression at the tissue level remains elusive. We hypothesized that subclinical inflammation in different joint tissues (synovitis, tenosynovitis, osteitis) increases in a distinct temporal order in patients with clinically suspect arthralgia (CSA) who develop rheumatoid arthritis (RA) and subsides in a different sequence when CSA spontaneously resolves. Methods: We studied 185 serial magnetic resonance images (MRIs) from CSA patients with subclinical joint inflammation from the placebo arm of the TREAT EARLIER trial: 52 MRIs from 21 RA progressors (MRIs conducted at 1 year before, at 4 months before, and upon RA development), and 133 MRIs from 35 patients with spontaneous resolution of pain (MRIs conducted at baseline and at 4, 12, and 24 months). MRIs were scored for osteitis, synovitis, and tenosynovitis. We used cross-lagged models to evaluate 2 types of time patterns between pairs of inflamed tissues: a simultaneous pattern (coinciding changes) and a subsequent pattern (inflammatory changes in 1 tissue preceding changes in another tissue). Results:In patients who developed RA, synovitis, tenosynovitis, and osteitis increased simultaneously. Increasing osteitis occurred in the final 4 months before RA diagnosis, following incremental tenosynovitis and synovitis changes during the 1 year to 4 months before diagnosis (P &lt; 0.01). In anti–citrullinated protein antibody (ACPA)-positive and ACPA-negative patients who progressed to RA, osteitis increased just before RA development. In patients with pain resolution, simultaneous decreases in synovitis, tenosynovitis, and osteitis occurred, with tenosynovitis decreasing in the first 4 months after CSA onset preceding decreasing synovitis and osteitis during 4–12 months (P = 0.02 and P &lt; 0.01). Conclusion:We identified natural sequences of subclinical inflammation in different joint tissues, which deepens our understanding of clinical arthritis and RA development. During RA progression, increasing osteitis followed previous increases in tenosynovitis and synovitis. During pain resolution, tenosynovitis decreased first, followed by decreasing synovitis and osteitis.</p

Rituximab in early systemic sclerosis

Objectives (1) Hypothesis testing of the potency of rituximab (RTX) in preventing fibrotic complications and (2) assessing acceptability and feasibility of RTX in early systemic sclerosis (SSc). Methods A small, 24-month, randomised, double-blind, placebo-controlled, single-centre trial in patients with SSc diagnosed <2 years was conducted. Patients received RTX or placebo infusions at t=0, t=15 days and t=6 months. Patients were clinically evaluated every 3 months, with lung function tests and high-resolution CT every other visit. Skin biopsies were taken at baseline and month 3. Immunophenotyping of peripheral blood mononuclear cells was performed at every visit, except at months 9 and 18. Adverse events, course of skin and pulmonary involvement and B cell populations in skin and peripheral blood were evaluated. Results In total 16, patients (rituximab n=8, placebo n=8) were included. Twelve patients had diffuse cutaneous SS

Using Optimal Test Assembly Methods for Shortening Patientâ Reported Outcome Measures: Development and Validation of the Cochin Hand Function Scaleâ 6: A Scleroderma Patientâ Centered Intervention Network Cohort Study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134498/1/acr22893_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134498/2/acr22893.pd

How do patients with systemic sclerosis experience currently provided healthcare and how should we measure its quality?

OBJECTIVES: To gain insight into SSc patients' perspective on quality of care and to survey their preferred quality indicators. METHODS: An online questionnaire about healthcare setting, perceived quality of care (CQ index) and quality indicators, was sent to 2093 patients from 13 Dutch hospitals. RESULTS: Six hundred and fifty patients (mean age 59 years, 75% women, 32% limited cutaneous SSc, 20% diffuse cutaneous SSc) completed the questionnaire. Mean time to diagnosis was 4.3 years (s.d. 6.9) and was longer in women compared with men (4.8 (s.d. 7.3) vs 2.5 (s.d. 5.0) years). Treatment took place in a SSc expert centre for 58%, regional centre for 29% or in both for 39% of patients. Thirteen percent of patients was not aware of whether their hospital was specialized in SSc. The perceived quality of care was rated with a mean score of 3.2 (s.d. 0.5) (range 1.0-4.0). There were no relevant differences between expert and regional centres. The three prioritized process indicators were: good patient-physician interaction (80%), structural multidisciplinary collaboration (46%) and receiving treatment according to SSc guidelines (44%). Absence of disease progression (66%), organ involvement (33%) and digital ulcers (27%) were the three highest rated outcome indicators. CONCLUSION: The perceived quality of care evaluated in our study was fair to good. No differences between expert and regional centres were observed. Our prioritized process and outcome indicators can be added to indicators suggested by SSc experts in earlier studies and can be used to evaluate the quality of care in SSc

Validation of the Body Concealment Scale for Scleroderma (BCSS): Replication in the Scleroderma Patient-centered Intervention Network (SPIN) Cohort

© 2016 Elsevier Ltd Body concealment is an important component of appearance distress for individuals with disfiguring conditions, including scleroderma. The objective was to replicate the validation study of the Body Concealment Scale for Scleroderma (BCSS) among 897 scleroderma patients. The factor structure of the BCSS was evaluated using confirmatory factor analysis and the Multiple-Indicator Multiple-Cause model examined differential item functioning of SWAP items for sex and age. Internal consistency reliability was assessed via Cronbach's alpha. Construct validity was assessed by comparing the BCSS with a measure of body image distress and measures of mental health and pain intensity. Results replicated the original validation study, where a bifactor model provided the best fit. The BCSS demonstrated strong internal consistency reliability and construct validity. Findings further support the BCSS as a valid measure of body concealment in scleroderma and provide new evidence that scores can be compared and combined across sexes and ages

Needs and preferences regarding health care delivery as perceived by patients with systemic sclerosis

This study aims to examine the needs and preferences regarding the delivery of health care services and information provision and their determinants in patients with systemic sclerosis (SSc). A questionnaire was sent to 77 SSc outpatients, comprising 27 items on health care needs within the domains physical, psychological, social support, employment/daily activities, or other health problems and 13 items on information needs. Moreover, the patients’ preferences regarding the provision of health care services and information were listed. Additional assessments included sociodemographic characteristics, physical functioning (SSc Health Assessment Questionnaire), and quality of life (SF-36). Sixty-four patients (83%) returned the questionnaire. Twenty-six patients (41%) reported one or more unmet health care needs, with the highest proportions of patients with unmet needs seen in the physical (28%) and psychological (20%) domain. The highest percentages of patients with information needs were observed for medical subjects (20–28%). A lower mental component summary scale score and younger age were associated with the presence of at least one health care need in the psychological domain. Worse physical functioning, a diagnosis of diffuse SSc and having a partner were associated with higher information need score. A yearly, standardized multidisciplinary assessment program was most frequently mentioned as a preferred, but not yet existing health care model (59%) and the rheumatologist as a preferred source of information supply (75%). Unmet health care and information needs are common among SSc patients. To improve SSc health care, more attention should be paid to health care services for specific physical and psychological problems and medical information supply by the rheumatologist. In addition, the development of new models of care, such as a yearly, standardized multidisciplinary diagnostic program seems warranted

Automatic Pulmonary Function Estimation From Chest CT Scans Using Deep Regression Neural Networks: The Relation Between Structure and Function in Systemic Sclerosis

Pulmonary function tests (PFTs) play an important role in screening and following-up pulmonary involvement in systemic sclerosis (SSc). However, some patients are not able to perform PFTs due to contraindications. In addition, it is unclear how lung function is affected by changes in lung structure in SSc. Therefore, this study aims to explore the potential of automatically estimating PFT results from chest CT scans of SSc patients and how different regions influence the estimation of PFTs. Deep regression networks were developed with transfer learning to estimate PFTs from 316 SSc patients. Segmented lungs and vessels were used to mask the CT images to train the network with different inputs: from entire CT scan, lungs-only to vessels-only. The network trained on entire CT scans with transfer learning achieved an ICC of 0.71, 0.76, 0.80, and 0.81 for the estimation of DLCO, FEV1, FVC and TLC, respectively. The performance of the networks gradually decreased when trained on data from lungs-only and vessels-only. Regression attention maps showed that regions close to large vessels were highlighted more than other regions, and occasionally regions outside the lungs were highlighted. These experiments show that apart from the lungs and large vessels, other regions contribute to PFT estimation. In addition, adding manually designed biomarkers increased the correlation (R) from 0.75, 0.74, 0.82, and 0.83 to 0.81, 0.83, 0.88, and 0.90, respectively. This suggests that that manually designed imaging biomarkers can still contribute to explaining the relation between lung function and structure