Publications by authors named "Filip de Keyser"

113 Publications

Incidence, prevalence and long-term progression of Goh algorithm rated interstitial lung disease in systemic sclerosis in two independent cohorts in flanders: A retrospective cohort study.

Semin Arthritis Rheum 2021 Oct 1;51(5):969-976. Epub 2021 Aug 1.

Department of Internal Medicine, Ghent University, Ghent, Belgium; Department of Rheumatology, Ghent University Hospital, Ghent, Belgium; Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center (IRC), Ghent, Belgium. Electronic address:

Objectives: The epidemiology of interstitial lung disease (ILD) in systemic sclerosis (SSc) in Belgium is unknown. In literature, its prevalence varies between 19% and 52% in limited/diffuse cutaneous SSc (LcSSc/DcSSc). However, its prevalence in "early" SSc (pre-clinically overt SSc without [yet] skin involvement), nor its incidence rate in SSc (LcSSc/DcSSc/"early" SSc) has ever been described. Against this background, we aimed to determine the prevalence/incidence (rate) and progression of ILD in SSc.

Methods: 12-year follow-up data of consecutive SSc patients, included in two Flemish cohorts (University Hospitals Ghent and Leuven), were retrospectively analysed. ILD was classified according to the simplified Goh algorithm. Progression of ILD was defined as a relative decline of FVC ≥10%, a combined relative decline of FVC 5-10% and DLCO ≥15%, or as an increase in HRCT extent.

Results: 722 patients (60% LcSSc/ 20% DcSSc/ 20% "early" SSc, median (IQR) follow-up 39 [12-80] months) had baseline HRCT. 243 were rated to have ILD at baseline and 39 during follow-up (prevalence of 34%/ incidence rate of 20.3/1000PY, 95%CI:14.5-27.8). Amongst those with baseline ILD, 60% had lung functional progression at five years of follow-up. In the "early" SSc subgroup, eight patients were rated to have ILD at baseline and three during follow-up (prevalence of 6%/ incidence rate of 5.8/1000 PY, 95%CI:1.2-17.0).

Conclusion: Both LcSSc and DcSSc patients should be monitored for ILD evolution. The low prevalence and incidence of ILD in the "early" SSc subgroup may instruct future decisions on the construction of uniform patient follow-up pathways in "early" SSc.
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http://dx.doi.org/10.1016/j.semarthrit.2021.07.018DOI Listing
October 2021

Association Between Nursing Support Levels and Effectiveness of Golimumab in the Management of Patients with Rheumatologic Diseases.

Rheumatol Ther 2020 Jun 2;7(2):401-413. Epub 2020 May 2.

MSD Belgium BV/SRL, Brussels, Belgium.

Introduction: The main objective of this study was to assess the level of nursing support received by biologic-naïve rheumatological patients treated with golimumab during their first cycle.

Methods: Adult patients (N = 119; aged 46.9 ± 13.4 years (mean ± standard deviation); 49.6% males), with rheumatoid arthritis (N = 40), ankylosing spondylitis (N = 58) or psoriatic arthritis (N = 21), and treated with golimumab (first tumor necrosis factor-α inhibitor) during a first reimbursement cycle were included by 17 Belgian centers. Patients were categorized in three levels of nursing support (intense, medium, or low). They filled in a non-validated and exploratory questionnaire about satisfaction, quality, and helpfulness of information.

Results: The nursing support was considered intense, medium, or low for 98 (82.4%), 10 (8.4%), and 11 (9.2%) patients, respectively. All disease activity scores improved versus baseline, and 90% of the patients qualified for treatment prolongation without major differences between nursing level groups. The proportion of patients able to self-inject golimumab was 88, 90, and 73% in the intense, medium, and low support groups, respectively. Satisfaction was high in all three nursing support groups.

Conclusions: This prospective open-label study has confirmed the short-term effectiveness of golimumab in three rheumatological diseases, with most of the patients qualifying for reimbursement renewal. The limited sample size and the fact that the vast majority of patients benefited from an intense nursing support did not allow drawing definite conclusions concerning the impact of the nursing level on the treatment effectiveness and changes in the disease activity. Nurses seem however to play a crucial role in this short-term study but this remains to be confirmed in a longer-term study.
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http://dx.doi.org/10.1007/s40744-020-00210-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211220PMC
June 2020

Evaluation of the primary biliary cholangitis-related serologic profile in a large cohort of Belgian systemic sclerosis patients.

Clin Chem Lab Med 2020 02;58(3):416-423

Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.

Background Systemic sclerosis (SSc) and primary biliary cholangitis (PBC) are autoimmune diseases that may occur concomitantly and are both strongly associated with disease-specific autoantibodies. This study investigated the prevalence and fine specificity of PBC-specific serology (PBC-Ab) and associations with the SSc-subtypes and SSc-specific antibodies as well as the association with cholestatic liver enzymes. Furthermore, three different techniques for the detection of PBC-Ab were compared. Methods Serum of 184 Belgian SSc patients with a known SSc-antibody profile, was analyzed for PBC-Ab (antimitochondrial antibodies [AMA], anti-Gp210, anti-Sp100 and anti-PML) using indirect immunofluorescence (IIF) analysis on human epithelioma-2000 (HEp-2000) cells (ANA-IIF, Immunoconcepts) and liver-kidney-stomach tissue sections (IIF-LKS) (Menarini), and a line immunoblot (LB) (EuroImmun). Alkaline phosphatase/γ-glutamyl transferase (ALP/GGT) were evaluated at time of first sampling (t0) and after 3 years of follow-up (t3). Results PBC-Ab were present in 13% of patients and significantly correlated with centromere antibodies (anti-CENP-B), but not correlated with the limited cutaneous SSc subgroup (lcSSc). The most frequent reactivities were AMA (11%, with 9% AMA-M2) and Sp-100 antibodies (5%), showing a major overlap. There was no relevant association between the presence of PBC-Ab and ALP or GGT elevation at t0 nor at t3. Detection of AMA with IIF-LKS is comparable to LB. ANA-IIF screening was less sensitive compared to LB. Conclusions A wide range of PBC-Ab is detectable in SSc in the absence of cholestatic liver enzyme elevations, even after 3 years of follow-up. However, as these antibodies may precede PBC-disease up to 10 years further prospective follow-up of our cohort will be necessary.
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http://dx.doi.org/10.1515/cclm-2019-0655DOI Listing
February 2020

Pitfalls in the detection of myositis specific antibodies by lineblot in clinically suspected idiopathic inflammatory myopathy.

Clin Exp Rheumatol 2020 Mar-Apr;38(2):212-219. Epub 2019 Jul 4.

Department of Laboratory Medicine, Ghent University Hospital, and Department of Diagnostic Science, Ghent University, Belgium.

Objectives: Today, the contribution of myositis-specific autoantibodies (MSA) in the diagnostic workup of idiopathic inflammatory myopathies (IIM) is on the rise. The aim of this study was to document MSA frequency as detected by lineblot in a set of consecutive MSA requests and to correlate the results with clinical diagnosis, IIM subtype and indirect immunofluorescence (IIF) findings. Additionally, a comparison between two lineblots was performed.

Methods: A total of 118 consecutive samples of patients with suspicion of IIM were analysed on IIF and two lineblots. A total of 107 patients with autoimmune rheumatic diseases served as controls.

Results: MSA were detected in 55% of IIM patients (n=31) and 7.9% (n=12) of patients without clinical diagnosis of IIM or myositis overlap syndrome. All the IIM patients had a MSA-compatible clinical subtype. There was no to fair agreement between both lineblots for the individual antibodies, with most discrepancies observed for anti-TIF1γ (κ=-0.021), anti-SRP (κ=-0.006) and anti-SAE (κ=0.395). Differences between both assays were mostly observed in the non-IIM patients, also showing signi cantly lower blot signal intensities compared to IIM patients (p=0.0013). MSA in the non-IIM patients frequently showed an incompatible IIF pattern.

Conclusions: Lineblot seems to be an interesting tool for MSA detection in a clinical context, allowing the identification of clinical subtypes. However, considerable caution must be exercised in interpreting the results in case of low positive MSA signal intensity, discordant lineblot results and/or an incompatible IIF pattern.
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April 2020

A prospective, longitudinal study evaluating the baseline six-minute walk test as an individual reference value in systemic sclerosis patients.

Clin Exp Rheumatol 2018 Jul-Aug;36 Suppl 113(4):95-101. Epub 2018 Aug 28.

Department of Internal Medicine, Ghent University, and Department of Rheumatology, Ghent University Hospital, Belgium.

Objectives: Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are the leading causes of death in systemic sclerosis (SSc). Although the six-minute walk test (6MWT) is used for evaluating ILD and PAH, no data are available on the evolution of the six-minute walk distance (6MWD) in SSc patients without ILD and PAH and whether the baseline 6MWD could serve as individual reference value for the management of those who will develop PAH or ILD.

Methods: Prospectively collected data of the first 6MWT (at baseline or 6-month follow-up) and the 6MWTs at 18-, 30-, 42-, 54-, and 66-month visit of 165 consecutive SSc patients without ILD and PAH, included in the Ghent University SSc Cohort between May 2006 and December 2016 were analysed.

Results: 96-100% of the included patients performed a 6MWT during the follow-up visits. The mean 6MWD during the baseline 6MWT of 165 SSc patients without ILD and PAH (35% limited, 56% limited cutaneous, 9% diffuse cutaneous SSc) was 484.20+/-92.65m with no significant difference in the 6MWD at different follow-up visits as compared to baseline. In 46 SSc patients without ILD and PAH who performed a 6MWT at baseline and at 66-month visit, the 6MWD walked at 66-month visit correlated with the baseline 6MWD (r=0.564, p<0.001).

Conclusions: In SSc without ILD and PAH, the 6MWT is feasible and the 6MWD is clinically stable over a 66 months period. Hence, the individual 6MWD might be used as individual reference value in management of those who will develop PAH or ILD.
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January 2019

Is laser speckle contrast analysis (LASCA) the new kid on the block in systemic sclerosis? A systematic literature review and pilot study to evaluate reliability of LASCA to measure peripheral blood perfusion in scleroderma patients.

Autoimmun Rev 2018 Aug 6;17(8):775-780. Epub 2018 Jun 6.

Department of Rheumatology, Ghent University Hospital, Department of Internal Medicine, Ghent University, Corneel Heymanslaan 10, Ghent, Belgium. Electronic address:

Objectives: A reliable tool to evaluate flow is paramount in systemic sclerosis (SSc). We describe herein on the one hand a systematic literature review on the reliability of laser speckle contrast analysis (LASCA) to measure the peripheral blood perfusion (PBP) in SSc and perform an additional pilot study, investigating the intra- and inter-rater reliability of LASCA.

Methods: A systematic search was performed in 3 electronic databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In the pilot study, 30 SSc patients and 30 healthy subjects (HS) underwent LASCA assessment. Intra-rater reliability was assessed by having a first anchor rater performing the measurements at 2 time-points and inter-rater reliability by having the anchor rater and a team of second raters performing the measurements in 15 SSc and 30 HS. The measurements were repeated with a second anchor rater in the other 15 SSc patients, as external validation.

Results: Only 1 of the 14 records of interest identified through the systematic search was included in the final analysis. In the additional pilot study: intra-class correlation coefficient (ICC) for intra-rater reliability of the first anchor rater was 0.95 in SSc and 0.93 in HS, the ICC for inter-rater reliability was 0.97 in SSc and 0.93 in HS. Intra- and inter-rater reliability of the second anchor rater was 0.78 and 0.87.

Conclusions: The identified literature regarding the reliability of LASCA measurements reports good to excellent inter-rater agreement. This very pilot study could confirm the reliability of LASCA measurements with good to excellent inter-rater agreement and found additionally good to excellent intra-rater reliability. Furthermore, similar results were found in the external validation.
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http://dx.doi.org/10.1016/j.autrev.2018.01.023DOI Listing
August 2018

Nailfold capillaroscopy in systemic lupus erythematosus: A systematic review and critical appraisal.

Autoimmun Rev 2018 Apr 8;17(4):344-352. Epub 2018 Feb 8.

Department of Rheumatology, Ghent University Hospital, C. Heymanslaan 10, Ghent, Belgium; Department of Internal Medicine, Ghent University, C. Heymanslaan 10, Ghent, Belgium. Electronic address:

Nailfold capillaroscopy is an easy, non-invasive technique to assess microvascular involvement in rheumatic diseases. Multiple studies describe capillaroscopic changes in systemic lupus erythematosus (SLE), including a wide range of non-specific findings. On behalf of the European League Against Rheumatism (EULAR) study group on microcirculation in rheumatic diseases, a systematic review was done to obtain all original research studies (in English) in which SLE patients had capillaroscopy. Forty such studies are identified. This article firstly provides a résumé of the results of these studies according to capillaroscopic parameters (density, dimensions, morphology, haemorrhages), semi-quantitative assessment and qualitative assessment of capillaroscopy in SLE patients. Secondly, the correlations between capillaroscopic parameters in SLE patients and clinical and laboratory parameters (including auto-immune parameters) are outlined. The following capillaroscopic parameters are found to be significantly more prevalent in SLE patients compared to healthy controls: tortuous capillaries, abnormal morphology and haemorrhages. Hairpin-shaped capillaries are significantly less prevalent than in healthy persons. The semi-quantitatively determined nailfold capillaroscopic score (NFC score) in SLE patients is also higher than in healthy controls. Several correlations between clinical and laboratory parameters and capillaroscopic parameters are identified in the review. Disease activity is correlated with NFC score in seven studies, with abnormal morphology (i.e. "meandering") in one study and with haemorrhages in one study. Frequent attacks of Raynaud's phenomenon (RP) and gangrene are significantly correlated with dilated capillaries. In two studies a possible correlation between anti-SSA antibodies and lower density of capillaries is withheld. About other immune parameters conflicting results are found. In one study a significant negative correlation is found between 24-hour proteinuria and abnormal morphology (i.e. "meandering"). For the first time, an overview of the nailfold capillaroscopic changes that have been described in SLE and their correlations with clinical and laboratory findings is given. Further large-scale research on the identification of capillaroscopic changes in SLE and their correlations with standardised clinical and laboratory parameters, is ongoing at the EULAR study group on microcirculation in rheumatic diseases.
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http://dx.doi.org/10.1016/j.autrev.2017.11.025DOI Listing
April 2018

Two years follow-up of an open-label pilot study of treatment with rituximab in patients with early diffuse cutaneous systemic sclerosis.

Acta Clin Belg 2018 Apr 11;73(2):119-125. Epub 2017 Sep 11.

a Department of Rheumatology , Universitair Ziekenhuis Gent , Ghent , Belgium.

Objectives: Following results in open-label studies of rituximab in patients with systemic sclerosis, a Belgian three-centre initiative was launched to explore safety and efficacy of rituximab in early, diffuse cutaneous systemic sclerosis (dcSSc).

Methods: Open-label study of 17 patients with early dcSSc, treated with two courses of rituximab, at month 0 and 6. Clinical examination, lung function testing, echocardiography, disease activity score (DAS) and functional status were performed at baseline and over 24 months of follow-up.

Results: Modified Rodnan skin score (MRSS) changed significantly over time, with a mean of 25.5 (standard deviation [SD] 6.0) at baseline to 12.6 (SD 5.1) at month 24 (Mixed Model Analysis [MMA] p < 0.0001), which is a decrease of 51% at month 24 vs. baseline. DAS showed significant decrease over the total study period, with a score of 4.1 (SD 1.7) at baseline to 1.5 (SD 1.8) at month 24 (MMA p < 0.0001). Additionally, this was significant at all time points vs. baseline, both for MRSS and DAS. Internal organ status remained clinically stable throughout the study period. No statistically significant differences compared to baseline were found at the follow-up time points. Seven serious adverse events took place, all except for one, considered unrelated to study medication.

Conclusions: This is the first multicentre Belgian collaboration investigating potential efficacy of rituximab in early dcSSc. Rituximab appears to be safe and tolerable and it may have beneficial effects on skin involvement, on overall disease activity and on stabilization of internal organ status in early dcSSc.
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http://dx.doi.org/10.1080/17843286.2017.1372244DOI Listing
April 2018

Screening for pulmonary arterial hypertension in an unselected prospective systemic sclerosis cohort.

Eur Respir J 2017 05 11;49(5). Epub 2017 May 11.

Dept of Internal Medicine, Ghent University, Ghent, Belgium.

Screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) improves outcomes. The DETECT screening algorithm is recommended in a high-risk SSc subgroup. This study aims to compare prospectively the positive predictive value of screening using the DETECT algorithm and the 2009 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines, and to compare their cost-effectiveness in an unselected, day-to-day SSc population. , screening according to the 2015 ESC/ERS guidelines using echocardiographic parameters alone ("2015 echo screening") or combined with the DETECT algorithm ("2015 combined screening") in high-risk subjects was analysed.195 consecutive SSc patients included in the Ghent University Hospital SSc cohort were screened using different algorithms.The referral rate for right heart catheterisation was 32% (63 out of 195 patients) (46/4/13/34/40 patients using the DETECT algorithm/2009 guidelines/both/2015 echo screening/2015 combined screening). Right heart catheterisation was performed in 53 patients (84%) (36 (78%)/four (100%)/13 (100%)/28 (82%)/32 (80%) patients recommended by the DETECT algorithm/2009 guidelines/both/2015 echo screening/2015 combined screening). PAH was diagnosed in three patients (incidence 1.5%·year, 95% CI 0.5-4.4), in whom all algorithms recommended a right heart catheterisation. The positive predictive value was 6% (95% CI 2-17%; three out of 49 patients) for the DETECT algorithm, 18% (95% CI 6-41%; three out of 17 patients) for the 2009 guidelines, 23% (95% CI 8-50%; three out of 13 patients) for both, 11% (95% CI 4-27%; three out of 28 patients) for the 2015 echo screening and 9% (95% CI 3-24%; three out of 32 patients) for the 2015 combined screening. The cost was EUR224/80/90/112 per patient using the DETECT algorithm/2009 guidelines/2015 echo screening/2015 combined screening.Echocardiography may remain a candidate first step for PAH screening in SSc.
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http://dx.doi.org/10.1183/13993003.02275-2016DOI Listing
May 2017

Six-minute walk test in or out in evaluation of systemic sclerosis patients?

Clin Exp Rheumatol 2017 Sep-Oct;35 Suppl 106(4):122-129. Epub 2017 Feb 15.

Department of Rheumatology, Ghent University Hospital; and Department of Internal Medicine, Ghent University, Belgium.

Objectives: Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are the leading causes of death in systemic sclerosis (SSc) patients. Although the six-minute walk test (6MWT) is used for evaluating ILD and PAH in clinical practice, no data are available on six-minute walk distance (6MWD) and oxygen desaturation in SSc patients without ILD and PAH.

Methods: Prospectively collected data of the 6MWTs at baseline and 6-month follow-up of 300 consecutive SSc patients, included in the Ghent University Hospital Systemic Sclerosis Unit between May 2006 and April 2015 were analysed.

Results: The mean 6MWD of 165 SSc patients without ILD and PAH who performed a 6MWT at baseline or at the 6-month visit was 484±93m. Patients in the diffuse cutaneous (DcSSc) subgroup (435±94m) walked less than in the limited (LSSc) subgroup (499±91m, p=0.04) and tended to walk less than in the limited cutaneous (LcSSc) subgroup (483±92m, p=0.15). In 115 SSc patients without ILD and PAH who walked at both moments, there was no significant difference between the 6MWDs (mean difference -7.60m 95%CI [-19.93m; 4.73m], p=0.23) and the oxygen desaturation was not statistically different in 102 of them (mean difference 0.41% 95%CI [-0.49%; 1.31%], p=0.37).

Conclusions: In SSc without ILD and PAH, the 6MWD and oxygen desaturation is clinically stable over a 6 months period. The DcSSc subgroup walks less than the LSSc and the LcSSc subgroup.
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December 2017

Assessment of sensitivity to change of the European Scleroderma Study Group activity index.

Clin Exp Rheumatol 2016 Sep-Oct;34 Suppl 100(5):148-151. Epub 2016 Jul 18.

Department of Internal Medicine, Faculty of Medicine and Health Sciences, Ghent University; and Department of Rheumatology, Ghent University Hospital, Belgium.

Objectives: The European Scleroderma Study Group (EScSG) activity index meets nearly all the OMERACT-standards of truth, discrimination and feasibility. The sensitivity to change remains to be attested. This study assesses sensitivity to change of the EScSG activity index in patients with early and severe diffuse cutaneous Systemic Sclerosis (dcSSc) treated with rituximab.

Methods: 12-month follow-up (open-label study) of 14 consecutive patients with early dcSSc. Patients received an infusion of two times 1000 mg rituximab at month 0 and 6, together with 100 mg methylprednisolone. Clinical read outs (modified Rodnan skin score [mRSS], lung function and echocardiography) and EScSG activity index were performed at month 0, 3, 6 and 12. Mixed models analyses (MMA) were used to evaluate changes in parameters over time.

Results: There was a clinically significant change in skin score with a mean (SD) mRSS of 24.8 (4.44) at baseline and 10.4 (3.12) at month 12 (MMA p<0.001). Also the EScSG activity index decreased significantly, with a mean (SD) of 4.3 (1.79) at baseline and 0.7 (0.83) at month 12 (MMA p<0.001). The estimated mean change of the EScSG activity index was -3.6 (95%CI -4.9; -2.4) over 12 months. Indices of internal organ involvement remained stable throughout the study.

Conclusions: A significant improvement of the EScSG activity index was observed, in line with the significant improvement of the mRSS and the stabilisation of internal organ involvement. To our knowledge, this is the first study to attest sensitivity to change of the EScSG activity index in the subset of 'early' dcSSc.

Trial Registration: ClinicalTrials.gov Registration, http://clinicaltrials.gov, number NCT00379431.
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January 2017

Disease activity indices in systemic sclerosis: a systematic literature review.

Clin Exp Rheumatol 2016 Sep-Oct;34 Suppl 100(5):186-192. Epub 2016 Jul 6.

Department of Internal Medicine, Faculty of Medicine and Health Sciences, Ghent University; and Department of Rheumatology, Faculty of Medicine and Health Sciences, Ghent University, Belgium.

Objectives: Reviewing disease activity indices (DAI) in systemic sclerosis (SSc) and reporting their validation status.

Methods: Literature was systematically reviewed on studies documenting the development of DAI, assessing the validation status of DAI and studies using a DAI in their analysis. The qualitative and quantitative validation status of existing DAI was assessed based on OMERACT and on definitions of the American College of Rheumatology (ACR) committee on quality measures.

Results: Three DAI in SSc have been proposed in literature: the European Scleroderma Study Group (EScSG) activity index, the 12-point DAI and the Combined Response Index for Systemic Sclerosis (CRISS). The EScSG activity index is yet applied as an outcome measure in 48 different studies. The EScSG activity index and the CRISS are provisional partially validated DAI.

Conclusions: Future studies are needed to fully validate the EScSG activity index and the CRISS and to assess the validation status of the 12-point DAI.
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January 2017

Nailfold Capillaroscopy and Clinical Applications in Systemic Sclerosis.

Microcirculation 2016 07;23(5):364-72

Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Genova, Italy.

Capillary microscopy is a safe and non-invasive tool to evaluate the morphology of the microcirculation typically affected in SSc. Next to being paramount for the "(very) early" diagnosis of SSc eyes are also geared toward capillaroscopy with the aim to be able to use it as a biomarker, especially in the prediction of future occurrence of DU. The following review will explain what capillary microscopy is and will focus additionally on studies evaluating the association between capillaroscopy and DU.
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http://dx.doi.org/10.1111/micc.12281DOI Listing
July 2016

The heart and pulmonary arterial hypertension in systemic sclerosis.

Acta Clin Belg 2016 Feb 5;71(1):1-18. Epub 2016 Feb 5.

c Department of Internal Medicine , Ghent University , Ghent , Belgium.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy and progressive fibrosis of the skin and visceral organs (gastrointestinal tract, heart, kidneys and lungs). Although the prevalence is low, SSc is a disease with high morbidity and mortality. Since pulmonary arterial hypertension (PAH) associated with SSc (SSc-PAH) and clinically evident cardiac involvement is associated with increased mortality, the cardiac complications and PAH in SSc are reviewed. Both diffuse cutaneous (DcSSc) and limited cutaneous (LcSSc) subgroups are at risk for cardiac involvement and SSc-PAH. Cardiac involvement can be divided in pericardial involvement, myocardial involvement and rhythm disturbances and mostly occurs asymptomatically. However, when symptomatic, it is associated with a poor prognosis. Screening for asymptomatic cardiac involvement should be considered in SSc in order to initiate treatment in an early stage. However, there are no randomized controlled trials on treatment options for cardiac involvement in SSc. SSc-PAH is a devastating complication of SSc, which can develop early in DcSSc and LcSSc. Screening for PAH should be performed since screening leads to earlier diagnosis and earlier treatment is associated with a better prognosis. Today, screening is performed by clinical judgement and echocardiography. Recently the DETECT algorithm, a 2-step screening algorithm is proposed in a SSc-subgroup at increased risk for PAH, but further validation is needed. Despite current treatment options with prostacyclins, endothelin-1 receptor antagonists and phosphodiesterase type-5 inhibitors, mortality remains high. Several promising new treatment options for PAH are evaluated in phase II and III clinical trials.
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http://dx.doi.org/10.1080/17843286.2015.1108538DOI Listing
February 2016

Six-minute walk test in systemic sclerosis: A systematic review and meta-analysis.

Int J Cardiol 2016 Jun 25;212:265-73. Epub 2016 Mar 25.

Department of Internal Medicine, Ghent University, Ghent, Belgium; Department of Rheumatology, Ghent University Hospital, Ghent, Belgium.

Background: Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) are the leading causes of death in systemic sclerosis (SSc). Although the six-minute walk test (6MWT) is generally used for evaluating PAH and ILD, utility in SSc is undetermined. This study evaluates the role of 6MWT in SSc by systematic review and meta-analysis.

Methods: A systematic literature search on PubMed, Web of Science and Cochrane Library Online was performed using the medical subject heading search terms for "systemic sclerosis", "CREST" and "six minute walk test", "six minute walk distance (6MWD)", "(cardiopulmonary) exercise test", "treadmill test" or "step test".

Results: Meta-analysis of 43 included studies (3185 SSc-all patients) revealed that the mean 6MWD was comparable between the SSc-PAH and SSc-ILD-PH subgroups (288m [95% CI: 259-317m] vs 286m [95% CI: 259-314m], p=0.93). The pooled mean of 725 SSc-PAH patients was significantly lower than the pooled mean of 413 SSc-noPAH patients (430m [95% CI: 402-458m], p<0.001). 95 SSc-ILD-PH patients walked significantly less than 328 SSc-ILD patients (388m [95% CI: 362-415m], p<0.001) and significantly less than 86 SSc-noILD patients (420m [95% CI: 325-515m], p=0.008). 81-98% of the SSc-PAH/ILD/ILD-PH patients performed a 6MWT.

Conclusions: During a 6MWT, SSc-PAH patients walk less than SSc-noPAH patients and SSc-ILD-PH patients walk less than SSc-ILD and SSc-noILD patients.
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http://dx.doi.org/10.1016/j.ijcard.2016.03.084DOI Listing
June 2016

Reliability of the quantitative assessment of peripheral blood perfusion by laser speckle contrast analysis in a systemic sclerosis cohort.

Ann Rheum Dis 2016 06 22;75(6):1263-4. Epub 2016 Mar 22.

Department of Rheumatology, Ghent University Hospital, Ghent, Belgium Department of Internal Medicine, Ghent University, Ghent, Belgium.

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http://dx.doi.org/10.1136/annrheumdis-2015-208857DOI Listing
June 2016

An EULAR study group pilot study on reliability of simple capillaroscopic definitions to describe capillary morphology in rheumatic diseases.

Rheumatology (Oxford) 2016 May 3;55(5):883-90. Epub 2016 Feb 3.

Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Genova, Italy and.

Objective: To propose simple capillaroscopic definitions for interpretation of capillaroscopic morphologies and to assess inter-rater reliability.

Methods: The simple definitions proposed were: normal--hairpin, tortuous or crossing; abnormal--not hairpin, not tortuous and not crossing; not evaluable--whenever rater undecided between normal and abnormal. Based upon an aimed kappa of 0.80 and default prevalences of normal (0.4), abnormal (0.4) and not evaluable (0.2) capillaries, 90 single capillaries were presented to three groups of raters: experienced independent raters, n = 5; attendees of the sixth EULAR capillaroscopy course, n = 34; novices after a 1-h course, n = 11. Inter-rater agreement was assessed by calculation of proportion of agreement and by kappa coefficients.

Results: Mean kappa based on 90 capillaries was 0.47 (95% CI: 0.39, 0.54) for expert raters, 0.40 (95% CI: 0.36, 0.44) for attendees and 0.46 (95% CI: 0.41, 0.52) for novices, with overall agreements of 67% (95% CI: 63, 71), 63% (95% CI: 60, 65) and 67% (95% CI: 63, 70), respectively. Comparing only normal vs the combined groups of abnormal and not evaluable capillaries did increase the kappa: 0.51 (95% CI: 0.37 ,: 0.65), 0.53 (95% CI: 0.49, 0.58) and 0.55 (95% CI: 0.49, 0.62). On the condition that the capillaries were classifiable, the mean kappa was 0.62 (95% CI: 0.50, 0.74) for expert raters (n = 65), 0.76 (95% CI: 0.69, 0.83) for attendees (n = 20) and 0.81 (95% CI: 0.74, 0.89) for novices (n = 44).

Conclusion: This multicentre, international study showed moderate reliability of simple capillaroscopic definitions for describing morphology of capillaries by rheumatologists with varying levels of expertise. Novices were capable of distinguishing normal from abnormal capillaries by means of a 1-h training session. In future studies, the class not evaluable may be obsolete.
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http://dx.doi.org/10.1093/rheumatology/kev441DOI Listing
May 2016

Comparison of the Belgian Rheumatoid Arthritis Disability Assessment and Health Assessment Questionnaires as Tools to Predict the Need for Support Measures in Patients with Rheumatoid Arthritis.

PLoS One 2016 22;11(1):e0146688. Epub 2016 Jan 22.

Department of Rheumatology, Ghent University Hospital, Ghent, Belgium.

Objective: Scores on the Health Assessment Questionnaire (HAQ) predict the need for support measures in patients with rheumatoid arthritis (RA). In this study we compare the performance of the HAQ in this context with that of the more disease-specific Belgian Rheumatoid Arthritis Disability Assessment (BRADA) questionnaire.

Methods: In this multicenter observational study, patients with RA and disease duration of at least one year who consulted their rheumatologist for a routine follow-up visit filled out the HAQ, and BRADA questionnaires. The performance of HAQ and BRADA to predict the need for support measures available to patients with RA was evaluated using Receiver Operator Characteristic (ROC) curves, with the expert opinion of the rheumatologist as a reference.

Results: The study analyzed data of 301 patients with RA (70.8% females) with mean age 59.8 ± 12.8, disease duration 11.4 ± 9.3 years, and DAS28 values of 2.84 ± 1.18. HAQ scores averaged 0.97 ± 0.73 and BRADA scores were 3.92 ± 3.49 over the last week and 3.89 ± 3.50 over the last 3 months. The area under the ROC curves for the BRADA scores for the support measures investigated ranged from 0.702 to 0.862 and did not differ significantly from those of the HAQ (range 0.725-0.860).

Conclusion: The disease-specific BRADA questionnaire is equivalent to the HAQ in predicting the need for support measures in patients with stable RA.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146688PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4723361PMC
July 2016

Specific Antinuclear Antibody Level Changes after B Cell Depletion Therapy in Systemic Sclerosis Are Associated with Improvement of Skin Thickening.

J Rheumatol 2016 Jan;43(1):247-9

Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, Ghent, Belgium.

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http://dx.doi.org/10.3899/jrheum.150105DOI Listing
January 2016

Fuchs' Uveitis Syndrome: No Longer a Syndrome?

Ocul Immunol Inflamm 2016 Jun 29;24(3):348-57. Epub 2015 Jul 29.

a University Hospital Ghent , Ophthalmology , Ghent , Belgium and.

Purpose: Rubella virus (RV) has a central role in the etiopathogenesis of Fuchs' uveitis syndrome (FUS). We aim to offer new insights by comprehensive analysis of recent laboratory and epidemiologic data.

Methods: We conducted a literature search for laboratory data and papers on etiopathogenesis.

Results: Aqueous humour samples of FUS patients show immunoreactivity to RV, in a specific and sensitive manner. Identification of RV genome confirm intraocular infection in a subset of FUS patients. Epidemiologic findings further support causality. The clinical spectrum of RV-associated uveitis is similar but not identical to FUS. FUS eyes exhibit a predominance of CD8 + T cells, high IFN-? and IL-10 levels.

Conclusions: RV is the leading cause of FUS. Cytokine-based findings mirror a viral etiology and chronic low-grade inflammation. RV-associated FUS represents a common pathway of intraocular RV inoculation after congenital or acquired infection. Other causes, including HSV and CMV, may lead to FUS.
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http://dx.doi.org/10.3109/09273948.2015.1005239DOI Listing
June 2016

Factors influencing the occupational trajectory of patients with systemic sclerosis: a qualitative study.

Clin Exp Rheumatol 2015 Jul-Aug;33(4 Suppl 91):S26-30. Epub 2015 Mar 20.

Faculty of Medicine and Health Sciences, Department of Public Health - Nursing Science, Ghent University, Belgium.

Objectives: To describe, from the patient's point of view, the factors influencing the occupational trajectory of patients with systemic sclerosis (SSc).

Methods: This was a qualitative study designed using grounded theory with constant comparison. Data were collected through semi-structured interviews with 14 patients who fulfilled the American College of Rheumatology or Leroy-Medsger criteria for SSc.

Results: Based on our interviews, we found that the occupational trajectory of patients with SSc is influenced by the continuous interplay between four groups of factors. The first group concerns the values patients attribute to work, including identity, normality, financial value, social contact, and structure. The meaning of these values and how they relate to each other underlies the desire to work. A second group of factors is those influencing the balance between daily life, work participation, and medical condition (e.g. job content, flexibility in organising work, and the willingness to ask for accommodations at work). The occupational trajectory is also influenced by external factors, including availability of support, know-ledge of the disease, pressure to work, contact with medical professionals, and existing regulations and the patient's knowledge about them. Finally, the occupational trajectory is influenced by personal factors, including socio-demographics, psychological assets, and disease- and work-related personal factors.

Conclusions: The decisions patients with SSc take concerning work depend on an interplay between many factors and, especially, on the patients' personal interpretation of these factors. These need to be taken into account when helping patients with SSc determine their occupational trajectory.
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October 2015

Assessment of activity limitations with the health assessment questionnaire predicts the need for support measures in patients with rheumatoid arthritis: a multicenter observational study.

PLoS One 2014 4;9(9):e106749. Epub 2014 Sep 4.

Department of Rheumatology, Ghent University Hospital, Ghent, Belgium.

Objective: This study investigated whether the Health Assessment Questionnaire (HAQ) can be used as an instrument to assess the need for social support measures that address activity limitations and participation issues in patients with rheumatoid arthritis (RA).

Methods: This multicenter observational study included patients with RA and disease duration of at least one year, consulting their rheumatologist for routine evaluation of disease activity. In the single study visit data on demographics, disease history and current treatment were collected. DAS28 values were collected to evaluate current RA disease activity. Patients were asked to fill out the HAQ and SF-36 questionnaires. Receiver Operator Characteristics (ROC) curves were constructed to evaluate the performance of the HAQ, SF-36 and DAS28 in predicting the need for nine supporting measures available for chronically ill patients in the Belgian social security system. The expert opinion of the treating rheumatologist was used as a reference.

Results: The study included 316 patients with a mean age of 59.8 ± 12.6 years, disease duration of 11.4 ± 9.3 years, mean DAS28 values of 2.83 ± 1.17. Mean HAQ score was 0.95 ± 0.73, mean SF-36 score 56.5 ± 21.3. HAQ scores >1 were observed in 39.4% of patients. The area under the HAQ ROC curve was consistently >0.7 and higher for the HAQ than for SF-36 or DAS28 for all support measures. Rheumatologists on average recommended 3.67 support measures.

Conclusion: The HAQ score was found to be a good predictor of the need for social support measures in patients with RA.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0106749PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154727PMC
December 2015

Longterm followup of rituximab therapy in patients with rheumatoid arthritis: results from the Belgian MabThera in Rheumatoid Arthritis registry.

J Rheumatol 2014 Sep 15;41(9):1761-5. Epub 2014 Aug 15.

From the Department of Rheumatology, Ghent University Hospital, Ghent; GZA St-Augustinus Hospital, Antwerp; Department of Rheumatology, University Hospital Liège, Liège; Pôle de Recherche en Rhumatologie; Institut de Recherche Expérimentale et Clinique; Université Catholique de Louvain and Cliniques Universitaires Saint-Luc, Brussels; Skeletal Biology and Engineering Research Center; the Department of Development and Regeneration; KU Leuven, Leuven, Belgium.F. De Keyser, MD, PhD, Department of Rheumatology, Ghent University Hospital; I. Hoffman, MD, PhD, GZA St-Augustinus Hospital; P. Durez, MD, PhD, Pôle de Recherche en Rhumatologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Cliniques Universitaires Saint-Luc; M.J. Kaiser, MD, PhD, Department of Rheumatology, University Hospital Liège; R. Westhovens, MD, PhD, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Rheumatology.

Objective: Our study reports the results of the MIRA (MabThera In Rheumatoid Arthritis) registry, set up to collect data about clinical usage, patient profile, and retention of rituximab (RTX) treatment in daily clinical practice in Belgium.

Methods: Patients with active rheumatoid arthritis (RA) who failed at least 1 anti-tumor necrosis factor (anti-TNF) treatment were included in our study between November 2006 and October 2011. At baseline, demographics, medication, disease history, disease activity, rheumatoid factor (RF), and anticyclic citrullinated peptide antibodies (anti-CCP) status were recorded. Evolution of the 28-joint Disease Activity Score (DAS28)-erythrocyte sedimentation rate, retreatments, and reasons for therapy stop were followed prospectively.

Results: The MIRA registry included 649 patients, with mean disease duration of 12.8 ± 0.4 years and DAS28 values at inclusion of 5.85 ± 0.48. Patients received on average 2.82 ± 0.07 (range 1-9) RTX treatments, over a mean followup period of 93.1 ± 2.6 weeks. At database lock, 433 patients (66.7%) were still under RTX treatment, 182 (28.0%) had stopped treatment, and 34 (5.2%) were lost to followup. Ineffectiveness (n = 108, 59%) and safety concerns (n = 39, 22%) were the most frequent reasons for discontinuing RTX therapy. From 2006 to 2011, RTX practice patterns clearly evolved toward RTX being started in patients with a lower number of previously failed anti-TNF drugs and lower baseline DAS28 values. A lower number of previous anti-TNF drugs, and positivity for RF and anti-CCP, predicted more successful longterm treatment. RTX treatment provided adequate longterm disease control.

Conclusion: In our daily practice study, RTX provided good longterm disease control and treatment retention in refractory patients with RA. Over the years, rheumatologists tended to start this treatment in patients with fewer previous anti-TNF treatments and lower disease activity.
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http://dx.doi.org/10.3899/jrheum.131279DOI Listing
September 2014

Ten-year followup of infliximab therapy in rheumatoid arthritis patients with severe, longstanding refractory disease: a cohort study.

J Rheumatol 2014 Jul 1;41(7):1276-81. Epub 2014 Jun 1.

From Department of Rheumatology, Ghent University, Ghent; MSD Belgium BVBA; Department of Rheumatology, Pôle de Recherche en Rhumatologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain and Cliniques Universitaires Saint-Luc, Brussels; Skeletal Biology and Engineering Research Center, Department of Development and Regeneration KU Leuven; and Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium.F. De Keyser, MD; J. De Kock, MD, Department of Rheumatology, Ghent University; H. Leroi, MSD Belgium BVBA, Brussels; P. Durez, MD, Department of Rheumatology, Pôle de Recherche en Rhumatologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain and Cliniques Universitaires Saint-Luc; R. Westhovens, MD, PhD, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration KU Leuven; and Department of Rheumatology, University Hospitals Leuven.

Objective: Our study describes the 10-year followup data of the Belgian Expanded Access Program (EAP) for infliximab (IFX), which included patients with active rheumatoid arthritis who were refractory to methotrexate. The objectives of the study were to evaluate the continuation rate, reasons for discontinuation, and longterm disease control under IFX treatment, and to study baseline characteristics associated with longterm successful IFX therapy.

Methods: Between February 2000 and September 2001, 511 patients were enrolled in the Belgian IFX EAP, and 507 effectively started IFX therapy. Previously reported data showed that 160 patients were still treated with IFX after 7 years of followup. We describe the therapy status, reasons for IFX discontinuation, and the level of disease activity of this subgroup after 10 years of followup. Baseline characteristics of the total EAP cohort were used to describe variables associated with longterm successful IFX treatment.

Results: After 10 years of followup, 110 of the 507 patients (21.7%) were still receiving IFX treatment. In the 7-year to 10-year period, which is the focus of the current study, 16 patients were lost to followup and 34 patients discontinued IFX treatment, mainly because of loss of efficacy. Patients successfully treated with IFX for 10 years had lower baseline values for 28-joint Disease Activity Score (DAS28), patient pain scale, physician visual analog scale, and Health Assessment Questionnaire in comparison with the rest of the study cohort. The mean DAS28 level of the subgroup still taking IFX after 10 years was 2.55 ± 1.01.

Conclusion: In the Belgian EAP, 21.7% of patients continued to receive maintenance IFX treatment after 10 years of followup. IFX provided good longterm disease control in these patients.
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http://dx.doi.org/10.3899/jrheum.131270DOI Listing
July 2014

Growth differentiation factor 15, a marker of lung involvement in systemic sclerosis, is involved in fibrosis development but is not indispensable for fibrosis development.

Arthritis Rheumatol 2014 Feb;66(2):418-27

Ghent University, Ghent, Belgium.

Objective: Transforming growth factor β superfamily members are involved in the pathogenesis of systemic sclerosis (SSc). Growth differentiation factor 15 (GDF-15) is a distant member of this family. We undertook this study to evaluate the role of GDF-15 in SSc pathogenesis.

Methods: A longitudinal prospective cohort of SSc patients was screened for serum GDF-15 levels using enzyme-linked immunosorbent assay, and associations with clinical data were analyzed. In vitro stimulation experiments were performed on lung fibroblasts. The role of GDF-15 in fibrosis development in vivo was evaluated in the bleomycin lung fibrosis model in GDF-15-deficient mice.

Results: GDF-15 was measured at baseline in serum samples from 119 SSc patients. An increase in GDF-15 levels was observed in patients classified as having no skin involvement, those with limited cutaneous SSc, and those with diffuse cutaneous SSc. Moreover, baseline serum GDF-15 levels correlated strongly with disease activity and extent of organ involvement, particularly clinical symptoms of lung fibrosis, including impact on lung function at prospective followup. This was mimicked in the bleomycin model of SSc, in which animals exposed to bleomycin had elevated expression levels of GDF-15 in lung tissue. Lung fibroblasts isolated from GDF-15-deficient mice showed reduced induction of interleukin-6 and CCL2 upon bleomycin stimulation. Surprisingly, no differences in fibrosis development were observed between wild-type and GDF-15-deficient animals.

Conclusion: An intriguing profile of serum GDF-15 levels was found in SSc patients. GDF-15 expression is induced during fibrosis development and markedly correlates with lung function impairment in this disease. The protein may participate in fibrosis initiation, but is not indispensable in the course of fibrosis development in vivo.
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http://dx.doi.org/10.1002/art.38241DOI Listing
February 2014

Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis.

N Engl J Med 2014 Jan 18;370(5):433-43. Epub 2013 Dec 18.

The authors' affiliations are listed in the Appendix.

Background: Plasmacytoid dendritic cells have been implicated in the pathogenesis of systemic sclerosis through mechanisms beyond the previously suggested production of type I interferon.

Methods: We isolated plasmacytoid dendritic cells from healthy persons and from patients with systemic sclerosis who had distinct clinical phenotypes. We then performed proteome-wide analysis and validated these observations in five large cohorts of patients with systemic sclerosis. Next, we compared the results with those in patients with systemic lupus erythematosus, ankylosing spondylitis, and hepatic fibrosis. We correlated plasma levels of CXCL4 protein with features of systemic sclerosis and studied the direct effects of CXCL4 in vitro and in vivo.

Results: Proteome-wide analysis and validation showed that CXCL4 is the predominant protein secreted by plasmacytoid dendritic cells in systemic sclerosis, both in circulation and in skin. The mean (±SD) level of CXCL4 in patients with systemic sclerosis was 25,624±2652 pg per milliliter, which was significantly higher than the level in controls (92.5±77.9 pg per milliliter) and than the level in patients with systemic lupus erythematosus (1346±1011 pg per milliliter), ankylosing spondylitis (1368±1162 pg per milliliter), or liver fibrosis (1668±1263 pg per milliliter). CXCL4 levels correlated with skin and lung fibrosis and with pulmonary arterial hypertension. Among chemokines, only CXCL4 predicted the risk and progression of systemic sclerosis. In vitro, CXCL4 down-regulated expression of transcription factor FLI1, induced markers of endothelial-cell activation, and potentiated responses of toll-like receptors. In vivo, CXCL4 induced the influx of inflammatory cells and skin transcriptome changes, as in systemic sclerosis.

Conclusions: Levels of CXCL4 were elevated in patients with systemic sclerosis and correlated with the presence and progression of complications, such as lung fibrosis and pulmonary arterial hypertension. (Funded by the Dutch Arthritis Association and others.).
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http://dx.doi.org/10.1056/NEJMoa1114576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4040466PMC
January 2014

Nailfold capillaroscopy for prediction of novel future severe organ involvement in systemic sclerosis.

J Rheumatol 2013 Dec 15;40(12):2023-8. Epub 2013 Oct 15.

From the Department of Rheumatology, Ghent University Hospital, Ghent, Belgium; Department of Internal Medicine and Medical Specialities, University Sapienza, Rome; Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Italy; Department of Internal Medicine, Biostatistics Unit, Department of Public Health, Ghent University, and Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium.

Objective: Assessment of associations of nailfold videocapillaroscopy (NVC) scleroderma (systemic sclerosis; SSc) ("early," "active," and "late") with novel future severe clinical involvement in 2 independent cohorts.

Methods: Sixty-six consecutive Belgian and 82 Italian patients with SSc underwent NVC at baseline. Images were blindly assessed and classified into normal, early, active, or late NVC pattern. Clinical evaluation was performed for 9 organ systems (general, peripheral vascular, skin, joint, muscle, gastrointestinal tract, lung, heart, and kidney) according to the Medsger disease severity scale (DSS) at baseline and in the future (18-24 months of followup). Severe clinical involvement was defined as category 2 to 4 per organ of the DSS. Logistic regression analysis (continuous NVC predictor variable) was performed.

Results: The OR to develop novel future severe organ involvement was stronger according to more severe NVC patterns and similar in both cohorts. In simple logistic regression analysis the OR in the Belgian/Italian cohort was 2.16 (95% CI 1.19-4.47, p = 0.010)/2.33 (95% CI 1.36-4.22, p = 0.002) for the early NVC SSc pattern, 4.68/5.42 for the active pattern, and 10.14/12.63 for the late pattern versus the normal pattern. In multiple logistic regression analysis, adjusting for disease duration, subset, and vasoactive medication, the OR was 2.99 (95% CI 1.31-8.82, p = 0.007)/1.88 (95% CI 1.00-3.71, p = 0.050) for the early NVC SSc pattern, 8.93/3.54 for the active pattern, and 26.69/6.66 for the late pattern versus the normal pattern.

Conclusion: Capillaroscopy may be predictive of novel future severe organ involvement in SSc, as attested by 2 independent cohorts.
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http://dx.doi.org/10.3899/jrheum.130528DOI Listing
December 2013
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