| 1. |
- Andréasson, Kristofer, et al.
(författare)
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Faecal calprotectin: a biomarker of gastrointestinal disease in systemic sclerosis.
- 2011
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 270, s. 50-57
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Tidskriftsartikel (refereegranskat)abstract
- Abstract. Andréasson K, Scheja A, Saxne T, Ohlsson B, Hesselstrand R. (Section for Rheumatology; Section for Gastroenterology and Hepatology, Lund University, Lund, Sweden). Faecal calprotectin: a biomarker of gastrointestinal disease in systemic sclerosis. J Intern Med 2010; doi: 10.1111/j.1365-2796.2010.02340.x. Background. Assessment of gastrointestinal (GI) involvement in systemic sclerosis (SSc) is difficult. Measurement of calprotectin in faeces is a valuable tool for the assessment of inflammatory bowel diseases. Calprotectin is an intracellular protein found in leucocytes and is a potent activator of the innate immune system. Objective. To determine whether faecal calprotectin (F-calprotectin) could serve as a biomarker of GI disease in SSc. Design. In a cross-sectional study, F-calprotectin and plasma calprotectin were measured in patients with SSc using an enzyme-linked immunosorbent assay. F-calprotectin concentrations were evaluated in relation to cineradiography, medical records, laboratory measurements and patients' subjective GI symptoms. Setting. The study was conducted at a tertiary referral centre for SSc. Subjects. The study comprised 81 consecutive patients with SSc. Results. A majority of the patients had pathological levels of F-calprotectin when compared to accepted clinical reference values for healthy adults. F-calprotectin did not correlate with calprotectin levels in plasma. F-calprotectin was associated with the following patient characteristics: pathological cineradiography, history of referral to another clinic because of GI disease, treatment of vitamin or mineral deficiency and use of proton pump inhibitors. We did not find any significant correlation between F-calprotectin and patient-reported GI symptoms. Conclusion. Faecal calprotectin is increased in a majority of patients with SSc. It correlates with objective and clinically important features of GI disease, and faecal concentrations do not vary with plasma concentrations. We suggest that F-calprotectin is a promising objective non-invasive biomarker of GI involvement in SSc.
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| 2. |
- Andréasson, Kristofer, et al.
(författare)
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Faecal levels of calprotectin in systemic sclerosis are stable over time and are higher compared to primary Sjogren's syndrome and rheumatoid arthritis
- 2014
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Faecal calprotectin (FC) has been proposed to be a biomarker of gastrointestinal (GI) disease in systemic sclerosis (SSc). The purpose of this study was to extend cross-sectional observations and prospectively assess the variability of FC over time in SSc patients. We also aimed to examine FC in relation to immunosuppressive therapy. Finally we wanted to analyse FC in other rheumatic diseases to evaluate the specificity of FC for SSc GI disease. Methods: FC was measured in consecutive patients with SSc, primary Sjogren's syndrome (pSS), rheumatoid arthritis (RA) and in healthy hospital workers. The intraindividual variability of FC in SSc was assessed with intra class correlation (ICC) and. statistics. Associations between FC and objective markers of GI disease and immunosuppressive medication were investigated. Results: FC was associated with micronutrient deficiency and GI pathology as assessed by cineradiography confirming our previous results. FC showed only a limited intra-individual variation in SSc, ICC = 0.69 (95% confidence interval, CI: 0.57-0.78) and kappa = 0.64 (95% CI: 0.56-0.73). Generalised immunosuppression did not have any significant impact on FC. FC was significantly higher in SSc patients compared to patients with pSS or RA as well as compared to healthy subjects. Conclusions: FC is a promising non-invasive biomarker for GI disease in SSc. In view of stable levels over time, FC could be a useful marker when novel, more specific drugs targeting the GI tract in SSc will be introduced.
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| 3. |
- Bartosik, I, et al.
(författare)
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Correlation between plasma concentrations of calcitonin gene related peptide and pulmonary pressure in patients with systemic sclerosis.
- 2002
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 61:3, s. 261-263
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine plasma levels of calcitonin gene related peptide (p-CGRP) in patients with systemic sclerosis (SSc) and pulmonary hypertension (PH). MATERIAL AND METHODS: Twenty nine patients with SSc, 10 with diffuse form, 18 with limited form and one with overlapping systemic lupus erythematosus were examined. Twelve patients displayed normal systolic pulmonary artery pressure (PAPsyst) < or =30 mm Hg and 17 increased PAPsyst
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| 4. |
- Bartosik, I, et al.
(författare)
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Vascular events are risk factors for anal incontinence in systemic sclerosis: a study of morphology and functional properties measured by anal endosonography and manometry.
- 2014
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 43:5, s. 391-397
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To study anal sphincter morphology, anal sphincter pressure, and rectoanal inhibitory reflex (RAIR) in patients with systemic sclerosis (SSc) complicated by anal incontinence (AI) and to investigate possible risk factors for AI in SSc. Method: Nineteen SSc patients with severe AI were investigated using anal endosonography, anal manometry, and rectal manovolumetry. To determine risk factors for AI, disease characteristics of SSc patients with AI were compared with those of 95 SSc patients without AI; there were five matched SSc patients without AI for each SSc patient with AI. Results: The mean (SD) internal sphincter thickness was 1.3 (0.46) mm in patients with AI, which was thinner (p < 0.001) than reference data from healthy individuals whose internal sphincter measured 2.2 (0.45) mm, whereas the external sphincter thickness did not differ. The mean (SD) resting pressure in AI patients was lower than the reference data from healthy individuals [60 (22) vs. 94 (29) mmHg, p < 0.002] whereas the squeeze pressure did not differ. Centromeric antibodies and features of vascular disease [i.e. the presence of pulmonary arterial hypertension (PAH), digital ulcers, pitting scars, or the need for iloprost infusions] were associated with AI whereas fibrotic manifestations [i.e. modified Rodnan skin score (mRss), the diffuse cutaneous SSc (dcSSc) subset, or low vital capacity (VC)] were not. Conclusions: SSc patients with AI have a thin internal anal sphincter and a low resting pressure. Risk factors for AI among SSc patients are centromeric antibodies and vascular disease, which supports the hypothesis that gastrointestinal involvement in SSc is in part a vascular manifestation of the disease.
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| 5. |
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| 6. |
- Chizzolini, C, et al.
(författare)
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Polarized subsets of human T-helper cells induce distinct patterns of chemokine production by normal and systemic sclerosis dermal fibroblasts
- 2006
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- The role of fibroblasts in inflammatory processes and their cross-talk with T cells is increasingly being recognized. Our aim was to explore the capacity of dermal fibroblasts to produce inflammatory chemokines potentially involved in fibrosis occurring in response to contact with polarized human T cells. Our findings indicate that the program of chemokine production by fibroblasts is differentially regulated depending on the T-helper (Th) cell subset used to activate them. Thus, Th1 and Th2 cells preferentially induced production of IFN-gamma inducible protein (IP)-10 and IL-8, respectively, whereas monocyte chemoattractant protein (MCP)-1 was equally induced by both subsets at mRNA and protein levels. Neutralization experiments indicated that membrane-associated tumour necrosis factor-alpha and IL-1 played a major role in the induction of IL-8 and MCP-1 by Th1 and Th2 cells, whereas membrane-associated lIFN-gamma (present only in Th1 cells) was responsible, at least in part, for the lower IL-8 and higher IP-10 production induced by Th1 cells. The contributions of tumour necrosis factor-alpha, IL-1 and IFN-alpha were confirmed when fibroblasts were cultured separated in a semipermeable membrane from living T cells activated by CD3 cross-linking. We observed further differences when we explored signal transduction pathway usage in fibroblasts. Pharmacological inhibition of c-Jun N-terminal kinase and nuclear factor-kappa B resulted in inhibition of IL-8 mRNA transcription induced by Th1 cells but not that by Th2 cells, whereas inhibition of MEK/ERK (mitogen-activated protein kinase of extracellular signal-regulated kinase/extracellular signal-regulated kinase) and nuclear factor-kappa B resulted in inhibition of MCP-1 mRNA induced by Th2 but not by Th1 cells. Finally, no distinct differences in chemokine production were observed when the responses to T cell contact or to prototypic Th1 and Th2 cytokines were examined in systemic sclerosis versus normal fibroblasts. These findings indicate that fibroblasts have the potential to participate in shaping the inflammatory response through the activation of flexible programs of chemokine production that depend on the Th subset eliciting their response.
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| 7. |
- Chizzolini, C, et al.
(författare)
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Systemic sclerosis Th2 cells inhibit collagen production by dermal fibroblasts via membrane-associated tumor necrosis factor alpha
- 2003
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 48:9, s. 2593-2604
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Tidskriftsartikel (refereegranskat)abstract
- Objective. In systemic sclerosis (SSc; scleroderma), T cells infiltrate organs undergoing fibrotic changes and may participate in dysregulated production of collagen by fibroblasts. The objective of this study was to functionally characterize T cells infiltrating skin lesions in early SSc and investigate their capacity to affect production of type I collagen and interstitial collagenase (matrix metalloproteinase 1 [MMP-1]) by dermal fibroblasts. Methods. Four-color cytometric analysis was used to characterize subset distribution and production of interferon-gamma (IFNgamma) and interleukin-4 (IL-4) in T cell lines generated from the skin of patients with SSc. T cell clones were generated, and their capacity to modulate collagen and MMP-1 production by fibroblasts derived from patients with SSc and from normal individuals was assessed. Neutralizing reagents were used to identify T cell mediators involved in fibroblast modulation. Results. The skin of individuals with early-stage SSc contained T cells preferentially producing high levels of IL-4. Cloned CD4+ Th2-like cells inhibited collagen production by normal fibroblasts. Th2 cell-dependent inhibition was, at least in part, contact-dependent, was essentially mediated by tumor necrosis factor alpha (TNFalpha), and was dominant over the enhancement induced by profibrotic IL-4 and transforming growth factor beta cytokines. The simultaneous induction of MMP-1 production confirmed the specificity of these observations. To be inhibitory, Th2 cells required activation by CD3 ligation. Th2 cells were less potent than were Th1 cells in inhibiting collagen production by normal fibroblasts via cell-to-cell interaction, and SSc fibroblasts were resistant to inhibition. Conclusion. These findings indicate that, despite their production of IL-4, Th2 cells reduce type I collagen synthesis by dermal fibroblasts because of the dominant effect of TNFalpha, and suggest that strategies based on TNFalpha blockade aimed at controlling fibrosis in SSc may be unwise.
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| 8. |
- Erikson, Martin G, et al.
(författare)
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Från Högskolan i Borås till Humboldt, volym 4
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna rapport består av åtta kapitel baserade på en seminarieserie om akademiskt ansvar, som arrangerades av Högskolan i Borås under 2015 och 2016. Seminarierna utgjorde den fjärde omgången av de så kallade Humboldtseminarierna, som högskolan arrangerat i olika omgångar sedan 2010. Vid Humboldtseminarierna har aktuella frågor kring akademins möjligheter och utmaningar belysts utifrån olika teman, inte minst kopplat till samhällets förväntningar på forskning och högre utbildning. I det perspektivet blev akademiskt ansvar ett naturligt tema för den fjärde och avslutande omgången av Humboldtseminarierna. Just kopplingen till samhällsnytta är också en röd tråd igenom rapporten. Författarna skriver utifrån skilda erfarenheter som forskare, lärare och akademiska ledare – inte minst är rektorsperspektivet väl företrätt. Ett annat återkommande ämne är kopplingen mellan akademiskt ansvar och akademisk frihet, där ansvaret inte minst bidrar till att legitimera friheten. Kollegialitet är en viktig fråga för flera av författarna, både som princip för kvalitetsstyrning och som beslutsform. Sammantaget visar de olika bidragen att akademiskt ansvar berör många frågor av stor relevans för forskare, lärare, ledare och studenter, men också för intressenter utanför akademin. Där har författarnas bidrag goda möjligheter att ge nya insikter och inspirera till fortsatta diskussioner inom många olika områden.
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| 9. |
- Halldén, Ola, et al.
(författare)
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Situating the concept of conceptual change
- 2002
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Ingår i: Reconsidering conceptual change: Issues in theory and practice. - : Kluwer (Dordrecht, Netherlands). - 9781402004940 ; , s. 137-48
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Bokkapitel (refereegranskat)
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| 10. |
- Halldén, Ola, et al.
(författare)
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Situating the question of conceptual change
- 2002
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Ingår i: Reconsidering conceptual change. - Dordrecht : Kluwer. - 9781402004940 ; , s. 137-148
-
Bokkapitel (refereegranskat)abstract
- The contemporary debate regarding the question of conceptual change relates to the learning paradox in Plato’s dialogue Menon, where Menon asks how it is possible to engage in a search for knowledge of something entirely new. How is it possible to change from a commonsense view of a phenomenon into a scientific one that also sometimes goes quite contrary to the commonsense view? Sociocultural analysis dispatch the question by talking of situated cognition and by that ignoring individual cognitions. Constructivist approaches describes cognitive development as an evolution from simple naïve models of a phenomenon to more complex and powerful models, often by implying that the simple models are abandoned in favour of the new ones. Here, another model for conceptual development and conceptual change will be advanced. It is proposed that conceptual development and conceptual change is constituted by a process of a continuous assimilation of new information into an all-embracing model and, simultaneously, a differentiation within this compounded model resulting eventually in different new models. This description that stick to the Piagetian way of describing cognitive development, will be illustrated by means of empirical data from a study of children’s conceptions of the shape of the earth.
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| 11. |
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| 12. |
- Hesselstrand, Roger, et al.
(författare)
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Biomarkers from bronchoalveolar lavage fluid in systemic sclerosis patients with interstitial lung disease relate to severity of lung fibrosis.
- 2013
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 107:7, s. 1079-1086
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Decision on treatment of systemic sclerosis (SSc) related interstitial lung disease (ILD) largely relies on the findings on high resolution computed tomography (HRCT) and there is a need for improvement in assessment of the fibrotic activity. The objectives of this study were to study biomarkers in bronchoalveolar lavage fluid (BALF) from SSc patients with ILD and to relate the findings to the severity and activity of lung fibrosis. METHODS: Fifteen patients with early SSc and 12 healthy controls were subjected to BAL. Cell counts and analyses of CXCL5, CXCL8 and S100A8/A9 were performed in BALF and serum. COMP and KL-6 were measured in serum. HRCT of lungs was quantified for ground glass opacities (GGO), reticulation and traction bronchiectases. RESULTS: BALF concentrations of CXCL8 (p < 0.001), CXCL5 (p = 0.002) and S100A8/A9 (p = 0.016) were higher in patients than controls. Serum KL-6 (p < 0.001) was increased in SSc patients and correlated with BALF concentration of eosinophils (rS = 0.57, p = 0.027). Patients with more widespread GGO on HRCT were characterised in BALF by a higher eosinophil count (p = 0.002) and in serum by higher KL-6 (p = 0.008). Patients with more fibrosis were characterised in BALF by higher eosinophil count (p = 0.014), higher CXCL8 (p = 0.005) and S100A8A/A9 (p = 0.014) concentration and in serum by a higher serum COMP (p = 0.023). CONCLUSIONS: In SSc related ILD, biomarkers from BALF and serum correlate to findings on HRCT suggesting usefulness as markers of presence and extent of lung fibrosis.
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| 13. |
- Hesselstrand, Roger, et al.
(författare)
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Enlarged right-sided dimensions and fibrosis of the right ventricular insertion point on cardiovascular magnetic resonance imaging is seen early in patients with pulmonary arterial hypertension associated with connective tissue disease
- 2011
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 40:2, s. 133-138
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To describe the findings of cardiovascular magnetic resonance (CMR) imaging in patients with pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD) and in consecutive patients with systemic sclerosis (SSc) without PAH. Methods: The study comprised nine consecutive patients who were admitted for right heart catheterization (RHC) under a suspicion of CTD-PAH and 25 consecutive patients who were admitted for evaluation because of a clinical suspicion of SSc. In addition to the regular assessment, they also underwent examination by CMR. Results: CMR measurements of right ventricular (RV) volumes and function showed severe pathology in patients with CTD-PAH. Patients with SSc without PAH had similar but much less severe findings. Right ventricular end-diastolic volume (RVEDV) and right ventricular ejection fraction (RVEF) were abnormal in all patients with CTD-PAH. In eight out of nine patients with CTD-PAH, fibrosis was seen in the RV insertion point, probably caused by increased tension, but only in one of the consecutive SSc patients. This patient was diagnosed with CTD-PAH 20 months later. Conclusions: In CTD-PAH, CMR shows severe changes in RV volumes and function, but also fibrosis in the RV insertion point. Similar abnormalities, although much less severe, may be seen at diagnosis of SSc. Further evaluation is warranted to determine whether these findings are of value in screening for early signs of PAH in SSc.
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| 14. |
- Hesselstrand, Roger, et al.
(författare)
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High-frequency ultrasound of skin involvement in systemic sclerosis reflects oedema, extension and severity in early disease.
- 2008
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 47:1, s. 84-87
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim was to compare skin assessment by palpation and by high-frequency ultrasound in patients with SSc with disease duration <2 yrs. METHODS: Skin thickness and skin echogenicity were measured by 20 MHz ultrasound at five different anatomical sites in 106 individuals within 2 yrs from the first non-Raynaud's symptom and compared with the modified Rodnan skin score (mRss). RESULTS: The patients with short disease duration were characterized by high skin thickness and low skin echogenicity, which correlated inversely, reflecting oedema. Patients with diffuse skin involvement displayed higher skin thickness and lower skin echogenicity than did patients with limited skin involvement. The ultrasound measurements correlated to the local mRss from the corresponding anatomical region and also to the total mRss. However, there was a considerable overlap in both skin thickness and skin echogenicity between different local mRss at all five anatomical sites. Skin involvement of the chest could be detected earlier by ultrasound than by palpation. CONCLUSION: In SSc patients with short disease duration, high-frequency ultrasound can identify the oedematous phase that may precede palpable skin involvement and may thus be useful to identify patients with diffuse skin involvement very early in the disease process. Ultrasound measurements also reflect the severity of the overall skin involvement.
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| 15. |
- Hesselstrand, Roger, et al.
(författare)
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Increased serum COMP predicts mortality in SSc: results from a longitudinal study of interstitial lung disease.
- 2012
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 51:5, s. 915-920
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. COMP is a regulator of assembly and maintenance of the fibrillar collagen I and II networks. Serum COMP reflects skin fibrosis in SSc. The purpose of this study was to examine whether serum COMP reflects fibrotic lung involvement in SSc patients and to study if serum COMP predicts mortality.Methods. Three overlapping cohorts of 244 SSc patients were studied. Two hundred and eighteen patients were included to study survival, 80 patients to study longitudinal changes of pulmonary function tests and 64 to study pulmonary involvement assessed by high-resolution CT (HRCT). Serum COMP was measured by ELISA. Skin involvement was assessed with the modified Rodnan skin score (mRSS). Data about survival were obtained from the central population registry.Results. Serum COMP measured within 5 years after the first non-Raynaud's manifestation was a predictor of death, and crude mortality increased by 6% for each COMP unit elevation. Serum COMP levels >15 U/l were associated with a 3.13-fold (95% CI 1.73, 5.64; P < 0.001) increased risk of death. During the first year of follow-up serum COMP and vital capacity (VC) changed inversely (r(s) = -0.32; P = 0.005), but there were no correlations between baseline serum COMP and concurrent findings by spirometry or HRCT.Conclusion. Serum COMP early in disease is a predictor of mortality in SSc patients. Serum COMP changes in parallel with lung fibrosis as measured by VC, but the release from fibrotic skin possibly obscures the influx from the lungs and therefore serum COMP seems to have little utility as a marker of lung fibrosis.
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| 16. |
- Hesselstrand, Roger, et al.
(författare)
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Mortality and causes of death in a Swedish series of systemic sclerosis patients
- 1998
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Ingår i: Annals of the Rheumatic Diseases. - 1468-2060. ; 57:11, s. 682-686
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To analyse survival rates and the causes of death in a systemic sclerosis (SSc) population, and to evaluate the occurrence of fatal malignant neoplasms and their possible association with oral cyclophosphamide (CYC) treatment. METHODS: Survival was calculated for 249 SSc patients followed up for up to 13 years. Mean (SD) follow up was 5.8 (4.2) years. The 49 decreased patients were subdivided according to causes of death and its relation to SSc. Fatal malignancies in CYC treated patients were compared with those occurring in non-CYC treated patients. RESULTS: The overall 5 and 10 year survival rates were 86% and 69% respectively. There was a 4.6-fold increased risk of death, as compared with the general population. Prognosis was worse in the diffuse cutaneous involvement (dSSc) and male subgroups than in the limited cutaneous involvement (1SSc) and female subgroups. Of the 49 deaths, 24 were attributable to pulmonary complications such as pulmonary fibrosis, pulmonary hypertension, pneumonia or pulmonary malignancy. Treatment with oral CYC did not increase the risk of dying of cancer. CONCLUSIONS: Mortality is increased both in the SSc population as a whole and in its different subsets (dSSc and 1SSc). Prognosis is worst among male patients with dSSc. However, the 5 year survival rate was better than those reported from earlier studies. Most patients die of cardiopulmonary disease. Five of seven fatal lung cancers were adenocarcinomas, possibly caused by chronic inflammatory disease of the lung. In this study, CYC treatment was not associated with an increased incidence of fatal malignant neoplasms.
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| 17. |
- Hesselstrand, Roger, et al.
(författare)
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Scleroderma renal crisis in a Swedish systemic sclerosis cohort: survival, renal outcome, and RNA polymerase III antibodies as a risk factor.
- 2012
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 41, s. 39-43
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To study survival, renal outcome, and RNA polymerase III antibodies (RNAP Abs) as a risk factor for scleroderma renal crisis (SRC) in a Swedish cohort of systemic sclerosis (SSc) patients. Methods: SRC was diagnosed in 16 SSc patients during the period from 1982 to 2010. For comparison, 112 (seven for each SRC patient) SSc patients without SRC were included. RNAP Abs were detected by a fully automated fluoroenzymeimmunoassay (EliA). Values greater than 15 μg/L were considered positive. Frozen serum samples from the time of diagnosis of SSc were used. Results: The 5- and 10-year survival rates were, respectively, 58% and 40% for SRC patients and 90% and 76% for patients without SRC (p < 0.001). The odds ratio (OR) for mortality was 4.39 [95% confidence interval (CI) 2.10-9.16, p < 0.001] in patients with SRC compared to those without SRC. Renal outcome was good in three patients. Haemodialysis was started in 10 patients and peritoneal dialysis in three. Renal function improved in three patients and dialysis was terminated. Four patients underwent renal transplantation. Seven SRC patients and nine without SRC were positive for RNAP Abs. Anti-RNAP Abs was a strong predictor of SRC. The sensitivity and specificity for development of SRC were 0.44 and 0.92, respectively. The OR for development of SRC was 8.90 (95% CI 2.68-29.6, p = 0.001) in RNAP-positive patients. Conclusions: RNAP positivity is a strong risk factor for SRC. Renal outcome was variable and survival is still notably decreased.
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| 18. |
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| 19. |
- Hesselstrand, Roger, et al.
(författare)
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Survival in patients with pulmonary arterial hypertension associated with systemic sclerosis from a Swedish single centre: prognosis still poor and prediction difficult
- 2011
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 40:2, s. 127-132
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To describe the survival rate in a cohort of systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) and to evaluate possible predictors for SSc-PAH in a cohort of SSc patients. Methods: Thirty patients with SSc-PAH and 150 SSc patients without PAH were included. Survival and survival on therapy were calculated. Clinical features at baseline were correlated to the risk for development of PAH during follow-up. Results: The 1-, 2-, 3-, and 4-year survival rates were 86, 59, 39, and 22%, respectively, from diagnosis of PAH. The hazard ratio for total mortality in the SSc-PAH group was 3.2 [95% confidence interval (CI) 1.8-5.7] compared to SSc without PAH (p < 0.001). Risk factors at baseline for the development of PAH were: limited skin involvement, low diffusing capacity of the lung for carbon monoxide (DLCO), high N-terminal pro-brain natriuretic peptide (NTProBNP), increased estimated systolic pulmonary arterial pressure (ESPAP), and the presence of teleangiectases. Severe peripheral vascular disease requiring iloprost treatment during follow-up was associated with an eightfold increased risk of PAH. Conclusion: Despite modern treatment and yearly screening by echocardiography, the survival in SSc-PAH is still low in our cohort. The identified risk factors should be assessed to select patients eligible for right heart catheterization (RHC) to make an earlier diagnosis.
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| 20. |
- Hesselstrand, Roger, et al.
(författare)
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The association between changes in skin echogenicity and the fibroblast production of biglycan and versican in systemic sclerosis
- 2002
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Ingår i: Clinical and Experimental Rheumatology. - 1593-098X. ; 20:3, s. 301-308
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate a possible association between the longitudinal changes in skin involvement and the fibroblast production of proteoglycans in vitro, among patients with early and untreated systemic sclerosis (SSc). Methods In 11 patients, 6 with diffuse cutaneous systemic sclerosis (dSSc) and 5 with limited cutaneous systemic sclerosis (lSSc), and in 6 controls skin thickness and skin echogenicity, of the forearm was measured by high frequency (20 MHz) ultrasound, A skin biopsy was taken from the area of the ultrasound measurements, and from cultivated fibroblasts the production of the proteoglycans versican, perlecan, biglycan and decorin were measured. To investigate longitudinal changes in skin involvement, the ultrasound examination was repeated after 1-3 years. Results Compared to controls, SSc Patients had increased skin thickness at the first evaluation. Patients with dSSc had lower skin echogenicity than both patients with ISSc and the controls. Patients with greater changes in skin thickness and skin echogenicity produced more versican, whereas the production of biglycan and decorin was higher only, in patients with greater changes in skin echogenicity. There was a negative correlation between fibroblast production of biglycan and disease duration. Conclusion High fibroblast synthesis of the proteoglycans versican and biglycan is associated with changes in skin echogenicity and may predict more progressive skin sclerosis in SSc.
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| 21. |
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| 22. |
- Hofstee, Herman M A, et al.
(författare)
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A multicentre study on the reliability of qualitative and quantitative nail-fold videocapillaroscopy assessment.
- 2012
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 51:4, s. 749-755
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 23. |
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| 24. |
- Ingegnoli, Francesca, et al.
(författare)
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Nailfold capillaroscopy in systemic sclerosis: Data from the EULAR scleroderma trials and research (EUSTAR) database
- 2013
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Ingår i: Microvascular Research. - : Elsevier BV. - 1095-9319 .- 0026-2862. ; 89, s. 122-128
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aims of this study were to obtain cross-sectional data on capillaroscopy in an international multi-center cohort of Systemic Sclerosis (SSc) and to investigate the frequency of the capillaroscopic patterns and their disease-phenotype associations. Methods: Data collected between June 2004 and October 2011 in the EULAR Scleroderma Trials and Research (EUSTAR) registry were examined. Patients' profiles based on clinical and laboratory data were obtained by cluster analysis and the association between profiles and capillaroscopy was investigated by multinomial logistic regression. Results: 62 of the 110 EUSTAR centers entered data on capillaroscopy in the EUSTAR database. 376 of the 2754 patients (13.65%) were classified as scleroderma pattern absent, but non-specific capillary abnormalities were noted in 55.48% of the cases. Four major patients' profiles were identified characterized by a progressive severity for skin involvement, as well as an increased number of systemic manifestations. The "early" and "active" scleroderma patterns were generally observed in patients with mild/moderate skin involvement and a low number of disease manifestations, while the "late" scleroderma pattern was found more frequently in the more severe forms of the disease. Conclusion: These data indicate the importance of capillaroscopy in SSc management and that capillaroscopic patterns are directly related to the extent of organ involvement. (C) 2013 Elsevier Inc. All rights reserved.
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| 25. |
- Larsen, Kristoffer, et al.
(författare)
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Functional and phenotypical comparison of myofibroblasts derived from biopsies and bronchoalveolar lavage in mild asthma and scleroderma
- 2006
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Activated fibroblasts, which have previously been obtained from bronchoalveolar lavage fluid (BALF), are proposed to be important cells in the fibrotic processes of asthma and scleroderma (SSc). We have studied the motility for BALF derived fibroblasts in patients with SSc that may explain the presence of these cells in the airway lumen. Furthermore, we have compared phenotypic alterations in activated fibroblasts from BALF and bronchial biopsies from patients with mild asthma and SSc that may account for the distinct fibrotic responses. Methods: Fibroblasts were cultured from BALF and bronchial biopsies from patients with mild asthma and SSc. The motility was studied using a cell migration assay. Western Blotting was used to study the expression of alpha-smooth muscle actin (alpha-SMA), ED-A fibronectin, and serine arginine splicing factor 20 (SRp20). The protein expression pattern was analyzed to reveal potential biomarkers using two-dimensional electrophoresis (2-DE) and sequencing dual matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-TOF). The Mann-Whitney method was used to calculate statistical significance. Results: Increased migration and levels of ED-A fibronectin were observed in BALF fibroblasts from both groups of patients, supported by increased expression of RhoA, Rac1, and the splicing factor SRp20. However, these observations were exclusively accompanied by increased expression of alpha-SMA in patients with mild asthma. Compared to BALF fibroblasts in mild asthma, fibroblasts in SSc displayed a differential protein expression pattern of cytoskeletal- and scavenger proteins. These identified proteins facilitate cell migration, oxidative stress, and the excessive deposition of extracellular matrix observed in patients with SSc. Conclusion: This study demonstrates a possible origin for fibroblasts in the airway lumen in patients with SSc and important differences between fibroblast phenotypes in mild asthma and SSc. The findings may explain the distinct fibrotic processes and highlight the motile BALF fibroblast as a potential target cell in these disorders.
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| 26. |
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| 27. |
- Parel, Yann, et al.
(författare)
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Presence of CD4+CD8+ double-positive T cells with very high interleukin-4 production potential in lesional skin of patients with systemic sclerosis
- 2007
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 56:10, s. 3459-3467
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Fibrotic skin changes in systemic sclerosis (SSc) are preceded by the appearance of an inflammatory infiltrate rich in T cells. Since no direct comparison with T cells in normal skin has been performed previously, this study was undertaken to functionally characterize T cells in the skin of patients with early active SSc and in normal skin. Methods. We characterized coreceptor expression, T cell receptor (TCR) usage, cytokine production, and helper and cytolytic activity of T cell lines and clones established from skin biopsy specimens from 6 SSc patients and 4 healthy individuals. Immunofluorescence analysis of skin biopsy and peripheral blood samples was performed to confirm the presence of specific subsets in vivo. Results. A distinct subset expressing both CD4 and CD8 alpha/beta coreceptors at high levels (double-positive [DP]) was present in T cell lines from SSc and normal skin. DP T cells actively transcribed both accessory molecules, exerted clonally distributed cytolytic and helper activity, and expressed TCR clonotypes distinct from those in CD4+ or CD8+ single-positive (SP) T cells. In SSc skin, DP T cells produced very high levels of interleukin-4 (IL-4) compared with CD4+ SP T cells. Furthermore, DP T cells were directly identified in SSc skin, thus providing evidence that they are a distinct subset in vivo. Conclusion. The present findings show that T cells with the unusual CD4+CD8+ DP phenotype are present in the skin. Their very high level of IL-4 production in early active SSc may contribute to enhanced extracellular matrix deposition by fibroblasts.
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| 28. |
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| 29. |
- Sandqvist, Gunnel, et al.
(författare)
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Managing work life with systemic sclerosis
- 2012
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 51:2, s. 319-323
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To explore how individuals with systemic sclerosis (SSc) manage their work life. Methods. We conducted four focus group interviews which included 17 patients. The interviews were tape recorded and transcribed verbatim. The transcribed texts were analysed according to thematic content analysis. Relevant statements, that generated preliminary categories, were identified after which, themes and underlying sub-themes were generated. Results. Four themes emerged: adaptation, strategy, communication and attitude. Flexible working hours, workplace and work assignments corresponding to the individuals’ recourses, were the most important adaptation requirements for SSc patients. Reluctance to disclose their illness was the most prominent reason for not requesting adaptations. Strategies to facilitate working at home, such as receiving assistance with household chores as well as buying in cleaning services were easy to realize and saved energy for meaningful activities. The participants tried to prioritize meaningful activities rather than spending energy on unnecessary activities both at work and outside of work. Fatigue influenced activities at work but mostly outside of work and to manage their working life the participants were dependent of having time for recovery, above all rest.Conclusion. The ability to develop adaptations and strategies, to a great extent, depends on the individual’s understanding and acceptance of their disease, awareness and respect for their own needs for meaningful activities and an ability to communicate this at work and outside of work. As health professionals we should enhance the confidence of persons with SSc to strengthen their ability to bring about the necessary dialogue.
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| 30. |
- Sandqvist, Gunnel, et al.
(författare)
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Pain, fatigue and hand function closely correlated to work ability and employment status in systemic sclerosis.
- 2010
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 49:9, s. 1739-1746
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify factors, individual and work related, influencing work ability, and to assess the association between work ability and employment status, activities of daily life (ADLs) and quality of life in patients with SSc. Methods: Fifty-seven consecutive patients (53 females/4 males) with SSc (47 lcSSc/10 dcSSc) were included. Median age was 58 [interquartile range (IQR) 47-62] years and disease duration 14 (9-19) years. The patients were assessed for socio-demographic characteristics, disease parameters, symptoms, work ability, empowerment and adaptations in a workplace, social support, ADLs and quality of life. Results: Work ability, assessed with the Work Ability Index (WAI) could be evaluated in 48 of 57 patients. The correlation between employment status and WAI was good (r(s) = 0.79, P < 0.001). Thirteen patients had good or excellent WAI, 15 had less good and 20 had poor WAI. There were no significant differences between subgroups of WAI and socio-demographic characteristics, disease duration or degree of skin and lung involvement. However, patients with good WAI expressed milder perceived symptoms (pain, fatigue and impaired hand function; P < 0.001). Patients with better WAI had better competence (P < 0.001), better possibility of adaptations at work (P < 0.01) and impact at work (P < 0.01) than those with poorer WAI. Conclusions: In SSc, pain, fatigue and impaired hand function have a dominant impact on the WAI. Employment interventions should include support in job adaptations as well as self-management strategies to help patients deal with pain and fatigue and to enhance the confidence to perform their work.
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| 31. |
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| 32. |
- Sandqvist, Gunnel, et al.
(författare)
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Working ability in relation to disease severity, everyday occupations and well-being in women with limited systemic sclerosis.
- 2008
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 47, s. 1708-1711
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To investigate how women with SSc and varying degrees of working ability differed regarding disease severity, everyday occupations and well-being. Working ability was operationalized according to the degree of sick leave. Methods. Forty-four women of working age with lcSSc were assessed regarding sociodemographic characteristics, disease severity including organ manifestation, perceived physical symptoms, hand function, and satisfaction with everyday occupations, self-rated health and well-being. Results. The subjects formed three groups with regard to reduction in working capacity. Twenty-one women (48%) had no sick leave, 15 women (34%) were on partial sick leave and eight women (18%) were temporarily on full-time sick leave or had a full disability pension. There were no statistically significant differences concerning sociodemographics between the groups. Women without sick leave had less physically demanding jobs (P = 0.026), and the hypothesis that working ability reflects lower disease severity was confirmed regarding dexterity grip force and perceived fatigue and breathlessness (P < 0.05). Greater working ability was associated with better capacity to perform activities of daily life (P < 0.01), greater satisfaction with occupations (P < 0.01), better well-being (P < 0.001) and better health (P < 0.001). Conclusions. Fifty per cent of the women were restricted in their working ability; the lower the working ability, the lower their perceived well-being. This emphasizes the need for further research into the factors that promote working ability and the development of suitable methods to improve working ability.
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| 33. |
- Scheja, Agneta, et al.
(författare)
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BAL fluid derived fibroblasts differ from biopsy derived fibroblasts in systemic sclerosis.
- 2007
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 29:3, s. 446-452
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Tidskriftsartikel (refereegranskat)abstract
- Growth of fibroblasts from bronchoalveolar lavage fluid (BALF) in patients with systemic sclerosis (SSc) has previously been described. The purpose of the present study was to characterise fibroblasts from BALF and bronchial biopsies from SSc patients with alveolitis and from controls, to analyse fibroblast proliferation, migration, stress fibres and proteoglycan production. BALF and bronchial biopsies were collected from 10 patients with SSc and alveolitis and from 15 controls. Outgrowth of fibroblasts was observed from the BALF of four patients, particularly in those with a markedly increased percentage of eosinophils in BALF, but not in any member of the control group. Increased levels of granulocyte-macrophage colony-stimulating factor, correlating with the percentage of eosinophils in BALF, were found in patients when compared with controls. Fibroblasts from BALF showed an elongated, mobile phenotype and increased proteoglycan production compared to the corresponding biopsy fibroblasts. In conclusion, outgrowth of fibroblasts with an altered phenotype is reported from bronchoalveolar lavage fluid in systemic sclerosis patients with alveolitis and an increased percentage of eosinophils in the bronchoalveolar lavage fluid. These findings indicate a possible role for eosinophil-fibroblast interaction in pulmonary fibrosis in systemic sclerosis.
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| 34. |
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| 35. |
- Scheja, Agneta, et al.
(författare)
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Progressive capillary loss over a decade in patients with systemic sclerosis, in particular in patients with early digital ischaemic manifestations.
- 2011
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 40, s. 457-461
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Characteristic capillary abnormalities occur early in systemic sclerosis (SSc). Our aim was to study the longitudinal development of capillary density in SSc patients. Methods: Forty-eight consecutive patients with SSc fulfilling a follow-up of at least 8 years were retrospectively analysed for capillary loss over the observation period. Eleven had diffuse cutaneous SSc (dcSSc) and 37 limited cutaneous SSc (lcSSc). The median disease duration at first assessment was 2.5 years. Capillary density was determined by direct counting of capillaries in the distal row on eight fingers in a stereo-zoom microscope at 20× magnification. Results: Capillary density decreased over the observation period in dcSSc (from median 5.1 to 4.4 loops/mm, p < 0.05) and in lcSSc (from 5.1 to 4.2 loops/mm, p < 0.001). No significant difference was found between the two forms at start or at follow-up. Digital ischaemic manifestations had already been found at the first assessment in 19 patients. They did not differ in capillary density from those without ischaemic manifestations at the first assessment (5.0 and 5.3 loops/mm), but did differ at follow-up (3.6 and 4.7 loops/mm, p < 0.001). Capillary loss was more pronounced in patients who already had digital ischaemic manifestations at the first assessment compared to those without (p < 0.02). Conclusion: In SSc, early digital ischaemic manifestations may precede a subsequent progressive capillary loss. The association between capillary loss and serious internal vascular complications remains to be studied.
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| 36. |
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| 37. |
- Scheja, Agneta, et al.
(författare)
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Renal function is mostly preserved in patients with systemic sclerosis.
- 2009
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 38, s. 295-298
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Chronic renal disease other than scleroderma renal crisis (SRC) is not well documented in systemic sclerosis (SSc). We examined the occurrence of decreased glomerular filtration rate (GFR) in a large consecutive SSc cohort and analysed whether it was related to SSc or could be related to other causes. Methods: During 1983-2004 GFR was measured by chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA) or iohexol clearance in 461 patients with SSc according to the American College of Rheumatology (ACR) criteria [356 with limited cutaneous SSc (lcSSc) and 105 with diffuse cutaneous SSc (dcSSc)] and the measurements were repeated once a year. Decreased GFR was defined as GFR<70% of the age-adjusted values. SRC was diagnosed in 4/360 lcSSc (1.1%) and in 10/115 dcSSc (8.7%). These patients were excluded from further analyses. Results: At the latest follow-up at a median duration of 7.7 (range 0.5-54) years, decreased GFR was found in 39 lcSSc (11%) and nine (8.6%) dcSSc patients. Among the 48 SSc patients with GFR<70p% (percentage of predicted value = p%), hypertension was diagnosed in 29 (60%) and cardiac involvement in 25 (52%). Different nephropathies were found in eight (19%) patients by renal biopsy. Fifteen patients with decreased GFR were followed up for >/=4 years and no progress was seen in 11/15. Conclusions: A minority of patients with SSc develop renal dysfunction other than SRC. Decreased GFR was associated with other manifestations such as hypertension and cardiac involvement indicating possible pre-renal causes.
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| 38. |
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| 39. |
- Scheja, Agneta, et al.
(författare)
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Von Willebrand factor propeptide as a marker of disease activity in systemic sclerosis (scleroderma)
- 2001
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1465-9913 .- 1465-9905. ; 3:3, s. 178-182
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Tidskriftsartikel (refereegranskat)abstract
- In 44 consecutive patients with systemic sclerosis (SSc), plasma concentrations of von Willebrand factor (vWf) were higher than those of the vWf propeptide, but the propeptide showed less variability within patient subgroups. Higher values of the propeptide were observed in patients with early pulmonary involvement. A closer correlation of the propeptide than of vWf to biochemical markers of activity was also evident. Our results suggest that the propeptide, despite a shorter circulating half-time and lower plasma concentrations than vWf, is more useful in the assessment of disease activity in SSc.
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| 40. |
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| 41. |
- Tufvesson, Ellen, et al.
(författare)
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Increased cysteinyl-leukotrienes and 8-isoprostane in exhaled breath condensate from systemic sclerosis patients.
- 2010
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 49, s. 2322-2326
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. SSc is a systemic CTD characterized by fibrosis in skin and internal organs. Interstitial lung disease is a frequent complication with fibrosis in the lung parenchyma. The fibrotic process is believed to be influenced by leukotrienes (LTs) and also by oxidative stress. The aim of this study was to investigate the amount of LTs and 8-isoprostane, a marker of oxidative stress, in exhaled breath condensate (EBC) from SSc patients. Methods. Twenty-two SSc patients with median disease duration of 2.1 years were investigated. Fifteen patients had lcSSc, four patients had dcSSc and three patients only fulfilled criteria for limited SSc. Sixteen healthy controls were enrolled. Cysteinyl-LTs (CysLTs), LTB(4) and 8-isoprostane were measured in EBC with EIA and related to the radiologic extent of pulmonary fibrosis. Results. Compared with controls, SSc patients displayed higher median (interquartile range) CysLT [6.1 (5.3-6.8) vs 4.9 (3.7-6.3) pg/ml; P = 0.040], 8-isoprostane [0.23 (0.20-0.46) vs 0.19 (0.12-0.20) pg/ml; P = 0.0020], but similar levels of LTB(4) [0.70 (0.50-0.83) vs 0.60 (0.42-0.70) pg/ml]. CysLT correlated to LTB(4), while 8-isoprostane did not correlate to any of the LTs. None of the biomarkers measured in EBC correlated to radiologic findings. Conclusion. Increased levels of CysLT and 8-isoprostane in EBC from patients with SSc reflect the inflammatory pattern involving LTs as well as oxidative stress. These findings may indicate a possible non-invasive assessment of pulmonary involvement in SSc with a potential value for assessment of disease progress and therapy evaluation.
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| 42. |
- Tyndall, Anthony J., et al.
(författare)
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Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database
- 2010
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 69:10, s. 1809-1815
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To determine the causes and predictors of mortality in systemic sclerosis (SSc). Methods Patients with SSc (n=5860) fulfilling the American College of Rheumatology criteria and prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) cohort were analysed. EUSTAR centres completed a structured questionnaire on cause of death and comorbidities. Kaplan-Meier and Cox proportional hazards models were used to analyse survival in SSc subgroups and to identify predictors of mortality. Results Questionnaires were obtained on 234 of 284 fatalities. 55% of deaths were attributed directly to SSc and 41% to non-SSc causes; in 4% the cause of death was not assigned. Of the SSc-related deaths, 35% were attributed to pulmonary fibrosis, 26% to pulmonary arterial hypertension (PAH) and 26% to cardiac causes (mainly heart failure and arrhythmias). Among the non-SSc-related causes, infections (33%) and malignancies (31%) were followed by cardiovascular causes (29%). Of the non-SSc-related fatalities, 25% died of causes in which SSc-related complications may have participated (pneumonia, sepsis and gastrointestinal haemorrhage). Independent risk factors for mortality and their HR were: proteinuria (HR 3.34), the presence of PAH based on echocardiography (HR 2.02), pulmonary restriction (forced vital capacity below 80% of normal, HR 1.64), dyspnoea above New York Heart Association class II (HR 1.61), diffusing capacity of the lung (HR 1.20 per 10% decrease), patient age at onset of Raynaud's phenomenon (HR 1.30 per 10 years) and the modified Rodnan skin score (HR 1.20 per 10 score points). Conclusion Disease-related causes, in particular pulmonary fibrosis, PAH and cardiac causes, accounted for the majority of deaths in SSc.
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| 43. |
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| 44. |
- Wildt, Marie, et al.
(författare)
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Assessment of capillary density in systemic sclerosis with three different capillaroscopic methods
- 2012
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Ingår i: Clinical and Experimental Rheumatology. - 1593-098X. ; 30:2, s. 50-54
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Tidskriftsartikel (refereegranskat)abstract
- 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 lcSSc 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. Conclusion: Assessment of capillary density with three different methods showed good agreement between methods. All methods could differentiate between SSc patients and controls.
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| 45. |
- Wildt, Marie, et al.
(författare)
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Simple counting of nailfold capillary density in suspected systemic sclerosis - 9 years' experience.
- 2007
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 36:6, s. 452-457
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Capillary damage is a characteristic feature of systemic sclerosis (SSc). This work aimed to explore the potential clinical value of simple microscopic counting of capillary density. Methods: In 325 patients admitted because of a clinical suspicion of SSc and in 80 healthy controls, nailfold capillary microscopy (NCM) was performed using a stereo-zoom microscope in 20x magnification and with a transparent ruler in one of the eyepieces. Capillaries were counted within 3 mm in the centre of the nailfold in eight fingers. Results: Capillary density (loops/mm) was decreased in patients with diffuse cutaneous SSc [median 4.7 (range 2.2-7.3)], limited cutaneous SSc [4.9 (2.0-7.3)], earlySSc [4.7 (2.8-7.3)], and preSSc [5.9 (4.3-8.2)] compared to healthy controls [7.2 (5.8-9.0)]. Patients with morphea and with primary Raynaud's phenomenon had normal numbers of capillaries [7.0 (6.2-7.2) and 7.0 (5.3-8.7), respectively]. In only 21/325 (6%) patients was it not possible to count the capillaries because of insufficient transparency of the skin. There was no discrepancy in capillary density based on counts of two or eight fingers. When 43 patients were reassessed after 1 to 4 years, there was no difference between the two assessments. Conclusion: Determination of capillary density by direct microscopy counts, a simple, inexpensive and rapid method, helps to identify patients with SSc, early in the disease course and in patients with very limited skin involvement.
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| 46. |
- Wuttge, Dirk, et al.
(författare)
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CD81 and CD48 show different expression on blood eosinophils in systemic sclerosis: new markers for disease and pulmonary inflammation?
- 2016
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 45:2, s. 107-113
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Tidskriftsartikel (refereegranskat)abstract
- In systemic sclerosis (SSc)-related interstitial lung disease (ILD), elevated eosinophil counts in bronchoalveolar lavage are associated with a worse outcome. We hypothesized that eosinophils may be activated in the peripheral circulation, thereby increasing their recruitment to affected tissues and contributing to inflammation and fibrosis. The aim of this study was to characterize the blood eosinophils in SSc patients.
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| 47. |
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| 48. |
- Wuttge, Dirk, et al.
(författare)
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Increased alveolar nitric oxide in early systemic sclerosis.
- 2010
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Ingår i: Clinical and Experimental Rheumatology. - 1593-098X. ; 28:5 Suppl 62, s. 5-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Assessment of inflammatory activity in interstitial lung disease of systemic sclerosis (SSc) is difficult. Nitric oxide (NO) has gained attention in the pathogenesis of SSc. The aim of the study was to investigate alveolar NO concentration (CA(NO)) in SSc patients with short disease duration and to relate CA(NO) to radiologic findings. METHODS: In a prospective study, 34 consecutive patients with disease duration of less than 2 years from onset of first non-Raynaud symptom and 26 healthy controls were enrolled. Exhaled NO was measured and CA(NO) was calculated. CA(NO) levels were related to the radiologic extent of pulmonary fibrosis measured as the extent of traction bronchiectasis within areas of ground glass opacities and reticulations. RESULTS: CA(NO) levels were increased in patients with early SSc compared to healthy controls (3.52 (2.94-4.09) versus 2.08 (1.6-2.6); p<0.001). Both SSc patients with SSc-ILD (3.56 (3.04-4.73), p<0.001) and SSc patients without SSc-ILD (2.98 (2.68-3.98), p<0.01) had higher CA(NO) levels compared with healthy controls (2.08 (1.6-2.6)). CA(NO) levels did not differ between SSc patients without SSc-ILD and SSc patients with SSC-ILD. CA(NO) levels did not correlate to the extent of pulmonary fibrosis but were associated with the extent of ground glass opacities (rs=0.37, p<0.05) and reticulations (rs=0.37, p<0.05) on HRCT. CA(NO) levels were not correlated to lung function tests. CONCLUSIONS: In patients with early SSc, alveolar NO is increased and may precede radiological changes of SSc-ILD. CA(NO) may therefore be a marker of early lung involvement.
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| 49. |
- Wuttge, Dirk, et al.
(författare)
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Increased serum type I interferon activity in early systemic sclerosis patients is associated with antibodies against Sjögren's syndrome antigens and nuclear ribonucleoprotein antigens.
- 2013
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 42:3, s. 235-240
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study serum type I interferon (IFN) activity in patients with early systemic sclerosis (SSc). Method: Serum type I IFN activity was measured in 33 consecutive patients with SSc and a disease duration of < 2 years and in 13 healthy individuals by calculating a type I IFN score according to the induction of six IFN-α regulated genes in a reporter cell line. Results: Twenty-seven per cent of the SSc patients had an increased type I IFN score compared to none of the healthy individuals (p < 0.05). The clinical SSc phenotype associated with high serum type I IFN activity did not differ from patients with low serum type I IFN activity regarding the presence of skin or lung fibrosis, pulmonary hypertension, or digital complications. Patients with high serum type I IFN activity were younger (p < 0.01) and had a lower frequency of cardiac involvement (p = 0.053), lower leucocyte count (p < 0.001), higher immunoglobulin (Ig)G levels (p < 0.05), and a higher amount of antibodies against extractable nuclear antigens (p < 0.01) than patients with low serum type I IFN activity. The presence of antibodies against topoisomerase I, Sjögren's syndrome antigen, and nuclear ribonucleoprotein antigens was associated with higher type I IFN activity (p < 0.05 for all comparisons). Conclusions: Our study indicates that increased serum type I IFN activity in early SSc patients is associated with an antibody and laboratory profile that may reflect a subclinical overlap of SSc with other type I IFN-driven connective tissue diseases (CTDs).
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| 50. |
- Wuttge, Dirk, et al.
(författare)
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Interleukin-15 attenuates transforming growth factor-beta1-induced myofibroblast differentiation in human fetal lung fibroblasts.
- 2010
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Ingår i: European Cytokine Network. - 1952-4005. ; 21, s. 165-176
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveFibroproliferative diseases are common causes of morbidity and mortality. Interleukin-15 (IL-15) is a pleiotropic cytokine with multiple effects on cells of the immune system. Although IL-15 is also expressed in mesenchymal cells, its effects on the development of fibrosis are unknown. We have previously described an association between serum IL-15 levels and the extent of pulmonary fibrosis in the connective tissue disease systemic sclerosis, suggesting that IL-15 may have profibrotic effects. To test this hypothesis, we studied the effects of IL-15 on myofibroblast differentiation, an in vitro model of fibrosis development.MethodsWe used human fetal lung fibroblasts for the cytokine stimulation. As a marker of myofibroblast differentiation, alpha-smooth muscle actin (alpha-SMA) was analyzed by western blot and quantitative real-time PCR. The well-known profibrotic cytokine, transforming growth factor-beta1(TGF-beta1), was used for comparison, and TGF-beta signaling paths were also studied.ResultsIL-15 did not induce alpha-SMA expression, a marker for myofibroblast differentiation. Unexpectedly, IL-15 counteracted TGF-beta1-mediated alpha-SMA expression. Moreover, TGF-beta1-induced expression of collagen, fibronectin and connective tissue growth factor was attenuated by addition of IL-15. There was no effect of IL-15 on early events in the TGF-beta signaling cascades.ConclusionIL-15 has anti-fibrotic properties that, speculatively however, may be insufficient in systemic sclerosis.
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