| 1. |
- Gorlova, Olga, et al.
(author)
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Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy
- 2011
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In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 7:7
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Journal article (peer-reviewed)abstract
- The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (IcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32x10(-12), OR = 0.75). Also, rs12540874 in GRB10 gene (P = 1.27 x 10(-6), OR = 1.15) and rs11047102 in SOX5 gene (P = 1.39x10(-7), OR = 1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79x10(-61), OR = 2.48), in the HLA-DPA1/B1 loci with ATA (P = 4.57x10(-76), OR = 8.84), and in NOTCH4 with ACA P = 8.84x10(-21), OR = 0.55) and ATA (P = 1.14x10(-8), OR = 0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and autoantibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc.
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| 2. |
- Radstake, Timothy R. D. J., et al.
(author)
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Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 71-426
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Journal article (peer-reviewed)abstract
- Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs that leads to profound disability and premature death. To identify new SSc susceptibility loci, we conducted the first genome-wide association study in a population of European ancestry including a total of 2,296 individuals with SSc and 5,171 controls. Analysis of 279,621 autosomal SNPs followed by replication testing in an independent case-control set of European ancestry (2,753 individuals with SSc (cases) and 4,569 controls) identified a new susceptibility locus for systemic sclerosis at CD247 (1q22-23, rs2056626, P = 2.09 x 10(-7) in the discovery samples, P = 3.39 x 10(-9) in the combined analysis). Additionally, we confirm and firmly establish the role of the MHC (P = 2.31 x 10(-18)), IRF5 (P = 1.86 x 10(-13)) and STAT4 (P = 3.37 x 10(-9)) gene regions as SSc genetic risk factors.
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| 3. |
- Alizadeh, Behrooz Z, et al.
(author)
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Functional Variants of Fc Gamma Receptor (FCGR2A) and FCGR3A Are Not Associated with Susceptibility to Systemic Sclerosis in a Large European Study (EUSTAR).
- 2010
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In: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; Jul 1, s. 1673-1679
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate the possible role of FCGR2A 519A>G and FCGR3A 559A>C functional polymorphisms in the genetic predisposition to susceptibility to systemic sclerosis (SSc) or clinical phenotype. METHODS: A total of 1566 patients with SSc and 2271 geographically matched controls were included in our study. We analyzed the genotype and allele frequencies of the FCGR2A 519A>G and FCGR3A 559A>C functional variants in 6 independent European cohorts of white patients with SSc, and white controls. The cohorts comprised 165 Dutch patients with SSc and 1326 controls, 236 Spanish patients with SSc and 257 controls, 267 German patients with SSc and 270 controls, 202 Swedish patients with SSc and 261 controls, 416 Italian patients with SSc and 157 controls, and additionally 280 English patients with SSc. Genotyping was performed using Taqman 5' allelic discrimination assay. The study reached a 99% power to detect the effect of a polymorphism at an OR of 1.3. RESULTS: Neither FCGR2A 519A>G nor FCGR3A 559A>C was significantly associated with susceptibility to SSc. We did not find an association with specific disease phenotypes, limited or diffuse cutaneous involvement, autoantibody profiles, or pulmonary involvement. CONCLUSION: Our study strongly suggests the lack of a role for the FCGR2A 519A>G and FCGR3A 559A>C polymorphisms in SSc susceptibility or clinical phenotype in 6 independent European cohorts.
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| 4. |
- Bossini-Castillo, Lara, et al.
(author)
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A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations
- 2012
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:4, s. 926-933
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Journal article (peer-reviewed)abstract
- A single-nucleotide polymorphism (SNP) at the IL12RB2 locus showed a suggestive association signal in a previously published genome-wide association study (GWAS) in systemic sclerosis (SSc). Aiming to reveal the possible implication of the IL12RB2 gene in SSc, we conducted a follow-up study of this locus in different Caucasian cohorts. We analyzed 10 GWAS-genotyped SNPs in the IL12RB2 region (2309 SSc patients and 5161 controls). We then selected three SNPs (rs3790567, rs3790566 and rs924080) based on their significance level in the GWAS, for follow-up in an independent European cohort comprising 3344 SSc and 3848 controls. The most-associated SNP (rs3790567) was further tested in an independent cohort comprising 597 SSc patients and 1139 controls from the USA. After conditional logistic regression analysis of the GWAS data, we selected rs3790567 [P-MH = 1.92 x 10(-5) odds ratio (OR) = 1.19] as the genetic variant with the firmest independent association observed in the analyzed GWAS peak of association. After the first follow-up phase, only the association of rs3790567 was consistent (P-MH = 4.84 x 10(-3) OR = 1.12). The second follow-up phase confirmed this finding (P-chi 2 = 2.82 x 10(-4) OR = 1.34). After performing overall pooled-analysis of all the cohorts included in the present study, the association found for the rs3790567 SNP in the IL12RB2 gene region reached GWAS-level significant association (P-MH = 2.82 x 10(-9) OR = 1.17). Our data clearly support the IL12RB2 genetic association with SSc, and suggest a relevant role of the interleukin 12 signaling pathway in SSc pathogenesis.
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| 5. |
- Bossini-Castillo, Lara, et al.
(author)
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A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort
- 2011
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:4, s. 638-641
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Journal article (peer-reviewed)abstract
- Objectives The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features. Methods A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers. Results A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively). Conclusions The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.
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| 6. |
- Broen, Jasper C A, et al.
(author)
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The Functional Polymorphism 844 A>G in Fc{alpha}RI (CD89) Does Not Contribute to Systemic Sclerosis or Rheumatoid Arthritis Susceptibility.
- 2011
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In: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 38:3, s. 446-449
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate the role of the Fc(α)RI 844 A>G functional polymorphism in the genetic predisposition to rheumatoid arthritis (RA) and systemic sclerosis (SSc) susceptibility. METHODS: The study population was composed of 1401 patients with SSc, 642 patients with RA, and 1317 healthy controls. The Fc(α)RI (CD89) single-nucleotide polymorphism rs16986050 was genotyped by pyrosequencing. RESULTS: We observed no significant deviation of the genotype and allele frequencies in RA and SSc compared to controls. A metaanalysis and a recessive and dominant model yielded similar negative results. CONCLUSION: Our data show that the Fc(α)RI 844 A>G polymorphism is not associated with SSc or RA susceptibility.
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| 7. |
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| 8. |
- Herrick, Ariane L, et al.
(author)
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Treatment outcome in early diffuse cutaneous systemic sclerosis : The European Scleroderma Observational Study (ESOS)
- 2017
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:7, s. 1207-1218
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Journal article (peer-reviewed)abstract
- Objectives: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. Methods: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. Results Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. Conclusions: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.
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| 9. |
- López-Isac, Elena, et al.
(author)
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Brief Report : IRF4 Newly Identified as a Common Susceptibility Locus for Systemic Sclerosis and Rheumatoid Arthritis in a Cross-Disease Meta-Analysis of Genome-Wide Association Studies
- 2016
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In: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 68:9, s. 2338-2344
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Journal article (peer-reviewed)abstract
- Objective: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc–RA genetic loci have been identified independently. The aim of the current study was to systematically search for new common SSc–RA loci through an interdisease meta–genome-wide association (meta-GWAS) strategy. Methods: The study was designed as a meta-analysis combining GWAS data sets of patients with SSc and patients with RA, using a strategy that allowed identification of loci with both same-direction and opposite-direction allelic effects. The top single-nucleotide polymorphisms were followed up in independent SSc and RA case–control cohorts. This allowed an increase in the sample size to a total of 8,830 patients with SSc, 16,870 patients with RA, and 43,393 healthy controls. Results: This cross-disease meta-analysis of the GWAS data sets identified several loci with nominal association signals (P < 5 × 10−6) that also showed evidence of association in the disease-specific GWAS scans. These loci included several genomic regions not previously reported as shared loci, as well as several risk factors that were previously found to be associated with both diseases. Follow-up analyses of the putatively new SSc–RA loci identified IRF4 as a shared risk factor for these 2 diseases (Pcombined = 3.29 × 10−12). Analysis of the biologic relevance of the known SSc–RA shared loci identified the type I interferon and interleukin-12 signaling pathways as the main common etiologic factors. Conclusion: This study identified a novel shared locus, IRF4, for the risk of SSc and RA, and highlighted the usefulness of a cross-disease GWAS meta-analysis strategy in the identification of common risk loci.
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| 10. |
- Peytrignet, Sébastien, et al.
(author)
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Disability, fatigue, pain and their associates in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study.
- 2018
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In: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 57:2, s. 370-381
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Journal article (peer-reviewed)abstract
- Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features.Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined.The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (s.d.) HAQ-DI 1.1 (0.83)], with 'grip' and 'activity' being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (ρ = 0.34, P < 0.0001 and ρ = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (ρ = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (ρ = 0.40, P < 0.0001), decreasing hand function (ρ = 0.57, P < 0.0001) and increasing fatigue (ρ = -0.53, P < 0.0001).The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability.
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| 11. |
- Spierings, Julia, et al.
(author)
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A randomised, open-label trial to assess the optimal treatment strategy in early diffuse cutaneous systemic sclerosis : The UPSIDE study protocol
- 2021
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In: BMJ Open. - : BMJ. - 2044-6055. ; 11:3
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Journal article (peer-reviewed)abstract
- Introduction Systemic sclerosis (SSc) is a chronic, autoimmune connective tissue disease associated with high morbidity and mortality, especially in diffuse cutaneous SSc (dcSSc). Currently, there are several treatments available in early dcSSc that aim to change the disease course, including immunosuppressive agents and autologous haematopoietic stem cell transplantation (HSCT). HSCT has been adopted in international guidelines and is offered in current clinical care. However, optimal timing and patient selection for HSCT are still unclear. In particular, it is unclear whether HSCT should be positioned as upfront therapy or rescue treatment for patients refractory to immunosuppressive therapy. We hypothesise that upfront HSCT is superior and results in lower toxicity and lower long-term medical costs. Therefore, we propose this randomised trial aiming to determine the optimal treatment strategy for early dcSSc by comparing two strategies used in standard care: (1) upfront autologous HSCT versus (2) immunosuppressive therapy (intravenous cyclophosphamide pulse therapy followed by mycophenolate mofetil) with rescue HSCT in case of treatment failure. Methods and analysis The UPSIDE (UPfront autologous hematopoietic Stem cell transplantation vs Immunosuppressive medication in early DiffusE cutaneous systemic sclerosis) study is a multicentre, randomised, open-label, controlled trial. In total, 120 patients with early dcSSc will be randomised. The primary outcome is event-free survival at 2 years after randomisation. Secondary outcomes include serious adverse events, functional status and health-related quality of life. We will also evaluate changes in nailfold capillaroscopy pattern, pulmonary function, cardiac MR and high-resolution CT of the chest. Follow-up visits will be scheduled 3-monthly for 2 years and annually in the following 3 years. Ethics and dissemination The study was approved by the Dutch Central Committee on Research Concerning Human Subjects (NL72607.041.20). The results will be disseminated through patient associations and conventional scientific channels. Trial registration numbers NCT04464434; NL 8720.
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| 12. |
- Bossini-Castillo, Lara, et al.
(author)
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Confirmation of association of the macrophage migration inhibitory factor gene with systemic sclerosis in a large European population.
- 2011
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In: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 50, s. 1976-1981
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Journal article (peer-reviewed)abstract
- Objectives. The aim of this study was to confirm the implication of macrophage migration inhibitory factor (MIF) gene in SSc susceptibility or clinical phenotypes in a large European population.Methods. A total of 3800 SSc patients and 4282 healthy controls of white Caucasian ancestry from eight different European countries were included in the study. The MIF -173 single nucleotide polymorphism (SNP) was selected as genetic marker and genotyped using Taqman 5' allelic discrimination assay.Results. The MIF -173 SNP showed association with SSc [P = 0.04, odds ratio (OR) = 1.10, 95% CI 1.00, 1.19]. Analysis of the MIF -173 polymorphism according to SSc clinical phenotype revealed that the frequency of the -173*C allele was significantly higher in the dcSSc group compared with controls (P = 5.30E-03, OR = 1.21, 95% CI 1.07, 1.38). Conversely, the frequency of the MIF -173*C allele was significantly underrepresented in the lcSSc group compared with dcSSc patients, supporting previous findings [(P = 0.04, OR = 0.86, 95% CI 0.75, 0.99); meta-analysis including previous results (P = 0.005, OR = 0.83, 95% CI 0.73, 0.94)].Conclusion. Our results confirm the role of MIF -173 promoter polymorphism in SSc, and provide evidence of a strong association with the dcSSc subgroup of patients. Hence, the MIF -173 variant is confirmed as a promising clinical phenotype genetic marker.
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| 13. |
- Bossini-Castillo, Lara, et al.
(author)
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KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor
- 2012
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In: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 14:6
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Journal article (peer-reviewed)abstract
- Introduction: Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort. Methods: The 2,343 SSc cases (179 PAH positive, confirmed by right-heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single-nucleotide polymorphism (SNP) was genotyped by using a TaqMan SNP genotyping assay. Results: Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (for example, limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH-positive group. The comparison of PAH-positive patients with PAH-negative patients showed no significant differences among patients. Conclusions: Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients.
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| 14. |
- Smith, Vanessa, et al.
(author)
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Standardisation of nailfold capillaroscopy for the assessment of patients with Raynaud's phenomenon and systemic sclerosis
- 2020
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In: Autoimmunity Reviews. - : Elsevier BV. - 1568-9972. ; 19:3
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Research review (peer-reviewed)abstract
- Capillaroscopy is a non-invasive and safe tool which allows the evaluation of the morphology of the microcirculation. Since its recent incorporation in the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for systemic sclerosis together with its assessed role to monitor disease progression, capillaroscopy became a ‘mainstream’ investigation for rheumatologists. Given its increasing use by a variety of physicians internationally both in daily practice to differentiate primary from secondary Raynaud's phenomenon, as well as in research context to predict disease progression and monitor treatment effects, standardisation in capillaroscopic image acquisition and analysis seems paramount. To step forward to this need, experts in the field of capillaroscopy/microcirculation provide in this very consensus paper their view on image acquisition and analysis, different capillaroscopic techniques, normal and abnormal capillaroscopic characteristics and their meaning, scoring systems and reliability of image acquisition and interpretation.
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| 15. |
- Tyndall, Anthony J., et al.
(author)
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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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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 69:10, s. 1809-1815
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Journal article (peer-reviewed)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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| 16. |
- van den Hombergh, Wieneke M.T., et al.
(author)
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Prediction of organ involvement and survival in systemic sclerosis patients in the first 5 years from diagnosis
- 2020
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In: Journal of Scleroderma and Related Disorders. - : SAGE Publications. - 2397-1983 .- 2397-1991. ; 5:1, s. 57-65
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Journal article (peer-reviewed)abstract
- Background: Organ involvement often occurs in early systemic sclerosis and has been related to premature death. Identifying patients at diagnosis at risk of developing early organ involvement would be useful to optimize screening and management strategies. Objective: To develop prediction models for the 5-year development of interstitial lung disease, pulmonary arterial hypertension and death. Methods: A European multicentre inception cohort was created. For modelling, predefined clinical variables with known predictive value at diagnosis were used. Univariate and multivariate regression analysis were done to select baseline predictors and build the prediction models. The models were tested using the area under the receiver operating characteristic curve comparing observed and expected frequencies. Results: Of 735 patients, 23% developed interstitial lung disease, 8% developed pulmonary arterial hypertension 12% died. The interstitial lung disease model included diffuse cutaneous systemic sclerosis (OR = 1.8), systemic sclerosis disease duration < 3 years (OR = 1.4), puffy fingers (OR = 1.6), and anti-topoisomerase-I-antibodies (OR = 1.8). The pulmonary arterial hypertension model included age > 65 years (OR = 3.2), forced vital capacity < 70% (OR = 2.5) and diffusing capacity of the lung for carbon monoxide < 55% (OR = 1.9). Death was predicted best by age > 65 years (OR = 4.1), male gender (OR = 1.9), no anti-centromere antibodies (OR = 0.5), proteinuria (OR = 1.9), forced vital capacity < 70% (OR = 1.8) and pulmonary arterial hypertension at diagnosis (OR = 10.1). The area under the receiver operating characteristic was 0.66 (95% CI 0.64–0.67), 0.66 (95% CI 0.64–0.68) and 0.70 (95% CI 0.69–0.72), respectively. Conclusion: We have shown that it is possible to predict interstitial lung disease, pulmonary arterial hypertension and death using established variables already available at the moment of systemic sclerosis diagnosis. Discriminatory performance of the models was suboptimal. Further research including new variables is necessary to improve performance.
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