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In: Rheumatology, Oxford University Press (OUP), Vol. 50, No. Supplement 3 ( 2011-04-01), p. iii93-iii104

Type of Medium: Online Resource

ISSN: 1462-0324 , 1462-0332

URL: Article

DOI: 10.1093/rheumatology/ker029

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2011

detail.hit.zdb_id: 1474143-X

In: Rheumatology, Oxford University Press (OUP), Vol. 62, No. SI ( 2023-02-06), p. SI54-SI63

Abstract: The early trajectory of skin fibrosis provides insights into the disease course of systemic sclerosis (SSc) including mortality; however, little is known about late skin fibrosis. The aims of our study were to ascertain the prevalence and characteristics of late skin fibrosis in SSc. Methods We developed and tested three conceptual scenarios of late ( & gt;5 years after first non-RP feature) skin fibrosis including new worsening of skin disease, and failure to improve after worsening within 5-year window. We defined skin worsening as change in modified Rodnan skin score (mRSS) ≥5 units or ≥25%. Using strict inclusion criteria including complete mRSS, we identified 1,043 (out of 19 115) patients within the EUSTAR database for our analysis. We further restricted analysis within 887 (out of 1043) patients who had lcSSc or dcSSc at baseline. Results One-fifth of patients among the whole cohort (n = 208/1043, 19.9%) experienced mRSS worsening, including in patients with lcSSc or dcSSc at baseline (n = 193/887, 21.8%). This was largely due to new skin worsening after the 5-year window or failure to improve with worsening within the 5-year window. Patients with lower baseline mRSS and lcSSc were more likely to develop late skin fibrosis. Anti-Scl-70 was associated with progression from baseline lcSSc to dcSSc, and anticentromere was protective. Conclusions Late skin fibrosis is not uncommon in SSc. We have identified different patterns relevant to clinical practice and trial design. Late skin fibrosis is a neglected manifestation of SSc and warrants further investigation including to determine clinical outcomes and optimal therapeutic strategy.

Type of Medium: Online Resource

ISSN: 1462-0324 , 1462-0332

URL: Article

DOI: 10.1093/rheumatology/keac363

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2023

detail.hit.zdb_id: 1474143-X

In: Annals of the Rheumatic Diseases, BMJ, Vol. 80, No. Suppl 1 ( 2021-06), p. 385-386

Abstract: In SSc, ILD is a major cause of morbidity and mortality. High resolution computed tomography (HRCT) is the gold standard for the diagnosis. Predictors of ILD onset are eagerly awaited to improve SSc-ILD management. Pulmonary function test (PFTs) are routinely performed to measure lung function changes. Objectives: Our aim was to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) in predicting the development of SSc-ILD. Methods: The longitudinal data of DLCO, FVC and ILD on HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t 0 ), after 12 (±4) (t 1 ) and 24 (±4) (t 2 ) months. Patients with negative HRCT for any sign of ILD both at t 0 and t 1 were included. Patients who presented or developed pulmonary hypertension during the study period were excluded. At baseline, demographic data, disease duration from Raynaud’s onset, disease subsets, autoantibodies and other laboratory and instrumental data were recorded. Results: 474/17805 patients were eligible for the study (403 females, 71 males): 26.0% dcSSc, 58.3% lcSSc, 220 (48.0%) patients with positive anticentromere antibodies (ACA) and 117 (25.4%) with positive antitopoisomerase I antibodies (Topo-I abs). Among all enrolled patients, 46 (9.7%) developed HRCT signs of ILD at t 2 . Patients with Topo-I abs showed an association with ILD development at t 2 (16.7% vs 7.8%, p=0.0031), contrarily ACA positive patients were negatively associated with ILD appearance after 2 years of follow-up (4.4% vs 14.4%, p=0.0001). Positive t 2 HRCT patients had a significant lower value of DLCO and FVC at all three assessments when compared to patients with a negative HRCT at t 2 (Table 1) and both t 0 DLCO and FVC values negatively correlated with ILD development (Table 1). The mean t 0 to t 1 change (Δ) of DLCO in patients with negative t 2 HRTC and positive t 2 HRCT were -0.5 (±12.6) and -1.0 (±15.1), respectively. The mean t 0 to t 1 ΔFVC in patients with negative t 2 HRTC and positive t 2 HRCT were -0.2 (±10.6) and 0.1 (±11.5), respectively. None of them predicted the appearance of ILD at t 2 (ΔDLCO: OR (IC) 0.997 (0.97-1.02), p=0.8024; ΔFVC OR (IC) 1.002 (0.97-1.03), p=0.8664). The data showed an association between t 0 DLCO value 〈 80% and ILD appearance after 2 years of follow-up [OR(IC): 3.09(1.49-6.40), p=0.0023]. Such association was not observed for t 0 FVC value 〈 80% [OR(IC): 1.95(0.81-4.68), p=0.1329]. The predictive capability of t 0 DLCO 〈 80% was moderate but stronger than FVC 〈 80% [AU ROC: 0.62 (0.56-0.69), 0.53 (0.48-0.59) respectively, p=0.0205]. Conclusion: Our data suggest that an impaired baseline DLCO ( 〈 80%) may have a predictive value for the development of ILD on HRCT after 2 years of follow-up. Further rigorous prospective studies are warranted to understand the role of DLCO evaluation in the course of SSc. Table 1. DLCO and FVC values at t 0 , t 1 and t 2 values in patients with positive or negative HRCT for ILD at t 2 and their statistical differences. Patients without ILD at t2 (mean±SD) Patients with ILD at t2 (mean±SD) OR (95%CL) p-value DLCO at t 0 79.0 ± 16.6 69.9 ± 17.4 0.97 (0.95 - 0.99) 0.0006 DLCO at t 1 78.4 ± 16.8 68.9 ± 18.6 0.97 (0.95 - 0.98) 0.0005 DLCO at t 2 78.0 ± 17.0 65.1 ± 19.1 0.95 (0.93 - 0.97) 〈 0.0001 FVC at t 0 102.2 ± 17.3 94.6 ± 16.2 0.97 (0.96 - 0.99) 0.0052 FVC at t 1 101.9 ± 17.9 94.7 ± 16.5 0.98 (0.96 - 0.99) 0.0092 FVC at t 2 101.6 ± 17.6 94.5 ± 20.0 0.98 (0.96 - 1) 0.0126 Disclosure of Interests: Gemma Lepri: None declared, Cosimo Bruni Speakers bureau: CB reports personal fees from Actelion, personal fees from Eli Lilly, Grant/research support from: CB reports personal fees from Actelion, personal fees from Eli Lilly, grants from European Scleroderma Trial and Research (EUSTAR) group, grants from New Horizon Fellowship, grants from Foundation for Research in Rheumatology (FOREUM), grants from Fondazione Italiana per la Ricerca sull’Artrite (FIRA), outside the submitted work, Lorenzo Tofani: None declared, Alberto Moggi Pignone: None declared, Martina Orlandi: None declared, Tomasetti Sara Speakers bureau: Speaker’s fees for Roche and Boehringer Ingelheim, Mike Hughes: None declared, Francesco Del Galdo: None declared, Rosaria Irace: None declared, Oliver Distler Grant/research support from: OD (last three years) has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Valeria Riccieri: None declared, Yannick Allanore Speakers bureau: YA received personal fees from Boehringer, Sanofi, Menarini and Medsenic and grants from Alpine with regards to the management of systemic sclerosis, Grant/research support from: YA received personal fees from Boehringer, Sanofi, Menarini and Medsenic and grants from Alpine with regards to the management of systemic sclerosis, Ana Maria Gheorghiu: None declared, Elise Siegert: None declared, Jeska de Vries-Bouwstra: None declared, Eric Hachulla: None declared, Mohammed Tikly: None declared, Nemanja Damjanov: None declared, Francois Spertini: None declared, Luc Mouthon: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: AMHV: received consulting fees from Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche; and grants from Boehringer Ingelheim., Consultant of: AMHV: received consulting fees from Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche; and grants from Boehringer Ingelheim., Grant/research support from: AMHV: received consulting fees from Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche; and grants from Boehringer Ingelheim., Armando Gabrielli: None declared, Serena Guiducci: None declared, Marco Matucci-Cerinic Speakers bureau: has received consulting fees or honorarium from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche, Grant/research support from: has received consulting fees or honorarium from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche, Daniel Furst: None declared, Silvia Bellando Randone: None declared

Type of Medium: Online Resource

ISSN: 0003-4967 , 1468-2060

URL: Article

DOI: 10.1136/annrheumdis-2021-eular.3027

Language: English

Publisher: BMJ

Publication Date: 2021

detail.hit.zdb_id: 1481557-6

In: South African Medical Journal, South African Medical Association NPC, Vol. 104, No. 5 ( 2014-04-01), p. 325-

Type of Medium: Online Resource

ISSN: 2078-5135

URL: Article

DOI: 10.7196/SAMJ.8178

Language: Unknown

Publisher: South African Medical Association NPC

Publication Date: 2014

detail.hit.zdb_id: 2260334-7

detail.hit.zdb_id: 2121030-5

In: Annals of the Rheumatic Diseases, BMJ, Vol. 69, No. 10 ( 2010-10-01), p. 1809-1815

Type of Medium: Online Resource

ISSN: 0003-4967

URL: Article

DOI: 10.1136/ard.2009.114264

Language: English

Publisher: BMJ

Publication Date: 2010

detail.hit.zdb_id: 1481557-6

In: Rheumatology, Oxford University Press (OUP), Vol. 39, No. 6 ( 2000-6), p. 655-665

Type of Medium: Online Resource

ISSN: 1462-0332 , 1462-0324

URL: Article

DOI: 10.1093/rheumatology/39.6.655

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2000

detail.hit.zdb_id: 1474143-X

In: Annals of the Rheumatic Diseases, BMJ, Vol. 71, No. 3 ( 2012-03), p. 463-469

Abstract: High serum interferon α (IFNα) activity is a heritable risk factor for systemic lupus erythematosus (SLE). Auto-antibodies found in SLE form immune complexes which can stimulate IFNα production by activating endosomal Toll-like receptors and interferon regulatory factors (IRFs), including IRF5. Genetic variation in IRF5 is associated with SLE susceptibility; however, it is unclear how IRF5 functional genetic elements contribute to human disease. Methods 1034 patients with SLE and 989 controls of European ancestry, 555 patients with SLE and 679 controls of African–American ancestry, and 73 patients with SLE of South African ancestry were genotyped at IRF5 polymorphisms, which define major haplotypes. Serum IFNα activity was measured using a functional assay. Results In European ancestry subjects, anti-double-stranded DNA (dsDNA) and anti-Ro antibodies were each associated with different haplotypes characterised by a different combination of functional genetic elements (OR 〉 2.56, p 〈 1.9×10 −14 for both). These IRF5 haplotype-auto-antibody associations strongly predicted higher serum IFNα in patients with SLE and explained 〉 70% of the genetic risk of SLE due to IRF5. In African–American patients with SLE a similar relationship between serology and IFNα was observed, although the previously described European ancestry-risk haplotype was present at admixture proportions in African–American subjects and absent in African patients with SLE. Conclusions The authors define a novel risk haplotype of IRF5 that is associated with anti-dsDNA antibodies and show that risk of SLE due to IRF5 genotype is largely dependent upon particular auto-antibodies. This suggests that auto-antibodies are directly pathogenic in human SLE, resulting in increased IFNα in cooperation with particular combinations of IRF5 functional genetic elements. SLE is a systemic autoimmune disorder affecting multiple organ systems including the skin, musculoskeletal, renal and haematopoietic systems. Humoral autoimmunity is a hallmark of SLE, and patients frequently have circulating auto-antibodies directed against dsDNA, as well as RNA binding proteins (RBP). Anti-RBP autoantibodies include antibodies which recognize Ro, La, Smith (anti-Sm), and ribonucleoprotein (anti-nRNP), collectively referred to as anti-retinol-binding protein). Anti-retinol-binding protein and anti-dsDNA auto-antibodies are rare in the healthy population.1 These auto-antibodies can be present in sera for years preceding the onset of clinical SLE illness2 and are likely pathogenic in SLE.3 4

Type of Medium: Online Resource

ISSN: 0003-4967 , 1468-2060

URL: Article

DOI: 10.1136/annrheumdis-2011-200463

Language: English

Publisher: BMJ

Publication Date: 2012

detail.hit.zdb_id: 1481557-6

In: Annals of the Rheumatic Diseases, BMJ, Vol. 72, No. Suppl 3 ( 2013-06), p. A375.3-A376

Type of Medium: Online Resource

ISSN: 0003-4967 , 1468-2060

URL: Article

DOI: 10.1136/annrheumdis-2013-eular.1150

Language: English

Publisher: BMJ

Publication Date: 2013

detail.hit.zdb_id: 1481557-6

In: Health and Quality of Life Outcomes, Springer Science and Business Media LLC, Vol. 17, No. 1 ( 2019-12)

Type of Medium: Online Resource

ISSN: 1477-7525

URL: Article

DOI: 10.1186/s12955-019-1132-y

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2019

detail.hit.zdb_id: 2098765-1

In: BMC Musculoskeletal Disorders, Springer Science and Business Media LLC, Vol. 16, No. 1 ( 2015-12)

Type of Medium: Online Resource

ISSN: 1471-2474

URL: Article

DOI: 10.1186/s12891-015-0587-1

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2015

detail.hit.zdb_id: 2041355-5