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  1. Article ; Online: Treatment efficacy in secondary Raynaud's phenomenon.

    Pauling, John D / Smith, Theresa / Domsic, Robyn T / Frech, Tracy M

    The Lancet. Rheumatology

    2024  Volume 2, Issue 3, Page(s) e132

    Language English
    Publishing date 2024-01-23
    Publishing country England
    Document type Letter
    ISSN 2665-9913
    ISSN (online) 2665-9913
    DOI 10.1016/S2665-9913(20)30030-8
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  2. Article ; Online: Preventative Care in Scleroderma: What Is the Best Approach to Bone Health and Cancer Screening?

    Calderon, Leonardo Martin / Domsic, Robyn T / Shah, Ami A / Pope, Janet E

    Rheumatic diseases clinics of North America

    2024  Volume 49, Issue 2, Page(s) 411–423

    Abstract: Systemic sclerosis (SSc) is a rare multisystem autoimmune disease characterized by fibrosis, vasculopathy, and autoimmunity. Lesser known complications inherent to SSc, such as malignancies and osteoporosis, can lead to decreased quality of life and ... ...

    Abstract Systemic sclerosis (SSc) is a rare multisystem autoimmune disease characterized by fibrosis, vasculopathy, and autoimmunity. Lesser known complications inherent to SSc, such as malignancies and osteoporosis, can lead to decreased quality of life and increased morbidity and mortality. Patients with SSc have a greater risk of developing malignancies than the general population. In addition, they are more likely to be vitamin D deficient and are at great risk of osteoporosis-related fractures. However, these complications can be addressed through preventative measures. The purpose of this review is to provide clinicians with an approach to bone health and cancer screening in SSc.
    MeSH term(s) Humans ; Bone Density ; Early Detection of Cancer ; Quality of Life ; Scleroderma, Systemic/complications ; Scleroderma, Systemic/diagnosis ; Osteoporosis/diagnosis ; Osteoporosis/etiology ; Osteoporosis/prevention & control ; Osteoporotic Fractures ; Neoplasms/diagnosis ; Neoplasms/epidemiology ; Neoplasms/prevention & control
    Language English
    Publishing date 2024-02-06
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 92118-x
    ISSN 1558-3163 ; 0889-857X
    ISSN (online) 1558-3163
    ISSN 0889-857X
    DOI 10.1016/j.rdc.2023.01.011
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  3. Article ; Online: Single-cell transcriptomes and chromatin accessibility of endothelial cells unravel transcription factors associated with dysregulated angiogenesis in systemic sclerosis.

    Huang, Mengqi / Tabib, Tracy / Khanna, Dinesh / Assassi, Shervin / Domsic, Robyn / Lafyatis, Robert

    Annals of the rheumatic diseases

    2024  

    Abstract: Objectives: Vasculopathy emerges early in systemic sclerosis (SSc) and links to endothelial cell (EC) injury and angiogenesis. Understanding EC transcriptomes and epigenomes is crucial for unravelling the mechanisms involved.: Methods: Transcriptomes ...

    Abstract Objectives: Vasculopathy emerges early in systemic sclerosis (SSc) and links to endothelial cell (EC) injury and angiogenesis. Understanding EC transcriptomes and epigenomes is crucial for unravelling the mechanisms involved.
    Methods: Transcriptomes and chromatin accessibility were assessed by single-cell RNA sequencing and single-nucleus transposase-accessible chromatin sequencing. Immunofluorescent staining of skin and proteomics assay were employed to confirm the altered SSc EC phenotypes. Gain-of-function assay was used to evaluate the effects of ETS transcription factors on human dermal ECs (hDECs).
    Results: Both control and SSc ECs shared transcriptomic signatures of vascular linages (arterial, capillary and venous ECs) and lymphatic ECs. Arterial ECs in SSc showed reduced number and increased expression of genes associated with apoptosis. Two distinct EC subpopulations, tip and proliferating ECs, were markedly upregulated in SSc, indicating enhanced proangiogenic and proliferative activities. Molecular features of aberrant SSc-ECs were associated with disease pathogenesis and clinical traits of SSc, such as skin fibrosis and digital ulcers. Ligand-receptor analysis demonstrated altered intercellular networks of SSc EC subpopulations with perivascular and immune cells. Furthermore, the integration of open chromatin profiles with transcriptomic analysis suggested an increased accessibility of regulatory elements for ETS family transcription factors in SSc ECs. Overexpression of ETS genes in hDECs suggested ELK4, ERF and ETS1 may orchestrate arterial apoptosis and dysregulated angiogenesis in SSc.
    Conclusions: This study unveils transcriptional and chromatin alterations in driving endovascular dysregulation in SSc, proposing ELK4, ERF and ETS1 as novel targets in ECs for addressing vascular complications in the condition.
    Language English
    Publishing date 2024-05-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 7090-7
    ISSN 1468-2060 ; 0003-4967
    ISSN (online) 1468-2060
    ISSN 0003-4967
    DOI 10.1136/ard-2023-225415
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  4. Article ; Online: Preventative Care in Scleroderma: What Is the Best Approach to Vaccination?

    Calderon, Leonardo Martin / Pope, Janet E / Shah, Ami A / Domsic, Robyn T

    Rheumatic diseases clinics of North America

    2023  Volume 49, Issue 2, Page(s) 401–410

    Abstract: Systemic sclerosis (SSc) is a rare multisystem autoimmune disease characterized by fibrosis, vasculopathy, and autoimmunity. There are multiple complications inherent to SSc and its management. One of these complications is increased infection risk, ... ...

    Abstract Systemic sclerosis (SSc) is a rare multisystem autoimmune disease characterized by fibrosis, vasculopathy, and autoimmunity. There are multiple complications inherent to SSc and its management. One of these complications is increased infection risk, which can lead to decreased quality of life and increased morbidity and mortality. Patients with SSc have lower vaccination rates and decreased vaccine seroconversion secondary to immunosuppressive medications compared with the general population. The purpose of this review is to provide clinicians with an approach to vaccinations in SSc.
    MeSH term(s) Humans ; Quality of Life ; Scleroderma, Systemic/complications ; Fibrosis ; Autoimmunity ; Vaccination/adverse effects
    Language English
    Publishing date 2023-04-26
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 92118-x
    ISSN 1558-3163 ; 0889-857X
    ISSN (online) 1558-3163
    ISSN 0889-857X
    DOI 10.1016/j.rdc.2023.01.012
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  5. Article: Pulmonary Arterial Hypertension In Systemic Sclerosis: Challenges In Diagnosis, Screening And Treatment.

    Saygin, Didem / Domsic, Robyn T

    Open access rheumatology : research and reviews

    2019  Volume 11, Page(s) 323–333

    Abstract: Systemic sclerosis (SSc) is a chronic, multisystem autoimmune disease characterized by vasculopathy, fibrosis and immune system activation. Pulmonary hypertension and interstitial lung disease account for majority of SSc-related deaths. Diagnosis of SSc- ... ...

    Abstract Systemic sclerosis (SSc) is a chronic, multisystem autoimmune disease characterized by vasculopathy, fibrosis and immune system activation. Pulmonary hypertension and interstitial lung disease account for majority of SSc-related deaths. Diagnosis of SSc-PAH can be challenging due to nonspecific clinical presentation which can lead to delayed diagnosis. Many screening algorithms have been developed to detect SSc-associated pulmonary arterial hypertension (SSc-PAH) in early stages. Currently used PAH-specific medications are largely extrapolated from IPAH studies due to smaller number of patients with SSc-PAH. In this review, we discuss the current state of knowledge in epidemiology and risk factors for development of SSc-PAH, and challenges and potential solutions in the diagnosis, screening and management of SSc-PAH.
    Language English
    Publishing date 2019-12-27
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 2508169-X
    ISSN 1179-156X
    ISSN 1179-156X
    DOI 10.2147/OARRR.S228234
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  6. Article ; Online: Advances in biological and targeted therapies for systemic sclerosis.

    Mulcaire-Jones, Erica / Low, Andrea Hsiu Ling / Domsic, Robyn / Whitfield, Michael L / Khanna, Dinesh

    Expert opinion on biological therapy

    2023  Volume 23, Issue 4, Page(s) 325–339

    Abstract: Introduction: Systemic sclerosis (SSc) is a severe, and often life-threatening, autoimmune disease, which causes inflammation and fibrosis of the skin and internal organs. There are currently limited effective therapeutic options for patients with SSc. ... ...

    Abstract Introduction: Systemic sclerosis (SSc) is a severe, and often life-threatening, autoimmune disease, which causes inflammation and fibrosis of the skin and internal organs. There are currently limited effective therapeutic options for patients with SSc. There are recently completed and ongoing phase 2 and 3 studies looking at biologic therapies for SSc that target the underlying pathogenesis of the disease.
    Areas covered: The purpose of this review is to describe completed and ongoing trials of different biologic therapies for the treatment of SSc. This review discusses biologic therapy directed at multiple pathways that are believed to contribute to inflammation and fibrosis in SSc including T cell, B cell, direct cytokines, and JAK signaling. Data presented is based on authors' expertise of completed and ongoing trials.
    Expert opinion: Tocilizumab and rituximab have supporting data to advocate for use in early SSc. Data from tocilizumab showed preservation of forced vital capacity (FVC) and beneficial effects on global composite measure. Recent data from different trials with rituximab in SSc (with and without interstitial lung disease) show beneficial effects on skin and FVC with good tolerability. We highlight the molecular heterogeneity in early SSc phenotype and the need to account for this in future trials.
    MeSH term(s) Humans ; Rituximab/therapeutic use ; Scleroderma, Systemic/drug therapy ; Scleroderma, Systemic/complications ; Lung Diseases, Interstitial/drug therapy ; Lung Diseases, Interstitial/etiology ; Fibrosis ; Inflammation/drug therapy
    Chemical Substances Rituximab (4F4X42SYQ6)
    Language English
    Publishing date 2023-04-26
    Publishing country England
    Document type Review ; Journal Article
    ZDB-ID 2052501-1
    ISSN 1744-7682 ; 1471-2598
    ISSN (online) 1744-7682
    ISSN 1471-2598
    DOI 10.1080/14712598.2023.2196009
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    Zs.A 6094: Show issues Location:
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  7. Article ; Online: Treatment of Polymyalgia Rheumatica by Rheumatology Providers: Analysis from the American College of Rheumatology RISE Registry.

    Sattui, Sebastian E / Xie, Fenglong / Wan, Zihan / Clinton, Cassie / Domsic, Robyn T / Curtis, Jeffrey R

    Arthritis care & research

    2023  Volume 76, Issue 2, Page(s) 259–264

    Abstract: Objective: This study describes the demographics, comorbidities, and treatment patterns in a national cohort of patients with polymyalgia rheumatica (PMR) who received care from rheumatology providers.: Methods: Patients with PMR were identified in ... ...

    Abstract Objective: This study describes the demographics, comorbidities, and treatment patterns in a national cohort of patients with polymyalgia rheumatica (PMR) who received care from rheumatology providers.
    Methods: Patients with PMR were identified in the American College of Rheumatology Rheumatology Informatics System for Effectiveness registry from 2016 to 2022. Use of glucocorticoids and immunomodulatory antirheumatic medications used as steroid-sparing agents were examined overall and in a subgroup of patients new to rheumatology practices, the majority with presumed new-onset PMR. In these new patients, multivariate logistic regressions were performed to identify factors associated with persistent glucocorticoid and steroid-sparing agent use at 12 to 24 months.
    Results: A total of 26,102 patients with PMR were identified, of which 16,703 new patients were included in the main analysis. Patients were predominantly female (55.8%) and White (46.7%), with a mean age of 72.0 years. Hypertension (81.2%), congestive heart failure (52.4%), hyperlipidemia (41.3%), and ischemic heart disease (36.0%) were the most prevalent comorbidities. At baseline, 92.3% of patients were on glucocorticoids, and only 13.1% were on a steroid-sparing agent. At 12 to 24 months, most patients remained on glucocorticoids (63.8%). Although there was an increase in use through follow-up, antirheumatic medications were prescribed only to a minority (39.0%) of patients with PMR.
    Conclusion: In this large US-based study of patients with PMR receiving rheumatology care, only a minority of patients were prescribed steroid-sparing agents during the first 24 months of follow-up; most patients remained on glucocorticoids past one year. Further identification of patients who would benefit from steroid-sparing agents and the timing of steroid-sparing agent initiation is needed.
    MeSH term(s) Humans ; Female ; United States/epidemiology ; Aged ; Male ; Polymyalgia Rheumatica/diagnosis ; Polymyalgia Rheumatica/drug therapy ; Polymyalgia Rheumatica/epidemiology ; Rheumatology ; Giant Cell Arteritis/drug therapy ; Glucocorticoids/therapeutic use ; Antirheumatic Agents/therapeutic use ; Steroids
    Chemical Substances Glucocorticoids ; Antirheumatic Agents ; Steroids
    Language English
    Publishing date 2023-10-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 645059-3
    ISSN 2151-4658 ; 0893-7524 ; 2151-464X
    ISSN (online) 2151-4658
    ISSN 0893-7524 ; 2151-464X
    DOI 10.1002/acr.25216
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    Zs.A 2446: Show issues Location:
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  8. Article ; Online: Scleroderma: the role of serum autoantibodies in defining specific clinical phenotypes and organ system involvement.

    Domsic, Robyn T

    Current opinion in rheumatology

    2014  Volume 26, Issue 6, Page(s) 646–652

    Abstract: Purpose of review: To discuss recent advances in serologic testing for systemic sclerosis (SSc)-associated antibodies with respect to the diagnosis and prognosis of the disease.: Recent findings: The importance of SSc antibodies for diagnosis has ... ...

    Abstract Purpose of review: To discuss recent advances in serologic testing for systemic sclerosis (SSc)-associated antibodies with respect to the diagnosis and prognosis of the disease.
    Recent findings: The importance of SSc antibodies for diagnosis has become increasingly recognized, as evidenced by incorporation into the 2013 American College of Rheumatology/the European League Against Rheumatism clinical classification criteria for SSc. Two new SSc-associated antibodies and their clinical associations have been described. Multiple cohort studies have reported variable antibody frequency distribution based on geography, but the clinical associations remain much the same. New associations include anti-RNA polymerase III antibodies with gastric antral vascular ectasia, and a temporal association between SSc onset and RNA polymerase III antibodies.
    Summary: The role and associations of SSc-associated antibodies for diagnosis and internal organ involvement are becoming increasingly accepted.
    MeSH term(s) Autoantibodies/blood ; Humans ; Phenotype ; Prognosis ; Scleroderma, Systemic/blood ; Scleroderma, Systemic/immunology
    Chemical Substances Autoantibodies
    Language English
    Publishing date 2014-09-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1045317-9
    ISSN 1531-6963 ; 1040-8711
    ISSN (online) 1531-6963
    ISSN 1040-8711
    DOI 10.1097/BOR.0000000000000113
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    Zs.A 3028: Show issues Location:
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  9. Article ; Online: Antibody response to graded dosing of coronavirus disease 2019 messenger RNA vaccines after allergic reaction to first dose.

    Van Meerbeke, Sara W / Fajt, Merritt L / Marini, Rachel V / Domsic, Robyn T / Petrov, Andrej A

    Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology

    2022  Volume 129, Issue 3, Page(s) 373–374

    MeSH term(s) Antibody Formation ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Humans ; Hypersensitivity ; RNA, Messenger ; mRNA Vaccines
    Chemical Substances COVID-19 Vaccines ; RNA, Messenger ; mRNA Vaccines
    Language English
    Publishing date 2022-05-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1228189-x
    ISSN 1534-4436 ; 0003-4738 ; 1081-1206
    ISSN (online) 1534-4436
    ISSN 0003-4738 ; 1081-1206
    DOI 10.1016/j.anai.2022.05.004
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  10. Article ; Online: The Impact of Radiation Therapy in Patients with Systemic Sclerosis and Head and Neck Cancer.

    Wallwork, Rachel S / Page, Brandi R / Wigley, Fredrick M / Hummers, Laura K / Paik, Julie J / McMahan, Zsuzsanna / Domsic, Robyn T / Shah, Ami A

    Practical radiation oncology

    2024  

    Abstract: Objective: Systemic sclerosis (SSc) is considered a relative, or in some cases, absolute contraindication for radiation therapy for various cancers; however, radiation is the standard of care and the best option for tumor control for locally advanced ... ...

    Abstract Objective: Systemic sclerosis (SSc) is considered a relative, or in some cases, absolute contraindication for radiation therapy for various cancers; however, radiation is the standard of care and the best option for tumor control for locally advanced head and neck (H&N) cancer. We present a case series to document postradiation outcomes in patients with SSc and H&N cancer.
    Methods: Patients with SSc and H&N cancer treated with radiation were identified from the Johns Hopkisn Scleroderma Center and the University of Pittsburgh Scleroderma Center research registries. Through chart review, we identified whether patients developed predetermined acute and late side effects or changes in SSc activity from radiation. We further describe therapies used to prevent and treat radiation-induced fibrosis.
    Results: Thirteen patients with SSc who received radiation therapy for H&N cancer were included. Five-year survival was 54%. Nine patients (69%) developed local radiation-induced skin thickening, and 7 (54%) developed reduced neck range of motion. Two patients required long-term percutaneous endoscopic gastrostomy use due to radiation therapy complications. No patients required respiratory support related to radiation therapy. Regarding SSc disease activity among the patients with established SSc before radiation therapy, none experienced interstitial lung disease progression in the postradiation period. After radiation, one patient had worsening skin disease outside the radiation field; however, this patient was within the first year of SSc, when progressive skin disease is expected. Treatment strategies to prevent radiation fibrosis included pentoxifylline, amifostine, and vitamin E, while intravenous immunoglobulin (IVIG) was used to treat it.
    Conclusion: Although some patients with SSc who received radiation for H&N cancer developed localized skin thickening and reduced neck range of motion, systemic flares of SSc were uncommon. This observational study provides evidence to support the use of radiation therapy for H&N cancer in patients with SSc when radiation is the best treatment option.
    Language English
    Publishing date 2024-05-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2655748-4
    ISSN 1879-8519 ; 1879-8500
    ISSN (online) 1879-8519
    ISSN 1879-8500
    DOI 10.1016/j.prro.2024.04.015
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