The Rheumatologist
COVID-19 NewsACR Convergence
  • Connect with us:
  • Facebook
  • Twitter
  • LinkedIn
  • YouTube
  • Feed
  • Home
  • Conditions
    • Rheumatoid Arthritis
    • SLE (Lupus)
    • Crystal Arthritis
      • Gout Resource Center
    • Spondyloarthritis
    • Osteoarthritis
    • Soft Tissue Pain
    • Scleroderma
    • Vasculitis
    • Systemic Inflammatory Syndromes
    • Guidelines
  • Resource Centers
    • Axial Spondyloarthritis Resource Center
    • Gout Resource Center
    • Psoriatic Arthritis Resource Center
    • Rheumatoid Arthritis Resource Center
    • Systemic Lupus Erythematosus Resource Center
  • Drug Updates
    • Biologics & Biosimilars
    • DMARDs & Immunosuppressives
    • Topical Drugs
    • Analgesics
    • Safety
    • Pharma Co. News
  • Professional Topics
    • Ethics
    • Legal
    • Legislation & Advocacy
    • Career Development
      • Certification
      • Education & Training
    • Awards
    • Profiles
    • President’s Perspective
    • Rheuminations
    • Interprofessional Perspective
  • Practice Management
    • Billing/Coding
    • Quality Assurance/Improvement
    • Workforce
    • Facility
    • Patient Perspective
    • Electronic Health Records
    • Apps
    • Information Technology
    • From the College
    • Multimedia
      • Audio
      • Video
  • Resources
    • Issue Archives
    • ACR Convergence
      • Gout Resource Center
      • Axial Spondyloarthritis Resource Center
      • Psoriatic Arthritis
      • Abstracts
      • Meeting Reports
      • ACR Convergence Home
    • American College of Rheumatology
    • ACR ExamRheum
    • Research Reviews
    • ACR Journals
      • Arthritis & Rheumatology
      • Arthritis Care & Research
      • ACR Open Rheumatology
    • Rheumatology Image Library
    • Treatment Guidelines
    • Rheumatology Research Foundation
    • Events
  • About Us
    • Mission/Vision
    • Meet the Authors
    • Meet the Editors
    • Contribute to The Rheumatologist
    • Subscription
    • Contact
  • Advertise
  • Search
You are here: Home / Articles / Targeted Therapy for Scleroderma Fibrosis

Targeted Therapy for Scleroderma Fibrosis

October 11, 2016 • By Sara R. Schoenfeld, MD, & Flavia V. Castelino, MD

  • Tweet
  • Email
Print-Friendly Version / Save PDF
CNK02 / shutterstock.com

CNK02 / shutterstock.com

Scleroderma, or systemic sclerosis (SSc), is an autoimmune disease characterized by vasculopathy and fibrosis. Although relatively rare, with a prevalence in North America of approximately 300 per 1 million people, SSc is associated with significant morbidity and high rates of mortality.1 Patients with scleroderma have four times greater mortality than age- and sex-matched controls, with the majority of deaths related to interstitial lung disease (ILD) and pulmonary hypertension (PH).2 Predicting disease course at baseline is, therefore, of great importance, with implications for the choice of therapy. In 2013, the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) developed new classification criteria for SSc.3 These criteria allow for the inclusion of patients with early manifestations of the disease, such as puffy fingers, Raynaud’s phenomenon, nailfold capillary changes and specific auto-antibodies.

You Might Also Like
  • From the Expert: New Advances in Treatment of Systemic Scleroderma
  • Studies Show Promise for Scleroderma Therapy and Prediction of Progressing Disease
  • The ACR’s State-of-the-Art Clinical Symposium: Patients with Scleroderma, Lung Disease May Benefit from Aggressive Therapy
Explore This Issue
October 2016

Identification of patients in the very early stages of disease is useful in helping establish care with a rheumatologist at a specialized center and for the implementation of treatment at earlier stages.

ad goes here:advert-1
ADVERTISEMENT
SCROLL TO CONTINUE

Pathogenesis

Historically, the pathogenesis of scleroderma has been poorly understood, but advances in recent years have shed light on some of the molecular and cellular pathways involved in the disease. Although not fully understood, the initial insult is thought to be vascular in nature, with injury to the vascular endothelial cells.

Damage to the endothelium and platelet aggregation result in the release of reactive oxygen species (ROS) and vasoactive mediators, such as thrombin, thromboxane and endothelin-1 (see Figure 1). Activation of the immune system leads to the generation of inflammatory cytokines and growth factors.

ad goes here:advert-2
ADVERTISEMENT
SCROLL TO CONTINUE

The central mediator of SSc fibrosis is the pleotropic cytokine, transforming growth factor-β (TGF-β). At baseline, TGF-β is in a latent form and must be activated by αv integrins. Active TGF-β then stimulates fibroblasts to proliferate and convert to myofibroblasts, which are responsible for laying down the extracellular matrix (ECM). Interleukin 6 (IL-6) is also secreted by activated immune cells and plays a role in fibroblast accumulation. Previous data suggest IL-6 levels are increased in skin and serum of patients with SSc and that elevated IL-6 levels predict severity of skin involvement in SSc.4

The bioactive lipid mediators, lyso­phosphatidic acid (LPA) and sphingo­sine-1-phosphate (S1P), are also implicated in SSc pathogenesis. Selective deletion of the LPA1 receptor in mouse models of fibrosis leads to a marked decrease in both lung and skin fibrosis.5,6 The interplay of these mediators leads to progressive ECM accumulation and structural remodeling, which causes further activation of fibroblasts and results in the progression of fibrosis.

Pages: 1 2 3 4 5 6 | Single Page

Filed Under: Conditions, Scleroderma Tagged With: Autoimmune disease, fibrosis, Research, rheumatologist, Scleroderma, Systemic sclerosis, therapy, vasculopathyIssue: October 2016

You Might Also Like:
  • From the Expert: New Advances in Treatment of Systemic Scleroderma
  • Studies Show Promise for Scleroderma Therapy and Prediction of Progressing Disease
  • The ACR’s State-of-the-Art Clinical Symposium: Patients with Scleroderma, Lung Disease May Benefit from Aggressive Therapy
  • 2014 ACR/ARHP Annual Meeting: Fibrotic Complications of Scleroderma

Meeting Abstracts

Browse and search abstracts from the ACR Convergence and ACR/ARP Annual Meetings going back to 2012.

Visit the Abstracts site »

Rheumatology Research Foundation

The Foundation is the largest private funding source for rheumatology research and training in the U.S.

Learn more »

ACR Convergence

Don’t miss rheumatology’s premier scientific meeting for anyone involved in research or the delivery of rheumatologic care or services.

Visit the ACR Convergence site »

The Rheumatologist newsmagazine reports on issues and trends in the management and treatment of rheumatic diseases. The Rheumatologist reaches 11,500 rheumatologists, internists, orthopedic surgeons, nurse practitioners, physician assistants, nurses, and other healthcare professionals who practice, research, or teach in the field of rheumatology.

About Us / Contact Us / Advertise / Privacy Policy / Terms of Use / Cookie Preferences

  • Connect with us:
  • Facebook
  • Twitter
  • LinkedIn
  • YouTube
  • Feed

Copyright © 2006–2023 American College of Rheumatology. All rights reserved.

ISSN 1931-3268 (print)
ISSN 1931-3209 (online)