What is systemic sclerosis (SSc)?

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Last updated: March 17, 2025View editorial policy

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From the Guidelines

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by fibrosis and vasculopathy, with substantial morbidity and mortality, and is often classified into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) based on the extent of skin involvement. The disease is associated with various clinical manifestations, including Raynaud's phenomenon, digital ulcers, gastrointestinal involvement, interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and scleroderma renal crisis 1. The estimated prevalence of SSc is 30-120 cases per million, and the disease can affect multiple organs, including the skin, lungs, heart, kidneys, and digestive tract 1.

Some of the key characteristics of SSc include:

  • Fibrosis and vasculopathy, leading to organ damage and dysfunction
  • Autoimmune nature, with the immune system mistakenly attacking healthy body tissue
  • Excessive collagen production, leading to hardening and tightening of the skin and connective tissues
  • Two main types: localized scleroderma (affecting mainly the skin) and systemic sclerosis (affecting blood vessels and internal organs)
  • Symptoms such as thickened, tight skin patches, Raynaud's phenomenon, joint pain, digestive problems, and shortness of breath

The diagnosis and treatment of SSc are crucial to manage symptoms and prevent complications, and may include medications like immunosuppressants, vasodilators, and proton pump inhibitors, as well as physical therapy to maintain joint mobility 1. Early diagnosis and treatment are essential to improve quality of life and reduce morbidity and mortality in patients with SSc. According to the most recent evidence, treatments for early dcSSc include immunosuppressive agents such as mycophenolate mofetil, methotrexate, cyclophosphamide, rituximab, and tocilizumab, and patients with rapidly progressive early dcSSc may be eligible for autologous haematopoietic stem cell transplantation 1.

From the Research

Definition and Characteristics of Systemic Sclerosis (SSc)

  • Systemic sclerosis (SSc), also known as systemic scleroderma, is a chronic connective tissue disease of unknown etiology that causes widespread microvascular damage and excessive deposition of collagen in the skin and internal organs 2.
  • It is characterized by skin fibrosis and visceral disease, with Raynaud phenomenon and scleroderma (hardening of the skin) being hallmarks of the disease 2, 3.
  • The disease can affect various internal organs, including the lungs, gastrointestinal system, kidneys, and heart, with pulmonary and cardiac disease being the leading causes of death 4.

Types and Classification of Systemic Sclerosis

  • Systemic sclerosis can be classified into two distinct clinical subsets: limited cutaneous and diffuse cutaneous, each with different clinical, systemic, and serologic findings 4.
  • Autoantibodies can be used to predict phenotype and internal organ involvement, helping to guide treatment and management 4.

Pathophysiology of Systemic Sclerosis

  • The pathophysiology of systemic sclerosis is complex and involves early endothelial damage, an inflammatory infiltrate, and a resulting fibrotic reaction 5.
  • It is triggered by an autoimmune response, with an altered balance of the acquired and innate immune system leading to the release of cytokines, chemokines, and autoantibodies 5.
  • The activation of fibroblasts and the formation of myofibroblasts result in the deposition of a stiff and rigid connective tissue, leading to skin sclerosis and organ fibrosis 5.

Treatment and Management of Systemic Sclerosis

  • While there is no cure for systemic sclerosis, various therapeutic interventions exist to improve quality of life and minimize organ-threatening involvement 4.
  • Treatment is based on organ involvement and requires a multidisciplinary approach, with options including medications, lifestyle modifications, and phototherapy 2, 3, 6.
  • Early management of systemic sclerosis is paramount to prevent progression, and screening for pulmonary and cardiac disease is important to identify potential complications 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Pathophysiology of systemic sclerosis (scleroderma).

The Kaohsiung journal of medical sciences, 2022

Research

Phototherapy in systemic sclerosis: Review.

Photodermatology, photoimmunology & photomedicine, 2017

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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