What is systemic sclerosis (SSc)?

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From the Guidelines

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disorder characterized by excessive collagen production leading to skin thickening and potential internal organ involvement, with a high morbidity and mortality rate despite recent improvements in survival 1.

Definition and Characteristics

Systemic sclerosis is a complex disease with variable outcomes, driven by the type and severity of organ involvement. The disease is characterized by autoimmune features, vascular manifestations, and tissue and vascular fibrosis of the skin and internal organs. The term SSc is preferred over scleroderma, as it encompasses both cutaneous and visceral manifestations of the disease.

Treatment and Management

Treatment of SSc focuses on managing symptoms and preventing complications, as there is no cure. According to the latest EULAR recommendations, treatment of SSc should be tailored to the individual patient, taking into account the extent of skin involvement, presence of internal organ involvement, and specific antibodies 1. For skin manifestations, methotrexate or mycophenolate mofetil may be used, while Raynaud's phenomenon is treated with calcium channel blockers like nifedipine or amlodipine. Gastrointestinal issues are managed with proton pump inhibitors, and pulmonary arterial hypertension may require endothelin receptor antagonists or phosphodiesterase-5 inhibitors.

Organ-Specific Treatment

  • For interstitial lung disease, cyclophosphamide, mycophenolate mofetil, or nintedanib may be used 1.
  • For pulmonary arterial hypertension, combination therapy with phosphodiesterase-5 inhibitors and endothelin receptor antagonists is recommended as first-line treatment 1.
  • For gastrointestinal involvement, proton pump inhibitors are recommended for the treatment of gastroesophageal reflux disease and prevention of esophageal ulcers and strictures 1.

Monitoring and Prevention

Regular monitoring of organ function is essential, including pulmonary function tests, echocardiograms, and renal function assessments. Patients should protect extremities from cold, avoid smoking, perform regular physical therapy to maintain joint mobility, and seek prompt medical attention for new symptoms, as early intervention for organ involvement improves outcomes 1.

From the Research

Definition and Characteristics of Systemic Sclerosis (SSc)

  • Systemic sclerosis (SSc) is a multi-system disease characterized by skin fibrosis and visceral disease 2
  • It is a chronic autoimmune disease with clinical manifestations resulting from immune activation, fibrosis development, and damage of small blood vessels 3
  • The disease presents two major clinical hallmarks: Raynaud's phenomenon (RP) and skin involvement, followed by varying prevalences of internal organ involvement 4

Pathogenesis and Management

  • SSc has a complex pathogenesis, and its management remains a challenge 5
  • Therapy should be adjusted individually, depending on disease subtype and activity 5
  • Treatment in SSc is targeted at reducing abnormal immune activation, microvascular abnormalities, and fibrosis 5
  • Immunosuppressive agents, such as cyclophosphamide or mycophenolate mofetil, and occasionally methotrexate or cyclosporine A, are indicated in rapidly progressing SSc 5

Treatment Options

  • Methotrexate, cyclophosphamide, calcium channel blockers, angiotensin converting enzyme inhibitors, prostacyclin analogues, D-penicillamine, and extracorporeal photopheresis are the most widely studied treatments for SSc 3
  • Endothelin receptor antagonists and phosphodiesterase-5 inhibitors are used for pulmonary arterial hypertension and peripheral vascular disease 3
  • High-dose immunosuppression and stem cell transplantation constitute a promising treatment, and data from randomized controlled trials are awaited 3
  • Autologous haematopoietic stem cell transplantation (HSTC) and intravenous immunoglobulins (IVIG) are advanced approaches reserved for unresponsive SSc patients 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Recent advances in the treatment of systemic sclerosis.

Clinical reviews in allergy & immunology, 2009

Research

Systemic sclerosis: markers and targeted treatments.

Acta reumatologica portuguesa, 2016

Research

[Current treatment of systemic sclerosis. Part I. Immunosuppressive treatment].

Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego, 2008

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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