Systemic Sclerosis (Scleroderma): A Comprehensive Overview

By SWA

What is Systemic Sclerosis?

Systemic sclerosis (SSc), also known as scleroderma, is a rare autoimmune systemic disease that primarily affects the connective tissue. It is characterized by excessive fibrosis (thickening and hardening) of the skin and internal organs, and by vascular abnormalities (vasculopathy). This chronic condition occurs when the immune system mistakenly attacks the body’s own healthy tissues, producing autoantibodies that target components within the nucleus of cells.

Although the disease primarily affects the skin, it can also involve vital organs such as the lungs, heart, kidneys, gastrointestinal tract, and the vascular and nervous systems, leading to serious complications and varying disease courses.

Classification of Systemic Sclerosis

Systemic sclerosis is classified into several subtypes based on the extent and location of the skin involvement:

1. Limited Cutaneous Systemic Sclerosis (lcSSc)

  • Formerly known as CREST syndrome.

  • Skin changes are confined to the face, hands, and feet (distal extremities).

  • Associated with anti-centromere antibodies (ACA).

2. Diffuse Cutaneous Systemic Sclerosis (dcSSc)

  • Skin thickening extends beyond elbows and knees, often involving the trunk.

  • More aggressive course and frequent organ involvement.

  • Associated with anti-Scl-70 and anti-RNA polymerase III antibodies.

3. Systemic Sclerosis sine scleroderma

  • No skin involvement.

  • Internal organs are affected.

4. Overlap Syndrome

  • SSc features coexist with symptoms of other autoimmune diseases like rheumatoid arthritis or lupus.

Key Autoantibodies in Systemic Sclerosis

Autoantibodies are critical markers used for diagnosis and prognosis:

  • Anti-centromere antibodies (ACA): Common in limited cutaneous SSc.

  • Anti-topoisomerase I (Anti-Scl-70): Linked to diffuse cutaneous SSc and lung involvement.

  • Anti-RNA polymerase III: Associated with dcSSc, scleroderma renal crisis, and possibly cancer.

  • Anti-Th/To and Anti-U3-RNP (fibrillarin): Found in both lcSSc and dcSSc with variable organ involvement.

Over 90% of patients with SSc test positive for antinuclear antibodies (ANA), which may appear years before clinical symptoms develop.

Warning Signs

The following triad of symptoms should raise suspicion for systemic sclerosis:

  • Raynaud's phenomenon

  • Swollen, puffy fingers

  • Elevated ANA titers

     

Symptoms and Organ Involvement

Skin

  • Thickening and hardening of skin (sclerodactyly)

  • “Puffy fingers” in early stage


  • “Tobacco pouch” mouth, pinched nose

     

     

     

     

  • Calcinosis (calcium deposits)

  • Pigmentation changes

  • Itching (pruritus)

Vascular System

  • Raynaud’s phenomenon: Cold or stress-induced spasm of blood vessels in fingers/toes.

  • Digital ulcers: Painful sores due to poor circulation.

  • Telangiectasia: Visible, widened capillaries on skin.

  • Nailfold capillary changes

Gastrointestinal Tract

  • Reflux, difficulty swallowing (dysphagia)

  • Nausea, diarrhea, bloating

  • Jaundice

  • Malabsorption or malnutrition in severe cases

Musculoskeletal System

  • Joint and muscle pain

  • Morning stiffness

  • Joint contractures

Lungs

  • Interstitial lung disease (ILD): Common and potentially fatal.

  • Shortness of breath, dry cough

  • Pulmonary arterial hypertension (PAH)

Heart

  • Arrhythmias, pericarditis, or congestive heart failure

  • PAH-related right heart failure

Kidneys

  • Scleroderma renal crisis: Sudden, life-threatening renal failure with high blood pressure.

  • Often associated with anti-RNA polymerase III.

Nervous System

  • Polyneuropathy

  • Restless legs syndrome

Exocrine Glands

  • Sicca symptoms: Dry eyes, mouth, or vaginal dryness.

Psychosocial and General Symptoms

  • Depression, anxiety, insomnia

  • Fatigue, weight loss, decreased performance

Diagnosis

Diagnosing systemic sclerosis involves a multidisciplinary approach and various tools:

  • Clinical examination and patient history

  • Blood tests: ANA, specific autoantibodies (ACA, anti-Scl-70, etc.)

  • Nailfold capillaroscopy

  • Imaging: CT scans to evaluate lung involvement

  • Pulmonary function tests

  • Echocardiography and ECG

  • Kidney function tests

  • MRI and lumbar puncture (to rule out differential diagnoses, especially in neurological symptoms)

Innovative Diagnostics and AI Tools

Recent advancements have integrated AI-based image analysis to detect early lung fibrosis and subtle changes in CT thorax images. For example, institutions like the Fraunhofer Institute MEVIS and University Hospital Mainz are working on AI tools for precise and fast CT evaluation in interstitial lung disease and lung cancer, which can significantly improve therapy planning and monitoring.

Treatment

There is currently no cure for systemic sclerosis. Treatment focuses on:

  1. Slowing disease progression

  2. Relieving symptoms

  3. Preserving quality of life

Non-Pharmacologic Therapies:

  • Physical and occupational therapy

  • Lymphatic drainage

  • Manual therapy and speech therapy

Pharmacologic Treatments:

  • Immunosuppressants (e.g., methotrexate, mycophenolate mofetil)

  • Antifibrotic agents for ILD

  • Sildenafil for Raynaud’s and PAH

  • Proton pump inhibitors (PPIs) for GI symptoms

  • ACE inhibitors for scleroderma renal crisis

Advanced Therapies:

  • Autologous stem cell transplantation in severe diffuse SSc

  • Lung transplantation in advanced lung disease

Psychological Support:

  • Self-help groups and psychotherapy

  • Antidepressants for depression

  • Relaxation techniques for Raynaud’s (e.g., autogenic training)

Prognosis

Systemic sclerosis typically progresses most rapidly within the first 3–5 years after the onset of Raynaud’s phenomenon. About 75% of organ involvement occurs within the first 5 years.

Leading causes of death:

  • Pulmonary fibrosis

  • Pulmonary arterial hypertension

  • Scleroderma renal crisis

  • Gastrointestinal complications

  • Cardiac involvement

  • Cancer and infections

Approximately 60% of patients die from direct complications of the disease.

Conclusion

Systemic sclerosis is a complex, multi-system autoimmune condition with a wide spectrum of symptoms and clinical courses. Early diagnosis and tailored, multidisciplinary management are key to improving outcomes and maintaining quality of life. Continued research and advances in imaging and immunotherapy are opening promising avenues for more targeted and effective treatments in the future.

References:

The 2024 British Society for Rheumatology guideline for management of systemic sclerosis—executive summary
https://pmc.ncbi.nlm.nih.gov/articles/PMC11534113/

Scleroderma and Primary Myocardial Diseasehttps://www.ncbi.nlm.nih.gov/books/NBK557686/figure/article-27737.image.f1/

Systemische Sklerose – klinisches Bild, Diagnostik und Therapie
https://link.springer.com/article/10.1007/s00393-019-0639-2

Disclaimer: By accessing and reading this blog, you acknowledge that the information provided is for general informational purposes only and does not constitute medical advice, diagnosis, or treatment. The content is intended to address commonly asked questions and is derived from reputable scientific literature. Always consult a qualified healthcare professional for medical concerns or conditions.

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9

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