Scleroderma – Causes, Symptoms and Treatment

What is Scleroderma?

Scleroderma (from Greek: skleros = hard, derma = skin) is a chronic autoimmune disease classified within the connective tissue disorders. In scleroderma, the immune system mistakenly attacks the body's own tissue, leading to an overproduction of collagen. This causes the skin to harden and thicken, and internal organs may also be affected. Women are significantly more likely to develop the disease than men, and it most commonly occurs between the ages of 30 and 50.

Types of Scleroderma

Localized Scleroderma (Morphea)

In the localized form, only specific areas of the skin are affected. Internal organs remain unaffected. This form generally has a milder course and is not life-threatening.

Systemic Scleroderma (Systemic Sclerosis)

The systemic form affects not only the skin but also internal organs such as the lungs, heart, kidneys, and gastrointestinal tract. Two subtypes are distinguished:

• Limited cutaneous systemic sclerosis (lcSSc): Skin changes are restricted to the hands, forearms, face, and feet. Frequently associated with CREST syndrome (Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia).
• Diffuse cutaneous systemic sclerosis (dcSSc): Skin changes affect large areas of the body including the trunk. Internal organs are more frequently and earlier involved, and the course is more severe.

Causes and Risk Factors

The exact cause of scleroderma has not yet been fully established. A combination of several factors is believed to contribute:

• Genetic predisposition: Certain genetic variants increase the risk of developing the disease.
• Autoimmune reactions: The immune system attacks connective tissue and blood vessels.
• Environmental factors: Exposure to certain chemical substances (e.g., silica dust, organic solvents) may increase the risk.
• Vascular dysfunction: Abnormalities in small blood vessels play a central role in the development of the disease.

Symptoms

The symptoms of scleroderma are diverse and depend on the type of disease and the extent of organ involvement:

• Raynaud phenomenon: Episodic blood flow disturbances in the fingers and toes, triggered by cold or stress (often the first symptom).
• Skin changes: Hardening, thickening, and a feeling of tightness in the skin; swelling of the fingers (sclerodactyly).
• Joint pain and muscle weakness.
• Difficulty swallowing due to esophageal involvement.
• Lung involvement: Shortness of breath due to interstitial lung disease or pulmonary hypertension.
• Kidney involvement: Renal crisis with sudden onset of high blood pressure (in dcSSc).
• Heart problems: Arrhythmias, heart failure.
• Telangiectasias: Visible dilated blood vessels on the skin.

Diagnosis

The diagnosis of scleroderma is made through a combination of clinical examination, laboratory testing, and imaging procedures:

• Clinical examination: Assessment of skin changes and typical symptoms.
• Blood tests: Detection of specific autoantibodies (e.g., ANA, anti-Scl-70/topoisomerase-I, anti-centromere antibodies).
• Nailfold capillaroscopy: Examination of the nailfold capillaries to assess vascular changes.
• Pulmonary function tests and high-resolution CT of the lungs: To detect lung involvement.
• Echocardiography: To assess cardiac function and pulmonary pressure.
• Kidney function tests and regular blood pressure monitoring.

Treatment

There is currently no curative therapy for scleroderma. Treatment aims to relieve symptoms, slow organ damage, and improve quality of life:

Pharmacological Therapy

• Immunosuppressants (e.g., methotrexate, mycophenolate mofetil, cyclophosphamide) to dampen the autoimmune response and slow fibrosis.
• Calcium channel blockers (e.g., nifedipine) and PDE-5 inhibitors for the Raynaud phenomenon.
• Endothelin receptor antagonists and prostacyclin analogues for pulmonary arterial hypertension.
• ACE inhibitors in cases of renal crisis.
• Antifibrotic therapy: Nintedanib is approved for scleroderma-associated interstitial lung disease.

Non-Pharmacological Measures

• Physiotherapy and occupational therapy to maintain mobility and joint function.
• Skin care with emollient creams to relieve dryness and skin tightness.
• Protection from cold to prevent Raynaud episodes.
• Dietary adjustments for swallowing or digestive difficulties.

Stem Cell Transplantation

In severe cases of diffuse systemic sclerosis, autologous stem cell transplantation may be considered at specialized centers. Clinical studies have demonstrated significant improvement in selected patients.

Prognosis and Disease Course

The course of scleroderma varies greatly between individuals. The localized form generally has a favorable prognosis. In the systemic form, prognosis depends largely on the extent of organ involvement. Regular monitoring by a rheumatologist and at specialized centers is essential to detect and treat complications at an early stage.

References

1. Denton CP, Khanna D. Systemic sclerosis. Lancet. 2017;390(10103):1685-1699.
2. van den Hoogen F et al. 2013 classification criteria for systemic sclerosis. Arthritis Rheum. 2013;65(11):2737-2747.
3. Kowal-Bielecka O et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis. 2017;76(8):1327-1339.