Scleroderma, also known as systemic sclerosis, is a rare autoimmune disease that causes hardening and tightening of the skin and, in many cases, affects internal organs. This chronic connective tissue disorder results from an overproduction of collagen, which leads to fibrosis (scarring), vascular damage, and immune system abnormalities. Scleroderma can be localized to the skin or systemic, involving the lungs, heart, kidneys, or digestive system. While it can be a life-altering condition, advances in diagnosis and treatment have significantly improved outcomes. This article provides a comprehensive overview of scleroderma, including its causes, symptoms, diagnosis, treatment, and strategies for living with the condition. 

The term “scleroderma” comes from the Greek words “skleros” (hard) and “derma” (skin), reflecting its hallmark symptom of skin thickening. The condition encompasses a spectrum of disorders ranging from mild localized disease to severe systemic involvement. 

Types of scleroderma: 

• Localized scleroderma (morphea and linear scleroderma): Involves only the skin and underlying tissues without internal organ involvement. 

• Systemic sclerosis (SSc): Affects the skin and internal organs and is divided into: 

• Limited cutaneous systemic sclerosis (lcSSc): Skin changes are confined to areas below the elbows and knees, sometimes including the face. It’s often associated with CREST syndrome (Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia). 

• Diffuse cutaneous systemic sclerosis (dcSSc): Characterized by widespread skin thickening that may include the trunk and upper arms and legs. This type carries a higher risk of internal organ complications. 

Scleroderma affects about 1 to 2 people per 100,000 annually. It is six times more common in women than men and tends to appear between the ages of 30 and 50. The disease varies across ethnic groups, with African Americans often experiencing more severe forms and complications. 

The exact cause of scleroderma remains unknown, but research suggests that it results from an interaction of genetic, environmental, and immune factors. 

Genetic predisposition 

• Certain genes, such as HLA-DRB1 and STAT4, may increase susceptibility. 

• Family members of patients with autoimmune diseases may have a slightly higher risk. 

Environmental triggers 

• Exposure to silica dust, solvents, or pesticides has been linked to scleroderma development. 

• Viral infections like Epstein-Barr virus or cytomegalovirus may act as triggers in genetically predisposed individuals. 

• Certain medications, such as bleomycin and some chemotherapy agents, can induce scleroderma-like symptoms. 

Immune system abnormalities 

• The immune system mistakenly attacks the body’s own tissues, leading to chronic inflammation and fibroblast activation. 

• Autoantibodies (anti-centromere, anti-topoisomerase I, anti-RNA polymerase III) are frequently present and help define disease subtypes. 

The disease process in scleroderma involves three key mechanisms: autoimmunity, vascular injury, and fibrosis. 

1. Autoimmunity and inflammation: Immune cells release cytokines like IL-6 and TGF-β, which stimulate inflammation and fibroblast activation. 

2. Vascular abnormalities: Damage to small blood vessels leads to reduced capillary density and tissue hypoxia, contributing to symptoms like Raynaud’s phenomenon. 

3. Fibrosis: Activated fibroblasts overproduce collagen, leading to skin thickening and stiffening of internal organs. 

Scleroderma’s symptoms differ widely depending on its type and the organs affected. The condition may begin gradually with symptoms like fatigue, joint stiffness, or Raynaud’s phenomenon. 

Common signs and symptoms include: 

• Skin changes: Thickening, tightness, or shiny appearance; limited flexibility; pigmentation changes; and small white calcium deposits (calcinosis). 

• Raynaud’s phenomenon: Color changes in fingers and toes (white to blue to red) triggered by cold or stress. 

• Joint and muscle symptoms: Pain, stiffness, or inflammation in joints; muscle weakness. 

• Digestive issues: Heartburn, reflux, bloating, diarrhea, or constipation due to slowed intestinal movement. 

• Lung involvement: Shortness of breath, dry cough, or fatigue due to interstitial lung disease or pulmonary hypertension. 

• Heart complications: Irregular heartbeat, chest pain, or heart failure from fibrosis or fluid buildup. 

• Kidney problems: Sudden high blood pressure and kidney failure (scleroderma renal crisis). 

Diagnosis requires a combination of clinical evaluation, laboratory testing, and imaging. Because scleroderma can mimic other autoimmune disorders, it may take time to confirm. 

Diagnostic tests may include: 

• Blood tests: Detect specific autoantibodies (anti-centromere, anti-Scl-70, anti-RNA polymerase III) and assess inflammation levels. 

• Nailfold capillaroscopy: Examines tiny blood vessels near the nails to identify characteristic vascular changes. 

• Imaging studies: High-resolution CT scans for lung involvement, echocardiograms for heart function, and esophageal manometry for digestive assessment. 

• Pulmonary function tests: Measure breathing capacity and detect early lung disease. 

The 2013 ACR/EULAR classification criteria are widely used to confirm systemic sclerosis, assigning scores for skin thickening, vascular features, and antibody profiles. 

Several conditions can resemble scleroderma, and understanding them helps ensure accurate diagnosis. Below is a brief description of each: 

• Eosinophilic fasciitis: A rare condition that causes inflammation and thickening of the fascia (connective tissue beneath the skin), leading to swelling and tightness, often in the limbs. 

• Systemic lupus erythematosus: An autoimmune disease that can affect the skin, joints, kidneys, brain, and other organs, often causing a characteristic butterfly-shaped facial rash. 

• Dermatomyositis: An inflammatory muscle disease marked by muscle weakness and a distinctive purple or red rash on the eyelids, face, and hands. 

• Mixed connective tissue disease: A disorder that shows overlapping features of lupus, scleroderma, and polymyositis, with antibodies against U1-RNP. 

• Nephrogenic systemic fibrosis: A fibrosing disorder associated with gadolinium exposure in patients with kidney failure, causing skin thickening similar to scleroderma. 

• Chronic graft-versus-host disease: A complication after bone marrow or stem cell transplant where donor immune cells attack the recipient’s tissues, leading to fibrosis and skin tightening.  

Although there is currently no cure for scleroderma, treatment focuses on controlling symptoms, slowing disease progression, and preventing complications. Management requires a multidisciplinary approach involving rheumatologists, pulmonologists, and other specialists. 

General measures 

• Avoid exposure to cold and stress to manage Raynaud’s phenomenon. 

• Use moisturizers to reduce skin tightness and dryness. 

• Maintain joint flexibility with regular exercise and physical therapy. 

• Stop smoking to improve blood flow. 

Medications 

1. Raynaud’s phenomenon: 
   • Calcium channel blockers (nifedipine, amlodipine) 
   • Phosphodiesterase inhibitors (sildenafil) 
   • Topical nitroglycerin or prostacyclin analogs for severe cases 

2. Skin fibrosis: 
   • Methotrexate or mycophenolate mofetil to slow fibrosis 
   • Cyclophosphamide for aggressive disease 
   • Rituximab or stem cell transplantation in refractory cases 

3. Gastrointestinal symptoms: 
   • Proton pump inhibitors (omeprazole) for reflux 
   • Prokinetic agents (metoclopramide) for motility 
   • Antibiotics for bacterial overgrowth 

4. Lung disease: 
   • Mycophenolate mofetil or cyclophosphamide for interstitial lung disease 
   • Nintedanib (antifibrotic agent) 
   • Sildenafil or bosentan for pulmonary hypertension 

5. Renal crisis: 
   • Prompt treatment with ACE inhibitors (captopril, enalapril) 
   • Avoid high-dose corticosteroids that can trigger kidney crisis 

6. Musculoskeletal symptoms: 
   • NSAIDs and low-dose steroids for joint pain 
   • Physical therapy for stiffness 

Non-pharmacologic management 

• Occupational therapy for hand and joint function 

• Counseling and psychological support 

• Nutritional guidance for digestive issues 

Scleroderma can lead to serious complications that may affect life expectancy and quality of life. The severity and range of complications depend on the extent of skin and organ involvement, with systemic sclerosis posing the highest risk. Below is a more detailed overview of major complications and how they affect the body: 

Major complications include: 

• Lung disease: One of the most serious complications. Interstitial lung disease (ILD) causes scarring and stiffness in the lungs, leading to progressive shortness of breath and reduced oxygen exchange. Pulmonary arterial hypertension (PAH) results from thickening of the blood vessel walls in the lungs, increasing pressure and straining the right side of the heart. 

• Kidney involvement: Scleroderma renal crisis is a medical emergency characterized by sudden severe hypertension and rapidly worsening kidney function. It can develop quickly and requires prompt treatment with ACE inhibitors to prevent permanent damage or kidney failure. 

• Heart problems: Fibrosis can affect the heart muscle, leading to arrhythmias, cardiomyopathy, or heart failure. Pericarditis (inflammation of the sac around the heart) can cause chest pain and fluid accumulation, while microvascular changes may reduce blood supply to cardiac tissue. 

• Gastrointestinal damage: Scleroderma can affect the entire digestive tract. Esophageal involvement leads to acid reflux and swallowing difficulties, while intestinal fibrosis can slow motility, causing bloating, bacterial overgrowth, and malabsorption. Severe cases may result in weight loss and malnutrition. 

• Digital ulcers and gangrene: Reduced blood flow from Raynaud’s phenomenon and small vessel damage can lead to painful fingertip ulcers that are slow to heal. In advanced cases, tissue death (gangrene) can occur, sometimes requiring surgical intervention. 

• Calcinosis cutis: The deposition of calcium salts beneath the skin causes firm, painful nodules that may ulcerate or become infected. These are common in long-standing limited systemic sclerosis and can significantly impact mobility and comfort. 

• Mental health challenges: Chronic pain, fatigue, and visible skin changes can contribute to anxiety, depression, and social isolation. Psychological support and mental health care are essential to improving overall quality of life. 

Outcomes vary widely depending on the disease subtype and organ involvement. Diffuse systemic sclerosis generally has a worse prognosis due to more extensive organ damage. Five-year survival rates range from 80–90%, though patients with severe lung or heart involvement face higher risks. Advances in treatment—especially for lung and kidney complications—have significantly improved survival rates. 

While there is no known way to prevent scleroderma, certain steps can help minimize complications: 

• Early screening for organ involvement 

• Avoiding cold exposure and smoking 

• Managing blood pressure carefully 

• Staying physically active to maintain flexibility 

• Keeping up with vaccinations (influenza, pneumococcal) 

• Seeking regular care from a multidisciplinary medical team 

Living with scleroderma involves managing chronic symptoms while maintaining quality of life. Emotional and social support are as important as medical treatment. 

Practical tips: 

• Practice stress management and relaxation techniques. 

• Use assistive devices for tasks that require hand strength. 

• Stay connected with support groups or counseling. 

• Schedule regular follow-ups to monitor organ health. 

• Work with healthcare professionals to adjust treatment as needed. 

Scleroderma is a complex autoimmune condition that can affect the skin and internal organs in unpredictable ways. While it cannot be cured, early diagnosis, careful monitoring, and comprehensive treatment can improve both longevity and quality of life. Advances in research continue to uncover new therapies that target the underlying immune and fibrotic mechanisms of the disease, offering hope for better outcomes in the future. 

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