Systemic sclerosis

Disease Description (Causes and Pathophysiology, Main Symptoms)

• Definition summary: Systemic sclerosis is an autoimmune disease characterized by fibrosis (excessive collagen accumulation) of the skin, blood vessels, and internal organs, as well as small-vessel lesions. Prognosis varies depending on the disease course and organs involved.
• Causes and pathophysiology: Although the exact mechanism of onset is unknown, the process involves an autoimmune response → endothelial cell injury → chronic inflammation and fibroblast activation → excessive accumulation of collagen and extracellular matrix proteins, leading to tissue thickening and hardening. Some occupational or environmental exposures (silica, organic solvents, etc.) may be associated. It is associated with antinuclear antibodies (anti-centromere, anti-Scl-70/topoisomerase I, and anti-RNA polymerase III).
• Main symptoms:
  • Skin hardening (beginning with the hands and face), limited ability to make a fist, changes in skin color, hair loss
  • Raynaud phenomenon (changes in the color of the hands and feet, pain), digital ulcers/gangrene
  • Joint pain and muscle weakness
  • Gastrointestinal motility disorders (difficulty swallowing, reflux, malabsorption, constipation/diarrhea)
  • Possible involvement of the lungs (interstitial lung disease, pulmonary arterial hypertension), heart (fibrosis and arrhythmia), and kidneys (from mild functional impairment to scleroderma renal crisis)

Treatment Methods

• Treatment goals: Suppress disease progression (prevent organ damage), relieve symptoms, manage complications, and maintain quality of life. As a cure is currently not possible, long-term follow-up and a multidisciplinary approach are necessary.
• Drug treatment (main items)
  • Immunosuppressants:
    • Mild-to-severe skin/pulmonary fibrosis → mycophenolate mofetil (primarily used) is recommended.
    • Severe, progressive SSc-ILD (interstitial lung disease) → cyclophosphamide (infusion or oral) followed by mycophenolate as maintenance therapy.
    • Methotrexate may be used in cases involving skin lesions and others.
    • Biologics: tocilizumab (some evidence; may suppress worsening of skin disease and ILD), while rituximab is used selectively.
  • Antifibrotic agent: nintedanib — approved and recommended for slowing progression in SSc-related ILD.
  • Vasodilators (for Raynaud phenomenon, peripheral ischemia, and pulmonary arterial hypertension):
    • Peripheral Raynaud phenomenon and digital ulcers: calcium channel blockers (e.g., amlodipine, nifedipine) as first-line treatment; topical nitrates and prostacyclin agents (e.g., iloprost infusion) may be considered if necessary.
    • Pulmonary arterial hypertension (PAH): endothelin receptor antagonists (erdafitinib class: bosentan, macitentan), PDE5 inhibitors (sildenafil, tadalafil), sGC stimulators (riociguat), and prostacyclin agents (epoprostenol, treprostinil, selexipag), used as monotherapy or in combination therapy.
  • Management of renal crisis: When scleroderma renal crisis occurs, ACE inhibitors (e.g., captopril) are essential for treatment and survival.
  • Symptomatic treatment: PPIs for GERD, prokinetics for reduced intestinal motility, and NSAIDs/medication therapy, physical therapy, and other measures for pain and joint symptoms.
• Procedures/surgery: Surgical intervention for severe complications (such as peripheral gangrene and pseudoaneurysm), and specialized treatment for permanent complications (such as enteral feeding and respiratory support).
• Lifestyle management and preventive measures:
  • Avoid cold and stress, protect the hands (to prevent worsening of Raynaud phenomenon), stop smoking, exercise regularly (taking lung and heart function into account), and manage weight and diet (to address GERD and malabsorption).
  • Regular monitoring (self-measurement of blood pressure, pulmonary function tests and DLCO, echocardiography/NT-proBNP, kidney function tests, blood tests, etc.).
• Precautions:
  • High-dose steroids may increase the risk of scleroderma renal crisis, so caution is required when using them (maintain the lowest possible dose).
  • Increased risk of infection during immunosuppressive treatment → vaccination (influenza, pneumococcal disease, etc.) is recommended (inactivated vaccines are preferred).
  • In patients of childbearing potential, some medications (e.g., cyclophosphamide and mycophenolate) are teratogenic → preconception counseling is necessary.

Checklist Before an Outpatient Visit (Examples of Items and Records to Bring, Questions to Prepare)

• Items/documents to bring:
  • A list of all medications currently being taken (including prescription drugs, over-the-counter drugs, and herbal medicines), along with dosing times and doses
  • Previous test results: blood tests (CBC, CRP, kidney function), autoantibody tests (ANA, anti-Scl-70, anti-centromere, anti-RNA pol III), PFTs (spirometry and DLCO), chest HRCT, echocardiography/ECG, and recent blood pressure records
  • Records of symptom changes: frequency and patterns of Raynaud episodes, photographs of digital ulcers (if present), timing of shortness of breath and whether it worsens with exercise, difficulty swallowing, reflux symptoms, etc.
  • Lifestyle information: smoking status, occupational exposure (silica, organic solvents, etc.), and pregnancy plans (if applicable)
• Questions that may be helpful to prepare for an outpatient visit (to ask the doctor in advance): how to contact the hospital in an emergency if symptoms worsen, what to do if medication side effects are suspected, and the timing and purpose of the next tests

Examples of General Questions to Ask the Doctor

• What are the main side effects and monitoring items for this medication (or new treatment)?
• How often should I undergo lung, heart, and kidney tests for my disease?
• What lifestyle precautions are particularly important for my current symptoms (Raynaud phenomenon, skin hardening, and digestive problems)?
• What additional measures are recommended for vaccination or infection prevention?

Examples of Disease-Specific Questions

• My blood pressure has recently increased slightly. What warning signs (early symptoms) could suggest scleroderma renal crisis, and when should I come to the hospital?
• I am planning a pregnancy and am currently taking medications (e.g., mycophenolate, cyclophosphamide, etc.). Which medications should be stopped or replaced before pregnancy, and what should the prenatal care plan be?

Note: The information above is general medical information. Individual diagnosis and treatment should be determined through consultation with the treating specialist.