Scleroderma: Drug Therapy

The disease cannot be treated causally (related to the cause).

General therapeutic goals

  • Relief of symptoms
  • Ensuring the quality of life
  • Avoidance or therapy of secondary diseases / complications

Therapy recommendations – Chronic cutaneous circumscritical scleroderma

  • Local therapy (topical therapy) with glucocorticoids, including occlusive or intralesional at the margin.
  • For eosinophilic fasciitis (Shulman syndrome) (affects the extremity fascia (fascia = soft tissue components of connective tissue) and subcutis (subcutaneous tissue), not affecting the hands and feet; acute onset, chronic course): Glucocorticoids

Therapy recommendations – systemic scleroderma

Taking into account the pathogenesis (development of the disease), the following therapeutic goals are the main focus:

  • Immunosuppression (measures to suppress defense responses).
  • Inhibition of fibrosis (pathological proliferation of connective tissue).
  • Improving microcirculation (blood flow in the very small vessels).

Furthermore, the therapy of systemic scleroderma is based on the symptoms. Limited-cutaneous form (no involvement of internal organs).

  • Local therapy with nitrate-containing ointments
  • Calcium antagonists such as nifedipine (alternatively angiotensin-converting enzyme (ACE) inhibitors) – to improve microcirculation in Raynaud’s syndromeDose: 20-30 mg/day.
  • For the prevention of ulcers (ulcers) on fingers and toes or for their therapy (accelerated healing):
    • Vasodilating prostaglandin analogues (as infusions).
      • Bosentan (endothelin-1 receptor antagonist) or phosphodiesterase-5 inhibitors (eg, sildenafil)
      • Alprostadil (Prostavasin)Dosage: 60 mg in 3 h over 10-14 days.
      • Carboprostacyclin infusions (iloprost)-prostaglandin derivative recommended for intravenous treatment of advanced stages of peripheral circulatory disordersDosing: initially 1.0-2.0 ng/kg/min over 6-8 h for 3-5 consecutive days, repeated infusions over 1-2 days every 3-7 weeks
  • Calcitonin – also vasoactiveDose: 100 IU over 10 days (i.v. infusion).
  • Prazosin (alpha-receptor blocker) – positive effect on symptoms of Raynaud’s syndromeDosage 4-5 mg/day (creeping dosage).
  • If necessary, glucocorticoids – use in the early edematous (swelling caused by storage of fluid in the tissue) stage and in arthritides (inflammatory joint diseases) and arthralgias (joint pain) that do not respond to the administration of non-steroidal anti-inflammatory drugs (NSAIDs)Cave: In systemic scleroderma, this increases the risk of life-threatening renal crisis (renal complication) → not suitable for basic therapy

Diffuse cutaneous form (involvement of internal organs).

  • Immunosuppressants (drugs that decrease the functions of the immune system).
    • Azathioprine – improvement of skin sclerosisDose: 2 mg/kg body weight/day.
    • Ciclosporin (cyclosporin A) – amelioration of skin sclerosisCave: increased risk of renal (affecting the kidney) complications such as renal insufficiency (kidney weakness)!
    • Methotrexate – significant improvement in skin score (parameter used to assess clinical severity of systemic scleroderma)Dosage: 15-20 mg/week.
    • Cyclophosphamide – for fibrosing alveolitis (proliferation of connective tissue between alveoli leading to inflammation)Dosage: 1-2.5 mg/kg body weight/day (oral) or pulse therapy (i.v.) every 3-4 weeks combined with prednisolone (different dosages possible); favorable effect on skin thickening, lung function, and survival rate
  • Glucocorticoids (medium-high dose) – A combination with prednisolone (dosage: 30 mg/day to 1 mg/kg body weight/day) is recommended for alveolitis (inflammation of the alveoli), myositis (inflammation of the muscles) and overlap syndromesCave: high-dose use of corticoids increases the risk of renal insufficiency!
  • D-penicillamine – antifibrotic effect; improvement of skin sclerosis as well as improvement of the overall prognosisCave: Since the active substance can lead to severe side effects (in about 40% of cases), its use is highly controversial! In addition, the therapeutic effect occurs only after about one year of therapy. Because of the side effects, however, the therapy is often discontinued before.
  • Medications or agents to improve microcirculation may also be recommended for this course of systemic scleroderma.