What is the treatment for scleroderma?

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Last updated: October 17, 2025View editorial policy

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Treatment of Scleroderma

The treatment of scleroderma requires an organ-specific approach targeting the affected systems, with methotrexate combined with systemic corticosteroids being the first-line therapy for active, potentially disfiguring or disabling forms of scleroderma. 1, 2

Types of Scleroderma and Treatment Approach

  • Scleroderma is classified into two major clinical subsets: systemic sclerosis (SSc) and localized scleroderma (morphea), with different treatment approaches for each 3
  • Treatment must target specific organ involvement early before irreversible damage occurs to improve quality of life and survival 4

Systemic Sclerosis (SSc) Treatment

Raynaud's Phenomenon and Digital Ulcers

  • Dihydropyridine-type calcium channel blockers (particularly oral nifedipine) are recommended as first-line therapy for Raynaud's phenomenon 5
  • Phosphodiesterase-5 (PDE-5) inhibitors should be considered for treatment of SSc-related Raynaud's phenomenon and digital ulcers 1, 5
  • Intravenous iloprost should be considered for severe Raynaud's phenomenon that fails to respond to oral therapy 5
  • Fluoxetine may be used for SSc-related Raynaud's phenomenon as an alternative treatment option 1, 5

Pulmonary Arterial Hypertension (PAH)

  • Treatment options for SSc-related PAH include:
    • Endothelin receptor antagonists
    • Prostacyclin analogues
    • PDE-5 inhibitors
    • Riociguat (a newer treatment option) 1

Skin and Lung Disease

  • For rapidly progressive SSc with skin and/or lung involvement, hematopoietic stem cell transplantation may be considered in selected patients 1
  • Immunosuppressants including methotrexate, cyclosporine, and cyclophosphamide may be used for skin and lung involvement 6

Scleroderma Renal Crisis

  • Angiotensin-converting enzyme inhibitors are the cornerstone of treatment for scleroderma renal crisis 4, 6

Gastrointestinal Involvement

  • Proton pump inhibitors are used for management of gastroesophageal reflux disease 7
  • Prokinetic agents may be beneficial for GI motility disorders 1

Localized Scleroderma (Morphea) Treatment

Assessment and Classification

  • Standardized assessment using the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) is recommended to evaluate disease activity and damage 2, 8
  • Classification based on subtype, extent, and depth should guide treatment decisions 2

Treatment Algorithm

  • For limited, superficial lesions (circumscribed morphea):

    • Topical treatments are generally sufficient 2
    • Topical imiquimod can decrease skin thickening 2
    • Medium-dose UVA1 therapy is effective in improving skin softness and reducing thickness 1, 2
  • For linear, deep, generalized, or pansclerotic morphea:

    • Methotrexate (MTX) at 15 mg/m²/week (oral or subcutaneous) combined with systemic corticosteroids during the initial inflammatory phase is recommended as first-line therapy 2, 8
    • MTX should be maintained for at least 12 months after achieving clinical improvement before tapering 2, 8
    • For MTX-refractory or MTX-intolerant patients, mycophenolate mofetil (500-1000 mg/m²) is recommended as second-line therapy 2, 8
    • Biologics, including TNF or IL-6 inhibitors, have been used in some patients with severe recalcitrant disease 2

Monitoring and Follow-up

  • Regular clinical assessment using standardized tools is essential to monitor disease activity and response to treatment 2, 8
  • Close monitoring for medication side effects, particularly with MTX which may cause nausea, headache, and transient hepatotoxicity 2
  • MTX or alternative disease-modifying drugs should be withdrawn once the patient is in remission and off steroids for at least 1 year 1, 2

Common Pitfalls in Treatment

  • Inadequate treatment duration is a common pitfall - treatment should be continued for sufficient time to prevent relapse 2
  • Underestimating the importance of treating skin disease aggressively can lead to significant physical and psychological morbidity 1, 2
  • For patients with facial and head involvement (such as "en coup de sabre" or Parry-Romberg syndrome), MRI of the head is highly recommended at the time of diagnosis, regardless of neurological symptoms 8

Future Therapeutic Directions

  • Biologic agents targeting collagen, cytokines, and cell surface molecules show promising therapeutic effects in SSc 3, 9
  • Target-based approaches focusing on vascular damage, fibrosis, and regulation of inflammation and autoimmune responses are being developed 3, 9

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Diagnosis and Management of Linear Morphea

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

My approach to the treatment of scleroderma.

Mayo Clinic proceedings, 2013

Guideline

Treatment of Raynaud's Phenomenon

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Treatment of scleroderma.

Archives of dermatology, 2002

Research

Novel therapy in the treatment of scleroderma.

Expert opinion on investigational drugs, 2001

Guideline

Parry-Romberg Syndrome and Localized Cranial Scleroderma Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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