Systemic sclerosis (scleroderma): remaining challenges.

Area of Science:

• Rheumatology
• Dermatology
• Fibrosis Research

Background:

• Systemic sclerosis (SSc) significantly impacts skin fibrosis, yet effective treatments remain elusive.
• Current disease-modifying antirheumatic drugs (DMARDS) lack proven efficacy for SSc skin fibrosis.
• No FDA-approved medications specifically target cutaneous fibrosis in SSc, with treatments being off-label.

Purpose of the Study:

• To review conventional therapies, biologics, and hematopoietic stem cell transplantation for SSc.
• To summarize ongoing clinical trials focused on cutaneous fibrosis in SSc.
• To highlight the challenges in assessing treatment efficacy due to disease natural history and lack of understanding of molecular mechanisms.

Main Methods:

• Review of existing literature on SSc treatments.
• Summary of current therapeutic approaches including conventional drugs, biologics, and stem cell transplantation.
• Cataloging of ongoing clinical trials for SSc cutaneous fibrosis.

Main Results:

• The modified Rodnan skin score (MRSSS) is the gold standard for measuring skin fibrosis, though disease fluctuation complicates trial assessment.
• Understanding of the molecular mechanisms driving SSc fibrosis is limited, contributing to the empirical nature of many treatments.
• Despite various interventions, effective treatments for SSc skin fibrosis remain a significant unmet need.

Conclusions:

• There is a critical need for novel and effective therapeutic strategies for cutaneous fibrosis in SSc.
• Further research into the underlying molecular mechanisms of SSc fibrosis is essential for developing targeted therapies.
• Ongoing clinical trials represent hope for future treatment advancements in managing SSc skin fibrosis.