Defining Skin Ulcers in Systemic Sclerosis: Systematic Literature Review and Proposed World Scleroderma Foundation...

Area of Science:

• Rheumatology
• Dermatology
• Clinical Trial Methodology

Background:

• Systemic sclerosis (SSc) is a connective tissue disease characterized by skin thickening and potential for ulceration.
• A standardized definition for SSc-related skin ulcers is lacking, hindering consistent clinical trial conduct and data interpretation.
• The absence of a validated definition complicates the assessment of therapeutic efficacy in clinical trials for SSc.

Purpose of the Study:

• To develop a consensus definition for skin ulcers in systemic sclerosis (SSc) suitable for clinical trial application.
• To evaluate the face validity, reliability, and feasibility of the proposed SSc-skin ulcer definition.

Main Methods:

• A systematic literature review (SLR) identified existing skin ulcer definitions.
• SSc experts refined and voted on definition components using a nominal group process.
• Reliability was assessed via expert evaluation of SSc patient cases, and face validity/feasibility by expert application of the definition to patient case report forms.

Main Results:

• The SLR screened 3464 abstracts, fully evaluating 446 articles, with 66 meeting eligibility criteria for definition extraction.
• The consensus definition was refined and voted upon by SSc experts.
• High inter-rater (0.51) and intra-rater (0.90) reliability was achieved, with a mean decision time of 7.4 seconds per lesion. Investigators endorsed the definition's face validity.

Conclusions:

• A preliminary, consensus-based definition for SSc-skin ulcers was successfully developed using SLR and nominal group techniques.
• The developed definition demonstrated strong face validity, feasibility, and reliability, making it suitable for clinical trials.
• This standardized definition is expected to improve consistency and comparability in SSc clinical research.