Re-thinking Strategies for a Pharmaceutical Approach to Pain-related to Connective Tissue Related Raynaud's Phenomenon in the United States.

Abstract

Introduction: There are no Food and Drug Administration (FDA) approved therapies for Raynaud's phenomenon (RP) treatment in the United States (U.S.). Clinical trials have been challenged by study design. Important advances in RP patient reported outcome measures and mechanistic quantification allows RP-related pain characterization. The rationale for this narrative review is current RP treatment guidelines that focus on vasodilation.

Methods: The question of why there are limitations to RP treatment in the US is addressed through a comprehensive search strategy of published RP-treatment guidelines up until September 1, 2025. Search databases included Medline (PubMed), Embase, and Scopus for index terms, "Raynaud's phenomenon treatment guidelines". If a society guideline was updated, only the most recent was included. Eligibility, data extraction, risk of bias and quality assessment were subject to review by two independent reviewers with a third reviewer resolving discrepancies. US specific considerations of published guidelines are reviewed.

Results: There were 118 published articles that were identified by the search terms 'Raynaud's phenomenon treatment guidelines,' and 27 abstracts were reviewed. There were 4 articles that were published as RP treatment recommendations or guidelines, which were reviewed for full content. Pain management for RP is not included in guideline-based care.

Conclusion: There are advances in outcome measures for quantifying pain now available for RP clinical trials. Large U.S. based registries for systemic sclerosis (SSc) utilizing patient reported outcomes can allow serial data collection on RP and RP-related digital lesions to provide real-world data on medication efficacy for pain relief.