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Rethinking Strategies for a Pharmaceutical Approach to Pain Related to Connective Tissue-Related Raynaud Phenomenon
Tracy M Frech1, Charles G Frech2, W David Merryman2
1Vanderbilt University Medical Center and Tennessee Valley Healthcare System, Nashville, Tennessee.
Objective:
There are no US Food and Drug Administration-approved therapies for Raynaud phenomenon (RP) in the United States. Clinical trials have been challenged by study design. Important advances in RP patient-reported outcome measures and mechanistic quantification allow 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 United States 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 the 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:
A total of 118 published articles were identified by the search terms "Raynaud's phenomenon treatment guidelines," and 27 abstracts were reviewed. Four articles published as RP treatment recommendations or guidelines 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 US-based registries for systemic sclerosis using 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.
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