Faculty Bibliography

Raynaud's Phenomenon is a relatively common disease with both primary and secondary forms. It is well understood as a vasospastic condition affecting the acral and digital arteries resulting in characteristic, well-demarcated color changes typically in the hands and feet in response to cold or stress. Secondary RP has been described in association with a variety of rheumatologic and non-rheumatologic diseases, environmental exposures, and/or medications. While both primary and secondary RP may impact quality of life, SRP may lead to permanent and potentially devastating tissue destruction when undiagnosed and untreated. It is therefore crucial for dermatologists to distinguish between primary and secondary disease forms early in clinical evaluation, investigate potential underlaying causes, and risk stratify SRP patients for the development of associated ACTD. The epidemiology, pathogenesis, and clinical presentation and diagnosis of both forms of Raynaud's Phenomenon are described in detail in this review article.

Raynaud's Phenomenon presents with either primary or secondary disease, of which both have the potential to negatively impact patient quality of life. First-line management of RP should include lifestyle modifications in all patients. Some patients with primary RP and most with secondary RP require pharmacologic therapies which may include CCBs, topical nitrates, PDE-5 inhibitors, or endothelin antagonists. Additional approaches to treatment for those with signs of critical ischemia or those who fail pharmacologic therapy include botulinum toxin injection and digital sympathectomy. Herein, we describe in detail the treatment options for patients with RP, as well as provide treatment algorithms for each RP subtype.

IMPORTANCE/UNASSIGNED:Janus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and vitiligo, but there is a current US Food and Drug Administration (FDA) boxed warning label for oral and topical JAK inhibitors regarding increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), serious infections, malignant neoplasm, and death. However, this boxed warning was precipitated by results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance study, which only included patients with rheumatoid arthritis, and the same association may not be observed in dermatologic conditions. OBJECTIVE/UNASSIGNED:To determine the risk of all-cause mortality, MACE, and VTE with JAK inhibitors in patients with dermatologic conditions. DATA SOURCES/UNASSIGNED:PubMed and ClinicalTrials.gov were searched from database inception to April 1, 2023. STUDY SELECTION/UNASSIGNED:This review included phase 3 randomized clinical trials with a placebo/active comparator group of JAK inhibitors used for a dermatologic indication with FDA approval or pending approval or with European Union or Japanese approval. Studies without a comparison group, case reports, observational studies, and review articles were excluded. DATA EXTRACTION AND SYNTHESIS/UNASSIGNED:This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Adverse events using odds ratios (ORs) and 95% CIs were calculated using a random-effects model and the DerSimonian-Laird method. Studies were screened, data abstracted, and quality assessed by 2 independent authors. The protocol was prospectively registered with PROSPERO. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Primary outcomes were a composite of adjudicated MACE and all-cause mortality, and VTE. RESULTS/UNASSIGNED:The analysis included 35 randomized clinical trials with 20 651 patients (mean [SD] age, 38.5 [10.1] years; male, 54%) and a mean (SD) follow-up time of 4.9 (2.68) months. Findings did not show a significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (OR, 0.83; 95% CI, 0.44-1.57) or VTE (OR, 0.52; 95% CI, 0.26-1.04). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this systematic review and meta-analysis, use of JAK inhibitors was not associated with increased risk of all-cause mortality, MACE, and VTE compared to the placebo/active comparator groups. Additional trials with long-term follow-up are needed to better understand the safety risks of JAK inhibitors used for dermatologic indications.