INTRODUCTION
Rosacea, a condition defined by persistent erythema, may also present with flushing, telangiectasias, edema, enlarged facial blood vessels, and/or vascular nets.1,2,3 The pathophysiology of rosacea is believed to be a culmination of neurovascular dysregulation, altered immune detection and response, and long-term changes to the skin’s superficial vasculature.3 Alterations in the vasculature result from increased angiogenesis, disruptions in cutaneous vascular homeostasis, and endothelial cell damage from inflammatory byproducts.2 These aberrant processes culminate in progressive vascular changes, beginning with increased blood flow to affected skin, followed by persistent vasodilation and proliferation, and ultimately permanent vascular changes.3
Rosacea management is multimodal, employing treatments that modulate inflammation and vascular function. Vessel-targeting therapies, including alpha (É‘) agonists, beta (β) blockers, and laser and light-based therapies, are mainstays in rosacea treatment. Modulation of É‘ and β receptors capitalizes on the sympathetic nervous system’s (SNS) role as the primary regulator of the cutaneous vasculature, while light and laser therapies target vasculature and related inflammation.2,3 This review highlights current evidence supporting the use of various vessel-targeting therapies for rosacea.
Alpha Agonists
As rosacea’s persistent facial erythema (PFE) is secondary to SNS-driven enlargement of superficial cutaneous vasculature, É‘-agonists are supported for use by level B evidence and recommendations published by the American Acne & Rosacea Society (AARS).1,2 É‘-agonists’ efficacy results from targeting É‘-adrenergic receptors in the smooth muscle layer of superficial cutaneous blood vessels.
Oxymetazoline hydrochloride 1% cream is an α1-adrenergic receptor agonist FDA-approved for treating PFE. Clinical studies have shown once daily oxymetazoline to be effective, safe, and tolerable in improving moderate-to-severe PFE. Oxymetazoline’s effects typically begin within 1 to 3 hours, lasting up to 12 hours. Phase III studies showed a 2.2% rate of worsening or rebound erythema (similar to 1.1% in controls), and 23.4% of oxymetazoline users reported increased itching. Brimonidine tartrate 0.33% gel, an α2-adrenergic receptor agonist, is FDA-approved for transient and PFE. Though generally safe, up to 8% of patients may experience transient worsening or rebound erythema.1,2,4 Proposed differences in the anatomic distribution, density, and mechanisms of α1 versus α2 receptors may explain the prevalence of paradoxical erythema with brimonidine.5 Regardless, the unintended erythema associated with brimonidine has made oxymetazoline the favored topical É‘-agonist.
The oral α-2 adrenergic agonist, clonidine, has been shown to reduce flushing and blushing without lowering blood pressure at doses of 0.05 mg twice daily (Figure 1). While some patients respond well to clonidine, no clinical markers have been identified to delineate which patients will benefit, making a trial course of clonidine practical.6
Beta Blockers
Studies of vessel reactivity have shown that β-adrenergic receptors, specifically β-1 receptors, are the most highly expressed adrenergic receptors in cutaneous arteries and arterioles, functionally facilitating vasodilation.7 β-blockers, a class of vasoconstrictors, have been used to treat flushing (supported by level B evidence) and erythema in rosacea.1
In a systematic review of nine studies investigating oral β-blockers for mostly treatment-refractory rosacea, the nonselective β-blockers carvedilol (6.25 to 37.5 mg daily) and propranolol (30 to 120 mg daily) effectively reduced erythema and flushing unresponsive to conventional therapy, while nadolol showed no significant improvement. Rosacea symptoms improved quickly with treatment, and carvedilol was better tolerated than propranolol despite risks like bradycardia, hypotension, and contraindications, including exacerbation of asthma and psoriasis.8
