Advances in pharmacotherapy for rosacea: what is the current state of the art?

ABSTRACT

Introduction

Rosacea is a chronic and relapsing facial dermatosis that encompasses a wide spectrum of clinical phenotypes (transient/persistent erythema, telangiectasias, papules/pustules, edema, phymatous changes, and ocular symptoms) often with uncomfortable symptoms such as flushing, pain, burning, edema, and dryness. Current pharmacological treatment includes topical agents, spanning from several conventional (azelaic acid, metronidazole, sodium sulfacetamide) to new ones (brimonidine, oxymetazoline, ivermectine, minocycline), and systemic agents (doxycycline 40 mg modified-release), all Food and Drug Administration approved.

Areas covered

The aim of our article is to review the state of art of pharmacological treatment, either as monotherapy or in combination therapy, tailored to the most common rosacea phenotypes (persistent erythema, inflammatory papules/pustules). Other off-label topical or systemic drugs and several adjuvant phytotherapeutic agents are considered.

Expert opinion

Combined therapies to target different phenotypes, when present in the same patient, represent one of the major achievements in the management of vascular and inflammatory papules and pustules of rosacea. Future investigations should be addressed to early inflammatory phyma or ocular rosacea, which have actually been neglected. Finally, there is still an ongoing need for therapeutic interventions able to relieve symptoms and social burden, all factors that greatly contribute to improve rosacea quality of life.

KEYWORDS:

• Rosacea
• pharmacotherapy
• topical treatment
• systemic treatment

Article highlights

• Current FDA-approved pharmacological treatment of rosacea includes conventional (azelaic acid, metronidazole, sodium sulfacetamide) and new (brimonidine, oxymetazoline, ivermectine, minocycline) topical agents.

• As of today, there is only one FDA-approved systemic agent (doxycycline 40 mg modified-release) available for inflammatory rosacea in adult patients.

• In case of treatment failure or contraindications, other off-label topical (calcineurin inhibitors, antiparasitic acaricidal agents, antimicrobials, retinoids, dapsone, tranexamic acid) or systemic (tetracyclines, azithromycin, metronidazole, isotretinoin) agents may be considered. Several adjuvant phytotherapeutic agents are also available.

• Optimal rosacea management should rely on the use of combined therapies to target different phenotypes, often present in clinical practice.

• Future areas of investigation should target early inflammatory phyma, ocular rosacea, subjective symptoms, and social burden reduction.

Abbreviations

AARS = American Acne and Rosacea Society

AZA = Azelaic Acid

BT = Brimonidine Tartrate

CEA = Clinician Erythema Assessment

DFD = Minocycline capsules Low-Dose Extended-Release

DLQ = Dermatology Life Quality

DMR = Doxycycline Modified-Release

EQ-5D = EuroQol-5 Dimension

ETR = Erythematotelangiectatic Rosacea

FDA = Food and Drug Administration

FLPP = Flash Lamp Pumped Dye

H = Helper

ILC = Inflammatory Lesions Count

IGA = Investigator Global Assessment

IL = Interleukin

IPL = Intense Pulsed Light

IVM = Ivermectin

KLK = Kallikrein

KTP = Potassium Titanyl Phosphate

LT = Lithium Triborate

MMPs = Matrix Metalloproteinases

MTZ = Metronidazole

Nd:YAG = Neodymium-doped:Yttrium Aluminum Garnet Laser

NLR = Nod-Like Receptor

NLRP3 = NLR Family Pyrin Domain Containing 3

NOS = Nitric Oxide Synthase

NRS = National Rosacea Society

NRSEC = National Rosacea Society Expert Committee

OH = Oxymetazoline Hydrochloride

PDL = Pulsed-Dye Laser

PPR = Papulo-Pustular Rosacea

PSA = Patient’s Self-Assessment

QoL = Quality of Life

RCTs = Randomized Clinical Trials

ROS = Reactive Oxygen Species

ROSCO = ROSacea COnsensus

SNPs = Single-Nucleotide Polymorphisms

SS = Sodium Sulfacetamide

SSA = Subjects’ Self-Assessment

SSS = Sodium Sulfacetamide with Sulfur

TLR-2 = Toll-Like Receptors-2

TNF-α = Tumor Necrosis Factor-α

TRP = Transient Receptors Potential

UV-B = Ultraviolet-B

VEGF = Vascular Endothelial Growth Factor

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.