The Use of Oral Antibiotics in the Management of Rosacea

June 2019 | Volume 18 | Issue 6 | Original Article | 506 | Copyright © June 2019

Arielle R. Nagler a, James Del Rosso b.c

aThe Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY &bDR Dermatology Research/Thomas Dermatology, Las Vegas, NV cTouro University Nevada, Henderson, NV

Abstract
Rosacea is common inflammatory facial dermatosis. Rosacea has variable manifestations including facial flushing, central facial erythema, telangiectasias, and papulopustular lesions. Treatment of rosacea is challenging given the varied manifestations and incompletely understood etiology, but the treatment of papulopustular presentations often relies on oral antibiotics. Tetracyclines, specifically doxycycline, are the most commonly prescribed antibiotics for rosacea. Other antibiotics that can be used include macrolides, commonly azithromycin, and rarely, metronidazole. This paper will review the evidence for the use of antibiotics in the treatment of rosacea. 

J Drugs Dermatol. 2019;18(6):506-513.

INTRODUCTION

Rosacea is a common chronic inflammatory facial dermatosis. The prevalence ranges from 1-20% of the population depending on the demographic of the population being studied and the definition of disease.1 The presentation can be variable, but it is often associated with recurrent facial flushing, central facial erythema, telangiectasias, and papulopustular lesions. In some patients, rosacea can progress to localized phymatous changes and fibrosis.2 Classically, rosacea has been classified into four main subtypes: erythematotelangiectatic (ETR), papulopustular (PPR), phymatous, and ocular.3 More recent publications, however, have recommended more individualized classification of rosacea based on clinical manifestations (phenotypic classification).4-6

Rosacea treatment is challenging due to the diversity of clinical manifestations and is often targeted to address the primary manifestations. The flushing (acute vasodilation), persistent background redness, and telangiectasia of rosacea are particularly challenging to treat. Management of these signs relies on topical α1 and α2-adrenergic agonists as well as laser and light-based devices. Selection of treatment for PPR depends on the severity of the lesions. For mild to moderate disease, topical therapies including azelaic acid, metronidazole, and ivermectin are typically utilized. Oral therapies, predominantly antibiotics, have usually been reserved for when topical therapy alone fails or when PPR is more severe.5 This article will review the usage of oral agents classified as antibiotics for the treatment of rosacea including the proposed mechanism of action, the indications for use, the specific agents used, sub-antibiotic doxycycline therapy, and important considerations when prescribing antibiotics.

Rosacea Pathogenesis
The pathophysiology of rosacea is complex, multifactorial, and incompletely understood. Although dysregulation of both the innate and adaptive immune systems, as well as vascular and neuronal dysfunction likely play a role in this complicated cutaneous condition, innate immune system dysfunction is thought to be a central component of rosacea pathogenesis.3 The innate immune system plays a key role in the skin’s response to insults such as microorganisms, reactive oxygen species (ROS) from ultraviolet radiation, and trauma. Normally, innate immune system activation leads to controlled production of pro-inflammatory cytokines and antimicrobial peptides (AMP) in the skin. In contrast, in patients with rosacea, innate immune system mediators are over expressed leading to increased downstream inflammation.2,6 Patients with rosacea have elevated baseline expression of cathelcidin, an AMP, and kallkrien 5.7 Kallikrein 5 is a serine-protease that is the responsible for cleaving cathelicidin into LL-37, its more active form.8 LL-37 promotes inflammation and angiogenesis. Matrix metalloproteinases (MMPs), in particular MMP2 and MMP9, are also overexpressed in patients with rosacea.9 MMP9 directly increases activation of kallkrien 5, thereby promoting LL-37 expression. MMPs also contribute to cytokine induced vascular dysfunction.10

The initial triggers inciting the innate immune system cascade in rosacea are still not well understood, but microorganisms such as Demodex folliculorum, Staphylococcus epidermidis, and Heliobacter pylori are hypothesized to contribute.11-14 The mechanisms by which these microorganisms promote the development of rosacea is unclear. Several studies have discovered differences in D. folliculorum, S. epidermidis, and H.