INTRODUCTION
Rosacea is a chronic inflammatory skin disease that is diagnosed based on clinical findings alone. Central facial erythema, telangiectasia, inflammatory lesions including papules and pustules, phymatous changes, and ocular manifestations characterize this condition.1 Symptoms including burning, stinging, itching, pain, and sensitive skin are commonly reported.2 The incidence of rosacea is estimated to be 5% worldwide.3-5 Traditionally, it has been said that this condition affects primarily Fitzpatrick skin types I and II but recent studies demonstrate that it can affect all skin types and ethnicities and is likely underdiagnosed in patients with skin of color.6 Rosacea is a multifactorial condition that involves a complex interaction between genetics, immune system dysregulation, microorganisms, UV light, neurovascular dysregulation, and impaired barrier function.
Dysregulation of the innate immune system plays a key role in the pathogenesis of rosacea. It occurs due to the activation of toll-like receptor 2 (TLR2) triggering the production of antimicrobial peptides (AMPs) including cathelicidins.7-9 The stimulus for TLR2 activation remains elusive although chitin from Demodex mites and Demodex-associated Bacillus oleronius have been implicated.1,10,11 Staphylococcus epidermidis has been cultured as the sole organism in rosacea-induced pustules.12 S. epidermidis antigens are recognized by TLR2 and can increase the expression of AMPs. Cathelicidins are cleaved by the serine protease kallikrein 5 (KLK5) which is overexpressed in the facial skin of rosacea patients. KLK5 cleaves the precursor protein to its active peptide form LL-37 and various other proteolytic fragments.13,14 These proteolytic fragments influence processes including cytokine release, angiogenesis, leukocyte chemotaxis, and extracellular matrix components.1,15
Dysregulation of the innate immune system plays a key role in the pathogenesis of rosacea. It occurs due to the activation of toll-like receptor 2 (TLR2) triggering the production of antimicrobial peptides (AMPs) including cathelicidins.7-9 The stimulus for TLR2 activation remains elusive although chitin from Demodex mites and Demodex-associated Bacillus oleronius have been implicated.1,10,11 Staphylococcus epidermidis has been cultured as the sole organism in rosacea-induced pustules.12 S. epidermidis antigens are recognized by TLR2 and can increase the expression of AMPs. Cathelicidins are cleaved by the serine protease kallikrein 5 (KLK5) which is overexpressed in the facial skin of rosacea patients. KLK5 cleaves the precursor protein to its active peptide form LL-37 and various other proteolytic fragments.13,14 These proteolytic fragments influence processes including cytokine release, angiogenesis, leukocyte chemotaxis, and extracellular matrix components.1,15
