Clinical, Cellular, and Molecular Aspects in the Pathophysiology of Rosacea

Abstract

Rosacea is a chronic inflammatory skin disease of unknown etiology. Although described centuries ago, the pathophysiology of this disease is still poorly understood. Epidemiological studies indicate a genetic component, but a rosacea gene has not been identified yet. Four subtypes and several variants of rosacea have been described. It is still unclear whether these subtypes represent a “developmental march” of different stages or are merely part of a syndrome that develops independently but overlaps clinically. Clinical and histopathological characteristics of rosacea make it a fascinating “human disease model” for learning about the connection between the cutaneous vascular, nervous, and immune systems. Innate immune mechanisms and dysregulation of the neurovascular system are involved in rosacea initiation and perpetuation, although the complex network of primary induction and secondary reaction of neuroimmune communication is still unclear. Later, rosacea may result in fibrotic facial changes, suggesting a strong connection between chronic inflammatory processes and skin fibrosis development. This review highlights recent molecular (gene array) and cellular findings and aims to integrate the different body defense mechanisms into a modern concept of rosacea pathophysiology.

Ocular rosacea: a review

“…Demodex, a microscopic mite found in hair follicles and sebaceous glands, is the most common ectoparasite in humans. Studies support its role in the activation of immune mechanisms in certain subtypes of rosacea, especially papulopustular rosacea (32) . The Demodex count was shown significantly higher in patients with facial rosacea, and a study demonstrated a strong correlation between positive serum immunoreactivity and ocular Demodex infestation in facial rosacea and lid margin inflammation (41,50,51) .…”

“…Significantly dilated blood and lymphatic vessels were reported in all subtypes of rosacea (29) . Studies further demonstrated an up-regulation of genes involved in vasoregulation and neurogenic inflammation and suggested that dysregulation of mediators and receptors implicated in neurovascular and neuroimmune communication may be crucial at early stages of rosacea (26,29,32) . Improvement of erythema and flushing in rosacea by topical administration of a-adrenergic receptor agonists, oxymetazoline and xylometazoline, helps support this theory (25,33,34) .…”

Infectious agents in the pathogenesis of rosacea

“…Współwystępowanie predyspozycji genetycznej oraz zewnętrznych czynników zaostrzających przyczynia się do nadaktywności szlaków neuroendokrynnych oraz rozwoju stanu zapalnego [2,10]. Do głównych czynników zaostrzających AR zalicza się: stres, spożywanie ostrych potraw i alkoholu, zmiany temperatury, ekspozycję na promieniowanie ultrafioletowe oraz czynniki infekcyjne [6].…”

“…Komórkami o najwyższej aktywności w początko-wym okresie choroby są limfocyty T pomocnicze, makrofagi oraz komórki tuczne. W postaci grudkowo-krostkowej AR następuje aktywacja komórek Langerhansa, eozynofilów i limfocytów NK [10]. Dochodzi do rozszerzenia naczyń krwionośnych, obrzęku oraz rozwoju utrwalonego rumienia (ryc.…”

Antibiotic Resistance Considerations of Importance to Clinical Dermatologists

“…[30][31][32][33][34] As a result, many of the studies of therapies used to treat rosacea (eg tetracyclines, azelaic acid, ivermectin) especially with presence of papulopustular lesions, appear to affect inflammatory pathways/modes of action unrelated to an underlying bacterial trigger that appear to be operative in rosacea pathophysiology (eg inhibition of matrix metalloproteinases, downregulation of cathelicidin pathway, reduction in number of Demodex mites). [35][36][37][38][39][40][41][42][43] The large body of evidence supporting an inflammatory pathogenesis of rosacea that is not triggered by a bacterial etiology has led globally to rosacea management recommendations supporting that avoidance of an antibiotic effect whenever possible is favorable in order to reduce the emergence of antibiotic-resistant bacteria.…”