INTRODUCTION
Psoriasis is a chronic inflammatory autoimmune condition that affects the skin and leads to a significantly reduced quality of life. Approximately 125 million people globally are estimated to be affected.1 Its pathogenesis is multifactorial, resulting from alterations in multiple skin cells including keratinocytes, immune cells, and dermal vascular endothelial cells. These alterations lead to the release of pro-inflammatory mediators inducing the recruitment of a diverse array of immune cells, increased vascularization, and, ultimately, hyperproliferation of keratinocytes in the epidermis, which result in raised, scaly plaques with a compromised epidermal barrier.2 The inflammatory milieu causes a cycle of cellular damage and further cytokine/ chemokine release, thus maintaining a disease state that is difficult to break.3 Furthermore, patients with greater body surface area involvement are at increased risk of cardiovascular co-morbidities.4 While systemic therapies such as biologics have resulted in incredible therapeutic outcomes, especially in those with severe disease, topical therapy remains critical as patients may not necessarily be candidates for systemic therapies or there may be residual cutaneous psoriatic plaques despite systemic therapy that could be cleared with additional topicals.5 These therapies target a particular cytokine/chemokine "hub" such as tumor necrosis factor (TNF)-α, interleukin-17 (IL-17), or interleukin-23 (IL-23). Although these molecules are among the most important mediators of psoriasis, therapies that target them do not necessarily exert direct effects on all key cellular pathways. Thus, there remains a need for comprehensive therapeutics that can simultaneously target all pathogenic cells, thus optimizing efficacy and reducing the likelihood of disease relapse.
Retinoids have long been used in many skin diseases as both topical and systemic therapeutics. As they have been in existence for decades, their effects have been well-studied in numerous cells. They are particularly interesting as they cause various changes in gene expression, which lead to long-standing effects even after their removal. This is clinically beneficial as retinoids may help achieve and maintain an effective therapeutic outcome despite discontinuation, thereby reducing adverse effects and increasing patient compliance. Tazarotene is a retinoid that was approved for the topical treatment of psoriasis over 20 years ago.6
Tazarotene has also been shown to have a desirable remittent effect for several weeks after discontinuation, likely due to its effect on gene expression and reversing the psoriatic transcriptome back toward a normal skin baseline.7,8 This review serves to highlight the cellular mechanisms underpinning the success of tazarotene in psoriasis and to provide a rationale for its use in almost all patients due to its broad effects on almost every cell type implicated in the pathogenesis of psoriasis. Furthermore, this review will discuss the clinical data and implications of the FDA-approved fixed-combination lotion
Retinoids have long been used in many skin diseases as both topical and systemic therapeutics. As they have been in existence for decades, their effects have been well-studied in numerous cells. They are particularly interesting as they cause various changes in gene expression, which lead to long-standing effects even after their removal. This is clinically beneficial as retinoids may help achieve and maintain an effective therapeutic outcome despite discontinuation, thereby reducing adverse effects and increasing patient compliance. Tazarotene is a retinoid that was approved for the topical treatment of psoriasis over 20 years ago.6
Tazarotene has also been shown to have a desirable remittent effect for several weeks after discontinuation, likely due to its effect on gene expression and reversing the psoriatic transcriptome back toward a normal skin baseline.7,8 This review serves to highlight the cellular mechanisms underpinning the success of tazarotene in psoriasis and to provide a rationale for its use in almost all patients due to its broad effects on almost every cell type implicated in the pathogenesis of psoriasis. Furthermore, this review will discuss the clinical data and implications of the FDA-approved fixed-combination lotion
