Resolving Hyperkeratotic Psoriasis: Mechanisms of Action and Additive Effects of Fixed-Combination Halobetasol Propionate and Tazarotene

August 2025 | Volume 24 | Issue 8 | 795 | Copyright © August 2025


Published online July 31, 2025

Emil A. Tanghetti MDa, Mark G. Lebwohl MDb, Linda Stein Gold MDc, Lawrence Green MDd, Zoe D. Draelos MDe, Abby Jacobson PA-Cf

aCenter for Dermatology and Laser Surgery, Sacramento, CA
bIcahn School of Medicine at Mount Sinai, New York, NY
cHenry Ford Health System, Detroit, MI
dGeorge Washington University School of Medicine, Washington, DC
eDermatology Consulting Services, PLLC, High Point, NC
fBausch Health Companies Inc, Bridgewater, NJ

Abstract
Background: Hyperkeratotic plaque psoriasis represents a distinct morphological variant that is difficult to treat with topical therapies because thick lesions may impede the penetration of active ingredients. The immunoregulatory mechanisms of topical corticosteroids (TCSs) and tazarotene (TAZ) may contribute to combating hyperkeratosis and long-term remittance of psoriasis. A fixed-combination lotion containing the potent-to-superpotent TCS halobetasol propionate (HP, 0.01%) and TAZ (0.045%), indicated for the topical treatment of plaque psoriasis in adults, was developed to harness the therapeutic benefits of each active ingredient while minimizing their safety concerns.
Methods: This review describes data supporting the efficacy of halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) and remittive effect after treatment cessation in patients with hyperkeratotic plaques.
Results: Pivotal trials demonstrate the superior efficacy and safety of HP/TAZ over each active ingredient alone. Furthermore, we summarize a recent clinical study, which showed that HP/TAZ reduces lesional levels of tumor necrosis factor alpha and interleukin 17A, critical proinflammatory cytokines involved in keratinocyte hyperproliferation and psoriasis pathogenesis.
Conclusion: This review suggests that HP/TAZ is a valuable option for the topical treatment of severe hyperkeratotic plaques through its additive mechanisms targeting inflammation and keratinocyte regulation.

INTRODUCTION

Hyperkeratotic psoriatic lesions (plaques that present with severe elevation and scaling) develop from dysregulated proliferation and differentiation of keratinocytes and may be difficult to treat with topical therapy owing to impaired penetration of active ingredients.1-3 Patients with moderate-to-severe scaling experience lower quality of life compared to patients with no-to-mild scaling.4 Therapies that induce long-term remittance by modulating genetic pathways driving inflammation and hyperkeratosis may mitigate these negative sequelae of psoriasis.

Topical corticosteroids (TCSs) have been a mainstay of psoriasis treatment because of their rapid and localized effect, antiinflammatory and antiproliferative properties, and safety when used according to current guidelines.5,6 However, thick hyperkeratotic plaques frequently require treatment with ultrahigh potency TCSs,6 and complete skin clearance may be less likely to occur in patients with thick- versus thin-plaque disease,2 suggesting reduced skin penetration.7 In addition, because of concerns regarding skin atrophy, use of most TCSs is limited to 2 to 4 weeks.6 An exception is halobetasol propionate (HP; 0.01%) lotion, a potent-to-superpotent TCS approved for 8 weeks of continuous use.8

To reduce this risk, TCS is used in combination with the retinoid tazarotene (TAZ),9 which normalizes keratinocyte differentiation and hyperproliferation by modulating the expression of psoriasis-associated genes and antagonizing the signaling of inflammatory mediators.10,11 TAZ is associated with remittance of psoriasis after treatment discontinuation.12,13 However, TAZ alone may cause local skin irritation,9 such as pruritus, erythema, and burning,12 and therefore is not frequently used as monotherapy. The complementary mechanisms of action of TAZ and TCSs, such as HP, in psoriasis warrant their use as a combination therapy to maximize therapeutic benefits and mitigate risks.11