INTRODUCTION
Psoriasis is an immune-mediated chronic inflammatory skin disease characterized by red, scaly plaques that is attributed to aberrant keratinocyte differentiation and alterations in adaptive and innate immune responses.1,2 Approximately 80% of patients have mild to moderate disease that can be safely and effectively treated with topical therapies.3 Corticosteroids and vitamin D analogs are well established, first-line topical treatments for the management of mild to moderate psoriasis.3
Corticosteroids are a mainstay of psoriasis treatment based on their anti-inflammatory, immunosuppressive, and antiproliferative properties.4,5 However, corticosteroid use is limited by a variety of well-known cutaneous side effects, including atrophy (characterized by reduced skin thickness and elasticity), telangiectasia, and purpura, as well as a risk of hypothalamic-pituitary-adrenal axis suppression due to systemic absorption.3,4 Skin atrophy results from inhibition of the synthesis of extracellular matrix proteins, particularly inhibition of collagen synthesis and lipids.6,7 Corticosteroids influence production of hyaluronic acid (HA), leading to a reduction in HA and associated changes in dermal and epidermal structure. Inhibition of lipid biosynthesis may lead to further disruptions in the stratum corneum, alterations in permeability barrier homeostasis, and increased transepidermal water loss.8,9
Another widely used topical intervention for the management of psoriasis is the vitamin D receptor agonist calcipotriol (Cp; international nonproprietary name [INN]; calcipotriene, US adopted name [USAN]). Vitamin D, or 1,25(OH)2D3, modifies
the differentiation of keratinocytes.10,11 In the management of psoriasis, topical vitamin D analogs directly affect keratinocyte proliferation and differentiation. Additionally, they may also suppress the expression of pro-inflammatory cytokines and thus regulate cytokine production.12,13 Modulation of epidermal lipids and antimicrobial peptides are other presumed actions of vitamin D derivatives. Nonetheless, the precise mechanism of action of vitamin D analogs in psoriasis is not fully understood. The use of topical vitamin D analogs is generally considered safe, although local side effects of burning, pruritus, and erythema are common; systemic effects of hypercalcemia, hypercalciuria, and parathyroid hormone suppression are quite rare.3
Rationale for Combination Therapy
Topical corticosteroids and topical vitamin D analogs appear to target different aspects of the pathogenesis of psoriasis with primarily anti-inflammatory and immunomodulatory effects exerted by corticosteroids and with stimulation of terminal differentiation of keratinocytes being the primary action of vitamin D derivatives. Accordingly, combined use of these 2 independent pharmacologic interventions could presumably enhance efficacy, permit dosage reduction of one or both of the products, and reduce the incidence of side effects.14 Evaluation of combination therapy has, in fact, shown that concomitant or sequential use of corticosteroids and vitamin D analogs is safe and effective for patients with plaque psoriasis.15-17
One specific combination that has been studied is Cp ointment with betamethasone dipropionate (BDP) ointment.18 An evalu-
