Psoriasis: Recommendations for topical corticosteroidsSee anadrol test deca patient information handout on psoriasis corticosteroid mechanism of action in psoriasis, provided by an AAFP staff patient education writer. Psoriasis is a common dermatosis, affecting from 1 to 3 percent of the population. Until recently, the mainstays of topical therapy have been corticosteroids, tars, anthralins and keratolytics. Recently, however, vitamin D analogs, a new anthralin preparation and topical retinoids have expanded physicians' therapeutic armamentarium. These new topical therapies offer increased hope and convenience to the large patient population corticosteroid mechanism of action in psoriasis psoriasis. Psoriasis, one of the most psoriasiis dermatoses, occurs in 1 to 3 percent of the population. While patients with extensive and severe disease may require potent oral therapy, less severe psoriasis is typically treated with topical medications.
Mechanisms of Action of Topical Corticosteroids in Psoriasis
FDA continues investigation of simulated IV s Psoriasis is a common, chronic, immune-mediated disease that primarily affects the skin.
Plaque psoriasis, the most prevalent type of psoriasis, can produce disfiguring, erythematous, scaly lesions. Dermatologists choose from an array of treatment approaches for their patients with psoriasis, often managing mild to moderate plaque psoriasis with topical therapy. Vitamin D analogs, corticosteroids, and sometimes topical retinoids are the mainstay of topical therapy. Each of these agents affects different aspects of the pathophysiologic process involved in psoriasis, including inflammation and abnormal differentiation and hyperproliferation of keratinocytes.
In combination, these agents may provide additive and sometimes synergistic effects. Clinical studies have demonstrated that enhanced efficacy and tolerability can be achieved using fixed-combination therapy with topical vitamin D analogs and corticosteroids as opposed to using each agent alone.
Pharmacists must understand the biologic rationale for the various treatment regimens prescribed for psoriasis, as well as the efficacy and safety profiles of each treatment, so that they can appropriately advise patients about their course of therapy. Factors that affect patient adherence also enter into the treatment decision, as these may affect treatment outcomes. Psoriasis is a chronic immune-mediated disease that manifests primarily in the skin.
Histologically, psoriasis is characterized by epidermal hyperproliferation with incomplete keratinocyte differentiation, inflammatory infiltration, and increased vascularity in the dermis. These immunoregulatory proteins stimulate the differentiation and proliferation of keratinocytes and increase the migration of inflammatory cells into the skin. Because the clinical features and triggers of psoriasis are highly variable, 1,3 the decision-making process for treatment can be complex.
Adding to this complexity is the myriad of therapeutic options available, 1,3 including over-the-counter OTC topical agents eg, salicylic acid, coal tar and prescription topical agents eg, vitamin D analogs, corticosteroids, topical retinoids Figure 1. It is important to note that although current therapies do not cure the disease, they reduce its severity and prolong the length of remissions. Many patients approach pharmacists for advice on psoriasis therapy. Pharmacists make at least one dermatologic recommendation each day, 9 despite having received minimal formal training in dermatology and despite having little opportunity to interact with dermatologists in everyday practice to better understand their treatment strategies.
The article begins with a discussion of patient adherence, as this is critical to successful outcomes.
By keeping in mind the factors that affect tolerability and patient adherence, pharmacists can give informed guidance to patients on their course of therapy. An important consideration in the treatment choice for an individual patient with psoriasis is the effect of the formulation on treatment adherence. The occlusive nature of ointments makes them useful for treating dry or thick hyperkeratotic lesions 14 ; however, they tend to be greasy, which often leads to poor patient satisfaction and adherence.
Adherence is also affected by the dosing frequency. Topical corticosteroids are the cornerstone of psoriasis treatment. Corticosteroids are categorized into seven strengths based on the degree of cutaneous vasoconstriction produced.
The potency of a corticosteroid-containing medication can be influenced by the vehicle in which the corticosteroid is formulated. Topical corticosteroids are effective for most patients with mild to moderate plaque psoriasis on the body and scalp.
Most topical corticosteroids are applied once or twice daily. Symptomatic suppression of the hypothalamic-pituitary-adrenal HPA axis is not commonly seen with low-potency topical corticosteroids. As with corticosteroids, the exact mechanism of action of vitamin D in psoriasis is unknown. Nongenomic effects of vitamin D are regulated by intracellular calcium. Vitamin D analogs are synthetic forms of vitamin D 3. Analogs available for the topical treatment of plaque psoriasis in the United States include calcitriol and calcipotriene calcipotriol.
These vitamin D analogs are available in ointment, cream, solution, and foam formulations, and they are also available in fixed-combination products consisting of calcipotriene and betamethasone dipropionate. The most common adverse effect seen with vitamin D analog therapy is mild irritant contact dermatitis.
Combination therapy with vitamin D analogs and corticosteroids. Vitamin D analogs and corticosteroids appear to act through different mechanisms to control the underlying inflammation and keratinocyte differentiation and proliferation associated with psoriasis.
There is a paucity of preclinical study data, however, to provide a mechanistic explanation for the efficacy of the two agents used in combination. One preclinical study in human T cells showed that the addition of the vitamin D analog calcipotriene to the corticosteroid betamethasone dipropionate in a fixed-combination formulation produced an enhanced immunoregulatory response that was different from the immunosuppressive effect seen with betamethasone dipropionate alone.
When a vitamin D analog and a corticosteroid are used in combination, each agent is applied at different times of day for a twice-daily application course. Multiple studies support the enhanced efficacy observed with the combination of topical vitamin D analogs and corticosteroids Table 2. First-line use of a vitamin D analog plus a corticosteroid improves psoriasis within 2 weeks of initiation and produces maximal improvement after 4 weeks of treatment in most patients.
Nonetheless, the recommendations for topical vitamin D and corticosteroid combination therapy are based on consistent and high-quality patient-oriented evidence. Combination therapy appears to be safe and well tolerated for both short- and long-term use. The low risk of cutaneous adverse events with simultaneously applied combination therapy may be a function of the complementary mechanisms of action of vitamin D analogs and corticosteroids.
The anti-inflammatory actions of corticosteroids are thought to reduce the local irritation caused by vitamin D analogs, whereas vitamin D analogs have the potential to restore epidermal function and counteract corticosteroid-induced atrophy. Systemic adverse events of concern with the combination include vitamin D analog-induced alteration of calcium homeostasis and corticosteroid-induced suppression of the HPA axis. No significant effects of this nature have been observed in clinical studies.
Serum cortisol levels were normal by 60 minutes after the challenge. Dermatologists approach the treatment of mild to moderate psoriasis with individualized treatment plans that take into account disease severity, tolerability of therapy, and potential side effects, as well as factors affecting adherence to the treatment regimen. Topical treatment with vitamin D analogs and corticosteroids is the mainstay of first-line therapy for patients with localized psoriasis.
Pharmacists involved in the care of patients with psoriasis can use their understanding of the pathophysiology of psoriasis and the efficacy and safety associated with various treatment options to provide patients with up-to-date recommendations. Editorial support was provided by Trina Ricci, PhD, of p -value communications. Guidelines of care for the management of psoriasis and psoriatic arthritis: Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics.
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