CHAPTER 60
Psoriasis Regimens^☆

Arjun M. Bashyam, Varun K. Ranpariya, and Steven R. Feldman

Center for Dermatology Research, Wake Forest University School of Medicine, Winston‐Salem, NC, USA

Introduction

Psoriasis is a chronic inflammatory skin disease that affects an estimated 8 million people in the United States and 125 million worldwide, with up to 30% of these patients also suffering from psoriatic arthritis. Men and women are affected equally. The disease may occur at any age, but most frequently starts in the late teens and early 1920s and is most prevalent in the fourth and fifth decades of life. Caucasians are twice as likely as African Americans to have been diagnosed with psoriasis, though this may not translate directly to prevalence in these populations [1]. The etiology of psoriasis is not yet fully characterized. There is tremendous variation in individuals’ disease presentation and response to treatment, adding to the complexity of psoriasis treatment.

The majority of patients with psoriasis have limited, or so called “mild”, disease, covering less than 3% of total body surface area [2]. However, the disease burden does not correlate closely with the extent of disease, and even patients with limited areas of psoriasis can suffer from significant psychosocial stress and depression [3, 4]. Only about one in six people with psoriasis sees a doctor for their disease in any given year; the remaining psoriasis patients do not seek treatment by a dermatologist. They may be untreated, or they may self‐treat with a variety of over‐the‐counter (OTC) medications.

Psoriasis has a large impact on quality of life. A survey by the National Psoriasis Foundation confirmed both the emotional and physical impact of psoriasis [5]. The poor quality of life seen in psoriasis patients is due, in part, to the cutaneous manifestations of the disease and the sometimes burdensome treatment regimens. Patients report physical appearance to be a large negative factor in quality of life. In addition to feeling embarrassed and self‐conscious, the majority of patients experience anger, frustration, and helplessness [5]. The concern over physical appearance increases as the extent of spread of disease increases. Treatment regimens themselves can also negatively impact quality of life, as they often require multiple daily applications, come in messy greasy vehicles, and can be very expensive.

This chapter focuses on the role of OTC medications in psoriasis and describes strengths and weaknesses of different OTC products. We will briefly discuss the role of OTC medications as part of a combination treatment regimen as well as the role of patient adherence in the effectiveness of psoriasis treatments. We also discuss the future development of OTC medications.

Physiology

Psoriasis is a multifactorial, T‐cell mediated autoimmune disease, involving genetics, immune system alterations, and environmental factors. Normal keratinocytes remain in the epidermis for 300 hours, but psoriatic keratinocytes only remain in the epidermis for 36 hours. This shortening of the keratinocyte life cycle is associated with an increased proliferation of keratinocytes and subsequent plaque formation [6]. The pathophysiology behind the shortened keratinocyte life cycle is at least in part due to a complex immune reaction. Both the innate and adaptive immune systems play a role. This cascade is largely driven by dysregulation of helper T cells and their release of cytokines and tumor necrosis factor α (TNF‐α) into the dermis. The presence of cytokines in the dermis triggers infiltration and activation of both polymorphonuclear and mononuclear leukocytes [7]. Many different proinflammatory cytokines, chemokines, and chemical mediators are present in the dermis and epidermis of psoriatic skin, including IL‐4, IL‐6, IL‐12, IL‐22, IL‐23, IL‐17, IFN‐γ and TGF‐β [6, 8]. The roles of each of these cytokines are yet to be fully understood; however, as their roles in psoriasis are becoming clearer, they are increasingly being targeted in biological therapies [9].

Genetics has a large role in psoriasis – up to 70% of identical twins both develop this disease [10]. Psoriasis is associated with certain HLA genotypes and psoriasis susceptibility 1 locus (PSORS1) that codes for the HLA‐Cw6 genotype, a major risk allele [11]. However, no single allele can be called the “psoriasis gene” because there are multiple alleles that contribute to the inheritance and risk of developing psoriasis. There are at least nineteen other genetic loci that have also been identified as psoriasis risk alleles [12]. Complex inherited diseases such as psoriasis require large studies of many affected families in order to begin to identify all the possible genetic loci. Although this is a task that has been difficult to achieve, recent progress has resulted in an increase in candidate genes.

A temporal relationship has been established between psychosocial stress and psoriasis flares [13]. At baseline, psoriasis patients have high stress levels and poor quality of life [14]. Up to 80% of psoriasis patients report that a stressful event triggered a psoriasis flare during the course of their disease. Most of these stress‐related flares occur within 2 weeks of the stressful event [15]. Obesity is a risk factor both for developing psoriasis and for increased severity of psoriasis [16]. Streptococcal type A infections also cause psoriasis outbreaks. The link between streptococcal infections and psoriasis has been extensively researched but no unanimous hypothesis has emerged. Some theories posit there exists molecular mimicry between streptococcal antigens and keratinocytes, while other theories blame bacterial superantigens [6].

These genetic, biologic, and environmental factors combine to create the “perfect storm” of psoriasis. The shortened keratinocyte life cycle results in thick scales that accumulate on the surface of the skin. The inflammatory infiltrates cause dysfunction of skin’s natural barrier. Inflammatory cytokines cause vascular capillary dilatation which results in skin erythema and helps perpetuate the inflammatory process [17]. The end result is dry, cracked, inflamed plaques that can be both painful and pruritic.

Role of OTC medications

Psoriasis education

The first step in any psoriasis treatment regimen is education. Empowering patients with knowledge about their disease allows them to make informed decisions about their care and creates realistic expectations for treatment outcomes. The National Psoriasis Foundation is a great resource for patients, providing educational content, as well as resources to help patients feel less isolated. The Foundation’s website has an OTC treatment guide that provides information on many OTC products commonly used for psoriasis (www.psoriasis.org/about‐psoriasis/treatments/topicals/over‐the‐counter). The site also provides information to help patients screen out nonprescription remedies that are touted for their efficacy, but are, at best, unproven [18].

Role of self‐treating

Patients who self‐treat their psoriasis tend to have mild, localized disease and can achieve a measure of control with OTC medications alone. For these patients, OTC medications may provide symptom relief (reduced pruritus) or improve the skin’s cosmetic appearance [19]. Based on their experiences, some dermatologists may feel OTC medications have little efficacy; however, such an impression may be based on seeing only the patients who have failed to adequately control their disease with OTC medications. People who do achieve adequate control with OTCs alone would be less likely to feel the need to visit a dermatologist – a selection bias. For those patients who do visit a dermatologist for prescription treatment, OTC medications may still play an important adjunctive role in reducing symptoms and improving appearance. For example, OTC medications like moisturizers and keratolytics can serve to increase the efficacy of prescription topical corticosteroids and phototherapy.

Adherence to psoriasis treatment

Psoriasis patients are among those with the poorest adherence to treatment regimens [20]. They have levels of depression and anxiety that are higher than patients with other dermatologic diseases [3]. Depression and disease burden can negatively affect a patient’s ability to adhere to treatment [21]. Adherence to topical medications is worse than adherence to oral medications – the number of daily applications, the chronicity of treatment, and the complexity of the treatment regimen all affect overall adherence [22].

Topicals have traditionally been messy, greasy, and generally unappealing from a cosmetic perspective. When choosing a topical preparation for a patient, that particular patient’s preferences are critical to consider. While ointments may be said to be more efficacious for psoriasis, they will not be efficacious for patients who find them too messy to apply.

OTC medications allow patients access to a wide variety of treatment options at relatively low cost. Patients can try out different vehicles and different combinations of products to achieve the best improvement. OTC products give patients the independence to experiment with products until they find a regimen they prefer, rather than having to go through a dermatologist each time they want to switch products or try something new.

Moisturizers and keratolytics

Dry skin is often a sign of poor barrier function, as is the case in psoriasis. Symptoms of psoriasis include scaling, itching, and increased sensitivity. Moisturizers can improve the skin’s hydration in two ways. First, hydrophobic emollients like petrolatum provide occlusive benefits, meaning they create a physical layer of protection on the surface of the skin that acts to slow epidermal water loss. Second, hydrophilic emollients like glycerine provide humectant benefits, meaning they attract moisture from the air and help skin preserve its water content. Some moisturizers only contain either hydrophobic or hydrophilic elements, but most contain both compounds. The net effect of this increase in moisture on psoriatic skin is a decrease in appearance of scale. The frequency of application and thickness of the applied layer affect success. Moisturizers can often make scale essentially invisible by changing the refractive index of scale so less light is reflected. Several skincare lines such as Cetaphil^® and CeraVe^® have moisturizers and cleansers that they recommend for psoriasis. While these may be popular choices amongst dermatologist in general for sensitive skin and skin diseases, we are unaware of evidence showing that they are any better or worse than other moisturizers. Interestingly, the National Psoriasis Foundation suggests that even cooking oils and shortening can be an effective alternative to often pricey commercial moisturizers [18].

Keratolytics differ from moisturizers in that they break up the scales on the skin’s surface. Keratolytics help decrease the thickness of the hyperkeratotic plaque from the top surface inward by softening the scaly layers allowing for easy removal [23]

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