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Psoriasis and Psoriatic Arthritis Overview

Alan Menter, MD
Psoriasis and psoriatic arthritis (PsA) are chronic immune-mediated diseases that primarily affect the skin and joints, respectively; these diseases are also associated with high rates of cardiovascular and other comorbidities. Despite over 40 genes proven to be related to the disease, the exact causes of psoriasis and PsA are still to be determined. Recent insights into the underlying pathophysiology of these diseases have revealed novel therapeutic targets. Effective management requires timely diagnosis and initiation of treatment. Yet, both psoriasis and PsA remain underrecognized and undertreated in current clinical practice. Recognizing the true physical, social, and emotional burden of psoriasis and PsA, as well as their associated comorbidities, is the first step to improving the prognosis for affected patients.

Am J Manag Care. 2016;22:S216-S224

     Psoriasis is a chronic, multifactorial, immune-mediated skin disease. The characteristic erythematous plaques of psoriasis are often painful and disfiguring, leading to a substantial decrease in quality of life.1 Cardiovascular disease (CVD), diabetes, and other autoimmune disorders are common among patients with psoriasis, contributing to the overall burden of disease and increasing healthcare

resource utilization.1


     Based on an analysis of National Health and Nutrition Examination Survey data from 2009 to 2010, the estimated prevalence of psoriasis among adults 20 years and older in the United States was 3.2%. The prevalence was highest among Caucasians (3.6%), followed by African Americans (1.9%), Hispanics (1.6%), and others (1.4%). Extrapolating to 2013 US census data, an estimated 7.4 million adults in the United States are living with psoriasis.2


The precise pathologic mechanisms that drive the development of psoriasis are extremely complex.However, recent insights into its pathophysiology have enabled a better understanding of the disease and revealed potential new therapeutic targets.4

Immunologic Mechanisms

     Psoriasis is an immune disease that involves abnormally activated cells and molecules of the innate and adaptive immune systems.4 Impaired T-cell activity contributes to the hyperproliferation and abnormal differentiation of epidermal skin cells. Whereas normal epidermal regeneration occurs every 21 to 28 days, the epidermis turns over every 3 to 4 days in patients with psoriasis.3

     Keratinocytes, the most predominant type of epidermal cells, are key mediators of impaired immune cell function. In patients with psoriasis, keratinocytes recruit inflammatory dendritic cells to release interleukin (IL)-12 and IL-23, which, in turn, activate T-cells to produce other psoriatic cytokines, such as IL-17, IL-22, interferon (IFN)-gamma, and tumor necrosis factor-α (TNF-α). In

particular, IL-17 and IL-23 appear to be the dominant cytokines driving the aberrant activity of T-cells and keratinocytes in psoriasis. Current and emerging biologic therapies target these two important cytokines, as well as others, to control psoriatic inflammation.4

Genetics of Psoriasis

     As a multifactorial disease, psoriasis has a complex genetic basis. Genetic studies have revealed more than 40 loci associated with psoriasis susceptibility, each with multiple genes that are involved in skin barrier functions, as well as innate and adaptive immunity. The involvement of these genes and their encoded proteins supports the central role of altered immune function in the pathogenesis of psoriasis.5

     The different clinical phenotypes of psoriasis appear to correspond with distinct immunogenetic profiles.The estimated heritability of psoriasis—a measure that describes how much of the observed phenotypic variation is attributable to genetic variation—is 60% to 90%; this is one of the highest rates among complex genetic diseases. In the future, genetic testing is likely to play an important role in predicting the clinical course of psoriasis, as well as the likelihood of response to specific treatment options.5

Other Risk Factors

In addition to genetics and altered immune function, several other risk factors may predispose patients to psoriasis. These include3:

      • Environmental triggers (infection, stress)

      • Medications (lithium, beta-blockers)

      • Other immune-mediated diseases (Crohn’s disease, multiple sclerosis)

      • Psychogenic stressors, particularly in pediatric patients (emotional or mental stress)

Presentation and Diagnosis

Most patients with psoriasis present without other clinical manifestations. In symptomatic patients, common manifestations include pruritus, fever, and malaise.Even in the absence of comorbid psoriatic arthritis (PsA), joint pain is a common presentation in patients with psoriasis. In one study, 51.8% of patients with psoriasis who did not have PsA reported joint pain. Of those with joint pain, 48.1% experienced pain in more than 4 joints.6

The onset of psoriasis can occur at any age; however, new diagnoses tend to follow a bimodal distribution around young adulthood (20-35 years old) and middle age (50-60 years old). Although male and female patients are affected equally across all age groups, younger men tend to be affected more frequently than younger women.3

The diagnosis of psoriasis is often delayed by several years after symptom onset. In one population-based cohort study of US patients with psoriasis (N = 1005), the median age of diagnosis was 37 years, and the median age of symptom onset was 34 years.6

Disease Classification

     The major subtypes of psoriasis are based on historic descriptions of its underlying histology and morphology. In the clinical setting, however, patients often present with more than 1 subtype of psoriasis.1

Plaque Psoriasis

The most common clinical phenotype is plaque psoriasis, which affects approximately 80% to 90% of patients with this disease (Figure 1). Plaque psoriasis is characterized by well-defined, sharply demarcated, erythematous plaques that vary in size from 1 cm to several centimeters. Plaque involvement can range from a few small lesions to multiple plaques that cover major portions of body surface. Individual plaques tend to be round or oval in shape, with a thin, dry, micaceous or silvery-white scale that can vary in appearance depending on regional anatomic differences. Plaques are most likely to affect the scalp, trunk, buttocks, and extensor aspect of the limbs (knees and elbows). Psoriasis lesions tend to be distributed symmetrically over the body. When lesions are present on the palms, soles, or over joint lines, painful fissuring frequently occur within the plaques, leading to significant disability.1

Pustular Psoriasis

     Neutrophils are commonly present in the outermost layer of the skin in patients with psoriatic lesions. When enough neutrophils accumulate to manifest in clinical signs and symptoms, it is classified as pustular psoriasis (Figure 2). There are 2 major subtypes of pustular psoriasis: generalized and localized. Acute generalized pustular psoriasis is a rare form of severe psoriasis characterized by pustules across multiple body sites, erythematous skin, fever, and systemic toxicity. Palmoplantar pustulosis is a localized form of pustular psoriasis that involves pustules on the palms of the hands and/or soles of the feet.1

Guttate Psoriasis

     Guttate psoriasis affects less than 2% of patients with psoriasis, and it is seen primarily in patients younger than 30 years (Figure 3). Lesions tend to be small (1 to 10 mm), salmon pink in color, and dew drop shaped, with a fine scale. The papules are most likely to affect the trunk and proximal extremities. In younger patients, an upper respiratory infection associated with group A beta-hemolytic streptococci often precedes guttate psoriasis by 2 to 3 weeks.It is not uncommon for papular lesions of guttate psoriasis to appear as suddenly as the initial manifestation of psoriasis in younger patients. Alternatively, guttate psoriasis may occur as an acute exacerbation in older patients with established plaque psoriasis.1

Nail Psoriasis

     Patients with any subtype of psoriasis can also exhibit characteristic psoriatic nail changes, such as pitting (partial loss of cells from the surface of the nail plate), onycholysis (separation of the nail from the nail bed), subungual hyperkeratosis (scaling under the nail), and the oil-drop sign (translucent discoloration in the nail bed). Approximately 60% of all patients with psoriasis will experience fingernail changes, and 35% will experience toenail changes. However, nail psoriasis is considered a marker for PsA, particularly in patients with distal interphalangeal joint involvement (Figure 4).1

Erythrodermic Psoriasis

     Patients with erythrodermic psoriasis present with generalized erythema that covers major portions of the body surface area (BSA). This type of psoriasis can occur suddenly in a patient with little history of the disease or develop gradually from chronic plaques. Erythrodermic skin exhibits altered thermoregulatory properties, leading to a range of potential symptoms, such as hypothermia, chills, dehydration from fluid loss, fever, malaise, lower leg edema, and congestive heart failure (Figure 5).1

Inverse Psoriasis

     Inverse psoriasis describes psoriatic lesions that occur in the skin folds, such as the axillary, genital, abdominal, perineal, intergluteal, and inframammary areas (Figure 6). Because these areas tend to be moist, lesions have minimal scale and are primarily erythemantous in nature; in addition, secondary candidiasis in the regions is not uncommon. Up to 60% of patients with psoriasis have genital involvement.7

Assessment of Disease Activity

     The severity of psoriasis is defined by the areas affected and the percentage of BSA covered. However, psoriasis is classified as severe when lesions affect the hands, feet, face, scalp, or genitals, regardless of the BSA affected. When these areas are not affected, psoriasis is described as:

      • Mild (<5% of BSA)

      • Moderate (5%-10% of BSA)

      • Severe (>10% of BSA)

The majority of patients with psoriasis (70% to 75%) will present with mild to moderate disease.3 Composite measures of disease activity can also be used to assess psoriasis disease severity and monitor the effect of treatment over time.1

Composite Measures of Disease Activity

The Psoriasis Area and Severity Index (PASI), the standard tool in psoriasis clinical trials for assessing baseline disease severity and monitoring therapeutic response, is the most common composite tool for measuring psoriasis severity.1 Calculating the total PASI score is a 2-step process. First, clinicians assign a score from 0 (complete lack) to 4 (most severe possible) to describe

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