Page 1 ... development of psoriasis are extremely complex.3. However ... in current clinical practice. ..... Reprinted from Dermatol Clin, 33(1), Tintle SJ, Gottlieb AB, Psoriatic .... Authorship information: Concept and design, drafting of the manu-.
Psoriasis and Psoriatic Arthritis Overview Alan Menter, MD
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
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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
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
The precise pathologic mechanisms that drive the development of psoriasis are extremely complex.3 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
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Psoriasis and Psoriatic Arthritis Overview 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.3 Even in the absence of comorbid psoriatic arthritis (PsA), VOL. 22, NO. 8
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,
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Report n Figure 1. Plaque Psoriasis
n Figure 2. Pustular Psoriasis
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.1 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
Printed with permission from Alan Menter, MD.
n Figure 3. Guttate Psoriasis
Biophoto Associates/Science Source.
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 erythema n www.ajmc.com n
Psoriasis and Psoriatic Arthritis Overview tous in nature; in addition, secondary candidiasis in the regions is not uncommon. Up to 60% of patients with psoriasis have genital involvement.7
n Figure 4. Nail Psoriasis
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 (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 the presence and severity of each of 3 components of psoriatic plaques (erythema, induration, and desquamation) within each of 4 regions of the body (head/neck, trunk, upper extremities, and lower extremities). Second, clinicians estimate the extent of skin involvement by assigning a grade from 0 (no psoriasis) to 6 (90%-100% involvement) to estimate the BSA within each of the 4 body regions. Utilizing a complex algorithm, the individual scores are used to calculate a total PASI score that can range from 0 to 72. In real-world clinical practice, PASI scores higher than 36 are rare.8 Critics of the PASI argue that the tool does not correspond well with the patient’s experience of psoriasis severity. The PASI algorithm assigns equal weight to lesions occurring anywhere on the body; however, plaques that affect the face, hands, and anogenital area are considered by patients to be more severe than those located elsewhere.8 Furthermore, the PASI does not capture other aspects of psoriasis that are important to patients. When patients with psoriasis (N = 1005) were asked to rank the top 5 most important factors contributing to disease severity, more than one-third (36.1%) ranked itching as the most imporVOL. 22, NO. 8
Oil Drop Sign
Nail Plate Dystrophy
Printed with permission from Alan Menter, MD.
n Figure 5. Erythrodermic Psoriasis
Printed with permission from Alan Menter, MD.
n Figure 6. Inverse Psoriasis of the Anus
Dr P. Marazzi/Science Source.
tant factor. Additional factors included location/size of lesions (21.8%), flaking (11.4%), scaling (8.3%), and pain/ swelling of joints (5.4%). Despite being the most important symptom for many patients, itching is not captured in the PASI or other instruments such as the Physician Global Assessment. Therefore, current tools may underestimate the true burden of psoriasis on patients.6 New options for assessing the severity of psoriasis, with an emphasis on patient-reported outcomes, have recently
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Report n Table 1. Social, Physical, and Behavioral Concerns Across the Patient Life Span11 Childhood (Birth to 21 years) • Hyperlipidemia • Obesity • Hypertension • Diabetes mellitus • Rheumatoid arthritis • Crohn’s disease • Depression • Anxiety
Young Adulthood (21 to 35 years) • Stigma • Relationships • Pregnancy • Tobacco use • Alcohol use • Depression • Obesity • Inflammatory bowel disease • Celiac disease • Nonmelanoma skin cancer • Myocardial infarction
Middle Adulthood (35 to 65 years) • Career • Psoriatic arthritis • Metabolic syndrome • Diabetes • Dyslipidemia • Hypertension • Chronic obstructive pulmonary disease • Hepatic disease
Late Adulthood (65 years and older) • Atherosclerosis • Chronic kidney disease • Stroke • Parkinsonism • Malignancy • Mortality
Reprinted from Dermatol Clin, 33(1), Garshick MK, Kimball AB, Psoriasis and the life cycle of persistent life effects, 25-39, Copyright (2015), with permission from Elsevier.
been implemented. These tools facilitate an improved understanding of the impact of psoriasis on patients’ lives, and provide better instruments for measuring the efficacy of powerful new treatments in clinical practice.8 Differential Diagnosis
Not all cases of psoriasis present with characteristic erythematous, scaling, or silvery plaques. When lesions are misleading, the differential diagnosis of psoriasis can be challenging, and it may vary by psoriasis subtype.3 Plaque type psoriasis is often confused with eczema, fungal infections such as tinea corporis, squamous cell carcinoma (Bowen’s disease), cutaneous T-cell lymphoma (CTCL) and subacute cutaneous lupus erythematous. Pustular psoriasis should be differentiated from candidiasis and acute generalized exanthematic pustulosis. Guttate psoriasis can appear similar to secondary syphilis or pityriasis rosea. Erythrodermic psoriasis should be differentiated from pityriasis rubra pilaris, Sézary syndrome, drug eruptions, and even Norwegian scabies. Finally, inverse psoriasis can have a similar presentation to intertrigo, candidiasis, or tinea cruris.3 Comorbidities
Patients with psoriasis, particularly those who are already burdened with moderate to severe skin disease and those with PsA, face a high risk of comorbidities.9 Approximately 75% of patients with psoriasis have at least 1 comorbid condition.6 A recent analysis of a large US administrative claims database revealed the scope and prevalence of comorbidities in patients with psoriasis. The study compared healthcare utilization patterns among patients with moderate to severe psoriasis (N = 5492) and controls without psoriasis
or PsA matched by age, gender, and geographic region (N = 5492). The most common comorbidities in patients with psoriasis were cardiometabolic risk factors such as hyperlipidemia, hypertension, and diabetes. These, as well as multiple other comorbidities including obesity and the metabolic syndrome, occurred with significantly greater frequency among patients with psoriasis than among controls. Hyperlipidemia was present in 33% versus 27%, hypertension in 33% versus 24%, and diabetes in 16% versus 10% of psoriasis versus non-psoriasis patients, respectively; in addition, 22.1% of patients with psoriasis also had a diagnosis of PsA.10 Given their high burden of comorbidities, patients with psoriasis have many interactions with the healthcare system. During the 12-month study period, patients with psoriasis were more likely than individuals without psoriasis to have any prescription medications filled (98.8% vs 76.6%; odds ratio [OR], 27.5; P