Background
Psoriasis is a chronic, noncontagious, multisystem inflammatory disorder. Patients with psoriasis have a genetic predisposition for the illness, which most commonly manifests itself on the skin of the elbows, knees, scalp, lumbosacral areas, intergluteal clefts, and glans penis. The joints are also affected by psoriasis in as many as 30% of patients with the disease. (See Pathophysiology and Etiology.)
Psoriasis has a tendency to wax and wane with flares related to systemic or environmental factors, including life stress events and infection. It impacts quality of life and (potentially) long-term survival. There should be a higher clinical suspicion for depression in the patient with psoriasis. (See Prognosis.)
Multiple types of psoriasis are identified, with plaque-type psoriasis (also known as discoid psoriasis or psoriasis vulgaris) being the most common type. This type usually presents with plaques on the scalp, trunk, and limbs (see the image below). The plaques appear as focal, raised, inflamed, edematous lesions covered with silvery-white “micaceous” scales. (See Clinical Presentation.)
Plaque psoriasis is most common on extensor surfaces of knees and elbows. Image from Randy Park, MD.
Ocular signs occur in approximately 10% of psoriasis patients, and they are more common in men than in women. Patients with ocular findings almost always have psoriatic skin disease; however, it is rare for the eye to become involved before the skin. [1]
The diagnosis of psoriasis is a clinical one. (See Workup.) Management of psoriasis may involve topical or systemic medications, light therapy, stress reduction, climatotherapy, and various adjuncts (eg, sunshine, moisturizers, and salicylic acid). (See Treatment and Management.)
The American Academy of Dermatology (AAD), in conjunction with the National Psoriasis Foundation (NPF), has issued clinical guidelines on the management of psoriasis. [2, 3, 4, 5, 6, 7] The British Association of Dermatologists (BAD) has issued guidelines on the use of biologic agents in the treatment of psoriasis. [8]
Pathophysiology
Psoriasis is a complex, multifactorial disease that appears to be influenced by genetic and immune-mediated components. This is supported by the successful treatment of psoriasis with immune-mediating biologic medications.
The pathogenesis of this disease is not completely understood. Multiple theories exist regarding possible triggers of the disease process, including an infectious episode, a traumatic insult, and a stressful life event. In many patients, no obvious trigger exists at all. However, once the disease process has been triggered, there appears to be substantial leukocyte recruitment to the dermis and epidermis, resulting in the characteristic psoriatic plaques.
Specifically, the epidermis is infiltrated by a large number of activated T cells, which appear to be capable of inducing keratinocyte proliferation. This is supported by histologic examination and immunohistochemical staining of psoriatic plaques revealing large populations of T cells within the psoriasis lesions. One report calculated that a patient with 20% body surface area (BSA) affected with psoriasis lesions has around 8 billion T cells circulating in the blood, compared with approximately 20 billion T cells located in the dermis and epidermis of psoriasis plaques. [9]
Ultimately, a ramped-up, deregulated inflammatory process ensues, with copious production of various cytokines (eg, tumor necrosis factor [TNF]-α, interferon gamma, and interleukin [IL]-12). Many of the clinical features of psoriasis are explained by the large production of such mediators. It is noteworthy that elevated levels of TNF-α specifically are found to correlate with flares of psoriasis. A study by Keaney et al added further support to the view that T-cell hyperactivity and the resulting proinflammatory mediators (in this case, IL-17 and IL-23) play a major role in the pathogenesis of psoriasis. [10]
Key findings in the affected skin of patients with psoriasis include vascular engorgement due to superficial blood vessel dilation and altered epidermal cell cycle. Epidermal hyperplasia leads to acceleration of the cell turnover rate (from 23 d to 3-5 d), resulting in improper cell maturation.
Cells that normally lose their nuclei in the stratum granulosum retain their nuclei, a condition known as parakeratosis. In addition to parakeratosis, affected epidermal cells fail to release adequate levels of lipids, which normally cement adhesions of corneocytes. Subsequently, poorly adherent stratum corneum is formed, leading to the flaking, scaly presentation of psoriasis lesions, the surface of which often resembles silver scales.
In a study by Pietrzak et al, conjunctival impression cytology demonstrated a higher incidence of squamous metaplasia, neutrophil clumping, and nuclear chromatin changes in patients with psoriasis. [11]
Etiology
Psoriasis involves hyperproliferation of the keratinocytes in the epidermis, with an increase in the epidermal cell turnover rate. (See Pathophysiology.) The cause of the loss of control of keratinocyte turnover is unknown. However, environmental, genetic, and immunologic factors appear to play a role.
Environmental factors
Many factors besides stress have also been observed to trigger exacerbations, including cold, trauma, infections (eg, by streptococci, staphylococci, or HIV), alcohol, and drugs (eg, iodides, steroid withdrawal, aspirin, lithium, beta blockers, botulinum A, or antimalarials). One study showed an increased incidence of psoriasis in patients with chronic gingivitis. [12] Satisfactory treatment of the gingivitis led to improved control of the psoriasis but did not influence longterm incidence, highlighting the multifactorial and genetic influences of this disease.
Hot weather, sunlight, and pregnancy may be beneficial, though not universally so. Perceived stress can exacerbate psoriasis. Some authors have suggested that psoriasis is a stress-related disease and have cited findings of increased concentrations of neurotransmitters in psoriatic plaques.
Genetic factors
Patients with psoriasis have a genetic predisposition for the disease. The gene locus is determined. The triggering event may be unknown in most cases, but it is likely immunologic. The first lesion commonly appears after an upper respiratory tract infection.
Psoriasis is associated with certain human leukocyte antigen (HLA) alleles, the strongest association being with HLA-Cw6. In some families, psoriasis is an autosomal dominant trait. Additional HLA antigens that have shown associations with psoriasis and psoriatic subtypes include HLA-B27, HLA-B13, HLA-B17, and HLA-DR7. [13]
A multicenter meta-analysis confirmed that deletion of two late cornified envelope (LCE) genes, LCE3C and LCE3B, is a common genetic factor for susceptibility to psoriasis in different populations. [14]
Obesity is another factor associated with psoriasis. Whether this association is related to weight alone, to genetic predisposition to obesity, or to a combination of the two remains to be established. Psoriasis has been observed to arise or worsen with weight gain, to improve with weight loss, or both. A meta-analysis showed that a body mass index (BMI) of 30 or higher is associated with a poorer response to biologics in patients with psoriasis. [15]
Immunologic factors
Evidence suggests that psoriasis is an autoimmune disease. Studies have shownhigh levels of dermal and circulating TNF-α. Treatment with TNF-α inhibitors is often successful. Psoriatic lesions are associated with increased activity of T cells in the underlying skin.
Psoriasis is related to excess T-cell activity. Experimental models can be induced by stimulation with streptococcal superantigen, which cross-reacts with dermal collagen. This small peptide has been shown to cause increased activity among T cells in patients with psoriasis but not in control groups. Some of the newer drugs used to treat severe psoriasis directly modify the function of lymphocytes.
Also of significance is that 2.5% of those with HIV develop worsening psoriasis with decreasing CD4 counts. This is a paradoxic finding, in that the leading hypothesis on the pathogenesis of psoriasis supports T-cell hyperactivity and treatments geared to reduce T-cell counts help reduce psoriasis severity. This finding is possibly explained by a decrease in CD4 T cells, which leads to overactivity of CD8 T cells, which then drives the worsening psoriasis. The HIV genome may drive keratinocyte proliferation directly.
HIV associated with opportunistic infections may see increased frequency of superantigen exposure, leading to cascades similar to those previously mentioned.
Guttate psoriasis often appears after certain immunologically active events (eg, streptococcal pharyngitis, cessation of steroid therapy, or use of antimalarial drugs).
Epidemiology
US and international statistics
In the United States, approximately 3% of individuals aged 20 years or old have psoriasis. [16]
Internationally, the incidence of psoriasis varies dramatically. A study of 26,000 South American Indians did not reveal a single case of psoriasis, whereas in the Faeroe Islands, an incidence of 2.8% was observed. Overall, as many as 4.4% of people may be affected by psoriasis worldwide. [17]
Age-, sex-, and race-related demographics
Prevalence generally increases with age, with the highest rates in those aged between 50 and 59 years and those older than 70 years; it is lowest in the 20- to 29-year age group. [16] Psoriasis, even severe psoriasis, may occur in the pediatric age group, with a prevalence of 0.5-2% of children. The disease can begin at any age; approximately 10-15% of new cases begin in children younger than 10 years.
Psoriasis appears to be slightly more prevalent among women than among men [16] ; however, men are thought to be more likely to experience the ocular disease.
The frequency of psoriasis is dependent on the climate and genetic heritage of the population. The disease is less common in the tropics and in persons with dark skin. In the United States, according to the NPF, the prevalence of psoriasis is 3.6% in Whites, compared with 2.5% in Asians, 1.9% in Hispanics, and 1.5% in Blacks. [16] A retrospective review found that Black children are significantly more likely than White children to have palmoplantar psoriasis, which is also more common among male children. [18] Both biologic and immunomodulating therapies may be used safely and effectively in pediatric patients. [19]
Prognosis
Although psoriasis is usually benign, it is a lifelong illness with remissions and exacerbations and is sometimes refractory to treatment. It progresses to arthritis in approximately 10% of cases. About 17-55% of patients experience remissions of varying lengths.
A population-based study by Gelfand et al found that mild psoriasis does not appear to increase the risk of death; however, men with severe psoriasis died 3.5 years earlier than men without the disease, and women with severe psoriasis died 4.4 years earlier than women without the disease. [20]
Psoriasis is associated with smoking, alcohol, metabolic syndrome, lymphoma, depression, suicide, potentially harmful drug and light therapies, and possibly melanoma and nonmelanoma skin cancers.
Comorbid conditions
In a population-based cross-sectional study of 9035 psoriasis patients and 90,350 matched controls without psoriasis, those with more extensive psoriatic skin disease were at greater risk for major medical comorbidities, including heart and blood vessel disease, chronic lung disease, diabetes, kidney disease, joint problems, and other health conditions. [21] Overall, the risk for any other type of serious illness was 11% higher for people with mild psoriasis, 15% higher for patients with moderate psoriasis, and 35% higher for those with severe psoriasis.
Findings from a large retrospective study in Canada indicated that the risk of mortality in patients with psoriasis is strongly associated with comorbidities such as liver injury, cardiovascular disease, and affective disorders; however, the risk seems to be reduced among those who receive biologic therapy. [22]
Heart disease
A systematic review of 90 studies confirmed that patients with psoriasis had a higher risk of ischemic heart disease, stroke, and peripheral arterial disease but also a greater prevalence of risk factors for cardiovascular disease, compared with controls. The authors concluded that large prospective studies with long-term followup are required to determine whether psoriasis is an independent risk factor for vascular disease or is merely associated with known risk factors. [23]
Another study identified psoriasis as an independent risk factor for cardiovascular disease in women, especially if they had psoriatic arthritis and suffered from psoriasis for a longer period (>9 y). [24] A large cross-sectional study found that almost one third of patients with severe psoriasis met criteria for coronary microvascular dysfunction. [25]
Hypertension
In a population-based cross-sectional study of 1322 hypertensive patients with psoriasis and 11,977 controls without psoriasis, Takeshita et al found that patients with psoriasis were more likely to suffer from uncontrolled hypertension than those without psoriasis. [26] Patients with moderate-to-severe psoriasis affecting more than 3% of BSA were at the greatest risk. The dose-response relation between uncontrolled hypertension and psoriasis severity remained significant after adjustment for age, sex, BMI, smoking status, alcohol use, comorbid conditions, and current use of antihypertensive medications and nonsteroidal anti-inflammatory drugs (NSAIDs).
Kidney disease
In a study that included more than 800,000 patients (142,883 with psoriasis, 7354 with severe psoriasis, 689,702 without psoriasis), severe psoriasis was associated with a greatly increased risk of chronic kidney disease (CKD). [27] After adjustment for age, sex, cardiovascular disease, diabetes mellitus, hyperlipidemia, hypertension, NSAID use, and BMI, the adjusted hazard ratio for CKD among patients with severe psoriasis was 1.93. In a nested analysis of 8731 psoriasis patients and 87,310 controls, the odds ratio of CKD after similar adjustment was 1.36 in patients with moderate psoriasis and 1.58 in those with severe psoriasis. The relative risk for CKD was highest in younger patients.
Quality of life
Psoriasis can significantly influence quality of life (QoL). The physical and mental disability experienced with this disease can be comparable to or even greater than that found in patients with other chronic illnesses. A study by Kurd et al further supported the notion that psoriasis has a substantial impact on QoL and potentially on long-term survival. [28] There should be a higher level of clinical suspicion for depression in the patient with psoriasis.
The clinical presentation of psoriasis, as well as whatever improvements are made during therapy, is usually evaluated by means of the Psoriasis Area and Severity Index (PASI). However, the effect of the disease on a patient's QoL may be more accurately evaluated by using the Dermatology Life Quality Index (DLQI) or the Children’s Dermatology Life Quality Index (CDLQI). Assessments made with these tools generally show improved QoL with more aggressive treatments (eg, systemic agents). [29, 30]
Studies have shown that psoriasis of the palms and soles tends to have a greater impact on the patient’s QoL than more extensive psoriatic involvement that does not include the palms and soles. [31, 32]
Patient Education
Dry eye and its manifestations may be present. Advising patients to avoid drying conditions and to use lubricants can be effective. Patient recognition of these symptoms is vital for effective early treatment of this disease. Most cases of psoriasis can be controlled at a tolerable level with the regular application of care measures.
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Plaque psoriasis is raised, roughened, and covered with white or silver scale with underlying erythema. Image from Randy Park, MD.
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Guttate psoriasis erupted in this patient after topical steroid therapy was withdrawn during pregnancy. Image from Randy Park, MD.
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Plaque psoriasis is most common on extensor surfaces of knees and elbows. Image from Randy Park, MD.
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Nail psoriasis. Pits, distal onycholysis (nail separation), and brownish staining ("oil spots") are classic nail findings
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Inverse psoriasis. Occurring in skin folds, this will often lack scale seen in other locations.
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Pustular psoriasis of soles. This may be confined to hands and feet (acrodermatitis continua of Hallepeau) or may be part of a generalized pustular psoriasis (von Zumbusch disease)
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- Overview
- Presentation
- DDx
- Workup
- Treatment
- Guidelines
- Medication
- AhR Agonists
- Antineoplastics, Antimetabolites
- Antipsoriatics, Topical
- Calcineurin Inhibitors
- Corticosteroids
- Corticosteroids, Ophthalmic
- Corticosteroids, Topical
- Dermatologics, Tyrosine Kinase Inhibitors
- DMARDs, Immunomodulators
- DMARDs, JAK Inhibitors
- DMARDs, PDE4 Inhibitors
- DMARDs, TNF Inhibitors
- Immunosuppressants
- Interleukin Inhibitors
- Keratolytic Agents
- Ophthalmic Lubricants
- PDE-4 Inhibitors, Topical
- Retinoid-like Agents
- Retinoid-like Agents, Topical
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- Media Gallery
- References
