Psoriasis
Classification and external resources
A person whose back and arms are affected by psoriasis
ICD-10	L40
ICD-9	696
OMIM	177900
DiseasesDB	10895
MedlinePlus	000434
eMedicine	emerg/489 Dermatology:derm/365 plaque derm/361 guttate derm/363 nails derm/366 pustular Arthritis derm/918 Radiology radio/578 Physical Medicine pmr/120
MeSH	D011565

Psoriasis ( /səˈraɪ.əsɨs/) is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious.^[1] However, psoriasis has been linked to an increased risk of stroke, ^[2] and treating high blood lipid levels may lead to improvement.^[3] There are five types of psoriasis: plaque, guttate, inverse, pustular and erythrodermic. The most common form, plaque psoriasis, is commonly seen as red and white hues of scaly patches appearing on the top first layer of the epidermis (skin). Some patients, though, have no dermatological symptoms. The name wikt:psoriasis is from Ancient Greek, meaning roughly "itching condition" (psora "itch" + -sis "action, condition").

In plaque psoriasis, skin rapidly accumulates at these sites, which gives it a silvery-white appearance. Plaques frequently occur on the skin of the elbows and knees, but can affect any area, including the scalp, palms of hands and soles of feet, and genitals. In contrast to eczema, psoriasis is more likely to be found on the outer side of the joint.

The disorder is a chronic recurring condition that varies in severity from minor localized patches to complete body coverage. Fingernails and toenails are frequently affected (psoriatic nail dystrophy) and can be seen as an isolated symptom. Psoriasis can also cause inflammation of the joints, which is known as psoriatic arthritis. Between 10-30% of all people with psoriasis also have psoriatic arthritis.^[4][5]

The cause of psoriasis is not fully understood, but it is believed to have a genetic component and local psoriatic changes can be triggered by an injury to the skin known as the Koebner phenomenon.^[6] Various environmental factors have been suggested as aggravating to psoriasis, including stress, withdrawal of systemic corticosteroid, as well as other environmental factors, but few have shown statistical significance.^[7] There are many treatments available, but because of its chronic recurrent nature, psoriasis is a challenge to treat. Withdrawal of corticosteroids (topical steroid cream) can aggravate the condition due to the 'rebound effect' of corticosteroids.^[8]

Classification[link]

The symptoms of psoriasis can manifest in a variety of forms. Variants include plaque, pustular, guttate and flexural psoriasis. This section describes each type (with ICD-10 code ^[9]).^[10]

Psoriasis is a chronic relapsing disease of the skin that may be classified into nonpustular and pustular types as follows^[11]:

Nonpustular[link]

• Psoriasis vulgaris (chronic stationary psoriasis, plaque-like psoriasis)(L40.0) is the most common form of psoriasis. It affects 80 to 90% of people with psoriasis. Plaque psoriasis typically appears as raised areas of inflamed skin covered with silvery white scaly skin. These areas are called plaques.

• Psoriatic erythroderma (erythrodermic psoriasis)(L40.85) involves the widespread inflammation and exfoliation of the skin over most of the body surface. It may be accompanied by severe itching, swelling and pain. It is often the result of an exacerbation of unstable plaque psoriasis, particularly following the abrupt withdrawal of systemic treatment. This form of psoriasis can be fatal, as the extreme inflammation and exfoliation disrupt the body's ability to regulate temperature and for the skin to perform barrier functions.^[12]

Pustular[link]

Pustular psoriasis (L40.1-3, L40.82) appears as raised bumps that are filled with noninfectious pus (pustules). The skin under and surrounding the pustules is red and tender. Pustular psoriasis can be localised, commonly to the hands and feet (palmoplantar pustulosis), or generalised with widespread patches occurring randomly on any part of the body. Types include:

• Generalized pustular psoriasis (pustular psoriasis of von Zumbusch)
• Pustulosis palmaris et plantaris (persistent palmoplantar pustulosis, pustular psoriasis of the Barber type, pustular psoriasis of the extremities)
• Annular pustular psoriasis
• Acrodermatitis continua
• Impetigo herpetiformis

Other[link]

Additional types of psoriasis include^[13]:

• Drug-induced psoriasis

• Inverse psoriasis (flexural psoriasis, inverse psoriasis)(L40.83-4) appears as smooth inflamed patches of skin. It occurs in skin folds, particularly around the genitals (between the thigh and groin), the armpits, under an overweight abdomen (panniculus), and under the breasts (inframammary fold). It is aggravated by friction and sweat, and is vulnerable to fungal infections.

• Napkin psoriasis

• Seborrheic-like psoriasis

Guttate psoriasis (L40.4) is characterized by numerous small, scaly, red or pink, teardrop-shaped lesions. These numerous spots of psoriasis appear over large areas of the body, primarily the trunk, but also the limbs and scalp. Guttate psoriasis is often preceded by a streptococcal infection, typically streptococcal pharyngitis. The reverse is not true.

Nail psoriasis (L40.86) produces a variety of changes in the appearance of finger and toe nails. These changes include discolouring under the nail plate, pitting of the nails, lines going across the nails, thickening of the skin under the nail, and the loosening (onycholysis) and crumbling of the nail.

Psoriatic arthritis (L40.5) involves joint and connective tissue inflammation. Psoriatic arthritis can affect any joint, but is most common in the joints of the fingers and toes. This can result in a sausage-shaped swelling of the fingers and toes known as dactylitis. Psoriatic arthritis can also affect the hips, knees and spine (spondylitis). About 10–15% of people who have psoriasis also have psoriatic arthritis.

The migratory stomatitis in the oral cavity mucosa and the geographic tongue that confined to the dorsal and lateral aspects of the tongue mucosa, are believed to be oral manifestations of psoriasis, as being histologically identical to cutaneous psoriasis lesions and more prevalent among psoriasis patients^[14], although these conditions are quite common in the non-psoriatic population, affecting 1% to 2.5% of the general population.^[14]

Signs and symptoms[link]

• 

  Plaque of psoriasis

• 

  Plaque of psoriasis

• 

  A person's arm covered with plaque psoriasis

• Psoriasis fingernail.jpg

  Psoriasis of a fingernail

Quality of life[link]

Severe cases of psoriasis have been shown to affect health-related quality of life to an extent similar to the effects of other chronic diseases, such as depression, hypertension, congestive heart failure or type 2 diabetes.^[15] Depending on the severity and location of outbreaks, individuals may experience significant physical discomfort and some disability. Itching and pain can interfere with basic functions, such as self-care, walking, and sleep. Plaques on hands and feet can prevent individuals from working at certain occupations, playing some sports, and caring for family members or a home. Plaques on the scalp can be particularly embarrassing, as flaky plaque in the hair can be mistaken for dandruff. Medical care can be costly and time-consuming, and can interfere with an employment or school schedule.

Individuals with psoriasis may also feel self-conscious about their appearance and have a poor self-image that stems from fear of public rejection and psychosexual concerns. Psychological distress can lead to significant depression and social isolation.

In a 2008 National Psoriasis Foundation survey of 426 psoriasis sufferers, 71 percent reported the disease was a significant problem in everyday life. More than half reported significant feelings of self-consciousness (63 percent) and embarrassment (58 percent). More than one-third said they avoided social activities and limited dating or intimate interactions.^[16]

Many tools exist to measure quality of life of patients with psoriasis and other dermatalogical disorders. Clinical research has indicated individuals often experience a diminished quality of life.^[17] A 2009 study looked at the impact of psoriasis by using interviews with dermatologists and exploring patients viewpoint. It found that in cases of mild and severe psoriasis, itch contributed most to the diminished health-related quality of life (HRQoL).^[18]

According to a study published in 2010 in the Journal of the American Academy of Dermatology, the reliability of a simple six-point Likert scale for self-assessment of pruritus (itching) by patients was validated in patients with moderate to severe plaque psoriasis.^[19] This will allow better communication, assessment, as well as staging and management of itching. It could also allow future studies to objectively evaluate the effectiveness of therapy directed towards itching, with consequent improvement in quality of life.^[20]

Severity[link]

Psoriasis is usually graded as mild (affecting less than 3% of the body), moderate (affecting 3–10% of the body) or severe.^{[citation needed]} Several scales exist for measuring the severity of psoriasis. The degree of severity is generally based on the following factors: the proportion of body surface area affected; disease activity (degree of plaque redness, thickness and scaling); response to previous therapies; and the impact of the disease on the person.

The Psoriasis Area Severity Index (PASI) is the most widely used measurement tool for psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease).^[21] Nevertheless, the PASI can be too unwieldy to use outside of trials, which has led to attempts to simplify the index for clinical use.^[22]

Cause[link]

The cause of psoriasis is not fully understood. There are two main hypotheses about the process that occurs in the development of the disease. The first considers psoriasis as primarily a disorder of excessive growth and reproduction of skin cells. The problem is simply seen as a fault of the epidermis and its keratinocytes. The second hypothesis sees the disease as being an immune-mediated disorder in which the excessive reproduction of skin cells is secondary to factors produced by the immune system. T cells (which normally help protect the body against infection) become active, migrate to the dermis and trigger the release of cytokines (tumor necrosis factor-alpha TNFα, in particular) which cause inflammation and the rapid production of skin cells. It is not known what initiates the activation of the T cells.

The immune-mediated model of psoriasis has been supported by the observation that immunosuppressant medications can clear psoriasis plaques. However, the role of the immune system is not fully understood, and it has recently been reported that an animal model of psoriasis can be triggered in mice lacking T cells.^[23] Animal models, however, reveal only a few aspects resembling human psoriasis.

Compromised skin barrier function has a role in psoriasis susceptibility.^[24]

Psoriasis is a fairly idiosyncratic disease. The majority of people's experience of psoriasis is one in which it may worsen or improve for no apparent reason. Studies of the factors associated with psoriasis tend to be based on small (usually hospital based) samples of individuals. These studies tend to suffer from representative issues, and an inability to tease out causal associations in the face of other (possibly unknown) intervening factors. Conflicting findings are often reported. Nevertheless, the first outbreak is sometimes reported following stress (physical and mental), skin injury, and streptococcal infection. Conditions that have been reported as accompanying a worsening of the disease include infections, stress, and changes in season and climate. Certain medicines, including lithium salt, beta blockers and the antimalarial drug chloroquine have been reported to trigger or aggravate the disease. Excessive alcohol consumption, smoking and obesity may exacerbate psoriasis or make the management of the condition difficult or perhaps these comorbidities are effects rather than causes.^[25][26] Hairspray, some face creams and hand lotions, can also cause an outbreak of psoriasis.^{[citation needed]} In 1975, Stefania Jablonska and collaborators advanced a new theory that special antibodies tend to break through into the lower layers of the skin and set up a complex series of chemical reactions.^[27]

Individuals suffering from the advanced effects of the human immunodeficiency virus, or HIV, often exhibit psoriasis.^[28] This presents a paradox to researchers, as traditional therapies that reduce T-cell counts generally cause psoriasis to improve. Yet, as CD4-T-cell counts decrease with the progression of HIV, psoriasis worsens.^[29] In addition, HIV is typically characterized by a strong Th2 cytokine profile, whereas psoriasis vulgaris is characterized by a strong Th1 secretion pattern.^[30] It is hypothesized that the diminished CD4-T-Cell presence causes an overactivation of CD8-T-cells, which are responsible for the exacerbation of psoriasis in HIV positive patients. It is important to remember that most individuals with psoriasis are otherwise healthy, and the presence of HIV accounts for less than 1% of cases. The prevalence of psoriasis in the HIV positive population ranges from 1 to 6 percent, which is about three times higher than the normal population.^[31] Psoriasis in AIDS sufferers is often severe, and untreatable with conventional therapy.^[32]

Psoriasis occurs more likely in dry skin than oily or well-moisturized skin, and specifically after an external skin injury such as a scratch or cut (see Koebner phenomenon). This is believed to be caused by an infection, in which the infecting organism thrives under dry skin conditions with minimal skin oil, which otherwise protects skin from infections. The case for psoriasis is opposite to the case of athlete's foot, which occurs because of a fungus infection under wet conditions as opposed to dry in psoriasis. This infection induces inflammation, which causes the symptoms commonly associated with psoriasis, such as itching and rapid skin turnover, and leads to drier skin, as the infecting organism absorbs the moisture that would otherwise go to the skin. To prevent dry skin and reduce psoriasis symptoms, it is advised to not use shower scrubs, as they not only damage skin by leaving tiny scratches, but they also scrape off the naturally occurring skin oil. Additionally, moisturizers can be applied to moisturize the skin, and lotions used to promote skin oil gland functions.^{[citation needed]}

Genetics[link]

Psoriasis has a large hereditary component, and many genes are associated with it, but it is not clear how those genes work together. Most of them involve the immune system, particularly the major histocompatibility complex (MHC) and T cells. The main value of genetic studies is they identify molecular mechanisms and pathways for further study and potential drug targets.^[33]

Classic genomewide linkage analysis has identified nine locations (loci) on different chromosomes associated with psoriasis. They are called psoriasis susceptibility 1 through 9 (PSORS1 through PSORS9). Within those loci are genes. Many of those genes are on pathways that lead to inflammation. Certain variations (mutations) of those genes are commonly found in psoriasis.^[33]

The major determinant is PSORS1, which probably accounts for 35–50% of its heritability. It controls genes that affect the immune system or encode proteins that are found in the skin in greater amounts in psoriasis. PSORS1 is located on chromosome 6 in the MHC, which controls important immune functions. Three genes in the PSORS1 locus have a strong association with psoriasis vulgaris: HLA-C variant HLA-Cw6, which encodes a MHC class I protein; CCHCR1, variant WWC, which encodes a coiled protein that is overexpressed in psoriatic epidermis; and CDSM, variant allele 5, which encodes corneodesmosin, which is expressed in the granular and cornified layers of the epidermis and upregulated in psoriasis.^[33]

Genome-wide association scans have identified other genes which are altered to characteristic variants in psoriasis. Some of these genes express inflammatory signal proteins, which affect cells in the immune system that are also involved in psoriasis. Some of these genes are also involved in other autoimmune diseases.^[33]

Two major genes under investigation are IL12B on chromosome 5q, which expresses interleukin-12B; and IL23R on chromosome 1p, which expresses the interleukin-23 receptor, and is involved in T cell differentiation. T cells are involved in the inflammatory process that leads to psoriasis.^[33]

These genes are on the pathway that ends up upregulating tumor necrosis factor-α and nuclear factor κB, two genes that are involved in inflammation.^[33]

Recently the first gene directly linked to psoriasis has been identified. Studies have suggested that a rare mutation in the gene encoding for the CARD14 protein plus an environmental trigger was enough to cause plaque psoriasis (the most common form of psoriasis).^[34][35]

Immunology[link]

In psoriasis, immune cells move from the dermis to the epidermis, where they stimulate skin cells (keratinocytes) to proliferate. Psoriasis does not seem to be a true autoimmune disease.^[33] In an autoimmune disease, the immune system confuses an outside antigen with a normal body component, and attacks them both. But in psoriasis, the inflammation does not seem to be caused by outside antigens (although DNA does have an immunostimulatory effect). Researchers have identified many of the immune cells involved in psoriasis, and the chemical signals they send to each other to coordinate inflammation. At the end of this process, immune cells, such as dendritic cells and T cells, move from the dermis to the epidermis, secreting chemical signals, such as tumor necrosis factor-α, interleukin-1β, and interleukin-6, which cause inflammation, and interleukin-22, which causes keratinocytes to proliferate.^[33]

The immune system consists of an innate immune system, and an adaptive immune system.

In the innate system, immune cells have receptors that have evolved to target specific proteins and other antigens which are commonly found on pathogens. In the adaptive immune system, immune cells respond to proteins and other antigens that they may never have seen before, which are presented to them by other cells. The innate system often passes antigens on to the adaptive system. When the immune system makes a mistake, and identifies a healthy part of the body as a foreign antigen, the immune system attacks that protein, as it does in autoimmunity.

In psoriasis, DNA is an inflammatory stimulus. DNA stimulates the receptors on plasmacytoid dendritic cells, which produce interferon-α, an immune stimulatory signal (cytokine). In psoriasis, keratinocytes produce antimicrobial peptides. In response to dendritic cells and T cells, they also produce cytokines, such as interleukin-1, interleukin-6, and tumor necrosis factor-α, which signals more inflammatory cells to arrive and produces further inflammation.^[33]

Dendritic cells bridge the innate and adaptive immune system. They are increased in psoriatic lesions and induce the proliferation of T cells and type 1 helper T cells. Certain dendritic cells can produce tumor necrosis factor-α, which calls more immune cells and stimulates more inflammation. Targeted immunotherapy, and psoralen and ultraviolet A (PUVA) therapy, reduces the number of dendritic cells.^[33]

T cells move from the dermis into the epidermis. They are attracted to the epidermis by alpha-1 beta-1 integrin, a signalling molecule on the collagen in the epidermis. Psoriatic T cells secrete interferon-γ and interleukin-17. Interleukin-17 is also associated with interleukin-22. Interleukin-22 induces keratocytes to proliferate.^[33]

One hypothesis is that psoriasis involves a defect in regulatory T cells, and in the regulatory cytokine interleukin-10.^[33]

Diagnosis[link]

A diagnosis of psoriasis is usually based on the appearance of the skin; there are no special blood tests or diagnostic procedures. Sometimes, a skin biopsy, or scraping, may be needed to rule out other disorders and to confirm the diagnosis. Skin from a biopsy will show clubbed rete pegs if positive for psoriasis. Another sign of psoriasis is that when the plaques are scraped, one can see pinpoint bleeding from the skin below (Auspitz's sign).

Management[link]

Schematic of psoriasis treatment ladder

There are a number of different treatment options for psoriasis. Typically topical agents are used for mild disease, phototherapy for moderate disease, and systemic agents for severe disease.^[36]

Topical agents[link]

Bath solutions and moisturizers, mineral oil, and petroleum jelly may help soothe affected skin and reduce the dryness which accompanies the build-up of skin on psoriatic plaques. Medicated creams and ointments applied directly to psoriatic plaques can help reduce inflammation, remove built-up scale, reduce skin turn over, and clear affected skin of plaques. Ointment and creams containing coal tar, dithranol (anthralin), corticosteroids like desoximetasone (Topicort), fluocinonide, vitamin D₃ analogues (for example, calcipotriol), and retinoids are routinely used. The use of the Finger tip unit may be helpful in guiding how much topical treatment to use.^[37] The mechanism of action of each is probably different, but they all help to normalise skin cell production and reduce inflammation. Activated vitamin D and its analogues can inhibit skin cell proliferation.

Phototherapy[link]

Phototherapy in the form of sunlight has long been used effectively for treatment.^[36] Wavelengths of 311–313 nm are most effective and special lamps have been developed for this application.^[36] The amount of light used is determined by a persons skin type.^[36] Increased rates of cancer from treatment appear to be small.^[36]

Psoralen and ultraviolet A phototherapy (PUVA) combines the oral or topical administration of psoralen with exposure to ultraviolet A (UVA) light. The mechanism of action of PUVA is unknown, but probably involves activation of psoralen by UVA light, which inhibits the abnormally rapid production of the cells in psoriatic skin. There are multiple mechanisms of action associated with PUVA, including effects on the skin immune system.

PUVA is associated with nausea, headache, fatigue, burning, and itching. Long-term treatment is associated with squamous cell carcinoma (but not with melanoma).^{[citation needed]}

Systemic agents[link]

Pictures of a patient with psoriasis (and psoriatic arthritis) at baseline and 8 weeks after initiation of infliximab therapy.

Psoriasis that is resistant to topical treatment and phototherapy is treated by medications taken internally by pill or injection (systemic). Patients undergoing systemic treatment are required to have regular blood and liver function tests because of the toxicity of the medication. Pregnancy must be avoided for the majority of these treatments. Most people experience a recurrence of psoriasis after systemic treatment is discontinued.

The three main traditional systemic treatments are methotrexate, cyclosporine and retinoids. Methotrexate and cyclosporine are immunosuppressant drugs; retinoids are synthetic forms of vitamin A. Patients taking methotrexate are prone to ulcerations. Methotrexate exposure may contribute to post-surgical events.^[38]

Biologics are manufactured proteins that interrupt the immune process involved in psoriasis. Unlike generalised immunosuppressant therapies such as methotrexate, biologics focus on specific aspects of the immune function leading to psoriasis. These drugs (interleukin antagonists) are relatively new, and their long-term impact on immune function is unknown, but they have proven effective in treating psoriasis and psoriatic arthritis. Biologics are usually given by self-injection or in a doctor's office. In the United Kingdom in 2005, the British Association of Dermatologists (BAD) published guidelines for use of biological interventions in psoriasis.^[39] A UK national register called the BAD Biological Register (BADBIR) has been set up to collect valuable information on side effects and benefits and will be used to inform doctors on how best to use biological agents and similar drugs.

Two drugs that target T cells are efalizumab and alefacept. Efalizumab is a monoclonal antibody which blocks the molecules that dendritic cells use to communicate with T cells. It also blocks the adhesion molecules on the endothelial cells that line blood vessels, which attract T cells. However, it suppressed the immune system's ability to control normally harmless viruses, which led to fatal brain infections. Efalizumab was voluntarily withdrawn from the US market in April, 2009 by the manufacturer. Alefacept also blocks the molecules that dendritic cells use to communicate with T cells and even causes natural killer cells to kill T cells as a way of controlling inflammation.^[33]

Several monoclonal antibodies (MAbs) target cytokines, the molecules that cells use to send inflammatory signals to each other. TNF-α is one of the main executor inflammatory cytokines. Four MAbs (infliximab, adalimumab, golimumab and certolizumab pegol) and one recombinant TNF-α decoy receptor, etanercept, have been developed against TNF-α to inhibit TNF-α signaling. Additional monoclonal antibodies have been developed against pro-inflammatory cytokines IL-12/IL-23 and Interleukin-17 ^[40] and inhibit the inflammatory pathway at a different point than the anti-TNF-α antibodies.^[33] IL-12 and IL-23 share a common domain, p40, which is the target of the recently FDA-approved ustekinumab. Ustekinumab (IL-12/IL-23 blocker) was shown to have higher efficacy than high-dose etanercept over a 12-week period in patients with psoriasis.^[41]

In 2008, the FDA approved three new treatment options^[42] available to psoriasis patients: 1) Taclonex Scalp, a new topical ointment for treating scalp psoriasis; 2) the Xtrac Velocity excimer laser system, which emits a high-intensity beam of ultraviolet light, can treat moderate to severe psoriasis; and 3) the biologic drug adalimumab (brand name Humira) was also approved to treat moderate to severe psoriasis. Adalimumab had already been approved to treat psoriatic arthritis. The most recent biologic drug that has been approved to treat moderate to severe psoriasis, as of 2010, is ustekinumab (brand name Stelara).

Medications with the least potential for adverse reactions are preferentially employed. If the treatment goal is not achieved, then therapies with greater potential toxicity may be used. Medications with significant toxicity are reserved for severe unresponsive psoriasis. This is called the psoriasis treatment ladder.^[43] As a first step, medicated ointments or creams, called topical treatments, are applied to the skin. If topical treatment fails to achieve the desired goal, then the next step would be to expose the skin to ultraviolet (UV) radiation. This type of treatment is called phototherapy. The third step involves the use of medications which are taken internally by pill or injection. This approach is called systemic treatment.

A 2010 meta-analysis compares the change in Psoriasis Area and Severity Index (PASI) improvement from baseline in 22 trials. The combination therapy for moderate to severe psoriasis using psoralen with ultraviolet A (PUVA) plus acitretin shows a 97.3% PASI improvement from baseline. Therapy limitations need to be taken into consideration in the treatment of moderate to severe psoriasis, such as the increased risk of skin cancer with phototherapy and birth defects with acitretin.^[44]

Alternative therapy[link]

Some studies suggest psoriasis symptoms can be relieved by changes in diet and lifestyle. Fasting periods, low energy diets and vegetarian diets have improved psoriasis symptoms in some studies,^[45] and diets supplemented with fish oil (in this study cod liver oil) have also shown beneficial effects.^[45] Fish oils are rich in the two omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and contain Vitamin E, furthermore cod liver oil contains Vitamin A and Vitamin D.

The severity of psoriasis symptoms may also be influenced by lifestyle habits related to alcohol, smoking, weight, sleep, stress and exercise.^[46]

It has been suggested that cannabis might treat psoriasis, due to the anti-inflammatory properties of its cannabinoids, and their regulatory effects on the immune system.^[47] The adverse effects of cannabis might be avoided with a topical preparation or by the use of (a) more specific endocannabinoid receptor agonist(s),^[48]

Prognosis[link]

Psoriasis is typically a lifelong condition. There is currently no cure, but various treatments can help to control the symptoms.^[49] Many of the most effective agents used to treat severe psoriasis carry an increased risk of significant morbidity including skin cancers, lymphoma and liver disease. However, the majority of people's experience of psoriasis is that of minor localized patches, particularly on the elbows and knees, which can be treated with topical medication. Psoriasis can get worse over time, but it is not possible to predict who will go on to develop extensive psoriasis or those in whom the disease may appear to vanish. Individuals will often experience flares and remissions throughout their lives. Controlling the signs and symptoms typically requires lifelong therapy.

According to one study,^[50] psoriasis is linked to 2.5-fold increased risk for nonmelanoma skin cancer in men and women, with no preponderance of any specific histologic subtype of cancer. This increased risk could also be attributed to antipsoriatic treatment.

Epidemiology[link]

Psoriasis affects both sexes equally, and can occur at any age, although it most commonly appears for the first time between the ages of 15 and 25 years.

The prevalence of psoriasis in Western populations is estimated to be around 2-3%. The prevalence of psoriasis among 7.5 million patients who were registered with a general practitioner in the United Kingdom was 1.5%.^[51] A survey^[52] conducted by the National Psoriasis Foundation (a US-based psoriasis education and advocacy group) found a prevalence of 2.1% among adult Americans. The study found 35% of people with psoriasis could be classified as having moderate to severe psoriasis.

Around one-third of people with psoriasis report a family history of the disease, and researchers have identified genetic loci associated with the condition. Studies of monozygotic twins suggest a 70% chance of a twin developing psoriasis if the other twin has psoriasis. The concordance is around 20% for dizygotic twins. These findings suggest both a genetic predisposition and an environmental response in developing psoriasis.^[53]

Onset before age 40 usually indicates a greater genetic susceptibility and a more severe or recurrent course of psoriasis.

History[link]

Some scholars believe psoriasis to have been included among the skin conditions called tzaraat in the Bible.^[54] In more recent times psoriasis was frequently described as a variety of leprosy.^{[citation needed]} The Greeks used the term lepra (λεπρα) for scaly skin conditions. They used the term psora to describe itchy skin conditions. It became known as Willan's lepra in the late 18th century when English dermatologists Robert Willan and Thomas Bateman differentiated it from other skin diseases. Leprosy, they said, is distinguished by the regular, circular form of patches, while psoriasis is always irregular. Willan identified two categories: leprosa graecorum and psora leprosa.^[55]

It was not until 1841 that the condition was finally given the name psoriasis by the Viennese dermatologist Ferdinand von Hebra. The name is derived from the Greek word psora which means to itch.^[56]

It was during the 20th century that psoriasis was further differentiated into specific types.^{[citation needed]}

Historical treatment[link]

This article may contain original research. Please improve it by verifying the claims made and adding references. Statements consisting only of original research may be removed. More details may be available on the talk page. (June 2011)

The history of psoriasis is littered with treatments of dubious effectiveness and high toxicity. These treatments received brief popularity at particular time periods or within certain geographical regions. The application of cat faeces to red lesions on the skin, for example, was one of the earliest topical treatments employed in ancient Egypt. Onions, sea salt and urine, goose oil and semen, wasp droppings in sycamore milk, and soup made from vipers have all been reported as being ancient treatments.

In the more recent past, Fowler's solution, which contains a poisonous and carcinogenic arsenic compound, was used by dermatologists as a treatment for psoriasis during the 18th and 19th centuries. Grenz rays (also called ultrasoft X-rays or Bucky rays) was a popular treatment of psoriasis during the middle of the 20th century. This type of therapy was superseded by ultraviolet therapy.

Undecylenic acid was investigated and used for psoriasis some 40 years ago (circa 1950).^[57]

All these treatments have fallen out of favour.

Sulphur was fashionable as a treatment for psoriasis in the Victorian and Edwardian eras. It has recently regained some credibility as a safe alternative to steroids and coal tar.^{[citation needed]}

Research[link]

Historically, agents used to treat psoriasis were discovered by experimentation or by accident. In contrast, current novel therapeutic agents are designed from a better understanding of the immune processes involved in psoriasis and by the specific targeting of molecular mediators. Examples can be seen in the use of biologics, which target T cells and TNF inhibitors.

Emerging clinical research has demonstrated the integral role of Janus kinase (JAK) proteins in the pathogenesis of psoriasis. As of 2010, two new oral JAK inhibitor drugs, ruxolitinib and tofacitinib (formerly called tasocitinib), have shown rapid and promising efficacy in Phase I/II trials with patients showing significant skin clearing within one week of beginning treatment.^[58][59] Ruxolitimib has completed Phase II clinical trials supplied as a topical cream.^[60]

Briakinumab is a human anti-IL-12/IL-23 monoclonal antibody directed against the shared p40 subunit of IL-12 and IL-23. Briakinumab is being developed by Abbott Laboratories in conjunction with Cambridge Antibody Technology for the treatment of multiple autoimmune diseases, including psoriasis. Abbott completed Phase III trials in 2010.^[61] Despite successful trials, in January 2011 Abbott withdrew their biologic drug application from United States and European regulatory offices.^[62]

Talarozole amplifies the effects of retinoic acid by inhibiting its metabolism. As of February 2009^[update], it is undergoing clinical trials.^[63]

Research into antisense oligonucleotides carries the potential to provide novel therapeutic strategies for treating psoriasis. Antisense oligonucleotides would be used to down regulate key cellular proteins known to play a role in psoriatic pathogenesis including inflammatory proteins such as ICAM-1 (intercellular adhesion molecule-1), IL-2 and IL-8, cellular proliferation proteins like insulin-like growth factor 1 receptor (IGF-IR) and epidermal growth factor and hyperangiogenesis vascular endothelial growth factor (VEGF).^[64]

A novel boron-containing topical anti-inflammatory, AN2728, is currently being developed by Anacor Pharmaceuticals and is in Phase 2b trials for mild-to-moderate plaque type psoriasis.^[65] The molecule works by inhibiting PDE4 and reducing the production of TNF-alpha, a precursor of the inflammation associated with psoriasis, as well as other cytokines, including IL-12 and IL-23.

Noting that botulinum toxin has been shown to have an effect on inhibiting neurogenic inflammation, and evidence suggesting the role of neurogenic inflammation in the pathogenesis of psoriasis,^[66] the University of Minnesota has begun a clinical trial to follow up on the observation that patients treated with botulinum toxin for dystonia had dramatic improvement in psoriasis.^[67]

In 2004, Tas and Avci demonstrated cyclopamine’s clinical potential for the treatment of psoriasis and basal cell carcinoma in two preliminary proof of concept studies.^[68] By treating 31 psoriatic lesions in 7 patients, these authors asserted topical cyclopamine was more effective in the clinical and histological clearance of guttate and plaque psoriasis than the topical steroid clobetasol-17 propionate. Furthermore, they demonstrated concurrent application of cylopamine and clobetasol-17 propionate accelerated regression and clearance of selected lesions greater than cyclopamine alone, with clearance times as early as 48 hours. They assert cyclopamine inhibits the abnormal proliferation of epithelial cells, induces terminal differentiation, and is associated with the decreased presence of inflammatory cells, including CD41 lymphocytes.

On 27 August 2006, scientists led by Jeung-Hoon Lee created the synthetic lipids pseudoceramides, which are involved in skin cell growth, and could be used in treating skin diseases such as atopic dermatitis, a form of eczema characterized by red, flaky and very itchy skin; psoriasis, and glucocorticoid-induced epidermal atrophy, in which the skin shrinks due to skin cell loss.^[69]

In children[link]

Psoriasis can affect children. Approximately one third of psoriasis patients report being diagnosed before age 20.^[70] Self-esteem and behavior can be affected by the disease. Bullying has been noted in clinical research.^[71]

See also[link]

• List of cutaneous conditions

References[link]

Further reading[link]

• Baker, Barbara S. (2008). From Arsenic to Biologicals: A 200 Year History of Psoriasis. Beckenham, UK: Garner Press. ISBN 0-9551603-2-4. 

External links[link]

Wikimedia Commons has media related to: Psoriasis

• Psoriasis at the Open Directory Project

Edgar Cayce
Circa October 1910
Born	Edgar Cayce (1877-03-18)March 18, 1877 Hopkinsville, Kentucky
Died	January 3, 1945(1945-01-03) (aged 67) Virginia Beach, Virginia
Resting place	Riverside Cemetery, Hopkinsville, Kentucky
Nationality	American
Occupation	Psychic Clairvoyant
Known for	Founder of Association for Research and Enlightenment
Religion	Disciples of Christ
Children	Hugh Lynn (b. 1907) Milton Porter (b. 1911) Edgar Evans (b. 1918)
Parents	Leslie B. Cayce Carrie Cayce
Website
www.edgarcayce.org

Edgar Cayce (/ˈkeɪsiː/; March 18, 1877 – January 3, 1945) was an American psychic who allegedly had the ability to give answers to questions on subjects such as healing or Atlantis while in a hypnotic trance. Though Cayce himself was a devout Christian and lived before the emergence of the New Age Movement, some believe he was the founder of the movement and influenced its teachings.^[1]

Cayce became a celebrity toward the end of his life and the publicity given to his prophecies has overshadowed what to him were usually considered the more important parts of his work, such as healing (the vast majority of his readings were given for people who were sick) and theology (Cayce was a lifelong, devout member of the Disciples of Christ). Skeptics^[2] challenge the statement that Cayce demonstrated psychic abilities, and traditional Christians also question his unorthodox answers on religious matters (such as reincarnation and Akashic records, although others accept his abilities as "God-given").

Cayce founded a nonprofit organization, the Association for Research and Enlightenment.^[3]

Biography[link]

Early life[link]

Edgar Cayce was born on March 18, 1877, near Beverly, Hopkinsville, Kentucky, one of the six children of farmers Leslie B. Cayce and Carrie Cayce.^[4]

Marriage and family[link]

Cayce was engaged on March 14, 1897 and married on June 17, 1903 to Gertrude Evans. They had three children: Hugh Lynn Cayce (March 16, 1907-July 4, 1982), Milton Porter Cayce (March 28, 1911-May 17, 1911), and Edgar Evans Cayce (February 9, 1918-).^[4]

1877 to 1920: Kentucky period[link]

In December 1893, the Cayce family moved to Hopkinsville, Kentucky, and occupied 705 West Seventh, on the south-east corner of Seventh and Young Street. During this time Cayce received an eighth-grade education, discovered his spiritual vocation and^[5] left the family farm to pursue various forms of employment (at Richard's Dry Goods Store and then in Hopper's Bookstore, both located on Main Street).

Cayce's education stopped with the ninth grade because his family could not afford the costs involved.^[6] A ninth-grade education was often considered more than sufficient for working-class children. Much of the remainder of Cayce's younger years would be characterized by a search for both employment and money.

Throughout his life, Cayce was drawn to church as a member of the Disciples of Christ. He read the Bible once for every year of his life, taught at Sunday school,^[7] and recruited missionaries. He is said^[who?] to have agonized over the issue of whether his psychic abilities, and the teachings which resulted, were spiritually legitimate.

In 1900, he formed a business partnership with his father to sell Woodmen of the World Insurance but was struck by severe laryngitis in March that resulted in a complete loss of speech.^[6] Unable to work, he lived at home with his parents for almost a year. He then decided to take up the trade of photography, an occupation that would exert less strain on his voice. He began an apprenticeship at the photography studio of W.R. Bowles in Hopkinsville.

A traveling stage hypnotist and entertainer called "The Laugh Man" was performing at the Hopkinsville Opera House in 1901. He heard about Cayce's condition and offered to attempt a cure. Cayce accepted, and the experiment took place on stage in front of an audience. Remarkably, Cayce's voice apparently returned while in a hypnotic trance but allegedly disappeared on awakening. Hart tried a posthypnotic suggestion that the voice would continue to function after the trance, but this proved unsuccessful.^[8]

Since Hart had appointments at other cities, he could not continue his hypnotic treatment of Cayce. However, a local hypnotist, Al Layne, offered to help Cayce in restoring his voice. Layne suggested that Cayce describe the nature of his condition and cure while in a hypnotic trance.^[8] Cayce described his own ailment from a first person plural point of view ("we") instead of the singular ("I").^[8] In subsequent readings he would generally start off with "We have the body." According to the reading, his voice loss was due to psychological paralysis and could be corrected by increasing the blood flow to the voice box. Layne suggested that the blood flow be increased, and Cayce's face supposedly became flushed with blood and his chest area and the throat turned bright red.^[8] After 20 minutes Cayce, still in trance, declared the treatment over. On awakening, his voice was alleged to have remained normal. Relapses were said to have occurred but were said to have been corrected by Layne in the same way, and eventually the cure was said to be permanent.

Layne had read of similar hypnotic cures effected by the Marquis de Puységur, a follower of Franz Mesmer, and was keen to explore the limits of the healing knowledge of the trance voice.^[9] He asked Cayce to describe Layne's own ailments and suggest cures and reportedly found the results both accurate and effective. Layne suggested that Cayce offer his trance healing to the public, but Cayce was reluctant. He finally agreed on the condition that readings would be free. He began with Layne's help to offer free treatments to the townspeople. Reports of Cayce's work appeared in the newspapers, inspiring many postal inquiries.^[9] Cayce was able to work just as effectively using a letter from the individual as with having the person present. Given the person's name and location, he said he could diagnose the physical and/or mental conditions and provide a remedy. He became popular and soon people from around the world sought his advice through correspondence.

Cayce's work grew in volume as his fame grew. He asked for voluntary donations to support himself and his family so that he could practice full-time. He continued to work in an apparent trance state with a hypnotist all his life. His wife and eldest son later replaced Layne in this role. A secretary, Gladys Davis, recorded his readings in shorthand.^[9]

1920 to 1923: Texas period[link]

Historic marker in downtown Selma, Alabama, in front of the building in which Cayce lived and worked.

The growing fame of Cayce coupled with the popularity he received from newspapers attracted several eager commercially-minded men who wanted to seek a fortune by using Cayce's clairvoyant abilities. Even though Cayce was reluctant to help them, he was persuaded to give the readings, which left him dissatisfied with himself and unsuccessful. A cotton merchant offered Cayce a hundred dollars a day for his readings about the daily outcomes in the cotton market. However, despite his poor finances, Cayce refused the merchant's offer.^[10] Others wanted to know where to hunt for treasures, while some wanted to know the outcome of horse races.^[11] Several times he was persuaded to give the readings as an experiment. However, he was not successful when he used his ability for such purposes, doing no better than chance alone would dictate. These experiments allegedly left him depleted of energy, distraught, and unsatisfied with himself. Finally, he came to the conclusion that he would use his gift only to help the distressed and sick.^[9]

He was persuaded to give readings on philosophical subjects in 1923 by Arthur Lammers, a wealthy printer who, by his own admission, had been "studying metaphysics for years".^[12] Cayce was told by Lammers that, while in his supposed trance state, he spoke of Lammers' past lives and of reincarnation, something Lammers believed in. Reincarnation was a popular subject of the day but not an accepted part of Christian doctrine. Cayce questioned his stenographer as to what he had said in his trance state and remained unconvinced. Cayce himself challenged Lammers's charge that he had validated astrology and reincarnation in the following dialogue:

Cayce: "I said all that?...I couldn't have said all that in one reading."

"No," Lammers said, "but you confirmed it. You see, I have been studying metaphysics for years, and I was able by a few questions, by the facts you gave, to check what is right and what is wrong with a whole lot of the stuff I've been reading. The important thing is that the basic system which runs through all the mystery religions, whether they come from Tibet or the pyramids of Egypt, is backed up by you. It's actually the right system." ^[13]

Cayce's stenographer recorded the following:

"In this we see the plan of development of those individuals set upon this plane, meaning the ability to enter again into the presence of the Creator and become a full part of that creation.

Insofar as this entity is concerned, this is the third appearance on this plane, and before this one, as the monk. We see glimpses in the life of the entity now as were shown in the monk, in this mode of living.

The body is only the vehicle ever of that spirit and soul that waft through all times and ever remain the same."

Cayce was quite unconvinced that he had been referring to and, as such, had validated the doctrine of reincarnation, and the best Lammers could offer was that the reading "opens up the door" and went on to share his beliefs and knowledge of the "truth" with Cayce.^[14] It appeared Cayce's instincts were telling him this was no ordinary reading. This client who came for a reading came with quite a bit of information of his own to share with Cayce and seemed intent upon convincing Cayce, now that he felt the reading had confirmed his strongly-held beliefs.^[15] It should be noted, however, that 12 years earlier Cayce had briefly alluded to reincarnation. In reading 4841-1, given April 22, 1911, Cayce referred to the soul being "transmigrated". Because nobody systematically recorded Cayce’s readings up until 1923, it is possible that he may have mentioned reincarnation in other earlier readings.

Cayce reported that his conscience bothered him severely over this conflict. Lammers overwhelmed, manipulated, confused, reassured and argued with Cayce. Ultimately his "trance voice", the "we" of the readings, also supposedly dialogued with Cayce and finally persuaded him to continue with these kinds of readings.^[16] In 1925 Cayce reported that his "voice" had instructed him to move to Virginia Beach, Virginia.^[17]

1925 to 1945: Virginia Beach period[link]

The Cayce Hospital 2006

Cayce's mature period, in which he created the several institutions which would survive him in some form, can be considered to have started in 1925. By this time he was a professional psychic with a small staff of employees and volunteers.^[18] The "readings" increasingly came to involve occult or esoteric themes.^[19]

In 1929, the Cayce hospital was established in Virginia Beach, sponsored by a wealthy recipient of the trance readings, Morton Blumenthal.

Cayce gained national prominence in 1943 through a high-profile article in Coronet titled "Miracle Man of Virginia Beach".^[18] He said he couldn't refuse people who felt they needed his help, and he increased the frequency of his readings to eight per day to try to make an impression on the ever-growing pile of requests. He said this took a toll on his health as it was emotionally draining and often fatigued him. He even went so far as to say that the readings themselves scolded him for attempting too much and that he should limit his workload to just two readings a day or else they would kill him.^[20]

Edgar Cayce suffered a stroke and died on January 3, 1945.^[21] He is buried in Riverside Cemetery^[22] in Hopkinsville, Kentucky.

Purported psychic abilities[link]

Cayce has variously been referred to as a "prophet" (cf. Jess Stearn's book, The Sleeping Prophet), a "mystic", a "seer". While giving a reading for a seeker he at times referred to consulting the Akashic Record (the etheric imprint) of that soul's experience.

Cayce's methods involved lying down and entering into a sleep state, usually at the request of a subject who was seeking help with health or other personal problems (subjects were not usually present). The subject's questions would then be given to Cayce, and Cayce would proceed with a reading. At first these readings dealt primarily with the physical health of the individual (physical readings); later, readings on past lives, business advice, dream interpretation, and mental or spiritual health were also given.

Until September 1923, his readings were not systematically preserved. However, an October 10, 1922, Birmingham Post-Herald article quotes Cayce as saying that he had given 8,056 readings as of that date, and it is known that he gave approximately 13,000-14,000 readings after that date. Today, only about 14,000 are available at Cayce headquarters and online. Thus, it appears that about 7,000-8,000 Cayce readings are missing.

When out of the trance he entered to perform a reading, Cayce said he generally did not remember what he had said during the reading. The unconscious mind, according to Cayce, has access to information which the conscious mind does not — a common assumption about hypnosis in Cayce's time. After Gladys Davis became Cayce's secretary on September 10, 1923, all readings were preserved and his wife Gertrude Evans Cayce generally conducted (guided) the readings.

Cayce said that his trance statements should be taken into account only to the extent that they led to a better life for the recipient. Moreover, he invited his audience to test his suggestions rather than accept them on faith.

Other abilities that have been attributed to Cayce include astral projection, prophesying, mediumship, viewing the Akashic Records or "Book of Life", and seeing auras. Cayce said he became interested in learning more about these subjects after he was informed about the content of his readings, which he reported that he never actually heard himself.^[23]