Psoriasis ( /sra.ss/) 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
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

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
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
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 1015% 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

Plaque of psoriasis

Plaque of psoriasis

A person's arm covered with plaque psoriasis

Psoriasis of a fingernail

Quality of life
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

Distribution of severity among people with psoriasis

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
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 immunemediated 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 TNF, 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
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 3550% 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- and nuclear factor B, 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
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-, interleukin-1, 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-, 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-, 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-, 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- and interleukin-17. Interleukin-17 is also associated with interleukin-22. Interleukin22 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
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

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
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
Phototherapy in the form of sunlight has long been used effectively for treatment.[36] Wavelengths of 311313 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

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- is one of the main executor inflammatory cytokines. Four MAbs (infliximab, adalimumab, golimumab and certolizumab pegol) and one recombinant TNF- decoy receptor, etanercept, have been developed against TNF- to inhibit TNF- 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- 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

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
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
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
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 () 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
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. (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
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, 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) [64]and epidermal growth factor and hyperangiogenesis vascular endothelial growth factor (VEGF).[65] 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.[66] 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 IL23. 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,[67] 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.[68]

In 2004, Tas and Avci demonstrated cyclopamines clinical potential for the treatment of psoriasis and basal cell carcinoma in two preliminary proof of concept studies.[69] 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.[70]

In children
Psoriasis can affect children. Approximately one third of psoriasis patients report being diagnosed before age 20.[71] Self-esteem and behavior can be affected by the disease. Bullying has been noted in clinical research.[72]

Psoriasis facts

Psoriasis is a chronic inflammatory skin disease. Psoriasis has no known cause. The tendency toward developing psoriasis is inherited in genes. Psoriasis is not contagious. Psoriasis gets better and worse spontaneously and can have periodic remissions (clear skin). Psoriasis is controllable with medication. Psoriasis is currently not curable. There are many promising therapies, including newer biologic drugs. Future research for psoriasis is promising.

What is psoriasis?

Psoriasis is a noncontagious skin condition that produces red, dry plaques of thickened skin. The dry flakes and skin scales are thought to result from the rapid proliferation of skin cells that is triggered by abnormal lymphocytes from the blood . Psoriasis commonly affects the skin of the elbows, knees, and scalp. Some people have such mild psoriasis (small, faint dry skin patches) that they may not even suspect that they have a medical skin condition. Others have very severe psoriasis where virtually their entire body is fully covered with thick, red, scaly skin. Psoriasis is considered a non-curable, long-term (chronic) skin condition. It has a variable course, periodically improving and worsening. It is not unusual for psoriasis to spontaneously clear for years and stay in remission. Many people note a worsening of their symptoms in the colder winter months. Psoriasis is seen worldwide, in all races, and both sexes. Although psoriasis can be seen in people of any age, from babies to seniors, most commonly patients are first diagnosed in their early adult years. Patients with more severe psoriasis may have social embarrassment, job stress, emotional distress, and other personal issues because of the appearance of their skin.

What causes psoriasis?

The exact cause remains unknown. There may be a combination of factors, including genetic predisposition and environmental factors. It is common for psoriasis to be found in members of the same family. The immune system is thought to play a major role. Despite research over the past 30 years looking at many triggers, the "master switch" that turns on psoriasis is still a mystery.

What does psoriasis look like? What are the symptoms and signs?
Psoriasis typically looks like red or pink areas of thickened, raised, and dry skin. It classically affects areas over the elbows, knees, and scalp. Essentially any body area may be involved. It tends to be more common in areas of trauma, repeat rubbing, use, or abrasions. Psoriasis has many different appearances. It may be small flattened bumps, large thick plaques of raised skin, red patches, and pink mildly dry skin to big flakes of dry skin that flake off. There are several different types of psoriasis, including psoriasis vulgaris (common type), guttate psoriasis (small, drop like spots), inverse psoriasis (in the folds like of the underarms, navel, and buttocks), and pustular psoriasis (pus-filled, yellowish, small blisters). When the palms and the soles are involved, this is known as palmoplantar psoriasis. Sometimes pulling of one of these small dry white flakes of skin causes a tiny blood spot on the skin. This is medically referred to as a special diagnostic sign in psoriasis called the Auspitz sign.

Genital lesions, especially on the head of the penis, are common. Psoriasis in moist areas like the navel or area between the buttocks (intergluteal folds) may look like flat red patches. These atypical appearances may be confused with other skin conditions like fungal infections, yeast infections, skin irritation, or bacterial Staph infections. On the nails, it can look like very small pits (pinpoint depressions or white spots on the nail) or as larger yellowish-brown separations of the nail bed called "oil spots." Nail psoriasis may be confused with and incorrectly diagnosed as a fungal nail infection. On the scalp, it may look like severe dandruff with dry flakes and red areas of skin. It may be difficult to tell the difference between scalp psoriasis and seborrhea (dandruff). However, the treatment is often very similar for both conditions.

Can psoriasis affect my joints?

Yes, psoriasis is associated with joint problems in about 10%-35% of patients. In fact, sometimes joint pains maybe the only sign of the disorder with completely clear skin. The joint disease associated with psoriasis is referred to as psoriatic arthritis. Patients may have inflammation of any joints (arthritis), although the joints of the hands, knees, and ankles tend to be most commonly affected. Psoriatic arthritis is an inflammatory, destructive form of arthritis and is treated with medications to stop the disease progression. The average age for onset of psoriatic arthritis is 30-40 years of age. In most cases, the skin symptoms occur before the onset of the arthritis.

How is psoriasis diagnosed?

The diagnosis of psoriatic arthritis is typically made by a physician examination, medical history, and relevant family history. Sometimes, lab tests and X-rays may be used to determine the severity of the disease and to exclude other diagnoses like rheumatoid arthritis and osteoarthritis.

Can psoriasis affect only my nails?

Yes, psoriasis may involve solely the nails in a limited number of patients. Usually, the nail symptoms accompany the skin and arthritis symptoms. Nails may have small pinpoint pits or large yellowish separations of the nail plate called "oil spots." Nail psoriasis is typically very difficult to treat. Treatment option are somewhat limited and include potent topical steroids applied at the nail-base cuticle, injection of steroids at the nail-base cuticle, and oral or systemic medications as described below for the treatment of psoriasis.

How many people have psoriasis?

Psoriasis is a fairly common skin condition and is estimated to affect approximately 1%-3% of the U.S. population. It currently affects roughly 7.5 million to 8.5 million people in the U.S. It is seen worldwide in about 125 million people. Interestingly, African Americans have about half the rate of psoriasis as Caucasians.

Is psoriasis curable?
No, psoriasis is not currently curable. However, it can go into remission and show no signs of disease. Ongoing research is actively making progress on finding better treatments and a possible cure in the future.

Is psoriasis contagious?
No. Research studies have not shown it to be contagious from person to person. You cannot catch it from anyone, and you cannot pass it to anyone else by skin-to-skin contact. You can directly touch someone with psoriasis every day and never catch the skin condition.

Can I pass psoriasis on to my children?

Yes, it is possible. Although psoriasis is not contagious from person to person, there is a known genetic tendency, and it may be inherited from parents to their children. It does tend to run in some families, and a family history is helpful in making the diagnosis.

What kind of doctor treats psoriasis?

Dermatologists specialize in the diagnosis and treatment of psoriasis, and rheumatologists specialize in the treatment of joint disorders and psoriatic arthritis. Many kinds of physicians may treat psoriasis, including dermatologists, family physicians, internal medicine physicians, rheumatologists, and other medical doctors. Some patients have also seen other allied health professionals such as acupuncturists, holistic practitioners, chiropractors, and nutritionists. The American Academy of Dermatology and the National Psoriasis Foundation are excellent references to help find physicians who specialize in this disease. Not all dermatologists and rheumatologists treat psoriasis. The National Psoriasis Foundation has one of the most up-to-date databases of current psoriasis specialists.

What is the treatment for psoriasis?

There are many effective treatment choices for psoriasis. The best treatment is individually determined by the treating physician and depends, in part, on the type of disease, the severity, and the total body area involved. For mild disease that involves only small areas of the body (like less than 10% of the total skin surface), topical (skin applied) creams, lotions, and sprays may be very effective and safe to use. Occasionally, a small local injection of steroids directly into a tough or resistant isolated psoriasis plaque may be helpful. For moderate to severe disease that involves much larger areas of the body (like 20% or more of the total skin surface), topical products may not be effective or practical to apply. These cases may require ultra-violet light treatments or systemic (total body treatments such as pills or injections) medications. Internal medications usually have greater risks.

For psoriatic arthritis, systemic medications are generally required to stop the progression of permanent joint destruction. Topical therapies are not effective. It is important to keep in mind that as with any medical condition, all medications carry possible side effects. No medication is 100% effective for everyone, and no medication is 100% safe. The decision to use any medication requires thorough consideration and discussion with your physician. The risks and potential benefit of medications have to be considered for each type of psoriasis and the individual patient. Some patients are not bothered at all by their skin symptoms and may not want any treatment. Other patients are bothered by even small patches of psoriasis and want to keep their skin clear. Everyone is different and, therefore, treatment choices also vary depending on the patient's goals and expressed wishes. An approach to minimize the toxicity of some of these medicines has been commonly called "rotational" therapy. The idea is to change the antipsoriasis drug every six to 24 months in order to minimize the possible side effects from any one type of therapy or medication. In another example, a patient who has been using strong topical steroids over large areas of their body for prolonged periods may benefit from stopping the steroids for a while and rotating onto a different therapy like calcitriol (Vectical), light therapy, or an injectable biologic.

What creams or lotions are available for psoriasis?

Topical (skin applied) medications include topical corticosteroids, vitamin D analogue creams calcitriol, topical retinoids (Tazorac), moisturizers, topical immunomodulators (tacrolimus and pimecrolimus), coal tar, anthralin, and others.

Topical corticosteroids (steroids, such as hydrocortisone) are very useful and often the first-line treatment for limited or small areas of psoriasis. These come in many preparations, including sprays, liquid, creams, gels, ointments, and mousses. Steroids come in many different strengths, including stronger ones are used for elbows, knees, and tougher skin areas and milder ones for areas like the face, underarms, and groin. These are usually applied once or twice a day to affected skin areas. Strong steroid preparations should be limited in use. Overuse or prolonged use may cause problems including potential permanent skin thinning and damage called atrophy. A vitamin D analogue cream called calcitriol has also been useful in psoriasis. The advantage of calcitriol is that it is not known to overly thin the skin like topical steroids. It is important to note that this drug is not regular vitamin D and is not the same as taking regular vitamin D or rubbing it on the skin. A similar drug, calcipotriene, may be used in combination with topical steroids for better results. There is a newer two-in-one combination preparation of calcipotriene and a topical steroid called Taclonex. Results with calcipotriene alone may be slower and less than results achieved with typical topical steroids. Not all patients may respond to calcipotriene as well as to topical steroids. A special precaution with vitamin D analogue creams is that it should not be used on more than 20% of the skin in one person. Overuse may cause absorption of the drug and an abnormal rise in body calcium levels.

Moisturizers, especially with therapeutic concentrations of salicylic acid, lactic acid, urea, and glycolic acid may be helpful in psoriasis. These moisturizers are available as prescription and nonprescription forms. These help moisten and lessen the appearance of thickened psoriasis scales. Some available preparations include Salex (salicylic acid), AmLactin (lactic acid), or Lac-Hydrin (lactic acid) lotions. These may be used one to three times a day on the body and do not generally have a risk of problematic skin thinning (atrophy). Overuse or use on broken, inflamed skin may cause stinging, burning, and more irritation. These stronger preparations should not be used over delicate skin like eyelids, face, or genitals. Other bland moisturizers including Vaseline and Crisco vegetable shortening may also be helpful in at least reducing the dry appearance of psoriasis. Immunomodulators (tacrolimus and pimecrolimus) have also been used with some success in limited types of psoriasis. These have the advantage of not causing skin thinning. They may have other potential side effects, including skin infections and possible malignancies (cancers). The exact association of these immunomodulator creams and cancer is controversial. Bath salts or bathing in high-salt-concentration waters like the Dead Sea in the Middle East may help some psoriasis patients. Epsom salt soaks (available over the counter) may also be helpful for a number of patients. Overall, these are quite safe with very few possible side effects. Coal tar is available in multiple preparations, including shampoos, bath solutions, and creams. Coal tar may help reduce the appearance and decrease the flakes in psoriasis. The odor, staining, and overall messiness with coal tar may make it harder to use and less desirable than other therapies. A major advantage with tar is lack of skin thinning. Anthralin is available for topical use as a cream, ointment, or paste. The stinging, possible irritation, and skin discoloration may make this less acceptable to use. Anthralin may be applied for 10-30 minutes to psoriatic skin.

What oral medications are available?

Oral medications include acitretin, cyclosporine, methotrexate, mycophenolate mofetil, and others. Oral prednisone (corticosteroid) is generally not used in psoriasis and may cause a disease flare if administered.

Acitretin (Soriatane) is an oral drug used for certain types of psoriasis. It is not effective in all types of the disease. It may be used in males and females who are not pregnant and not planning to become pregnant for at least three years. The major side effects include dryness of skin and eyes and temporarily elevated levels of triglycerides and cholesterol (fatty substance) in the blood. Blood tests are generally required before starting this therapy and periodically to monitor triglyceride levels. Patients should not become pregnant while on this drug and usually for at least three years after stopping this medication. Cyclosporine is a potent immunosuppressive drug used for other medical uses, including organ-transplant patients. It may be used for severe, difficult-to-treat cases of widespread psoriasis. Improvement and results may be very rapid in onset. It may be hard to get someone off of cyclosporine without flaring their psoriasis. Because of the potential

cumulative toxicity, cyclosporine should not be used for more than one to two years for most psoriasis patients. Major possible side effects include kidney and blood-pressure problems. Methotrexate is a common drug used for rheumatoid arthritis, and it has been used effectively for many years in psoriasis. It is usually given in small weekly doses (5 mg-15 mg). Blood tests are required before and during therapy. The drug may cause liver damage in some patients, particularly if there is preexisting liver disease or if given for prolonged periods of time. Close physician monitoring and monthly to quarterly visits and labs are generally required.

What injections or infusions are available for psoriasis?

The newest category of psoriasis drugs are called biologics. All biologics modulate (adjust) and sometime suppress (quiet) the immune system that is overactive in psoriasis. Currently available biologic drugs include alefacept (Amevive), adalimumab (Humira), infliximab (Remicade), etanercept (Enbrel), and ustekinumab (Stelara). Newer drugs are in development and may be on the market in the near future. As this class of drugs is fairly new, ongoing monitoring and adverse effect reporting continues and long-term safety continues to be monitored. Although previously available, efalizumab (Raptiva) was removed from the U.S. market in early 2009 due to reported safety concerns for the development of a serious brain disease, progressive multifocal leukoencephalopathy (PML). Individuals still taking Raptiva should contact their health-care professional to discuss risks and benefits of treatment with this drug. A recently approved biologic product for adults who have a moderate to severe form of psoriasis is ustekinumab (Stelara). Stelara is a laboratory-produced antibody that treats psoriasis by blocking the action of two proteins (interleukins) that contribute to the overproduction of skin cells and inflammation. Some biologics are self-injections for home use while others are intramuscular injections or intravenous infusions in the physician's office. Biologics have some screening requirements such as a tuberculosis screening test (TB skin test or PPD test) and other labs prior to starting therapy. As with any drug, side effects are possible with all biologic drugs. Common potential side effects include mild local injection-site reactions (redness and tenderness). There is concern of serious infections and potential malignancy with nearly all biologic drugs. Precautions include patients with known or suspected hepatitis B or C infection, active tuberculosis, and possibly HIV/AIDS. As a general consideration, these drugs may not be an ideal choice for patients with a history of cancer and patients actively undergoing cancer therapy. In particular, there may be an increased association of lymphoma in patients taking biologics. It is not at all certain if this association is directly caused by these drugs. In part, this is because it is known that certain diseases like rheumatoid arthritis or psoriasis may be associated with an inherent increase in the overall risk of some infections and malignancies.

Biologics are expensive medications ranging in price from several to tens of thousands of dollars per year per person. Their use may be limited by availability, cost, and insurance approval. Not all insurance drug plans may fully cover these drugs for all conditions. Patients need to check with their insurance and may require a prior authorization request for coverage approval. Some of the biologics manufacturers have patient-assistance programs to help with financial issues. The choice of the right medication for your condition depends on many medical factors. Additionally, convenience of receiving the medication and lifestyle may be factors in choosing the right biologic medication. Currently, the four main classes of biologic drugs for psoriasis are: 1. 2. 3. 4. TNF (tumor necrosis factor) blockers, drugs that block T-cell activation and the movement of T-cells, drugs that decrease the number of activated T-cells, and drugs that interfere with interleukin chemical messengers of inflammation.

TNF blockers TNF blockers include Enbrel (etanercept), Remicade (infliximab) and Humira (adalimumab). TNF-alpha blocking drugs may have an advantage of treating psoriatic arthritis and psoriasis skin disease. Their disadvantage is that some patients may notice a decrease in the effectiveness of TNF-alpha blocking drugs over months to years. TNF blockers are generally not used in patients with demyelinating (neurological) diseases like multiple sclerosis, congestive heart failure, or patients with severe overall low blood counts called pancytopenia. The major side effect of these class of drugs is suppression of the immune system. Because of the increased risk of infections while on these drugs, patients should promptly report fevers or signs of infection to their physicians. Minor side effects have included autoimmune conditions like lupus or flares in lupus. Additionally, it is best to avoid any live vaccines while using TNF blockers.

Enbrel (etanercept) is a self-injectable medication for home use. It is injected via a small needle just under the skin, called subcutaneous injection. It is usually dosed once or twice week by patients at home after training with their physician or the nursing staff. Sometimes a higher loading dose is used for the first 12 weeks and then it is "stepped down" to half the dose after the first 12 weeks. Enbrel has the advantage of at least 16 years of clinical use and long-term experience. Remicade (infliximab) is an intravenous (IV) medication strictly for physician office or special infusion medical center use. It is dosed specifically based on your weight. It is currently not for home use or self-injection. It is injected slowly over time via a small needle into a vein. It may usually be dosed once a week. There have been reports of antibodies to this drug in patients taking it for some time. These antibodies may cause a greater drug-dose requirement for achieving disease improvement or failure to improve.

The IV route may be more time-consuming, requiring physician during the infusions. Remicade has the advantage of fast disease response and good potency. Humira (adalimumab) is a self-injectable medication for home use. It is injected via a small needle just under the skin as a subcutaneous dose. It is usually dosed once every other week, totaling 26 injections in one year. Dosing is individualized and should be discussed with your physician. Sometimes a higher loading dose is used for the first dose (80 mg) and then it is continued at 40 mg every other week. It may give results as soon as one to two weeks of therapy. Humira has the advantage of at least 11 years of clinical use and long-term experience.

Drugs that decrease the number of activated T-cells

Amevive (alefacept) decreases the number of available activated T-cells that play a role in causing psoriasis. It is given intramuscularly (injected in the muscle) usually in the physician's office and given once a week for 12 weeks. Many patients may see improvement in their symptoms that lasts approximately 12 months (more or less). Amevive may not be uniformly effective for all patients, and some patients improve more than others. The average time to maximum improvement for many patients is about 14 weeks. Amevive should generally not be used in patients with HIV infections as the drug causes a decrease in the CD4 cells (part of the immune system that HIV also attacks). Also, because of the immune-system suppression, Amevive may not be a good choice in patients with active cancer or infection. As Amevive is one of the two currently available drugs that inhibits T cells directly, there may be a potential concern for immunosuppression and increased susceptibility to infections including PML. The risks and benefits of treatment with biologics need to be assessed for each individual.

Drugs that interfere with interleukin mechanisms

Ustekinumab is the newest biologic injectable medication used to modulate the immune system. It is an interleukin-12/23 human monoclonal antibody. Ustekinumab targets chemical messengers in the immune system involved in skin inflammation and skin-cell production. This drug is dosed subcutaneously (just under the skin) once a quarter (every three months). It has been very promising with very good clearance rates in the clinical trials. A major advantage may be the convenience of a quarterly medication. The concerns for infection and malignancy may be similar to the other biologics.