psoriatic

• adj.

• 乾癬性の、乾癬の

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psoriasis

WordNet

1. a chronic skin disease characterized by dry red patches covered with scales; occurs especially on the scalp and ears and genitalia and the skin over bony prominences

PrepTutorEJDIC

1. 乾癬(かんせん)(慢性の非伝染性皮膚病)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/01/15 02:15:38」(JST)

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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 (pron.: /sɵˈraɪ.əsɨs/) is an immune-mediated disease that affects the skin. It is typically a lifelong condition. There is currently no cure, but various treatments can help to control the symptoms.

Psoriasis occurs when the immune system mistakes a normal skin cell for a pathogen, and sends out faulty signals that cause overproduction of new skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of stroke, and treating high blood lipid levels may lead to improvement. 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 signs or symptoms. The name psoriasis (ψωρίασις) is from the Greek language, 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 sign. 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.

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. Various environmental factors have been suggested as aggravating to psoriasis, including oxidative stress, stress, withdrawal of systemic corticosteroid, as well as other environmental factors, but few have shown statistical significance. 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.

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).

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

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.

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:

• 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, although these conditions are quite common in the non-psoriatic population, affecting 1% to 2.5% of the general population.

Signs and symptoms

• Plaque of psoriasis

• Plaque of psoriasis

• An arm covered with plaque type 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. 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.

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.

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. 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).

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. 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.

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. 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). Nevertheless, the PASI can be too unwieldy to use outside of trials, which has led to attempts to simplify the index for clinical use.

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 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. Animal models, however, reveal only a few aspects resembling human psoriasis.

Compromised skin barrier function has a role in psoriasis susceptibility.

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. 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.

Individuals suffering from the advanced effects of the human immunodeficiency virus, or HIV, often exhibit psoriasis. 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. In addition, HIV is typically characterized by a strong Th2 cytokine profile, whereas psoriasis vulgaris is characterized by a strong Th1 secretion pattern. 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. Psoriasis in AIDS sufferers is often severe, and untreatable with conventional therapy.

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

See also: List of human leukocyte antigen alleles associated with cutaneous conditions

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.

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.

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.

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.

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.

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.

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).

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. 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.

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.

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.

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.

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

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.

Topical agents

Bath solutions (epsom salt) 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. 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. Wavelengths of 311–313 nm are most effective and special lamps have been developed for this application. The exposure time should be controlled to avoid over exposure and burning of the skin. The UVB lamps should have a timer that will turn off the lamp when the time ends. The amount of light used is determined by a person's skin type. Increased rates of cancer from treatment appear to be small.

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.

A fourth oral agent, fumaric acid esters (FAE) (brand name Fumaderm®, main active ingredient dimethyl fumarate (DMF)) is approved only in Germany but widely used in Europe due to its unique immunemodulatory properties without significant immunosuppression which makes it suitable for long-term treatment.

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. 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.

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 and inhibit the inflammatory pathway at a different point than the anti-TNF-α antibodies. 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.

In 2008, the FDA approved three new treatment options 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. 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.

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 and diets supplemented with fish oil (in this study cod liver oil) have also shown beneficial effects – though evidence is still inconclusive and more research is needed to determine whether there is any benefit from diet manipulations. 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.

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. The adverse effects of cannabis might be avoided with a topical preparation or by the use of (a) more specific endocannabinoid receptor agonist(s),

Prognosis

Psoriasis is typically a lifelong condition. There is currently no cure, but various treatments can help to control the symptoms. 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, 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%. A survey 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.

Within the United States, psoriasis is most common in the Northeast.

Prevalence across different racial groups is similar; race does not appear to be a risk factor.

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 Hebrew Bible, defined by chazal as the result of talking lashon hara (slander). The patient deemed "impure" (see tumah and taharah) during their afflicted phase and is ultimately treated by the kohen. 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.

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.

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

Historical treatment

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).

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. Ruxolitinib has completed Phase II clinical trials supplied as a topical cream.

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. Despite successful trials, in January 2011 Abbott withdrew their biologic drug application from United States and European regulatory offices.

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

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).

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. 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.

FP187, an oral drug containing dimethyl fumarate, was found to be safe and efficacious in the treatment of moderate to severe psoriasis in a pivotal registration study completed in 2012. The molecule is thought to work in part through GSH depletion and subsequent induction of the anti-inflammatory stress protein HO-1, leading to depression of inflammatory cytokine secretion (e.g. TNF-α, IL-12, IFN-γ).

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, 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.

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. 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.

The International Federation of Psoriasis Associations (IFPA) supports research in the field of psoriasis. The IFPA is a non-profit organization made up of psoriasis associations from around the world. The Psoriasis International Network, a program of the Fondation René Touraine, is part of the IFPA.

In children

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

See also

• List of cutaneous conditions
• List of human leukocyte antigen alleles associated with cutaneous conditions

References

Further reading

• 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

• Psoriasis at the Open Directory Project

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 乾癬性関節炎の臨床症状および診断 clinical manifestations and diagnosis of psoriatic arthritis
• 2. 乾癬性関節炎の治療 treatment of psoriatic arthritis
• 3. 乾癬性若年性特発性関節炎：病因、臨床症状、および診断 psoriatic juvenile idiopathic arthritis pathogenesis clinical manifestations and diagnosis
• 4. 乾癬性若年性特発性関節炎：管理および予後 psoriatic juvenile idiopathic arthritis management and prognosis
• 5. 乾癬性関節炎の病因 pathogenesis of psoriatic arthritis

English Journal

• Coexistence of psoriasis and bullous pemphigoid: remission with low-dose methotrexate.

• Gunay U, Gunduz K, Ermertcan AT, Kandiloğlu AR.SourceDepartment of Dermatology, Celal Bayar University, Manisa, Turkey.
• Cutaneous and ocular toxicology.Cutan Ocul Toxicol.2013 Jun;32(2):168-9. doi: 10.3109/15569527.2012.667030. Epub 2012 Mar 20.
• The coexistence of psoriasis vulgaris and bullous pemphigoid is rare. Here, we report a 90-year-old patient with a 20-year history of psoriasis. She developed vesicles and bullae suddenly and was diagnosed as bullous pemphigoid. Low-dose methotrexate therapy quickly cleared both psoriatic and bullou
• PMID 22429144

• Gender difference in disease expression, radiographic damage and disability among patients with psoriatic arthritis.

• Eder L, Thavaneswaran A, Chandran V, Gladman DD.SourceCorrespondence to Dafna D Gladman, University of Toronto, Toronto Western Research Institute, Psoriatic Arthritis Clinic, Centre for Prognostic Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto 97914, Canada; dafna.gladman@utoronto.ca.
• Annals of the rheumatic diseases.Ann Rheum Dis.2013 Apr;72(4):578-82. doi: 10.1136/annrheumdis-2012-201357. Epub 2012 May 15.
• OBJECTIVE: The authors aimed to assess gender-related differences in severity of psoriatic arthritis (PsA) as reflected by measures of disease activity, joint damage, quality of life and disability.METHODS: A cross-sectional analysis was performed among patients who have been followed in a large PsA
• PMID 22589379

Japanese Journal

• 教育研修講座 整形外科医に役立つ皮膚疾患の知識

• 加藤 則人
• 日本整形外科学会雑誌 86(12), 1149-1154, 2012-12
• NAID 40019555705

• 症例報告 インフリキシマブが奏功した乾癬性関節炎の1例

• 上杉 和秀,山岸 栄紀,茂呂 貴知 [他]
• 臨床整形外科 47(12), 1251-1254, 2012-12
• NAID 40019507565

Related Links

• Psoriasis - Wikipedia, the free encyclopedia

Psoriasis is an immune-mediated disease that affects the skin. It is typically a lifelong condition. There is currently no cure, but various treatments can help to control the symptoms. Psoriasis occurs when the immune system mistakes a normal ...

• Psoriatic Arthritis Symptoms, Treatment, Causes, Diagnosis ...

Learn more about psoriatic arthritis causes, symptoms, diagnosis, treatment, medications, and prognosis.

Related Pictures

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★リンクテーブル★

リンク元	「100Cases 27」「100Cases 16」「乾癬性」

「100Cases 27」

　　[★]

☆case27　関節痛

■症例

37歳　女性

主訴：関節痛

現病歴：数ヶ月、膝の痛みがだんだん強くなっていると感じていた。痛みは手や足の小関節に多く、朝歩くときに最もこわばる。痛みはジクロフェナクを飲むと和らぐ。そのほかの症状として疲労感を感じ、最近、体重が３ヶ月で４ｋｇ減っている。

喫煙歴：なし。

飲酒歴：機会飲酒

既往歴：なし

家族歴：既婚、子供は２人

服薬歴：ジクロフェナク

職業歴：legal sevretary

身体所見 examination

　顔貌　青白、臨床的な貧血を認める。近位指節間関節・中手指節関節　腫脹・effusionを伴う疼痛。中足趾節関節　圧痛。それ以外は正常。

検査　investigation

　血液検査

　　Hb低下

　　ESR上昇

　　尿素軽度上昇

　　クレアチニン軽度上昇

　　正常：白血球、MCV、血小板、ナトリウム、カリウム、グルコース、アルブミン

　尿検査

　　蛋白(-)、尿糖(-)、潜血(-)、

■問題

　本症例では診断とその根拠を考えるのは簡単なので、鑑別疾患をあげてその疾患に特徴的な症候を列挙しましょう。

■関節痛 DIF.283

　V Vascular

　　血友病 hemophilia　血友病性関節症(急性：疼痛、腫脹、熱感(SOR.241)

慢性：可動域の低下、変形、関節周囲筋萎縮(SOR.241))。家族歴

　　壊血病 scurvy　。生活環境。食事歴

　　無菌性骨壊死 aseptic bone necrosis (Osgood-Schlatter diseaseとか)

　I Inflammatory

　　感染性関節炎(細菌性関節炎(化膿性関節炎・淋菌性関節炎・結核性関節炎・嫌気性菌関節炎 )、真菌性関節炎、スピロヘータ関節炎(梅毒性関節炎・ライム関節炎)、マイコプラズマ関節炎、ウイルス性関節炎)

　N Neoplastic disorders

　　骨原性肉腫 osteogenic sarcoma

　　巨細胞腫 giant cell tumors

　D Degenerative disorders

　　degenerative joint disease

　　変形性関節症 osteoarthritis

　I Intoxication

　　痛風 gout (uric acid)

　　偽痛風 pseudogout (calcium pyrophosphate)

　　ループス症候群 lupus syndrome of hydralazine (Apresoline) and procainamide

　　gout syndrome of diuretics

　C Congenital and acquired malformations bring to mind the joint deformities of tabes dorsalis and syringomyelia and congenital dislocation of the hip. Alkaptonuria is also considered here.

　A Autoimmune indicates

　　関節リウマチ RA

　　血清病 serum sickness

　　全身性エリテマトーデス lupus erythematosus

　　リウマチ熱 rheumatic fever

　　ライター症候群 Reiter syndrome

　　潰瘍性大腸炎 ulcerative colitis

　　クローン病=限局性回腸炎 regional ileitis

　　乾癬性関節炎 psoriatic arthritis

　　リウマチ性多発筋痛症 polymyalgia rheumatica

　T Trauma

　E Endcrine

　　先端肥大症 acromegaly

　　閉経 menopause

　　糖尿病 diabetes mellitus

■関節炎の分類

・炎症部位の数

　単関節炎：痛風、偽痛風、離断性骨軟骨炎、血行性の化膿性関節炎のほとんど

　多関節炎：リウマチ性疾患、ウイルス性疾患、白血病での関節症状、易感染性宿主における血行性の化膿性関節炎

■関節リウマチ

　診断基準

　関節症状

　　朝のこわばり、疼痛、腫脹、関節の動揺、関節可動域制限、変形(手指、足趾、膝関節)。(SOR.211)

　　手指の近位指節間関節(PIP関節)、中手指節関節(MP関節)。遠位指節間関節(DIP関節)に初発することは稀。(SOR.211)

　　左右対称性に生じることが多い。手関節、足趾、膝関節に初発する。(SOR.211)

　関節外症状

　　全身症状：発熱

　　皮膚症状：リウマトイド結節(肘の伸側、後頭部、手指)

　　眼症状：上胸膜炎(10日の経過で治癒)、強膜炎(予後不良)。稀に角膜穿孔

　　血液障害：(高頻度)貧血、白血球減少(Felty病。DMARDs投与中の場合は薬剤性の骨髄抑制を考慮)

　　アミロイドーシス：ネフローゼや下痢を来した症例で疑う。アミロイド蛋白はAA

　　腎障害：稀。アミロイドーシスの続発症か薬剤性を考慮。

　　呼吸器症状：間質性肺炎の合併多い。下肺野に好発。通常無症状。メトトレキセートなどの使用により薬剤性の急性間質性肺炎を生じることがある。

　　心・血管障害：リンパ管炎による難治性の浮腫。

　　神経症状：環軸関節亜脱臼により項部痛や脊髄症上が出現しうる。

　　骨粗鬆症

　　腱鞘滑膜炎：手指、手関節、足関節

■両側性多関節炎の鑑別疾患

　OA：遠位指節間関節を冒すのが特徴的で、近位指節間関節、中手指節関節を冒しうる。

　RA：

　SLE：軽度、症状の程度が変動する非びらん性の関節炎

　gout：単関節炎からはじまる。

　血清陰性関節炎：強直性脊椎炎、感染、ライター病：中～大関節に非対称性の関節炎。仙腸関節と遠位指節間関節にも関節炎

　急性ウイルス性関節炎：風疹。

■KEY POINTS

・RAでは遠位指節間関節は冒されない傾向がある。

・RAの全身症状は関節症状に先行することがある。

・RAの活動性と貧血及びESRは相関している。

・NSAIDsは腎機能に悪影響を与えることがある。

■initial plan

　Dx 1. 単純X線写真

　　　　・亜脱臼、関節周囲の骨萎縮(傍関節性骨骨粗鬆症,juxta-articular osteoporosis)、関節裂隙の狭小化、関節辺縁のびらん(bony erosion)

　　　　　・初期のRAで第5趾に骨びらんが一般的に見られる。

　　　　・血液検査

　　　　　・RF、抗DNA抗体

　Tx 1. 鎮痛薬

　　　　・NSAIDs：鎮痛とこわばりの軽減

　　 2. DMARDs(メトトレキセート、レフルノミド、金製剤、ペニシラミン)

　　　　・NSAIDsで症状が治まらない場合に考慮

　　 3. 抗TNF抗体

　　　　・重症のRAで効果がある場合がある。

■参考文献

SOR　標準整形外科学 第10版 医学書院

DIF　Differential Diagnosis in Primary Care Fourth Edition版 Lippincott Williams & Wilkins

「100Cases 16」

　　[★]

☆case16　膝の痛み

■glossary

indigestion 消化障害、消化不良

■症例

80歳　男性

主訴：左膝の痛みと腫脹

現病歴：左膝の痛みを2日前から認めた。膝は発熱・腫脹しており、動かすと疼痛を生じる。時々胸焼けと消化不良が見られる。6ヶ月前のhealth checkで、高血圧(172/102mmHg)と血中クレアチニンが高い(正常高値)こと以外は正常といわれた。その4週間数回血圧を測定したが、高値が継続したため、2.5mg bendrofluamethizide(UK)/ベンドロフルメチアジドbendroflumethiazide(US)で治療を開始した。最近の血圧は138/84 mmHgであった。

喫煙歴：なし。

飲酒歴：一週間に平均4unit。

既往歴：股関節に中程度(mild)の変形性関節症

家族歴：特記なし

服薬歴：アセトアミノフェン(股関節の疼痛に対して)

身体所見 examination

　血圧 142/86mmHg。体温37.5℃。脈拍88/分。grade 2 hypertensive retinopathy(高血圧症性網膜症)。心血管系、呼吸器系に検査場異常なし。手にDIPにヘバーデン結節なし。

　左膝が発熱し腫脹している。関節内に液、patellar tap陽性。90℃以上膝関節を屈曲させると痛みを生じる。右の膝関節は正常に見える。

検査　investigation

　生化学：白血球増多、ESR上昇、尿素高値、グルコース高値

　単純X線：関節間隙やや狭小。それ以外に異常は認めない。

■problem list

　#1 左膝の痛み

　#2 胸焼け

　#3 消化不良

　#4 高血圧

　#5 クレアチニン正常高値

　#6 股関節の変形性リウマチ

　#7 高血圧性網膜症

■考え方

　・関節痛の鑑別診断を考える。

　・VINDICATEで考えてみてもよいでしょう。

　・関節痛の頻度としては　外傷＞慢性疾患(OAなど)＞膠原病＞脊椎疾患＞悪性腫瘍

■関節痛の鑑別疾患

DIF 282

V Vascular 血友病 hemophilia, 壊血病 scurvy, 無菌性骨壊死 aseptic bone necrosis (Osgood-Schlatter diseaseとか)

I Inflammatory 淋疾 gonorrhea, ライム病 lyme disease, 黄色ブドウ球菌 Staphylococcus, 連鎖球菌 Streptococcus, 結核 tuberculosis, 梅毒 syphilis, 風疹 rubella, 単純ヘルペス herpes simplex, HIV human immunodeficiency virus, サイトメガロウイルス cytomegalovirus

N Neoplastic disorders 骨原性肉腫 osteogenic sarcoma, 巨細胞腫 giant cell tumors

D Degenerative disorders degenerative joint disease or 変形性関節症 osteoarthritis

I Intoxication 痛風 gout (uric acid), 偽痛風 pseudogout (calcium pyrophosphate), ループス症候群 lupus syndrome of hydralazine (Apresoline) and procainamide, gout syndrome of diuretics

C Congenital and acquired malformations bring to mind the joint deformities of tabes dorsalis and syringomyelia and congenital dislocation of the hip. Alkaptonuria is also considered here.

A Autoimmune indicates (多い)関節リウマチ RA (可能性)血清病 serum sickness, 全身性エリテマトーデス lupus erythematosus, リウマチ熱 rheumatic fever, ライター症候群 Reiter syndrome, 潰瘍性大腸炎 ulcerative colitis, クローン病=限局性回腸炎 regional ileitis, 乾癬性関節炎 psoriatic arthritis (老人であり得る)リウマチ性多発筋痛症 polymyalgia rheumatica

T Trauma 外傷性滑膜炎 traumatic synovitis, tear or rupture of the collateral or cruciate ligaments, 亜脱臼 subluxation or laceration of the meniscus (semilunar cartilage), 脱臼 dislocation of the joint or patella, a 捻挫　sprain of the joint, and fracture of the bones of the joint.

E Endcrine 先端肥大症 acromegaly, 閉経 menopause, 糖尿病 diabetes mellitus

■答え

　骨格筋系-関節炎-単関節炎-急性単関節炎

　痛風　尿酸　→　発熱、ESR↑、白血球↑

　偽痛風　ピロリン酸カルシウム

　高齢女性でチアジド系利尿薬の使用により痛風が誘発されやすい。特に腎機能低下、糖尿病の人はこのリスクが高まる。

■(BSTからの知識「)循環器領域での利尿薬

・心不全の治療において、循環血漿量を減らし、心臓の前負荷を軽減する。

・利尿薬は高尿酸血症を起こす。(けど、心不全の治療において高尿酸血症になったからといって痛風を発症している患者はみたことない)

・電解質異常を起こしやすいので、血液生化学の検査でモニタして注意する。たとえば低Kで不整脈のリスクが高まる。

・チアジド系の利尿薬は血糖を上げるし、尿酸を上げる

・長期の使用で腎機能を低下させる

■initial plan

　Dx 1. 関節液の吸引：関節液の一般検査、生化学検査、培養検査、

　　　　・白血球が増加していれば急性炎症性であることを示す。

　　　　・偏光顕微鏡で関節液を検鏡する。

　　　　　・尿酸の結晶：針状結晶。negatively birefringent

　　　　　・ピロリン酸カルシウムの結晶：positively birefringent

　Tx 1. 関節液の吸引：炎症が軽度改善

　　 2. NSAIDによる疼痛管理

　　 3. PPI：NSAID潰瘍を予防するため

　　 4. ACE inhibitorの導入

「乾癬性」

　　[★]

英

psoriatic

関

乾癬