pustular psoriasis

膿疱性乾癬

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）』「2013/10/12 03:38:39」(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 /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. It is not contagious. 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% and 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 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%). 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. In general, the degree of severity is 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 also scrape off the naturally occurring skin oil. In addition, 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 that 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 that 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 that 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 turnover, 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 that 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 that 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, a condition imposed as a punishment for slander. The patient was deemed "impure" (see tumah and taharah) during their afflicted phase and is ultimately treated by the kohen., However, it is more likely that this confusion arose from the use of the same Greek term for both conditions. 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.

Sulfur 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) is the global umbrella organization for national and regional psoriasis patient associations and also gathers the leading experts in psoriasis and psoriatic arthritis research for scientific conferences every three years. The Psoriasis International Network, a program of the Fondation René Touraine, gathers dermatologists, rheumatologists and other caregivers involved in the management of psoriasis.

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
• Guidelines for the care and treatment of psoriasis and psoriatic arthritis National Guideline Clearinghouse -- U.S.)
• Guidelines for the assessment and management of psoriasis. National Guideline Clearinghouse -- U.S.)

UpToDate Contents

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• 1. 膿疱性皮膚病変を有する患者へのアプローチ approach to the patient with pustular skin lesions
• 2. 乾癬の治療 treatment of psoriasis
• 3. 乾癬の疫学、臨床症状、および診断 epidemiology clinical manifestations and diagnosis of psoriasis
• 4. 急性汎発性発疹性膿疱症（AGEP） acute generalized exanthematous pustulosis agep
• 5. 好中球性皮膚症 neutrophilic dermatoses

English Journal

• Cutaneous allergic drug reactions: update on pathophysiology, diagnostic procedures and differential diagnosic.

• Balakirski G1, Merk HF1.
• Cutaneous and ocular toxicology.Cutan Ocul Toxicol.2017 Dec;36(4):307-316. doi: 10.1080/15569527.2017.1319379. Epub 2017 Apr 27.
• PMID 28412864

• Intracorneal pustular drug eruption, a novel cutaneous adverse event in anti-programmed cell death-1 patients that highlights the effect of anti-programmed cell death-1 in neutrophils.

• Zhao CY1, Consuegra G, Chou S, Fernández-Peñas P.
• Melanoma research.Melanoma Res.2017 Dec;27(6):641-644. doi: 10.1097/CMR.0000000000000397.
• PMID 28984691

• UVA1 vs. narrowband UVB phototherapy in the treatment of palmoplantar pustulosis: a pilot randomized controlled study.

• Su LN1,2, Ren J3, Cheng SM3, Liu JL3, Ding YF4, Zhu NW3.
• Lasers in medical science.Lasers Med Sci.2017 Nov;32(8):1819-1823. doi: 10.1007/s10103-017-2280-0. Epub 2017 Jul 11.
• PMID 28699044

Japanese Journal

• 白血球除去療法が奏効した膿疱性乾癬 (特集 乾癬)

• 古川 紗綾佳,今井 康友,上田 英一郎 [他]
• 皮膚科の臨床 54(10), 1337-1340, 2012-10-00
• NAID 40019458369

• PUVAバス療法にて奏効した膿疱性乾癬の3例 (特集 乾癬)

• 青山 正子,森田 明理
• 皮膚科の臨床 54(10), 1331-1335, 2012-10-00
• NAID 40019458349

Related Links

• Guide to Pustular Psoriasis eczema: Natural Psorisis plaques ...

Have you seen a person with skin that seems to have red-scaly patches like a snake? If yes, then that person is most likely suffering from the skin disease psoriasis – often mistakenly spelled as psorisis. While you might feel ...

• Psoriasis types: Pustular - National Psoriasis Foundation

Information about the types of pustular psoriasis including von Zumbusch psoriasis, palmoplantar pustulosis and acropustulosis or acrodermatitis continua of Hallopeau. ... Pustular Psoriasis Pustular [PUHS-choo-lar] psoriasis in ...

Related Pictures

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★リンクテーブル★

リンク元	「乾癬」「膿疱性乾癬」「コゴイ微小膿瘍」

「乾癬」

　　[★]

英

psoriasis

関

角化症

概念

• 慢性再発性難治性の炎症性角化症
• 代表的炎症性疾患のひとつで原因は不明：遺伝因子＋環境因子(生活習慣、気候、薬物)　→　HLA-B27と関連していることからautoimmune diseaseとも考えられている。
• 青年から中年に好発。厚い銀白色の麟屑を伴った紅斑・丘疹が出没、表皮の炎症と表皮細胞のターンオーバーの亢進を認める。

乾癬の階層

• 角化症

• 後天性角化症

• 炎症性角化症

• 乾癬

• 尋常性乾癬 psoriasis vulgaris
• 膿疱性乾癬 pustular psoriasis
• 乾癬性紅皮症 psoriatic erythroderma
• 乾癬性関節炎 psoriatic arthritis

病型

• 尋常性乾癬 psoriasis vulgaris

• 四肢で著名で厚い麟屑を付着した紅斑

• 滴状乾癬 guttate psoriasis

• 背部に散在する軽度の麟屑を伴う紅斑、丘疹　Gibertばら色粃糠疹との区別が重要
• 先行感染(溶連菌)や慢性経過の乾癬が存在していることが多い。

• 膿疱性乾癬 pustular psoriasis

• 広範囲の皮膚の潮紅　紅潮皮膚の上に環状に配列する無菌性膿疱
• 通常尋常性乾癬を伴う　　長期間のコントロールが必要
• 難病指定

• 乾癬性紅皮症 psoriatic erythroderma

• 膜様の麟屑を伴う　全身皮膚潮紅

• 乾癬性関節炎 psoriatic arthritis

• 関節炎を伴う
• 爪の租造化

• 爪の租造化は水虫でも見られる

• 手指の関節の著名な変形
• 尋常性乾癬を伴うことがある

病因

• 遺伝的+誘発因子, 悪化因子

• 誘発因子、悪化因子(外傷、感染症、日光、薬剤、低Ca血症、肥満、妊娠、アルコール摂取、ストレス)

遺伝的背景

• 家族内発症率→多因子遺伝が発症に関与

• 両親が乾癬：50%、片親：16.4%、家族歴：4倍
• HLA-Cw6と相関

HLA-A1, HLA-B13, HLA-BW16, HLA-B17, HLA-B37, HLA-CW6, HLA-DR7も関連

HLA-B27

疫学

• 初発年齢：20歳前後に大きなピーク。60歳代に小さなピーク。
• 白人1-2%(5%に達する国もある), 日本人0.1%　←人種者あり

病変形成＆病理

• keratinocyteとlymphocyteの相互作用

• 乾癬患者と正常者の角化細胞を比べると、乾癬患者の方がT細胞の増殖への影響が大きい
• 乾癬患者のT細胞は正常者の表皮に乾癬を生じさせた
• 表皮細胞の遊走能などをTNF-α、IL-8などによって促進
• 炎症部位に好中球や樹上細胞などを呼び寄せるようなケモカインが出される
• 血管増殖因子を出す

• transglutaminaseが感染患者では表皮全てで発現？

• keratinocyteの分化に関わる

• 通常は顆粒層のみで発現

• 樹状細胞の関与？

• 表皮細胞がケモカインを放出→樹状細胞がT細胞を刺激(IL-12/IL-23で抑制される)→T細胞がケラチノサイトの増殖させる。

病理組織像

• 表皮肥厚 acanthosis：規則的に波打っている
• 顆粒層消失　→　ケラトヒアリン顆粒を作らないうちに角層に移行するため。
• 錯核化 parakeratosis：角質層に核が残る
• ムンロ微小膿瘍（好中球による無菌性膿瘍）
• 真皮上層までリンパ球浸潤。好中球、樹状細胞の浸潤が認められる。

• 病変部、非病変部移行部のkeratin16発現

• keratinocyteの最終分化に関与
• ケラチン16は炎症がひどいときに発現する

症状

• 角化性丘疹が癒合した大小さまざまな紅色の局面を特徴とし、表面には典型的な鱗屑が付着

検査

• 蝋片現象陽性：皮疹の爪を爪などでこすった際に白色鱗屑が見られる
• Auspitz現象陽性：鱗屑を剥がすと点状出血を認める(顆粒層減少と毛細血管拡張による)
• Kobner現象陽性：しヒンのない部位に外傷などの刺激が加わるとそこに乾癬の皮疹ができる。

治療

• 完全に治癒することはなく慢性に経過し、悪化・軽快の反復。日常生活に支障がなくなる程度まで直す。

軽症

• 外用療法(つまり、局所療法)

• 第一選択薬は活性型ビタミンD3　→　再発までの期間を延長できる

• ボンアルファ、ボンアルファハイ、カルシポトリオール(ボネックス)、オキサロール

• 効果が不十分な場合はステロイド外用も考慮
• ただし、very strong以上のステロイドを漫然と投与することは避けるべき
• 少量のステロイドとビタミンD3の併用療法がトレンドらしい？

ビタミンD3による高カルシウム血症に注意

• 全身療法

• 紫外線照射、ビタミンA酸誘導体内服、免疫抑制薬内服

中等症

• 紫外線治療(PUVA、narrow band UVB）

作用メカニズム；表皮角化細胞の増殖抑制、免疫抑制作用

副作用；火傷、発癌作用（ほかの免疫抑制剤との併用禁忌）、色素沈着(UVAの場合、まだら模様になりうる→narrow band UVBなら防ぐことができる)

• PUVA：オキソラレン+UVA。
• narrow band UVB：311nm。発癌↓

重症

• 全身療法

• シクロスポリン

• 作用メカニズム:T cellの活性化抑制
• 副作用:腎機能障害（血清クレアチニンが30％以上上昇した場合、投与量を少なくするか、投与を中止することが必要）。紫外線療法との併用は禁忌(発癌リスク↑)

• エトレチナート

• 作用メカニズム:分化誘導作用
• 副作用；催奇形性（女性2年、男性6ヶ月の避妊が必要）、骨形成阻害（小児への長期投与は慎重に）、肝機能障害、高脂血症。(高頻度)口唇炎、手指の落屑。

• メトトレキサート

• 副作用が強いので最後の手段として使用する。
• 作用メカニズム:表皮角化細胞の増殖抑制
• 副作用:肝機能障害

日常生活治療、指導、補助

• 痒みに対する処置～抗ヒスタミン剤、入浴、食べ物(刺激の強い食べ物)
• 肥満、糖尿病、高脂血症の予防
• アルコールの抑制、肝機能障害
• スキンケア

• 角化傾向が強い場合はサリチル酸

参考

• 1. [charged] Epidemiology, pathophysiology, clinical manifestations, and diagnosis of psoriasis - uptodate [1]
• 2.

http://sweetmemory.sakura.ne.jp/kansen/kansen03_1.html

USMLE

• Q book p.289 9
• A 30-year-old woman has chronic, silver-white, scaly patches with an erythematous border on the skin of her knees and elbows.

「膿疱性乾癬」

　　[★]

英

pustular psoriasis

関

角化症、乾癬、コゴイ海綿状膿疱=コゴイ微小膿瘍

病因

• 肝機能異常？：肝機能異常との関連が指摘されている。本疾患を発症した患者の90%に以前から存在する肝機能障害が存在していたという報告がある。(参考1)
• 妊娠、感染、糖質コルチコイドの中止と関連があると言われている。(参考1)

参考

• 1. [charged] Epidemiology, pathophysiology, clinical manifestations, and diagnosis of psoriasis - uptodate [2]

「コゴイ微小膿瘍」

　　[★]

英

Kogoj's spongiform pustule, Kogoj spongiform pustule

同

コゴイ海綿状膿疱

関

膿疱性乾癬 pustular psoriasis、海綿状膿疱

• http://missinglink.ucsf.edu/lm/DermatologyGlossary/psoriasis.html