Psoriasis
Encyclopedia
Psoriasis is an autoimmune disease
that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of stroke. There are five types of psoriasis: plaque, guttate, inverse, pustular and erythrodermic. The most common form, plaque psoriasis, is commonly seen as red and white hues of scaly patches appearing on the top first layer of the epidermis (skin). Some patients, though, have no dermatological symptoms.
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 knee
s, but can affect any area, including the scalp
, palms of hands and soles of feet, and genitals
. In contrast to eczema
, psoriasis is more likely to be found on the outer side of the joint.
The disorder
is a chronic recurring condition that varies in severity from minor localized patches to complete body coverage. Fingernails
and toenails are frequently affected (psoriatic nail dystrophy) and can be seen as an isolated symptom. Psoriasis can also cause inflammation of the joints, which is known as psoriatic arthritis
. Between 10-30% of all people with psoriasis also have psoriatic arthritis.
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
, see Koebnerisin. Various environmental factors have been suggested as aggravating to psoriasis, including stress
, withdrawal of systemic corticosteroid
, as well as other environmental factors, but few have shown statistical significance. 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 but this may be followed by cure.
code ).
Psoriasis is a chronic relapsing disease of the skin that may be classified into nonpustular and pustular types as follows:
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.
, 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
. Medical care can be costly and time-consuming, and can interfere with an employment or school schedule.
Individuals with psoriasis may also feel self-conscious about their appearance and have a poor self-image that stems from fear of public rejection and psychosexual concerns. Psychological distress can lead to significant depression
and social isolation
.
In a 2008 National Psoriasis Foundation
survey of 426 psoriasis sufferers, 71 percent reported the disease was a significant problem in everyday life. More than half reported significant feelings of self-consciousness (63 percent) and embarrassment (58 percent). More than one-third said they avoided social activities and limited dating or intimate interactions.
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.
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.
in which the excessive reproduction of skin cells is secondary to factors produced by the immune system
. T cell
s (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 model
s, 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 blocker
s 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. 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.
(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.
. 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 cell
s 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.
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
).
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.
s, 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), corticosteroid
s like desoximetasone (Topicort), fluocinonide
, vitamin D
3 analogues (for example, calcipotriol
), and retinoid
s 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.
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 amount of light used is determined by a persons 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
).
Psoriasis that is resistant to topical treatment
and phototherapy
is treated by medication
s 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. Post-surgical eventration may be associated to methotrexate exposure.
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.
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. Fish oils are rich in the two omega-3 fatty acid
s 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 the regulatory effects of THC
on the immune system. The adverse effects of cannabis might be overcome by use of more specific cannabinoid receptor medications, to inhibit keratinocyte proliferation.
s, 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.
es 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.
Onset before age 40 usually indicates a greater genetic susceptibility and a more severe or recurrent course of psoriasis.
in the Bible
. In more recent times psoriasis was frequently described as a variety of leprosy
. 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.
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 viper
s 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.
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. Ruxolitimib 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. , it is undergoing clinical trials.
Research into antisense oligonucleotide
s 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.
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.
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of stroke. There are five types of psoriasis: plaque, guttate, inverse, pustular and erythrodermic. The most common form, plaque psoriasis, is commonly seen as red and white hues of scaly patches appearing on the top first layer of the epidermis (skin). Some patients, though, have no dermatological symptoms.
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 knee
Knee
The knee joint joins the thigh with the leg and consists of two articulations: one between the fibula and tibia, and one between the femur and patella. It is the largest joint in the human body and is very complicated. The knee is a mobile trocho-ginglymus , which permits flexion and extension as...
s, but can affect any area, including the scalp
Scalp
The scalp is the anatomical area bordered by the face anteriorly and the neck to the sides and posteriorly.-Layers:It is usually described as having five layers, which can conveniently be remembered as a mnemonic:...
, palms of hands and soles of feet, and genitals
Sex organ
A sex organ, or primary sexual characteristic, as narrowly defined, is any of the anatomical parts of the body which are involved in sexual reproduction and constitute the reproductive system in a complex organism; flowers are the reproductive organs of flowering plants, cones are the reproductive...
. In contrast to eczema
Eczema
Eczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...
, psoriasis is more likely to be found on the outer side of the joint.
The disorder
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
is a chronic recurring condition that varies in severity from minor localized patches to complete body coverage. Fingernails
Nail (anatomy)
A nail is a horn-like envelope covering the dorsal aspect of the terminal phalanges of fingers and toes in humans, most non-human primates, and a few other mammals. Nails are similar to claws, which are found on numerous other animals....
and toenails are frequently affected (psoriatic nail dystrophy) and can be seen as an isolated symptom. Psoriasis can also cause inflammation of the joints, which is known as psoriatic arthritis
Psoriatic arthritis
Psoriatic arthritis is a type of inflammatory arthritis that, according to the National Psoriasis Foundation, will develop in up to 30 percent of people who have the chronic skin condition psoriasis...
. 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
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
component and local psoriatic changes can be triggered by an injury to the skin known as the Koebner phenomenon
Koebner Phenomenon
The Koebner phenomenon, also called the "Koebner response" or the "isomorphic response", refers to skin lesions appearing on lines of trauma. The Koebner phenomenon may result from either a linear exposure or irritation...
, see Koebnerisin. Various environmental factors have been suggested as aggravating to psoriasis, including stress
Stress (medicine)
Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...
, withdrawal of systemic corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
, 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
Rebound effect
The rebound effect, or rebound phenomenon, is the tendency of some medications, when discontinued suddenly, to cause a return of the symptoms it relieved, and that, to a degree stronger than they were before treatment first began...
' of corticosteroids but this may be followed by cure.
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-10ICD
The International Statistical Classification of Diseases and Related Health Problems is a medical classification that provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or disease...
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 erythrodermaPsoriatic erythrodermaPsoriatic erythroderma represents a generalized form of psoriasis that affects all body sites, including the face, hands, feet, nails, trunk, and extremities....
(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 psoriasisGeneralized pustular psoriasisGeneralized pustular psoriasis is an extremely rare type of [psoriasis] that can present in a variety of forms. Unlike the most general and common forms of psoriasis, GPP usually covers the entire body and with pus-filled blisters rather than plaques. GPP can present at any age, but is rarer in...
(pustular psoriasis of von Zumbusch) - Pustulosis palmaris et plantarisPustulosis palmaris et plantarisPustulosis palmaris et plantaris is a chronic recurrent pustular dermatosis localized on the palms and soles only, characterized histologically by intraepidermal vesicles filled with...
(persistent palmoplantar pustulosis, pustular psoriasis of the Barber type, pustular psoriasis of the extremities) - Annular pustular psoriasisAnnular pustular psoriasisAnnular pustular psoriasis is a rare variant of pustular psoriasis, having an annular, or circinate, lesion morphology that may appear at the onset of pustular psoriasis, with a tendency to spread and form enlarged rings....
- Acrodermatitis continua
- Impetigo herpetiformisImpetigo herpetiformisImpetigo herpetiformis is a form of severe pustular psoriasis occurring in pregnancy which may occur during any trimester.It is the only well known pustular psoriasis which is treated with steroids.- References :...
Other
Additional types of psoriasis include:- Drug-induced psoriasisDrug-induced psoriasisDrug-induced psoriasis may be induced by beta-blockers, lithium, antimalarials, terbinafine, calcium channel blockers, captopril, glyburide, granulocyte colony-stimulating factor, interleukins, interferons, and lipid-lowering drugs....
- Inverse psoriasisInverse psoriasisInverse psoriasis is a form of psoriasis that selectively and often exclusively involves the folds, recesses, and flexor surfaces such as the ears, axillae, groins, inframammary folds, navel, intergluteal crease, penis, lips, and webspaces....
(flexural psoriasis, inverse psoriasis)(L40.83-4) appears as smooth inflamed patches of skin. It occurs in skin foldSkin foldSkin folds are areas of skin where it folds. Many skin folds are distinct, heritable anatomical features, and may be used for identification of animal species, while others are non-specific and may be produced either by individual development of an organism or by arbitrary application of force to...
s, particularly around the genitals (between the thigh and groin), the armpits, under an overweight abdomen (panniculusPanniculusPanniculus is a medical term describing a dense layer of fatty tissue growth, consisting of subcutaneous fat in the lower abdominal area. It can be a result of obesity and can be mistaken for a tumor or hernia. Abdominal panniculus can be removed during abdominal panniculectomy, a type of...
), and under the breasts (inframammary foldInframammary foldInframammary fold , inframammary crease or inframammary line is the feature of human anatomy which is a natural boundary of a breast from below, the place where the breast and the chest meet. The choice of the term depends on the prominence of the feature. It is also sometimes called inframammary...
). It is aggravated by frictionFrictionFriction is the force resisting the relative motion of solid surfaces, fluid layers, and/or material elements sliding against each other. There are several types of friction:...
and sweatSWEATSWEAT is an OLN/TSN show hosted by Julie Zwillich that aired in 2003-2004.Each of the 13 half-hour episodes of SWEAT features a different outdoor sport: kayaking, mountain biking, ice hockey, beach volleyball, soccer, windsurfing, rowing, Ultimate, triathlon, wakeboarding, snowboarding, telemark...
, and is vulnerable to fungal infections.
- Napkin psoriasisNapkin psoriasisNapkin psoriasis, or psoriasis in the diaper area, is characteristically seen in infants between two and eight months of age....
- Seborrheic-like psoriasisSeborrheic-like psoriasisSeborrheic-like psoriasis is a skin condition characterized by psoriasis with an overlaping seborrheic dermatitis....
Guttate psoriasis
Guttate psoriasis
Guttate psoriasis is a type of psoriasis that presents as small lesions over the upper trunk and proximal extremities; it is found frequently in young adults...
(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
Psoriatic nails
Psoriatic nails is a nail disease. It is common in those suffering from psoriasis, with reported incidences varying from 10% to 78%. Elderly patients and those with psoriatic arthritis are more likely to have psoriatic nails.-Symptoms:...
(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
Onycholysis
Onycholysis refers to the detachment of the nail from the nail bed, starting at its distal and/or lateral attachment. It is said to occur particularly on the ring finger but can occur on any of the fingernails. The most common cause of onycholysis is psoriasis. It can also occur in thyrotoxicosis...
) and crumbling of the nail.
Psoriatic arthritis
Psoriatic arthritis
Psoriatic arthritis is a type of inflammatory arthritis that, according to the National Psoriasis Foundation, will develop in up to 30 percent of people who have the chronic skin condition psoriasis...
(L40.5) involves joint and connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
. 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
Dactylitis
Dactylitis or sausage digit is inflammation of an entire digit , and can be painful.The word dactyl comes from the Greek word "daktylos" meaning "finger"...
. Psoriatic arthritis can also affect the hips, knees and spine (spondylitis
Spondylitis
Spondylitis is an inflammation of the vertebra. It is a form of spondylopathy. In many cases, spondylitis involves one or more vertebral joint as well, which itself is called spondylarthritis.-Examples:...
). About 10–15% of people who have psoriasis also have psoriatic arthritis.
The migratory stomatitis
Migratory stomatitis
Migratory stomatitis is a benign condition on the oral soft tissue. This condition has two forms: the common form, which is consisted from red lesions with white borders on the tongue only. This form is called geographic tongue...
in the oral cavity mucosa and the geographic tongue
Geographic tongue
Geographic tongue, an inflammatory condition of the tongue affecting approximately 2% of the population, is characterized by discolored regions of taste buds or sometimes even cracks in the tongue...
that confined to the dorsal and lateral aspects of the tongue
Tongue
The tongue is a muscular hydrostat on the floors of the mouths of most vertebrates which manipulates food for mastication. It is the primary organ of taste , as much of the upper surface of the tongue is covered in papillae and taste buds. It is sensitive and kept moist by saliva, and is richly...
mucosa, are believed to be oral manifestations of psoriasis, as being histologically
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...
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.
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 depressionClinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
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
Walking
Walking is one of the main gaits of locomotion among legged animals, and is typically slower than running and other gaits. Walking is defined by an 'inverted pendulum' gait in which the body vaults over the stiff limb or limbs with each step...
, and sleep
Sleep
Sleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than...
. Plaques on hands and feet
Foot
The foot is an anatomical structure found in many vertebrates. It is the terminal portion of a limb which bears weight and allows locomotion. In many animals with feet, the foot is a separate organ at the terminal part of the leg made up of one or more segments or bones, generally including claws...
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
Dandruff
Dandruff is the shedding of dead skin cells from the scalp . Dandruff is sometimes caused by frequent exposure to extreme heat and cold. As it is normal for skin cells to die and flake off, a small amount of flaking is normal and common; about 487,000 cells/cm2 get released normally after...
. Medical care can be costly and time-consuming, and can interfere with an employment or school schedule.
Individuals with psoriasis may also feel self-conscious about their appearance and have a poor self-image that stems from fear of public rejection and psychosexual concerns. Psychological distress can lead to significant depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
and social isolation
Social isolation
Social isolation refers to a lack of contact with society for members of social species. There may be many causes and individuals in numerous generally social species are isolated at times, it need not be a pathological condition. In human society, in those cases where it is viewed as a pathology,...
.
In a 2008 National Psoriasis Foundation
National Psoriasis Foundation
The National Psoriasis Foundation is the United States’ leading patient-driven, nonprofit advocacy organization that serves the estimated 7.5 million Americans affected by psoriasis and psoriatic arthritis....
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
The Psoriasis Area Severity Index
Psoriasis Area Severity Index
Psoriasis Area and Severity Index is the most widely used tool for the measurement of severity of psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 to 72 .- Calculation :The body is divided into four sections Psoriasis Area...
(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 disorderImmune-mediated disease
Immune-mediated diseases are conditions which result from abnormal activity of the body's immune system. The immune system may over-react or start attacking the body . Autoimmune diseases are a subset of immune-mediated diseases....
in which the excessive reproduction of skin cells is secondary to factors produced by the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
. T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s (which normally help protect the body against infection) become active, migrate to the dermis
Dermis
The dermis is a layer of skin between the epidermis and subcutaneous tissues, and is composed of two layers, the papillary and reticular 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
Immunosuppressant
An immunosuppressant is any substance that performs immunosuppression of the immune system. They may be either exogenous, as immunosuppressive drugs, or endogenous, as ,e. g., testosterone...
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
Animal model
An animal model is a living, non-human animal used during the research and investigation of human disease, for the purpose of better understanding the disease without the added risk of causing harm to an actual human being during the process...
of psoriasis can be triggered in mice lacking T cells. Animal model
Animal model
An animal model is a living, non-human animal used during the research and investigation of human disease, for the purpose of better understanding the disease without the added risk of causing harm to an actual human being during the process...
s, 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
Stress (medicine)
Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...
(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
Climate
Climate encompasses the statistics of temperature, humidity, atmospheric pressure, wind, rainfall, atmospheric particle count and other meteorological elemental measurements in a given region over long periods...
. Certain medicines, including lithium salt, beta blocker
Beta blocker
Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...
s and the antimalarial drug
Antimalarial drug
Antimalarial medications, also known as antimalarials, are designed to prevent or cure malaria. Such drugs may be used for some or all of the following:* Treatment of malaria in individuals with suspected or confirmed infection...
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. 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
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, 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
T helper cell
T helper cells are a sub-group of lymphocytes, a type of white blood cell, that play an important role in the immune system, particularly in the adaptive immune system. These cells have no cytotoxic or phagocytic activity; they cannot kill infected host cells or pathogens. Rather, they help other...
cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
profile, whereas psoriasis vulgaris is characterized by a strong Th1
T helper cell
T helper cells are a sub-group of lymphocytes, a type of white blood cell, that play an important role in the immune system, particularly in the adaptive immune system. These cells have no cytotoxic or phagocytic activity; they cannot kill infected host cells or pathogens. Rather, they help other...
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
Koebner Phenomenon
The Koebner phenomenon, also called the "Koebner response" or the "isomorphic response", refers to skin lesions appearing on lines of trauma. The Koebner phenomenon may result from either a linear exposure or irritation...
). 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
Athlete's foot
Athlete's foot is a fungal infection of the skin that causes scaling, flaking, and itch of affected areas. It is caused by fungi in the genus Trichophyton and is typically transmitted in moist areas where people walk barefoot, such as showers or bathhouses...
, 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.
Genetics
Psoriasis has a large hereditary component, and many genes are associated with it, but it is not clear how those genes work together. Most of them involve the immune system, particularly the major histocompatibility complexMajor histocompatibility complex
Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
(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
Major histocompatibility complex
Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
, 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
CCHCR1
Coiled-coil alpha-helical rod protein 1, also known as CCHCR1, is a protein which in humans is encoded by the CCHCR1 gene.- Clinical significance :...
, 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.
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 diseaseAutoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
. 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
Dermis
The dermis is a layer of skin between the epidermis and subcutaneous tissues, and is composed of two layers, the papillary and reticular 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
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
consists of an innate immune system
Innate immune system
The innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner...
, and an adaptive immune system
Adaptive immune system
The adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogenic growth. Thought to have arisen in the first jawed vertebrates, the adaptive or "specific" immune system is activated by the “non-specific” and evolutionarily older innate...
.
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 cell
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...
s 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 diagnosisMedical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...
of psoriasis is usually based on the appearance of the skin; there are no special blood tests or diagnostic procedures. Sometimes, a skin biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
, or scraping, may be needed to rule out other disorders and to confirm the diagnosis. Skin from a biopsy will show clubbed rete pegs
Rete pegs
Rete pegs are the epithelial extensions that project into the underlying connective tissue.In the epithelium of the mouth, the attached gingiva exhibit rete pegs, while the sulcular and junctional epithelia do not....
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
Auspitz's sign
Auspitz's sign is the appearance of punctate bleeding spots when psoriasis scales are scraped off, named after Heinrich Auspitz....
).
Management
Topical agents
Bath solutions and moisturizerMoisturizer
Moisturizers or emollients are complex mixtures of chemical agents specially designed to make the external layers of the skin softer and more pliable, by increasing its hydration by reducing evaporation. Naturally occurring skin lipids and sterols as well as artificial or natural oils,...
s, mineral oil
Mineral oil
A mineral oil is any of various colorless, odorless, light mixtures of alkanes in the C15 to C40 range from a non-vegetable source, particularly a distillate of petroleum....
, and petroleum jelly
Petroleum jelly
Petroleum jelly, petrolatum, white petrolatum or soft paraffin, CAS number 8009-03-8, is a semi-solid mixture of hydrocarbons , originally promoted as a topical ointment for its healing properties...
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
Coal tar
Coal tar is a brown or black liquid of extremely high viscosity, which smells of naphthalene and aromatic hydrocarbons. Coal tar is among the by-products when coal iscarbonized to make coke or gasified to make coal gas...
, dithranol
Dithranol
Dithranol or Anthralin is a Hydroxyanthrone, anthracene derivative, medicine applied to the skin of people with psoriasis. It is available as creams, ointment or pastes in 0.1 to 2% strengths...
(anthralin), corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s like desoximetasone (Topicort), fluocinonide
Fluocinonide
Fluocinonide is a potent glucocorticoid steroid used topically as anti-inflammatory agent for the treatment of skin disorders such as eczema and seborrhoeic dermatitis...
, vitamin D
Vitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
3 analogues (for example, calcipotriol
Calcipotriol
Calcipotriol or calcipotriene is a synthetic derivative of calcitriol or vitamin D. It is used in the treatment of psoriasis, marketed under the trade name Dovonex or Daivonex.-Mechanism:...
), and retinoid
Retinoid
The retinoids are a class of chemical compounds that are related chemically to vitamin A. Retinoids are used in medicine, primarily due to the way they regulate epithelial cell growth....
s are routinely used. The use of the Finger tip unit
Finger tip unit
In medicine, a finger tip unit is defined as the amount of ointment, cream or other semi-solid dosage form expressed from a tube with a 5mm diameter nozzle, applied from the distal skin-crease to the tip of the index finger of an adult. One FTU is enough to treat an area of skin twice the size...
may be helpful in guiding how much topical treatment to use. The mechanism of action
Mechanism of action
In pharmacology, the term mechanism of action refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect...
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 sunlightSunlight
Sunlight, in the broad sense, is the total frequency spectrum of electromagnetic radiation given off by the Sun. On Earth, sunlight is filtered through the Earth's atmosphere, and solar radiation is obvious as daylight when the Sun is above the horizon.When the direct solar radiation is not blocked...
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 amount of light used is determined by a persons skin type. Increased rates of cancer from treatment appear to be small.
Psoralen
Psoralen
Psoralen is the parent compound in a family of natural products known as furocoumarins. It is structurally related to coumarin by the addition of a fused furan ring, and may be considered as a derivative of umbelliferone...
and ultraviolet A phototherapy (PUVA
PUVA
PUVA is a psoralen + UVA treatment for eczema, psoriasis, graft-versus-host disease and vitiligo, and mycosis fungoides. The psoralen is applied or taken orally to sensitize the skin, then the skin is exposed to UVA. Long term use has been associated with higher rates of skin cancer.Psoralens are...
) combines the oral or topical administration of psoralen with exposure to ultraviolet A (UVA) light. The mechanism of action
Mechanism of action
In pharmacology, the term mechanism of action refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect...
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
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, fatigue
Fatigue (physical)
Fatigue is a state of awareness describing a range of afflictions, usually associated with physical and/or mental weakness, though varying from a general state of lethargy to a specific work-induced burning sensation within one's muscles...
, burning, and itching. Long-term treatment is associated with squamous cell carcinoma
Squamous cell carcinoma
Squamous cell carcinoma , occasionally rendered as "squamous-cell carcinoma", is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of malignant cells deriving from epithelium, or showing particular cytological or tissue architectural characteristics of...
(but not with melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
).
Systemic agents
Topical
In medicine, a topical medication is applied to body surfaces such as the skin or mucous membranes such as the vagina, anus, throat, eyes and ears.Many topical medications are epicutaneous, meaning that they are applied directly to the skin...
and phototherapy
Light therapy
Light therapy or phototherapy consists of exposure to daylight or to specific wavelengths of light using lasers, light-emitting diodes, fluorescent lamps, dichroic lamps or very bright, full-spectrum light, usually controlled with various devices...
is treated by medication
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
s taken internally by pill
Pill (pharmacy)
A pill is a small, round, solid pharmaceutical oral dosage form that was in use before the advent of tablets and capsules. Pills were made by mixing the active ingredients with an excipient such as glucose syrup in a mortar and pestle to form a paste, then rolling the mass into a long cylindrical...
or injection
Injection (medicine)
An injection is an infusion method of putting fluid into the body, usually with a hollow needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body...
(systemic). Patients undergoing systemic treatment are required to have regular blood
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
and liver function tests
Liver function tests
Liver function tests , are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. The parameters measured include PT/INR, aPTT, albumin, billirubin and others...
because of the toxicity
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
of the medication
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
. Pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
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
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
, cyclosporine and retinoids. Methotrexate and cyclosporine are immunosuppressant
Immunosuppressive drug
Immunosuppressive drugs or immunosuppressive agents are drugs that inhibit or prevent activity of the immune system. They are used in immunosuppressive therapy to:...
drugs; retinoids are synthetic forms of vitamin A
Vitamin A
Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
. Patients taking methotrexate are prone to ulcerations. Post-surgical eventration may be associated to methotrexate exposure.
Biologics
Biologics
A biologic is a medicinal product such as a vaccine, blood or blood component, allergenic, somatic cell, gene therapy, tissue, recombinant therapeutic protein, or living cells that are used as therapeutics to treat diseases...
are manufactured proteins that interrupt the immune process involved in psoriasis. Unlike generalised immunosuppressant
Immunosuppressive drug
Immunosuppressive drugs or immunosuppressive agents are drugs that inhibit or prevent activity of the immune system. They are used in immunosuppressive therapy to:...
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
Efalizumab
Efalizumab is a formerly available medication designed to treat autoimmune diseases, origianally marketed to treat psoriasis. As implied by the suffix -zumab, it is a recombinant humanized monoclonal antibody administered once weekly by subcutaneous injection...
and alefacept
Alefacept
Alefacept is a genetically engineered immunosuppressive drug sold under the brand name Amevive in Canada, the United States, Israel, Switzerland and Australia. It is used to control inflammation in moderate to severe psoriasis with plaque formation, where it interferes with lymphocyte activation...
. 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
Monoclonal antibodies
Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell....
(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
Infliximab
Infliximab is a monoclonal antibody against tumour necrosis factor alpha . It is used to treat autoimmune diseases. Remicade is marketed by Janssen Biotech, Inc...
, adalimumab
Adalimumab
Adalimumab is the third TNF inhibitor, after infliximab and etanercept, to be approved in the United States. Like infliximab and etanercept, adalimumab binds to TNFα, preventing it from activating TNF receptors; adalimumab was constructed from a fully human monoclonal antibody, while infliximab...
, golimumab
Golimumab
Golimumab is a human monoclonal antibody which is used as an immunosuppressive drug and marketed under the brand name Simponi. Golimumab targets tumor necrosis factor alpha , a pro-inflammatory molecule and hence is a TNF inhibitor....
and certolizumab pegol
Certolizumab pegol
Certolizumab pegol is a therapeutic monoclonal antibody produced by UCB for the treatment of Crohn's disease and rheumatoid arthritis.-Method of action:...
) and one recombinant TNF-α decoy receptor, etanercept
Etanercept
Etanercept is a drug that treats autoimmune diseases by interfering with the tumor necrosis factor by acting as a TNF inhibitor. Pfizer describes in a SEC filing that the drug is used to treat rheumatoid, juvenile rheumatoid and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis...
, 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
Interleukin 12
Interleukin 12 is an interleukin that is naturally produced by dendritic cells, macrophages and human B-lymphoblastoid cells in response to antigenic stimulation.-Gene and structure:...
/IL-23
Interleukin 23
Interleukin-23 subunit alpha is a protein that in humans is encoded by the IL23A gene. IL-23 is produced by dendritic cells and macrophages...
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
Adalimumab
Adalimumab is the third TNF inhibitor, after infliximab and etanercept, to be approved in the United States. Like infliximab and etanercept, adalimumab binds to TNFα, preventing it from activating TNF receptors; adalimumab was constructed from a fully human monoclonal antibody, while infliximab...
(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
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
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
Ultraviolet
Ultraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...
(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
Injection (medicine)
An injection is an infusion method of putting fluid into the body, usually with a hollow needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body...
. 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 energydiets and vegetarian diets have improved psoriasis symptoms in some studies, and diets supplemented with fish oil
Fish oil
Fish oil is oil derived from the tissues of oily fish. Fish oils contain the omega-3 fatty acids eicosapentaenoic acid , and docosahexaenoic acid , precursors of certain eicosanoids that are known to reduce inflammation throughout the body, and are thought to have many health benefits.Fish do not...
(in this study cod liver oil
Cod liver oil
Cod liver oil is a nutritional supplement derived from liver of cod fish. It has high levels of the omega-3 fatty acids, EPA and DHA, and very high levels of vitamin A and vitamin D. It is widely taken to ease the symptoms of arthritis and for other health benefits...
) have also shown beneficial
effects. Fish oils are rich in the two omega-3 fatty acid
Omega-3 fatty acid
N−3 fatty acids are essential unsaturated fatty acids with a double bond starting after the third carbon atom from the end of the carbon chain....
s eicosapentaenoic acid
Eicosapentaenoic acid
Eicosapentaenoic acid is an omega-3 fatty acid. In physiological literature, it is given the name 20:5. It also has the trivial name timnodonic acid...
(EPA) and docosahexaenoic acid
Docosahexaenoic acid
Docosahexaenoic acid is an omega-3 fatty acid that is a primary structural component of the human brain and retina. In chemical structure, DHA is a carboxylic acid with a 22-carbon chain and six cis double bonds; the first double bond is located at the third carbon from the omega end...
(DHA) and contain Vitamin E
Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...
, furthermore cod liver oil contains Vitamin A
Vitamin A
Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
and Vitamin D
Vitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
.
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
Cannabis (drug)
Cannabis, also known as marijuana among many other names, refers to any number of preparations of the Cannabis plant intended for use as a psychoactive drug or for medicinal purposes. The English term marijuana comes from the Mexican Spanish word marihuana...
might treat psoriasis, due to the anti-inflammatory properties of its cannabinoids
Cannabinoids
Cannabinoids are a class of chemical compounds that include the phytocannabinoids , and chemical compounds that mimic the actions of phytocannabinoids or have a similar structure...
, and the regulatory effects of THC
THC
THC commonly refers to tetrahydrocannabinol, the main active chemical compound in Cannabis.THC may also refer to:* Tan Holdings Corporation...
on the immune system. The adverse effects of cannabis might be overcome by use of more specific cannabinoid receptor medications, to inhibit keratinocyte proliferation.
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 cancerSkin cancer
Skin neoplasms are skin growths with differing causes and varying degrees of malignancy. The three most common malignant skin cancers are basal cell cancer, squamous cell cancer, and melanoma, each of which is named after the type of skin cell from which it arises...
s, lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
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 sexSex
In biology, sex is a process of combining and mixing genetic traits, often resulting in the specialization of organisms into a male or female variety . Sexual reproduction involves combining specialized cells to form offspring that inherit traits from both parents...
es equally, and can occur at any age
Ageing
Ageing or aging is the accumulation of changes in a person over time. Ageing in humans refers to a multidimensional process of physical, psychological, and social change. Some dimensions of ageing grow and expand over time, while others decline...
, although it most commonly appears for the first time between the ages of 15 and 25 years.
The prevalence
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
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
Statistical survey
Survey methodology is the field that studies surveys, that is, the sample of individuals from a population with a view towards making statistical inferences about the population using the sample. Polls about public opinion, such as political beliefs, are reported in the news media in democracies....
conducted by the National Psoriasis Foundation
National Psoriasis Foundation
The National Psoriasis Foundation is the United States’ leading patient-driven, nonprofit advocacy organization that serves the estimated 7.5 million Americans affected by psoriasis and psoriatic arthritis....
(a US-based psoriasis education
Education
Education in its broadest, general sense is the means through which the aims and habits of a group of people lives on from one generation to the next. Generally, it occurs through any experience that has a formative effect on the way one thinks, feels, or acts...
and advocacy group
Advocacy group
Advocacy groups use various forms of advocacy to influence public opinion and/or policy; they have played and continue to play an important part in the development of political and social systems...
) found a prevalence of 2.1% among adult
Adult
An adult is a human being or living organism that is of relatively mature age, typically associated with sexual maturity and the attainment of reproductive age....
Americans
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
. 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
Family history (medicine)
In medicine, a family history consists of information about disorders from which the direct blood relatives of the patient have suffered. Genealogy typically includes very little of the medical history of the family, but the medical history could be considered a specific subset of the total history...
of the disease, and researchers have identified genetic loci
Locus (genetics)
In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map...
associated with the condition. Studies of monozygotic twins
Twin
A twin is one of two offspring produced in the same pregnancy. Twins can either be monozygotic , meaning that they develop from one zygote that splits and forms two embryos, or dizygotic because they develop from two separate eggs that are fertilized by two separate sperm.In contrast, a fetus...
suggest a 70% chance of a twin developing psoriasis if the other twin has psoriasis. The concordance
Concordance (genetics)
Concordance as used in genetics usually means the presence of the same trait in both members of a pair of twins. However, the strict definition is the probability that a pair of individuals will both have a certain characteristic, given that one of the pair has the characteristic. For example,...
is around 20% for dizygotic twins
Twin
A twin is one of two offspring produced in the same pregnancy. Twins can either be monozygotic , meaning that they develop from one zygote that splits and forms two embryos, or dizygotic because they develop from two separate eggs that are fertilized by two separate sperm.In contrast, a fetus...
. These findings suggest both a genetic predisposition and an environmental response in developing psoriasis.
Onset before age 40 usually indicates a greater genetic susceptibility and a more severe or recurrent course of psoriasis.
History
Psoriasis is probably one of the longest known illnesses of humans and simultaneously one of the most misunderstood. Some scholars believe psoriasis to have been included among the skin conditions called tzaraatTzaraath
The Hebrew noun tzaraath describes a disfigurative condition mainly referred to in chapters 13-14 of Leviticus, as well as conditions equivalent to be "mildew" on clothes and houses.Tzaraath affects both animate...
in the Bible
Bible
The Bible refers to any one of the collections of the primary religious texts of Judaism and Christianity. There is no common version of the Bible, as the individual books , their contents and their order vary among denominations...
. In more recent times psoriasis was frequently described as a variety of leprosy
Leprosy
Leprosy or Hansen's disease is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. Named after physician Gerhard Armauer Hansen, leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions...
. 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
Robert Willan
Robert Willan was an English physician and the founder of dermatology as a medical specialty. He received his MD at Edinburgh in 1780 and was elected a Fellow of the Royal Society in 1809...
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
Vienna
Vienna is the capital and largest city of the Republic of Austria and one of the nine states of Austria. Vienna is Austria's primary city, with a population of about 1.723 million , and is by far the largest city in Austria, as well as its cultural, economic, and political centre...
dermatologist Ferdinand von Hebra
Ferdinand Ritter von Hebra
Ferdinand Ritter von Hebra was an Austrian physician and dermatologist,...
. The name is derived from the Greek
Greek language
Greek is an independent branch of the Indo-European family of languages. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. Its writing system has been the Greek alphabet for the majority of its history;...
word psora which means to itch.
It was during the 20th century that psoriasis was further differentiated into specific types.
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 catCat
The cat , also known as the domestic cat or housecat to distinguish it from other felids and felines, is a small, usually furry, domesticated, carnivorous mammal that is valued by humans for its companionship and for its ability to hunt vermin and household pests...
faeces to red lesions on the skin, for example, was one of the earliest topical treatments employed in ancient Egypt
Egypt
Egypt , officially the Arab Republic of Egypt, Arabic: , is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Southwest Asia. Egypt is thus a transcontinental country, and a major power in Africa, the Mediterranean Basin, the Middle East and the Muslim world...
. Onions, sea salt and urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
, goose oil and semen
Semen
Semen is an organic fluid, also known as seminal fluid, that may contain spermatozoa. It is secreted by the gonads and other sexual organs of male or hermaphroditic animals and can fertilize female ova...
, wasp droppings in sycamore
Sycamore
Sycamore is a name which is applied at various times and places to three very different types of trees, but with somewhat similar leaf forms....
milk, and soup made from viper
Viperidae
The Viperidae are a family of venomous snakes found all over the world, except in Antarctica, Australia, Ireland, Madagascar, Hawaii, various other isolated islands, and above the Arctic Circle. All have relatively long, hinged fangs that permit deep penetration and injection of venom. Four...
s have all been reported as being ancient treatments.
In the more recent past, Fowler's solution
Fowler's solution
Fowler's solution is a solution containing potassium arsenite that once was prescribed as a remedy or a tonic. A Dr. Fowler of Stafford, England proposed its use in 1786 as a substitute for a patent medicine, "tasteless ague drop." It was prescribed in the United States until the late 1950s for a...
, which contains a poisonous and carcinogenic arsenic
Arsenic
Arsenic is a chemical element with the symbol As, atomic number 33 and relative atomic mass 74.92. Arsenic occurs in many minerals, usually in conjunction with sulfur and metals, and also as a pure elemental crystal. It was first documented by Albertus Magnus in 1250.Arsenic is a metalloid...
compound, was used by dermatologists as a treatment for psoriasis during the 18th and 19th centuries. Grenz rays
Grenz Rays
Grenz Rays are part of the electromagnetic spectrum comprising low energy X-rays. These were first developed by Gustav Bucky in 1923 using a cathode vacuum tube with a Lithium borate glass window which he labeled Grenz rays as he believed that the biological effects resembled UV light &...
(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
Undecylenic acid
Undecylenic acid is an organic unsaturated fatty acid derived from castor oil. It is the common name of the 10-undecenoic acid, . It is used in the manufacture of pharmaceuticals, cosmetics and perfumery, including antidandruff shampoos, antimicrobial powders and as a musk in perfumes and aromas...
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.
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
Janus kinase
Janus kinase is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. They were initially named "just another kinase" 1 & 2 , but were ultimately published as "Janus kinase"...
(JAK) proteins in the pathogenesis of psoriasis. As of 2010, two new oral JAK inhibitor drugs, ruxolitinib and tofacitinib
Tofacitinib
Tofacitinib is a drug being investigated by Pfizer for the treatment of rheumatoid arthritis , psoriasis, inflammatory bowel disease, and other immunological diseases, as well as for the prevention of organ transplant rejection...
(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. Ruxolitimib has completed Phase II clinical trials supplied as a topical cream.
Briakinumab
Briakinumab
Briakinumab is a human monoclonal antibody being developed by Abbott Laboratories for the treatment of psoriasis, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis....
is a human anti-IL-12
Interleukin 12
Interleukin 12 is an interleukin that is naturally produced by dendritic cells, macrophages and human B-lymphoblastoid cells in response to antigenic stimulation.-Gene and structure:...
/IL-23
Interleukin 23
Interleukin-23 subunit alpha is a protein that in humans is encoded by the IL23A gene. IL-23 is produced by dendritic cells and macrophages...
monoclonal antibody directed against the shared p40 subunit of IL-12 and IL-23. Briakinumab is being developed by Abbott Laboratories
Abbott Laboratories
Abbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr....
in conjunction with Cambridge Antibody Technology
Cambridge Antibody Technology
Cambridge Antibody Technology was a biotechnology company headquartered in Cambridge, United Kingdom...
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
Talarozole
Talarozole is an investigational drug for the treatment of acne, psoriasis and other keratinization disorders....
amplifies the effects of retinoic acid by inhibiting its metabolism. , it is undergoing clinical trials.
Research into antisense oligonucleotide
Oligonucleotide
An oligonucleotide is a short nucleic acid polymer, typically with fifty or fewer bases. Although they can be formed by bond cleavage of longer segments, they are now more commonly synthesized, in a sequence-specific manner, from individual nucleoside phosphoramidites...
s 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
ICAM-1
ICAM-1 also known as CD54 is a protein that in humans is encoded by the ICAM1 gene. This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system...
(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
Epidermal growth factor
Epidermal growth factor or EGF is a growth factor that plays an important role in the regulation of cell growth, proliferation, and differentiation by binding to its receptor EGFR...
and hyperangiogenesis vascular endothelial growth factor
Vascular endothelial growth factor
Vascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate....
(VEGF).
A novel boron-containing topical anti-inflammatory, AN2728, is currently being developed by Anacor
Anacor
Anacor Pharmaceuticals , based in Palo Alto, California, is a biopharmaceutical company focused on discovering, developing and commercializing novel small-molecule therapeutics derived from its boron chemistry platform. Anacor was founded in 2002 based on technology created by Dr. Lucy Shapiro at...
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.
Noting that botulinum toxin
Botulinum toxin
Botulinum toxin is a protein produced by the bacterium Clostridium botulinum, and is considered the most powerful neurotoxin ever discovered. Botulinum toxin causes Botulism poisoning, a serious and life-threatening illness in humans and animals...
has been shown to have an effect on inhibiting neurogenic inflammation
Neurogenic inflammation
Neurogenic inflammation is inflammation arising from the local release from afferent neurons of inflammatory mediators such as Substance P and Calcitonin Gene-Related Peptide ....
, and evidence suggesting the role of neurogenic inflammation
Neurogenic inflammation
Neurogenic inflammation is inflammation arising from the local release from afferent neurons of inflammatory mediators such as Substance P and Calcitonin Gene-Related Peptide ....
in the pathogenesis
Pathogenesis
The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...
of psoriasis, the University of Minnesota
University of Minnesota
The University of Minnesota, Twin Cities is a public research university located in Minneapolis and St. Paul, Minnesota, United States. It is the oldest and largest part of the University of Minnesota system and has the fourth-largest main campus student body in the United States, with 52,557...
has begun a clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
to follow up on the observation that patients treated with botulinum toxin for dystonia
Dystonia
Dystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning or reaction to...
had dramatic improvement in psoriasis.
In 2004, Tas and Avci demonstrated cyclopamine
Cyclopamine
Cyclopamine is a naturally occurring chemical that belongs to the group of steroidal jerveratrum alkaloids. It is a teratogen isolated from the corn lily that causes usually fatal birth defects. It can prevent the fetal brain from dividing into two lobes and cause the development of a single eye...
’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
Atopic dermatitis
Atopic dermatitis is an inflammatory, chronically relapsing, non-contagious and pruritic skin disorder...
, a form of eczema
Eczema
Eczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...
characterized by red, flaky and very itchy skin; psoriasis, and glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
-induced epidermal atrophy, in which the skin shrinks due to skin cell loss.