| Caption | A person whose back and arms are affected by psoriasis |
|---|
In plaque psoriasis, skin rapidly accumulates at these sites, which gives it a silvery-white appearance. Plaques frequently occur on the skin of the elbows and knees, but can affect any area, including the scalp, palms of hands and soles of feet, and genitals. In contrast to eczema, psoriasis is more likely to be found on the outer side of the joint.
The disorder is a chronic recurring condition that varies in severity from minor localized patches to complete body coverage. Fingernails and toenails are frequently affected (psoriatic nail dystrophy) and can be seen as an isolated symptom. Psoriasis can also cause inflammation of the joints, which is known as psoriatic arthritis. Between 10% and 40% of all people with psoriasis 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.
Psoriasis is a chronic relapsing disease of the skin that may be classified into nonpustular and pustular types as follows:
Psoriatic erythroderma (erythrodermic psoriasis)(L40.85)involves the widespread inflammation and exfoliation of the skin over most of the body surface. It may be accompanied by severe itching, swelling and pain. It is often the result of an exacerbation of unstable plaque psoriasis, particularly following the abrupt withdrawal of systemic treatment. This form of psoriasis can be fatal, as the extreme inflammation and exfoliation disrupt the body's ability to regulate temperature and for the skin to perform barrier functions.
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.
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.
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.
The immune-mediated model of psoriasis has been supported by the observation that immunosuppressant medications can clear psoriasis plaques. However, the role of the immune system is not fully understood, and it has recently been reported that an animal model of psoriasis can be triggered in mice lacking T cells. Animal models, however, reveal only a few aspects resembling human psoriasis.
Compromised skin barrier function has a role in psoriasis susceptibility.
Psoriasis is a fairly idiosyncratic disease. The majority of people's experience of psoriasis is one in which it may worsen or improve for no apparent reason. Studies of the factors associated with psoriasis tend to be based on small (usually hospital based) samples of individuals. These studies tend to suffer from representative issues, and an inability to tease out causal associations in the face of other (possibly unknown) intervening factors. Conflicting findings are often reported. Nevertheless, the first outbreak is sometimes reported following stress (physical and mental), skin injury, and streptococcal infection. Conditions that have been reported as accompanying a worsening of the disease include infections, stress, and changes in season and climate. Certain medicines, including lithium salt, beta blockers and the antimalarial drug chloroquine have been reported to trigger or aggravate the disease. Excessive alcohol consumption, smoking and obesity may exacerbate psoriasis or make the management of the condition difficult or perhaps these comorbidities are effects rather than causes. Hairspray, some face creams and hand lotions, can also cause an outbreak of psoriasis. 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. It is recommended to use talc powder after washing, as that helps absorb excess moisture which would otherwise go to the infecting agent. Additionally, moisturizers can be applied to moisturize the skin, and lotions used to promote skin oil gland functions.
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.
Apricus Biosciences is currently developing PsoriaVa, a topical cream for the treatment of psoriasis. It contains Calcipotriol and Betamethasone as the active ingredients and a permeation enhancer DDAIP which facilitates the delivery of the drug into the blood stream.
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. and inhibit the inflammatory pathway at a different point than the anti-TNF-α antibodies.
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.
The severity of psoriasis symptoms may also be influenced by lifestyle habits related to alcohol, smoking, weight, sleep, stress and exercise.
Another treatment is ichthyotherapy, which is practised at some spas in Turkey, Croatia, Ireland, Hungary and Serbia. Doctor fish living in outdoor thermal pools are encouraged to feed on the psoriatic skin, only consuming the affected areas. The outdoor location of the spa may also have a beneficial effect. This treatment can provide temporary relief of symptoms. A revisit to the spas every few months is often required. This treatment has been examined in two small clinical trials, with positive results.
Hypnotherapy may be effective for psoriasis.
A psychological symptom management programme has been reported as being a helpful adjunct to traditional therapies in the management of psoriasis. In the UK, The Psoriasis and Psoriatic Arthritis Alliance (PAPAA, a not-for-profit charity) has funded research, carried out by the University of Manchester, to develop a symptom management programme called Electronic Targeted Intervention for Psoriasis (eTIPs) using a modified Cognitive Behaviour Therapy model. This research follows research by Fortune, et al. on psychological stress, distress and disability in patients with psoriasis.
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.
On 17 November 2008, researchers led by Yin-Ku Lin of Chang Gung Memorial Hospital and Chang Gung University in Taoyuan, Taiwan, told Reuters by telephone that Indigo naturalis (qing dai, 青黛), a dark blue plant used in traditional Chinese medicine, appears to be effective in treating psoriasis. In the latest issue of Archives of Dermatology, they wrote, "The Indigo naturalis ointment-treated lesions showed an 81 percent improvement, the (nonmedicated) ointment-treated lesions showed a 26 percent improvement."
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.
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.
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.
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 oligonucleotides carries the potential to provide novel therapeutic strategies for treating psoriasis. Antisense oligonucleotides would be used to down regulate key cellular proteins known to play a role in psoriatic pathogenesis including inflammatory proteins such as ICAM-1 (intercellular adhesion molecule-1), IL-2 and IL-8, cellular proliferation proteins like insulin-like growth factor 1 receptor (IGF-IR) and epidermal growth factor and hyperangiogenesis vascular endothelial growth factor (VEGF).
A novel boron-containing topical anti-inflammatory, AN2728, is currently being developed by Anacor Pharmaceuticals and is in Phase 2b trials for mild-to-moderate plaque type psoriasis. The molecule works by inhibiting PDE4 and reducing the production of TNF-alpha, a precursor of the inflammation associated with psoriasis, as well as other cytokines, including IL-12 and IL-23.
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.
Category:Psoriasis Category:Autoimmune diseases
This text is licensed under the Creative Commons CC-BY-SA License. This text was originally published on Wikipedia and was developed by the Wikipedia community.
