Psoriasis

Psoriasis (IPA pronunciation: ) is an immune-mediated disease which affects the skin and joints. It commonly causes red scaly patches to appear on the skin. The scaly patches caused by psoriasis are often called psoriasis plaques or lesions. Psoriasis plaques are areas of excessive skin cell production and inflammation. Skin rapidly accumulates at these sites and sometimes takes a silvery-white appearance. Plaques frequently occur on the skin of the elbows and knees, but can affect any area including the scalp and genitals. Psoriasis is not contagious; it cannot be passed from person to person.

Psychological aspects of psoriasis
The disorder is a chronic or recurring condition which can vary in severity, from minor localised patches to complete body coverage. Fingernails and toenails are frequently affected (psoriatic nail dystrophy). Psoriasis can also cause inflammation of the joints. This is known as psoriatic arthritis. 10-15 % of people with psoriasis have psoriatic arthritis.

Several factors are thought to aggravate psoriasis. These include stress and excessive alcohol consumption. Individuals with psoriasis may also suffer from depression and loss of self-esteem. As such, quality of life is an important factor in evaluating the severity of the disease. There are many treatments available but because of its chronic recurrent nature psoriasis is a challenge to treat.

History
Psoriasis is probably one of the longest known illnesses of humans and simultaneously one of the most misjudged and misunderstood. Some scholars believe psoriasis to have been included among the skin conditions called tzaraat in the Bible. Tzaraat was a punishment for sin whose cure could only be found in repentance and forgiveness. In more recent times psoriasis was frequently described as a variety of leprosy. 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 and provided the first rational nomenclature based on the appearance of lesions. Willan identified two categories: leprosa graecorum and psora leprosa.

While it may have been visually, and later semantically, confused with leprosy 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.

Types of psoriasis
The symptoms of psoriasis can manifest in a variety of forms. Variants include plaque, pustular, guttate and flexural psoriasis. This section describes each type (with ICD-10 code ).



Plaque psoriasis (psoriasis vulgaris) (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.

Flexural psoriasis (inverse psoriasis) (L40.83-4) appears as smooth inflamed patches of skin. It occurs in skin folds, particularly around the genitals, the armpits, and under the breasts. It is aggravated by friction and sweat, and is vulnerable to fungal infections.

Guttate psoriasis (L40.4) is characterized by numerous small oval (teardrop-shaped) spots. These numerous spots of psoriasis appear over large areas of the body, such as the trunk, limbs, and scalp. Guttate psoriasis is associated with streptococcal throat infection.

Pustular psoriasis (L40.1-3, L40.82) appears as raised bumps that are filled with non-infectious pus (pustules). The skin under and surrounding 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.

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.

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.

Diagnosis
A diagnosis of psoriasis is usually based on the appearance of the skin. There are no special blood tests or diagnostic procedures for psoriasis. Sometimes a skin biopsy, or scraping, may be needed to rule out other disorders and to confirm the diagnosis.

Severity
Psoriasis is usually graded as mild (affecting less than 3% of the body), moderate (affecting 3-10% of the body) or severe. Several other scales exist for measuring the severity of psoriasis. These scales are 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).

Effect on the quality of life
Psoriasis has been shown to affect health-related quality of life to an extent similar to the effects of other chronic diseases such as depression, myocardial infarction, 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. The frequency of medical care is costly 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.

Epidemiology
Psoriasis affects both sexes equally and can occur at any age, although it most commonly appears for the first time between the ages of 15 and 25 years.

The prevalence of psoriasis in Western populations is estimated to be around 2-3%. A survey conducted by the National Psoriasis Foundation (a US based psoriasis education and advocacy group, which is partly funded by pharmaceutical companies) found a prevalence of 2.1% among adult Americans. The study also found that 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 finding suggests 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.

Cause
The cause of psoriasis is not fully understood. There are two main theories 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. An alternate viewpoint sees the disease as being an immune-mediated disorder in which the excessive reproduction of skin cells is secondary to factors produced by the immune system. It is thought that T cells (which normally help protect the body against infection) become active, migrate to the dermis and trigger the release of cytokines (tumor necrosis factor-alpha TNFα, in particular) which cause inflammation and the rapid production of skin cells. It is not known what initiates the activation of the T cells.

The immune-mediated model of psoriasis has been supported by the observation that immunosuppressant medications can clear psoriasis plaques. However, the role of the immune system is not fully understood, and it has recently been reported that an animal model of psoriasis can be triggered in mice lacking T cells. Animal models, however, reveal only a few aspects resembling human psoriasis.

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 and beta blockers, 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.

Treatment
There can be substantial variation between individuals in the effectiveness of specific psoriasis treatments. Because of this, dermatologists often use a trial-and-error approach to finding the most appropriate treatment for their patient. The decision to employ a particular treatment is based on the type of psoriasis, its location, extent and severity. The patient’s age, gender, quality of life, comorbidities, and attitude toward risks associated with the treatment are also taken into consideration.

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 are applied to the skin. This is called topical treatment. 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 ingested orally or by injection. This approach is called systemic treatment.

Over time, psoriasis can become resistant to a specific therapy. Treatments may be periodically changed to prevent resistance developing and to reduce the chance of adverse reactions occurring. This is called treatment rotation.

Topical treatment
Bath solutions and moisturizers help sooth affected skin and reduce the dryness which accompanies the build-up of skin on psoriasis plaques. Medicated creams and ointments applied directly onto psoriasis plaques can help reduce inflammation, remove built-up scale, reduce skin turn over, and clear affected skin of plaques. Ointment and creams containing coal tar, dithranol (anthralin), corticosteroids, vitamin D3 analogues (for example, calcipotriol), and retinoids are routinely used. The mechanism of action of each is probably different but they all help to normalise skin cell production and reduce inflammation.

The disadvantages of topical agents are variabily that they can often irritate normal skin, can be awkward to apply, cannot be used for long periods, can stain clothing or have a strong odour. As a result, it is sometimes difficult for people to maintain the regular application of these medications. Abrupt withdrawal of some topical agents, particularly corticosteroids, can cause an aggressive recurrance of the condition. This is known as a rebound of the condition. Topical lotions and creams that contain fragrances should be avoided as they will sting when applied.

Some topical agents are used in conjunction with other therapies, especially phototherapy.

Phototherapy
It has long been recognised that daily, short, nonburning exposure to sunlight helped to clear or improve psoriasis. Niels Finsen was the first physician to investigate the theraputic effects of sunlight scientifically and to use sunlight in clinical practice. This became known as phototherapy.

Sunlight contains many different wavelengths of light. It was during the early part of the 20th century that it was recognised that for psoriasis the therapeutic property of sunlight was due to the wavelengths classified as ultraviolet (UV) light. Ultraviolet wavelengths are subdivided into UVA (380–315 nm), UVB (315–280 nm), and UVC (< 280 nm). Ultraviolet B (UVB) (315–280 nm) is absorbed by the epidermis and has a beneficial effect on psoriasis. Narrowband UVB (311 to 312 nm), is that part of the UVB spectrum that is most helpful for psoriasis. Exposure to UVB several times per week, over several weeks can help people attain a remission from psoriasis.

Ultraviolet light treatment is frequently combined with topical (coal tar, calcipotriol) or systemic treatment (retinoids) as there is a synergy in their combination. The Ingram regime, involves UVB and the application of anthralin paste. The Goeckerman regime, combines coal tar ointment with UVB.

Photochemotherapy
Psoralen and ultraviolet A phototherapy (PUVA) combines the oral or topical administration of psoralen with exposure to ultraviolet A (UVA) light. Precisely how PUVA works is not known. The mechanism of action 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.

Dark glasses must be worn during PUVA treatment because there is a risk of cataracts developing from exposure to sunlight. PUVA is associated with nausea, headache, fatigue, burning, and itching. Long-term treatment is associated with squamous-cell and melanoma skin cancers.

Systemic treatment
Psoriasis which is resistant to topical treatment and phototherapy is treated by medications that are taken internally by pill or injection. This is called systemic treatment. 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 the immunosupressant drugs methotrexate and ciclosporin, and retinoids, which are a synthetic forms of vitamin A. Other additional drugs, not specifically licensed for psoriasis, have been found to be effective. These include the antimetabolite tioguanine, the cytotoxic agent hydroxyurea, sulfasalazine, the immunosupressants mycophenolate mofetil, azathioprine and oral tacrolimus. These have all been used effectively to treat psoriasis when other treatments have failed. Although not licensed in many other countries fumaric acid esters have also been used to treat severe psoriasis in Germany for over 20 years.

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 are relatively new, and their long-term impact on immune function is unknown. They are very expensive and only suitable for very few patients with psoriasis.

Alternative Therapy

 * Antibiotics are not indicated in routine treatment of psoriasis. However, antibiotics may be employed when an infection, such as that caused by the bacteria Streptococcus, triggers an outbreak of psoriasis, as in certain cases of guttate psoriasis.


 * Climatotherapy involves the notion that some diseases can be successfully treated by living in particular climate. Several psoriasis clinics are located throughout the world based on this idea. The Dead Sea is one of the most popular locations for this type of treatment.


 * In Turkey, doctor fish which live in the outdoor pools of spas, are encouraged to feed on the psoriatic skin of people with psoriasis. The fish only consume the affected areas of the skin. 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.


 * Some people subscribe to the view that psoriasis can be effectively managed through a healthy lifestyle. This view is based on anecdote, and has not been subjected to formal scientific evaluation. Nevertheless, some people report that minimizing stress and consuming a healthy diet, combined with rest, sunshine and swimming in saltwater keep lesions to a minimum.  This type of "lifestyle" treatment is suggested as a long-term management strategy, rather than an initial treatment of severe psoriasis.


 * Some psoriasis patients use herbology as a holistic approach that aims to treat the underlying causes of psoriasis.


 * A psychological symptom management programme has been reported as being a helpful adjunct to traditional therapies in the management of psoriasis.


 * It is possible that Epsom salt may have a positive effect in reducing the effects of psoriasis.

Historical Treatment
The history of psoriasis is littered with treatments of dubious effectiveness and high toxicity. These treatments received brief popularity at particular time periods or within certain geographical regions. The application of cat faeces to red lesions on the skin, for example, was one of the earliest topical treatments employed in ancient Egypt. Onions, sea salt and urine, goose oil and semen, wasp droppings in sycamore milk, and soup made from vipers have all been reported as being ancient treatments. In the more recent past Fowler's solution, which contains a poisonous and carcinogenic arsenic compound, was used by dermatologists as a treatment for psoriasis during the 18th and 19th centuries. Grenz Rays (also called ultrasoft X-rays or Bucky rays) was a popular treatment of psoriasis during the middle of the 20th century. This type of therapy was superseded by ultraviolet therapy.

All these treatments have fallen out of favour.

Future drug development
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. Future innovation should see the creation of additional drugs that refine the targeting of immune-mediators further.

Research into antisense oligonucleotides is in its infancy but carries the potential to provide novel theraputic strategies for treating psoriasis.

Prognosis
Psoriasis is a chronic lifelong condition. There is currently no cure but various treatments can help to control the symptoms. Many of the most effective agents used to treat severe psoriasis carry an increased risk of significant morbidity including skin cancers, lymphoma and liver disease. However, the majority of people's experience of psoriasis is that of minor localised patches, particularly on the elbows and knees, which can be treated with topical medication. Psoriasis does 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 life. Controlling the signs and symptoms typically requires lifelong therapy.

"The heartbreak of psoriasis"
The phrase "the heartbreak of psoriasis" is often used both seriously and ironically to describe the emotional impact of the disease. It can be found in various advertisements for topical and other treatments; conversely, it has been used to mock the tendency of advertisers to exaggerate (or even fabricate) aspects of a malady for financial gain. (In Bloom County, the character of Opus once considered the possibility of his suffering from "the heartbreak of nose hemorrhoids.") While many products today use the phrase in their advertising, it originated in a 1960s advertising campaign for Tegrin, a coal tar-based medicated soap.

Notable people who have had psoriasis
Jason Donovan, Ben Elton, Benjamin Franklin, Mark Gastineau, Abimael Guzmán, Stan Jones, Shawn Lane, Gordon Lish, Jerry Mathers, Vladimir Nabokov, Dennis Potter, Eli Roth, Joseph Stalin, Kenneth Winston Starr, August Strindberg, John Updike.