Psoriasis Animation

Psoriasis (pronounced /səˈraɪəsɪs/) (suh-RI-uh-sus) is a disorder which affects the skin and joints. It commonly causes red scaly patches to appear on the skin. The scaly patches caused by psoriasis, called psoriatic plaques, are areas of inflammation and excessive skin production. Skin rapidly accumulates at these sites and takes on 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.

The disorder is a chronic recurring condition which varies in severity from minor localised patches to complete body coverage. Fingernails and toenails are frequently affected (psoriatic nail dystrophy) - and can be seen as an isolated finding. Psoriasis can also cause inflammation of the joints, which is known as psoriatic arthritis. Ten to fifteen percent of people with psoriasis have psoriatic arthritis.

The cause of psoriasis is not known, but it is believed to have a genetic component. Several factors are thought to aggravate psoriasis. These include stress, excessive alcohol consumption, and smoking. Individuals with psoriasis may 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.

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 (between the thigh and groin), the armpits, under an overweight stomach (pannus), and under the breasts (inframammary fold). It is aggravated by friction and sweat, and is vulnerable to fungal infections.

Guttate psoriasis (L40.4) is characterized by numerous small round spots (differential diagnosis - pityriasis rosea - oval shape lesion). 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. Skin from a biopsy will show clubbed Rete pegs if positive for psoriasis. Another sign of psoriasis is that when the plaques are scraped,

Cause

The cause of psoriasis is not fully understood. There are two main hypotheses about the process that occurs in the development of the disease. The first considers psoriasis as primarily a disorder of excessive growth and reproduction of skin cells. The problem is simply seen as a fault of the epidermis and its keratinocytes. The second hypothesis sees the disease as being an immune-mediated disorder in which the excessive reproduction of skin cells is secondary to factors produced by the immune system. T cells (which normally help protect the body against infection) become active, migrate to the dermis and trigger the release of cytokines (tumor necrosis factor-alpha TNFα, in particular) which cause inflammation and the rapid production of skin cells. It is not known what initiates the activation of the T cells.

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

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.

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's hypothesized that the diminished CD4-T-Cell presence causes an over-activation 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 3 times higher than the normal population.

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, sex, 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, 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.

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

Topical treatment

Bath solutions and moisturizers help soothe affected skin and reduce the dryness which accompanies the build-up of skin on psoriatic plaques. Medicated creams and ointments applied directly to psoriatic plaques can help reduce inflammation, remove built-up scale, reduce skin turn over, and clear affected skin of plaques. Ointment and creams containing coal tar, dithranol (anthralin), corticosteroids like desoximetasone (Topicort), vitamin D3 analogues (for example, calcipotriol), and retinoids are routinely used. Argan oil has also been used with some promising results. 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 are highly effective inhibitors of skin cell proliferation.

The disadvantages of topical agents are variably that they can often irritate normal skin, can be time consuming and 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 recurrence of the condition. This is known as a rebound of the condition.

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

Phototherapy

It has long been recognized that daily, short, non-burning exposure to sunlight helped to clear or improve psoriasis. Niels Finsen was the first physician to investigate the therapeutic 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.

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 methotrexate, cyclosporine and retinoids. Methotrexate and cyclosporine are immunosupressant drugs; retinoids are 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 (interleukin antagonists) 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. Ustekinumab (IL-12 and IL-23 blocker) shows hopeful results for psoriasis therapy.

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 a 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 & in Croatia (Altermedica), 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. Treatment in this hot spring has been examined until now in two small clinical trials, with positive results.

Some people subscribe to the view that psoriasis can be effectively managed through a healthy lifestyle. This view is based on anecdotal evidence, 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. The effectiveness of the Dead Sea in treating psoriasis has been the topic of some research and studies from all over the world. One particular study is the use of Dead Sea salts to psoriasis patients in partial or full baths. In a controlled manner, these patients have undergone the treatment with the waters having a specific temperature and lasted for 20 minutes. This lasted for about 3-4 weeks, with the patients having 3-4 baths per week. Several noticeable symptoms were reduced.

A number of patients have reported significant improvements from sun and sea water: unfortunately, salt alone does not have any effect. Sea water contains so many minerals and different life forms (thousands of species of bacteria alone) that it will be hard to determine which of these is causing the observed effects. Interestingly, people in the tropics differentiate between "live" and "dead" sea water: "live" sea water is water that has never been covered.

Some psoriasis patients use herbology as a holistic approach that aims to treat the underlying causes of psoriasis. Some alternative therapies consider Oil of Oregano to be a powerful herbal method of treatment.

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

Zinc oxide (ZnO) is used for several skin afflictions and according to some patients also provides relief.

At least one source states that Milk thistle may prevent psoriasis outbreaks by encouraging proper liver function; the claimed mechanism is neutralization of "certain toxins associated with psoriasis attacks" but neither the identity of these toxins, the nature of the association nor the mechanism of neutralization is cited.

Historical treatment

The history of psoriasis is littered with treatments of dubious effectiveness and high toxicity. These treatments received brief popularity at particular time periods or within certain geographical regions. The application of cat faeces to red lesions on the skin, for example, was one of the earliest topical treatments employed in ancient Egypt. Onions, sea salt and urine, goose oil and semen, wasp droppings in sycamore milk, and soup made from vipers have all been reported as being ancient treatments.

In the more recent past Fowler's solution, which contains a poisonous and carcinogenic arsenic compound, was used by dermatologists as a treatment for psoriasis during the 18th and 19th centuries. Grenz rays (also called ultrasoft X-rays or Bucky rays) was a popular treatment of psoriasis during the middle of the 20th century. This type of therapy was superseded by ultraviolet therapy.

Undecylenic acid was investigated and used for psoriasis some 40 years ago.(cir. 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 re-gained some credibility as a safe alternative to steroids and coal tar.

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.

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.

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

Research into antisense oligonucleotides carries the potential to provide novel therapeutic strategies for treating psoriasis.

ABT-874 is a human anti-IL-12 monoclonal antibody being developed by Abbott Laboratories in conjunction with Cambridge Antibody Technology for the treatment of multiple autoimmune diseases including psoriasis. Phase II trials have been completed and showed promising results. Abbott was planning to initiate Phase III trials in 2007.

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 that 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 that 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 that 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 August 27, 2006, scientists led by Jeung-Hoon Lee created in the laboratory synthetic lipids called 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.