Psoriasis is an immune-mediated disease which affects the skin and joints. When it affects the skin it commonly appears as red scaly elevated patches called plaques. Psoriasis plaques are areas of excessive skin cell production and inflammation. Skin rapidly accumulates and sometimes takes a silver scaly appearance. Plaques frequently occur on the elbows and knees, but can affect any area of skin including the scalp and genital area.
| Psoriasis | |
|---|---|
| Specialty | Dermatology  |
Psoriasis can vary in severity, from minor localised patches to complete body coverage. Fingernails and toenails are often affected (psoriatic nail dystrophy). Psoriasis can also cause inflammation of the joints. This is known as psoriatic arthritis.
The prevalence of psoriasis in Western populations is estimated to be around 2-3%. It affects both sexes equally and occurs at all ages.
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.
Types of psoriasis
Psoriasis can appear in several forms. Variants include plaque, pustular, guttate and flexural psoriasis. This section describes each type (with ICD-10 code [1]).
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 10-20% 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.
Severity
Psoriasis is generally graded as mild, moderate or severe. Several different scales for measuring the severity of psoriasis are also used. These scales are variably based on the following: the proportion of body surface area affected; the disease activity (degree of plaque redness, thickness and scaling); the 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). A PASI score of more than ten is associated with a number of indicators commonly associated with severe disease such as the need for hospital admission.
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.
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 TNF-α, 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 (Zenz et al, 2005).
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.
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 the build-up of scale, reduce skin turn over, and clear affected skin of plaques. Ointment and creams containing coal tar, anthralin, corticosteroids, vitamin D3 analogues, and retinoids are routinely used. The mode of action of each is probably different but they all help to normalise skin cell production and reduce inflammation. A drawback is that topical agents can often irritate normal skin. This section briefly describes commonly used topical agents.
- Moisturizers and bath solutions when used regularly have a soothing effect and help to remove the build-up of dry skin.
- Salicylic acid is a peeling agent which helps to remove the build up of scale on the skin. It is often added to ointments, creams, gels, and shampoos.
- Coal tar preparations are often applied directly to the skin, added to bath water, or used as a shampoo. Coal tar increases the skin's sensitivity to light and is sometimes combined with ultraviolet B (UVB) phototherapy. Coal tar is messy, has a strong odour, and may stain the skin or clothing.
- Anthralin (Dithranol) is applied for short periods of time and then washed off to prevent irritation. This treatment often stains skin and clothing.
- Corticosteroids are available in different strengths. Long-term use of potent corticosteroids is discouraged as this can cause thinning of the skin, internal side effects, and resistance to the treatment's benefits. It is possible for psoriasis to be aggravated on ceasing steroid treatment, particularly after long term use (rebound effect).
- Calcipotriol (Calcipotriene (USAN)) is a synthetic form of vitamin D3. It is not recommended for use in the genital area or on the face. Overuse can cause high levels of calcium in the blood (hypercalcemia). Calcipotriol can be combined with betamethasone dipropionate, a steroid.
- Retinoids are synthetic forms of vitamin A. The retinoid tazarotene (Tazorac) is available as a gel or cream that is applied to the skin. Retinoids are teratogenic, and are not recommended for women of childbearing age.
Phototherapy
Natural ultraviolet light from the sun and controlled delivery of artificial ultraviolet light have a therapeutic effect on psoriasis. Sunlight contains many different wavelengths of ultraviolet (UV) light. UV wavelengths are subdivided into UVA (380–315 nm), UVB (315–280 nm), and UVC (< 280 nm). UVA and UVB are beneficial in treating psoriasis. When absorbed by the skin, UV light is thought to suppress the immune-mediated processes involved in psoriasis. Daily, short, nonburning exposure to sunlight can therefore help to clear or improve psoriasis.
- 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. Narrowband UVB treatment is thought to be superior than using the full UVB spectrum. Exposure to UVB several times per week, over several weeks may be required to attain a remission.
- In contrast to full body exposure, targeted multiwavelength systems deliver narrow band UVB to psoriatic lesions through a fibre optic delivery system. Only psoriatic lesions are targeted and normal skin is not exposed to the harmful effects of UVB. This method of delivering UVB is of limited use when psoriasis is extensive.
- Psoralen and ultraviolet A phototherapy (PUVA) combines the administration of psoralen with exposure to ultraviolet A (UVA) light. UVA penetrates deeper into the skin than UVB. Psoralen makes the skin more sensitive to UVA. Compared with broadband UVB treatment, PUVA clears psoriasis more consistently and in fewer treatments. However, it is associated with nausea, headache, fatigue, burning, and itching. Sunlight must be avoided after ingesting psoralen to avoid sunburn, and the eyes must be protected with UVA-absorbing glasses. Long-term treatment is associated with squamous-cell and melanoma skin cancers.
- Ultraviolet light treatment is frequently combined with topical (coal tar, calcipotriol) or systemic treatment (retinoids) as there is a synergy in their combination. One combined therapy program, referred to as the Ingram regime, involves a coal tar bath, UVB phototherapy, and application of an anthralin-salicylic acid paste that is left on the skin for 6 to 24 hours. A similar regime, the Goeckerman treatment, combines coal tar ointment with UVB phototherapy.
- A form of X-ray radiation called Grenz Rays was a popular form of treatment of psoriasis during the middle of the 20th century. This type of therapy was superseded by ultraviolet therapy and is no longer used in most countries.
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 therapy are required to have regular blood and liver function tests because of the toxicity of the medications. Pregnancy must be avoided for the majority of these treatments. Most patients experience a recurrence of psoriasis after these medications are discontinued.
- Retinoids are synthetic forms of vitamin A. Retinoids are teratogenic and women must not become pregnant during and for up to 2 years after treatment. Common side effects include dry lips, and peeling skin on the hands and feet. Retinoids are sometimes used in conjunction with UVB treatment.
- Methotrexate slows cell turnover and suppresses the immune system. It can cause liver damage and decrease the production of red blood cells, white blood cells, and platelets. It is not suitable for people who have liver disease or anaemia. Methotrexate should not be used by pregnant women, or by men or women who are planning to have children, because it may cause birth defects. A liver biopsy may be required after long term use.
- Ciclosporin (also spelled as cyclosporin(e)) works by suppressing the immune system. Candidates for this therapy are those with severe psoriasis who have not responded to, or cannot tolerate, other systemic therapies. Ciclosporin may impair kidney function or cause high blood pressure (hypertension). Ciclosporin is not recommended for patients who have a weak immune system or those who have had skin cancers as a result of PUVA treatment. It should not be given with phototherapy.
- Tioguanine is generally used in the treatment of acute leukaemias, but is sometimes used in the management of severe psoriasis. It is an antimetabolite, and works by preventing the growth and division of cells. It must not be used by pregnant women or by men or women who are planning to have children, because it may cause birth defects.
- Hydroxyurea (Hydrea) is a cytotoxic agent and is thought to work by reducing the replication of DNA within the basal cell of the epidermis. Possible side effects include anaemia and a decrease in white blood cells and platelets. Hydroxyurea must be avoided by pregnant women or those who are planning to become pregnant, because it may cause birth defects.
- Mycophenolate mofetil is an immune suppressive agent occasionally used for the management of severe psoriasis.
- Fumaric acid esters have been used to treat severe psoriasis in northern Europe for over 20 years. This product is mainly used in Germany and is not licensed in many other countries. Side effects include flushing, diarrhoea, nausea and stomach pains.
- Biologics[2] are the newest class of treatment for psoriasis. These 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. Examples include Amevive®, etanercept (Enbrel®), Humira®, infliximab (Remicade®) and Raptiva.
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.
- 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 consumption of alcohol, sugar and other "aggressive" foods, 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 have looked towards herbology as a more holistic approach that aims to treat the underlying causes as opposed to external, topical treatments, such as ointments and phototherapy, which only treat the symptoms of the condition.
- A psychological symptom management programme has been reported as being a helpful adjunct to traditional therapies in the management of psoriasis. [3]
Future Drug Development
Historicaly, agents used to treat psoriasis were discovered by accident. In contrast, current novel therapeutic agents are characterized by 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.
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. 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.
References
Some of the information on this page was taken from the public-___domain resource at:
For descriptions of innate immunity aggravation amd immunopathogenic mechanisms in psoriasis:
- Bos J, de Rie M, Teunissen M, Piskin G (2005). "Psoriasis: dysregulation of innate immunity". Br J Dermatol. 152 (6): 1098–107. PMID 15948970.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Gudjonsson JE, Johnston A, Sigmundsdottir H, Valdimarsson H.; (2004). "Immunopathogenic mechanisms in psoriasis". Clin Exp Immunol. 135 (1): 1–8. PMID 14678257.
{{cite journal}}: CS1 maint: extra punctuation (link) CS1 maint: multiple names: authors list (link) - Zenz R, Eferl R, Kenner L, Florin L, Hummerich L, Mehic D, Scheuch H, Angel P, Tschachler E, Wagner E (2005). "Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins". Nature. 437 (7057): 369–75. PMID 16163348.
{{cite journal}}: CS1 maint: multiple names: authors list (link)
For an in-depth coverage of the causes of psoriasis:
- Krueger G, Ellis C (2005). "Psoriasis--recent advances in understanding its pathogenesis and treatment". J Am Acad Dermatol. 53 (1 Suppl 1): S94-100. PMID 15968269.