Psoriasis

Psoriasis symptoms

Psoriasis is a chronic, inflammatory condition of the skin in which both genetic and environmental factors are thought to be an influence. There are five clinical subtypes, each with unique signs and symptoms, but is generally characterized by thick, red skin with overlying silver-white patches called scales, referred to as psoriatic plaques. The scaly patches are caused by excessive skin production and the accumulation of skin leads to the silvery-white appearance. Regardless of what subtype of psoriasis, patients can experience burning, itching or soreness at the affected site. Psoriasis frequently develops on the elbows, knees, scalp and back but can affect any part of the body.

Incidence

Psoriasis is a very common condition. It affects an estimated 2-3 percent of the world’s population (with estimates around125 million people affected globally) and according to the National Institute of Health (NIH), between 5.8 and 7.5 million Americans have psoriasis. While it affects men and women equally, occurrence varies according to race, environmental factors and geography. There seems to be a higher occurrence rate among Caucasian populations but rare or absent among African-American, West-African and North American-Indian populations. Psoriasis seems to be an inherited disorder. Over a third of people with psoriasis also have an affected family member.

Psoriasis may develop at any age, but most commonly begins between ages 15 and 35. In 75% of cases, patients developed psoriasis before the age of 40. It can appear suddenly or slowly and in many cases, psoriasis subsides and then flares up again repeatedly over time.

Between 10 and 30 percent of people with psoriasis will also develop psoriatic arthritis. It can develop at any time but commonly occurs between the ages of 30 – 50.

Causes

Inherited

Psoriasis seems to be inherited disorder, with over a third of people with psoriasis also having an affected family member. Nearly one-quarter of people with psoriasis have cases that are considered moderate to severe. Mild psoriasis is defined as affecting less than 3 percent of the body (according to The National Psoriasis Foundation); 3-10% is considered moderate; and more than 10% of the body is considered severe.

At least nine Psoriatic susceptibility loci have been identified (PSORS1-9). An association with the PSORS has been found with functional polymorphisms in modifier genes that mediate inflammation (i.e TNF-α) and vascular growth (i.e VEGF). These genes could determine how a person’s immune system would react. Research also indicates that a “trigger” is needed to set off psoriasis.

Cellular involvement – T cells and psoriasis

Psoriasis was first thought to be immune mediated when transplant patients with psoriasis experienced clearing of the plaques when taking cyclosporine, an immunosuppressant. Now it is known that T-cell activation is central to the inflammation and hyperproliferative nature of the skin found in psoriasis.

Psoriasis involves a complex interaction between keratinocytes (skin cells) and the immune system, mainly with a type of white blood cell called a T cell. Normally, skin cells take 28 days to mature, migrate to the skins surface and shed but in psoriasis, this process occurs in 3 – 6 days. The skin cells are immature and instead of shedding, they pile up causing psoriatic plaques.

T cells function to regulate all immune responses to protein antigens and serve as effector cells to eliminate any foreign particles or microbes, helping to protect the body from disease. In order to function, T cells need to be activated by binding to an antigen presenting cell (APC). In the skin the most efficient APC’s are Langerhans cells. Once bound, a naïve T cell is activated and converted to an antigen specific cell and can develop memory for long lasting immunity against that particular antigen. Upon activation, T cells then proceed to recruit inflammatory cells such as macrophages, dendritic cells and keratinocytes. Together these cells release a variety of chemical mediators, primarily cytokines, which induce inflammatory responses leading to the clinical features presented in psoriasis.

Cytokines involved in the development of psoriasis include: granulocyte-macrophage colony stimulating factor (GMCSF), some interleukins, epidermal growth factor (EGF), interferon-α and tumour necrosis factor-α. TNF-α has been strongly implicated in psoriasis and can lead to keratinocyte proliferation. This hyperproliferative response decreases the approximate time it takes for normal maturation of skin cells (epidermal transit time) from 28 days to 3-6 days. Instead of shedding, the immature keratinocytes layer up and produce the typical scaly plaques of psoriasis.

In short, it is thought that T cells are activated by mistake by faulty signals in the immune system. They become overactive and set off other immune responses, leading to a faster turnover of skin cells.

Environmental causes

Research has helped the understanding of the role of environmental factors and genetics in psoriasis. So far nine gene mutations have been discovered that could be associated with psoriasis, yet it can be activated or worsened by specific environmental factors. Common triggers include:

• Infections
• Trauma in the skin or sunburn
• Stress
• Smoking
• Strep infection
• Drugs
• Some medications: anti-malarial drugs, beta-blockers (medication used to treat high blood pressure and heart failure) and lithium (anti-depressant)

Psoriasis is also associated with several co-morbidities, including depression, decreased quality of life, increased cardiovascular risk, metabolic syndrome and other immune-mediated conditions such as type 2 diabetes, Crohn’s disease, and psoriatic arthritis. TNF-? has also been implicated in Psoriatic arthritis. High TNF-α levels found in the synovium of psoriasis patients confirm this. The understanding of the involvement of TNF-? in the pathogenic mechanisms has led to the development of TNF-α blocking agents, termed ‘biologicals’, for therapeutic use.

Symptoms

Psoriasis is characterized by reoccurring outbreaks of distinct red areas of skin, covered by silvery-white flaky skin. It may affect any or all parts of the skin. There are five clinical subtypes of psoriasis, each associated in with different symptoms.

• Plaque Psoriasis – This is the most common type of psoriasis, seen in over 80% of individuals with the disease. Thick, raised, red patches of skin are covered by flaky, silver-white scales. Lesions may be single or numerous and may coalesce into large areas. Common sites for lesions to develop are the elbows, knees, back and scalp but can occur all over the body.
• Guttate Psoriasis – Small, pink-red scaly spots in the order of 2 -10 mm in size appear on the trunk and limbs. The number of lesions may range from 5 or 10 to over 100. Guttate psoriasis accounts for 2% of the total cases of psoriasis. It is typically seen in young adulthood and might be triggered by a streptococcal infection in the upper respiratory tract. Guttate psoriasis may persist despite clearance of the strep infection. In children, an acute episode is usually self limiting; in adults, flares may complicate chronic plaque disease.
• Inverse Psoriasis – Skin redness and irritation occurs in the armpits, groin, breasts and skin folds around the genitals. It has a smooth red appearance and is more common in overweight people as the skin is aggravated by sweat and friction.
• Pustular Psoriasis – Primarily seen in adults, it is characterized by white, non-infectious blisters that are surrounded by red, irritated skin. It may be localized to certain areas of the body or can be generalized, covering most of the body. Pustular psoriasis reportedly may be triggered by medications, irritating topical agents, overexposure to UV light, infections, emotional stress and sudden withdrawal of medications.
• Erythrodermic Psoriasis – The least common form. Involvement of the entire skin surface may occur in a sudden burst or as a result from gradual extension of psoriatic plaques. The redness of the skin is very intense usually accompanied by severe itching and pain. Edema, especially around the ankles, may also develop along with infection. Erythroderma may also be a manifestation of unstable psoriasis, possibly precipitated by drugs, infection, tar, or withdrawal of corticosteroids. The body’s temperature regulation is often disrupted, producing shivering episodes. Infection, pneumonia and congestive heart failure brought on by erythrodermic psoriasis can be life threatening. People with severe cases of this condition often require hospitalization.

Up to 30% of patients will go on to develop psoriatic arthritis. Along with skin lesions, joints become painfully swollen and can potentially lead to compromised joint function.

Other variations of the disease include:

• Nail Psoriasis – Psoriasis of the nail may present as lifting (onycholysis) or pitting of the nail. It often mimics fungal infections.
• Scalp Psoriasis – At least half of all people who have psoriasis have it on their scalp. Scalp psoriasis can be very mild, with slight, fine scaling. It can also be very severe with thick, crusty plaques covering the entire scalp, which can cause hair loss. Occasionally it will extend beyond the hairline to the back of the neck and forehead.
• Genital Psoriasis – Psoriasis may be confined only to the genital area without sign of it being anywhere else. It usually lacks the scaling associated with psoriasis on other parts of the body.

Treatments

Depending on the type of psoriasis, its size, location and the patient’s previous medical history, different treatments will be recommended. The goal of treatment is to reduce symptoms and prevent secondary infections because it cannot be cured. They can include one or combinations of the following therapies. Generally, topical treatments are used as a first line of therapy before other types.

Topical treatments

Topical creams should be tailored to the patients need and take into account the extent of the disease, site involved, patient’s age and the likelihood of compliance with the treatment.

• Corticosteroids – Anti-inflammatory effects by inhibiting cytokine production. More potent preparations are used to treat more severe cases of psoriasis. Adverse effects include skin atrophy, irritation and telangiectasias.
• Tars – Anti-inflammatory agent with antipruritic effects. Compliance is often an issue due to their color and odour. Examples include coal tar and pine tar.
• Emollients – Relieves irritation by soothing lesions.
• Keratolytics – used to lift and soften thick scales in psoriasis.
• Calipotriol/calcipotriene – a derivative of Vitamin D that helps regulate proliferation and differentiation of keratinocytes. Results often take a minimum of 6 weeks to show.
• Tazarotene – a selective retinoid that affects keratinocyte differentiation.
• Over the counter moisturizers and creams – sorbelene and vaseline are suitable preparations.

Systemic treatments

Often used when psoriasis is severe, widespread or causing disfigurement. Most drugs have immunosuppressive, anti-proliferative or anti-inflammatory effects.

• Acitretin – affects proliferation and differentiation mechanisms as well as having anti-inflammatory properties. It also increases the efficacy of phototherapy.
• Methotrexate – an immunosuppressant that slows epidermal cell proliferation. It is the most common prescribed oral antipsoriasis drug. Long term use could lead to liver or pulmonary fibrosis.
• Cyclosporine – an immunosuppressant that inhibits activated T cells, reduces T cell proliferation and the production of cytokines. Long term use is not advised due to adverse effects. They include hypertension, decreased renal function and development of neoplasias.
• Immunobiologics – proteins such as antibodies are created in living cells and are targeted at blocking specific proteins or pathways involved in the development of psoriasis. This innovation has showed great promise in working at specific immunological targets.

Phototherapy

Ultraviolet light suppresses cell mediated immunity by inhibiting the function of epidermal Langerhan cells. Three forms of phototherapy are used in psoriasis and some come with adverse effects.

• Narrowband UVB – used at a wavelength of 311nm. It has a lack of long term side effects and should be used as a first line of phototherapy.
• Broadband UVB – used at a wavelength between 290 – 320 nm. Usually combined with tar therapy for added efficacy.
• Psolaren + UVA (PUVA) – Psolaren sensitizes the skin to UV light. Adverse effects include photosensitivity and nausea. Long term use can lead to skin atrophy and increases the risk of developing skin cancer.

Differential Diagnosis

The different subtypes of psoriasis can commonly be mistaken for other diseases. Listed below are common diagnoses for particular subtypes.

• Plaque Psoriasis – discoid eczema, cutaneous T cell lymphoma (CTCL) and tinea corporis
• Guttate Psoriasis – pityriasis rosea, lichen planus and pityriasis lichenoides chronica
• Erythrodermic Psoriasis – drug induced erythroderma, eczema, pityriasis rubra pilaris and CTCL
• Pustular Psoriasis – impetigo, superficial candidiasis, reactive arthritis syndrome and superficial folliculitis

Prevention

There is no way of preventing psoriasis, but people living with the disease can ease their discomfort and maximize the effectiveness of treatment by minimizing flare-ups. This can be done by avoiding certain stimuli that trigger psoriasis and overall maintenance of good health to help the body avoid stress and feel tired.

Prognosis

Psoriasis is a chronic, lifelong condition but can be controlled with treatment. There is no cure and it will usually have negative effect on the patient’s quality of life. It usually does not adversely affect general health, unless it is neglected or occurs in the elderly or very young. It is likely that psoriatic arthritis will develop so early diagnosis and treatment will be beneficial in prolonging the health and integrity of the joints.

References

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• Joshi, R (2004) ‘Immunopathogenisis of Psoriasis’. Indian Journal of Dermatology, Venereology and Leprology. Vol 70, pp.10-12.
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• Therapeutic Guidelines (2004). Therapeutic Guidelines: Dermatology, North Melbourne, Therapeutic guidelines Limited.
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