Section 1 Epidemiology and aetiology
Psoriasis is a chronic, common inflammatory relapsing and remitting papulosquamous skin disease, characterised by well-defined, dull red plaques with silvery scales, localised on extensor surfaces and the scalp.1
Although rarely life-threatening, it can have a significant impact on quality of life and is associated with type 2 diabetes, hypertension, hyperlipidaemia, coronary artery disease, obesity and metabolic syndrome.
The incidence and prevalence of psoriasis vary according to ethnic background. It occurs in 1-3% of the global population2,3 and about 2% of the UK population is affected.4
Epidemiological studies indicate an equal sex distribution, with two main peaks of incidence in the second and fifth decades, although individuals of any age may be affected.
Family studies point to the genetic nature of the condition, with first-degree relatives of affected individuals having a 10-fold higher risk of developing psoriasis.
T-cell mediated disease
Psoriasis is a T-cell mediated disease with inflammatory plaques containing cytokines, including interleukins 17 and 23 and TNF-alpha, involved in the inflammatory pathways. These abnormal immune processes lead to increased proliferation of keratinocytes, which manifests clinically as psoriasis.
Human leucocyte antigen (HLA) analysis has linked the risk of psoriasis most strongly to HLA-C*0602, although genes involved in the function of inflammatory molecules, such as interleukin-23 receptor (IL23R) and TNF-alpha, have also been implicated.5
Histologically, psoriasis is characterised by acanthosis (epidermal thickening) and increased angiogenesis of the upper (papillary) dermis. There is impaired maturation of keratinocytes (parakeratosis) and an inflammatory T-cell infiltrate in the dermis, with additional neutrophils in the epidermis sometimes forming microabscesses.
Environmental factors can exacerbate psoriasis; these include alcohol, smoking, certain drugs, skin injury, obesity, psychological stress, streptococcal infections of the throat and HIV. Hormonal changes in the teenage and postmenopausal years may account for the two peaks of incidence.
Sunlight can improve psoriasis, but may also exacerbate it, particularly if there is sunburn. Physical injury can induce psoriasis in the so-called Koebner phenomenon.
Section 2 Making the diagnosis
A typical psoriatic lesion is a well-demarcated erythematous plaque covered with white silvery scales, of variable thickness.
The plaque type of psoriasis (psoriasis vulgaris) is the most common, accounting for 80-90% of cases. Plaques may be oval or annular, and are usually symmetrically distributed, typically over the extensor surfaces of the limbs as well as the trunk and scalp. Facial involvement is less common.
Guttate psoriasis is triggered by a streptococcal throat infection. The plaques may be numerous, all with the same appearance and a diameter of less than 1cm. It is often the first episode of psoriasis a patient may experience but usually transforms into vulgaris, some patients have repeated episodes guttate.
Less commonly, psoriasis may occur only in body folds, such as the axillae, groins and umbilicus. This type is called flexural (or inverse) psoriasis and owing to the humid nature of body folds, the plaques tend to be shiny, red and less scaly. Flexural psoriasis is often associated with fungal infection.
The scalp is commonly affected by plaque psoriasis and by a type of psoriasis along the hairline, which may resemble flexural psoriasis.
Occasionally, very adherent nodules of scale may be attached to the hair (pityriasis amiantacea). Hair loss owing to psoriasis, however, is very rare and psoriasis affecting the scalp alone is uncommon.
A pattern of psoriasis involving the palms and soles with inflammatory pustules is known as palmoplantar pustulosis. This most commonly affects women and is associated with cigarette smoking.
The pustules can have a yellowish-brown colour.
Rarely, psoriasis can become widespread and very erythematous, with little scale. In this form, the inflammatory component predominates. In extensive disease, the term ‘erythrodermic psoriasis’ is used to describe when at least 90% of the body surface area is affected. If pustules are also present, the term ‘generalised pustular psoriasis’ may be used; both entities are dermatological emergencies.
Joint and nail involvement
When psoriasis affects the nails, it may be in the form of plaques under the nail plate, which gives rise to onycholysis and subungual hyperkeratosis. If psoriasis affects the nail matrix, it can cause pits.
Nail involvement is often a marker for psoriatic joint disease.
Occasionally, nail psoriasis can occur in isolation, with no other evidence of cutaneous disease, so can be confused with fungal nail infection.
Joint involvement in psoriasis is common. The prevalence of inflammatory arthritis in patients with psoriasis is estimated at up to 30%.6
Psoriatic arthritis can mimic osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. It can sometimes involve just one large joint and very rarely, may cause a destructive form of arthritis known as arthritis mutilans.
While these patterns of psoriasis can occur in isolation, more commonly they occur in combination.
Differentials and severity
Diagnosis is usually made on clinical history and appearance, and a biopsy is rarely needed. Occasionally, other conditions can resemble psoriasis and care is needed to avoid misdiagnosis.
Solitary scaly plaques are not typical of psoriasis and conditions such as Bowen’s disease or superficial basal cell carcinoma should be excluded.
Pityriasis rosea may be confused with guttate psoriasis, while hypertrophic lichen planus (especially on the lower legs) can be psoriasis-like. In the nails, fungal nail may resemble psoriasis, although pits are usually not present in fungal conditions.
The severity of psoriasis can be measured with the PASI. A high score (>20) indicates severe disease.
Section 3 Managing the condition
The most important part of the assessment is evaluating the impact of psoriasis on the patient’s daily life and treatments to encompass that.
Psoriasis is not just a skin disease. This is recognised by NICE, which recommends that the quality standards listed in table 1 should be maintained to provide clinically effective care for this chronic condition.
|Table 1 NICE quality standards for psoriasis|
Quality statement 1
Quality statement 2
Quality statement 3
Quality statement 4
Quality statement 5
Quality statement 6
Source: NICE QS40 www.nice.org.uk
Once the diagnosis has been made, factors that can be modified, such as alcohol intake, should be altered. Further management includes topical agents, phototherapy and systemic treatments, all of which can be used as monotherapy, but more commonly as combination treatments.
Topical agents are usually the first-line therapy. Daily use of an emollient will have a mild anti-inflammatory effect and improve scaliness. In mild disease, a medium-potency topical corticosteroid, used intermittently, may be sufficient.
Additional ingredients, such as coal tar extracts or anti-yeast treatments, may be added to augment the effect of the topical steroid, or used in isolation.
Alternatives to topical steroids include topical vitamin D analogues, such as calcipotriol, which may be used in isolation or in combination with topical steroids.
Gels and liquids tend to be preferable on the scalp, while ointments and creams are usually used on the trunk and limbs. Patients often have to combine topical products to achieve maximal effectiveness.
If topical therapies are insufficient, the next line of treatment to consider is phototherapy. Current best practice is to use narrowband, rather than broadband, UVB, to maximise effectiveness and minimise unnecessary UV radiation.
An alternative combination is the use of an oral photosensitising drug (psoralen) with UVA (PUVA).
The duration of effect of phototherapy varies from a few weeks to a year or longer. Repeated phototherapy can increase the risk of skin cancer and causes photoageing; it should not be used in patients with photosensitivity.
In patients who do not respond to, or are intolerant of, phototherapy, the next option is systemic treatment.
The main systemic agents are methotrexate, ciclosporin, acitretin and fumaric acid esters. These all work differently and require monitoring for adverse effects.
Patients being considered for systemic treatment should be screened (FBC, LFT, renal function and increasingly, HIV). N-terminal procollagen peptide is tested before use of methotrexate, and fasting cholesterol and triglycerides are profiled before use of oral acitretin.
The European Commission has licensed apremilast, an oral phosphodiesterase type 4 inhibitor, for moderate to severe chronic plaque psoriasis in those who fail to respond, or are intolerant of or unable to take oral systemic therapy. The Scottish Medicines Consortium has accepted it and it is under review by NICE.
Patients failing to respond to oral systemic agents may be considered for treatment with biologics (see box 1), such as adalimumab, etanercept and ustekinumab. Secukinumab was also recently licensed by the European Commission and NICE guidance on its use is due shortly.
The benefit of these drugs is similar to that of systemic agents and the risks mostly relate to infection.
Owing to their cost, these agents are restricted, according to NICE, to those patients who have failed to respond to two systemic agents and who have severe psoriasis, defined by a PASI and Dermatology Life Quality Index (DLQI) score of 10 or more.
The British Association of Dermatologists (BAD) has created a checklist of investigations that should be carried out before and during the period for which a patient remains on biologic treatment.7
Newer biologics, such as guselkumab, and other oral biosimilar drugs are still in trial phase. With biologics expected to be among the world’s best-selling drugs by 2016, the field of personalised medicine could prove critical to ensure they are only given to those who will benefit.8
Section 4 Prognosis
Psoriasis is life-long and chronic, and patients will experience flares and remissions throughout their lives.
Most patients require topical therapy, which does not need frequent follow-up. Those on systemic treatment or biologics need regular follow-up at least every three months.
Side-effects, such as liver toxicity, bone marrow suppression or renal impairment, must be monitored in patients on systemic agents.
Good practice includes use of the BAD Biologic Interventions Register to establish a cohort of patients having treatment with biological or systemic agents, to monitor trends in complications or side-effects.
Section 5 Case study
A 35-year-old woman was referred following failure of first-line and systemic treatment. She had been diagnosed with psoriasis at the age of five years.
Past medical history included depression diagnosed at the age of 25, and she was taking fluoxetine. There was no past medical history or evidence on examination of psoriatic arthritis or nail involvement.
Management of her psoriasis had included one course of PUVA at the age of 18 and she had started taking ciclosporin at the age of 30, which was stopped and then restarted following a flare. After taking ciclosporin for two consecutive years, her psoriasis was still not under control and her PASI was 12.4.
On examination, her chronic plaque psoriasis was widespread and scored as moderately severe on the physician’s global assessment (PGA). Total body surface area (BSA) covered by psoriasis was 51%.
She was treated with apremilast as part of a clinical trial. Following two months of apremilast, her PASI had reduced to 8.2 and her BSA to 27%. After 18 months of treatment, her PASI is now 2.4, PGA, almost clear, and BSA, 2%. She is very stable and happy about her skin.
She continues to take fluoxetine for other reasons, but her confidence and self-esteem have significantly improved. Her DLQI score, which was 21 before commencing apremilast, is currently two.
Section 6 Evidence base
- Rott S, Mrowietz U. Recent developments in the use of biologics in psoriasis and autoimmune disorders. The role of autoantibodies. BMJ 2005; 330: 716-20.
This review summarises knowledge of problems associated with treatment with biologics, with particular emphasis on TNF-alpha inhibitors and autoantibody development.
- NICE. Psoriasis. The assessment and management of psoriasis. CG153. London, NICE, October 2012. www.nice.org.uk/guidance/cg153/resources/guidance-psoriasis-pdf
- NICE. Psoriasis. QS40. London, NICE, August 2013. www.nice.org.uk/guidance/qs40/resources/guidance-psoriasis-pdf
- British Association of Dermatologists and Primary Care Dermatology Society. Recommendations for the initial management of psoriasis. 2009.
- Smith CH, Anstey AV, Barker JN et al. British Association of Dermatologists’ guidelines for biologic interventions for psoriasis 2009. Br J Dermatol 2009; 161: 987-1019.
- British Association of Dermatologists. UK Biologics Checklist. www.bad.org.uk/shared/get-file.ashx?itemtype=document&id=1824
- Weller R, Hunter J, Savin J et al. Clinical Dermatology (fourth edition). Oxford, Blackwell Publishing, 2008.
- Cox N, English J. British Association of Dermatologists’ Management Guidelines. Chichester, Wiley-Blackwell, 2010.
|These action points may provide opportunities for further CPD on this subject:
1. Fitzpatrick JE, Morelli J. Dermatology secrets in color. Philadelphia, Mosby Elsevier, 2007.
2. SIGN Guideline 121. Diagnosis and management of psoriasis and psoriatic arthritis in adults. Edinburgh, SIGN, September 2013.
3. Naldi L, Griffiths CEM. Br J Dermatol 2005; 152(4): 597-615.
4. Eedy DJ, Griffiths CEM. Br J Dermatol 2009; 160: 557-64.
5. Weller R, Hunter J, Savin J et al. Clinical Dermatology. Oxford, Blackwell Publishing, 2008.
6. NICE. Etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis. TA199. London, NICE, August 2010.
7. British Association of Dermatologists. UK Biologics Checklist. www.bad.org.uk/shared/get-file.ashx?itemtype=document&id=1824
8. Malik NN. Personalized drugs should cut care costs. Nature 2012; 485(7400): 582.