Psoriasis is a common inflammatory skin disease, affecting approximately 2% of the population.¹ A complex interplay between genetic susceptibility, environmental factors and activation of the immune system is thought to underpin the pathogenesis.  

Genetic research has suggested multiple potential susceptibility genes for the condition, including a number of genes called PSORS 1-9.²

Psoriasis can be divided into type 1 and type 2 depending on the age at onset. Patients with type 1 disease typically develop psoriasis in the second or third decade of life (before 30 years of age). It is in this category that a genetic role is regarded to be strongest, and a significant, positive family history can often be elicited.  

Type 1 psoriasis is strongly associated with HLA-Cw*0602.³ Excess alcohol, smoking, psychological distress and streptococcal infections are recognised environmental triggers.^4-6 Excess activation of cutaneous immunity is evident with cutaneous over-expression of certain immune cells and cytokines, in particular T-helper 1 (Th1) and 17 (Th17) lymphocytes and tumour necrosis factor-alpha (TNF-α).⁷

Psoriasis and cardiovascular disease

Psoriasis is associated with several medical conditions: psoriatic arthritis; premature cardiovascular disease; obesity; type 2 diabetes mellitus; and depression.⁸ Several epidemiological studies have demonstrated an increased relative risk of myocardial infarction in patients with psoriasis.^9-11 Systemic inflammation with resultant insulin resistance may explain these findings.¹²

Close monitoring

Given the significantly higher risk of cardiovascular disease among psoriasis patients, it is critical that patients are monitored closely for cardiovascular risk factors to allow early intervention. Blood pressure, body mass index, blood glucose levels and lipid profile should be measured yearly in all age groups and appropriate therapies initiated. Weight loss interventions should be employed where appropriate and patients should be screened for depression and treated as necessary.  

Patients should also be encouraged to reduce alcohol intake and cease smoking. This may benefit their skin disease and reduce their cardiac risk. At every consultation, patients should be assessed for the development of psoriatic arthritis.

Advances in management

A stepwise approach to treatment of psoriasis patients is used, cognisant of disease severity and its associated impact on the patient’s quality of life. Those with minimal impact on quality of life may benefit from topical treatment. Phototherapy is the next option for disease that impacts significantly on quality of life.  

A number of systemic treatments for moderate to severe psoriasis are available, including methotrexate, fumaric acid esters, acitretin and ciclosporin. The individual patient profile, lifestyle factors, associated arthritis, drug cost and patient preference all influence the drug chosen.

The severity of psoriasis can be determined by both objective and subjective measures. The Psoriasis Area and Severity Index (PASI) is a clinical tool which incorporates a calculation of the severity of individual psoriasis plaques and the extent of the body surface area involved.¹³

Subjective measures, which reflect the impact of psoriasis on a patient’s daily life, include the Dermatology Life Quality Index (DLQI).¹⁴

Values of 10 or greater in PASI and/or DLQI signify moderate to severe psoriasis. The efficacy of biologic agents in the treatment of moderate to severe psoriasis has led to significant improvement in the management of this chronic and often psychologically debilitating disease.  

Most of these biologic agents act by inhibition of TNF-alpha, an inflammatory cytokine that is implicated in psoriasis. Etanercept is a fusion protein of portions of the human TNF receptor and immunoglobulin G1 (IgG1), given by subcutaneous injection once or twice weekly.  

Adalimumab is a humanised anti-TNF monoclonal antibody. A loading dose is given, followed by standard dose (40mg) one week later. Maintenance is usually at fortnightly intervals, escalated to weekly injections in selected patients.  

Infliximab is an anti-TNF monoclonal antibody which is partly derived from mouse antibodies and given by intravenous infusion. The dose is based on body weight (5mg/kg) and initiated at zero, two and six weekly intervals. Following induction, infusions are usually given at intervals of eight weeks.  

Ustekinumab, a human monoclonal antibody directed against p40, a sub-unit common to both interleukins 12 and 23, is the most recently approved biologic agent currently in use in Ireland.¹⁵

As there is a cohort of patients in whom treatment response is inadequate or wanes over time, there is an ongoing need for the development of new treatments. Within the past 12 months, clinical trials have revealed initial promising results with new biologic treatments.  

Th17 lymphocytes are important in the development of psoriasis. These cells induce the inflammatory cytokine, interleukin 17 (IL-17), and therefore, methods of targeting this pathway have been the focus of recent research.  

More than 70% of patients with moderate to severe psoriasis treated with Brodalumab, a human anti-IL-17 receptor monoclonal antibody, in a phase II randomised controlled trial, achieved a 75% reduction in PASI (referred to as PASI-75) at week 12.¹⁶ Similar results were found with Ixekizumab, a humanised, anti-IL-17 monoclonal antibody.¹⁷

Apremilast is a novel agent that is currently under investigation for the treatment of moderate to severe psoriasis. It is an inhibitor of phosphodiesterase 4 and acts by modulating the immune response.  In a recent clinical trial, it appears to be effective at a dose of 20mg or 30mg po daily.¹⁸

New therapeutic strategies

Exciting advances in the understanding of psoriasis and new therapeutic strategies for its management continue to evolve. It is important to recognise the opportunity that a clinical encounter with a patient with moderate to severe psoriasis provides. A holistic approach should be taken, aiming to modify both the appearance of the skin as well as helping to reduce associated psychological distress.  

The early detection of psoriatic arthritis is crucial for optimal long-term outcomes.  Appropriate screening and treatment of cardiovascular risk factors is also important in the management of this multifaceted disease. 

References

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2. Lowes MA, Bowcock AM et al. Pathogenesis and therapy of psoriasis. Nature 2007; (445): 866-73
3. Mallon E, Bunce M, Wojnarowska F et al. HLA-CW*0602 is a susceptibility factor in type I psoriasis, and evidence Ala-73 is increased in male type I psoriasis. J Invest Dermatol. 1997; (109): 183-6
4. Higgins E. Alcohol, smoking and psoriasis. Clin Exp Dermatol. 2000; (25): 107-10
5. Poikolainen K, Reunala T, Karvonen J et al. Alcohol intake: a risk factor for psoriasis in young and middle aged men. BMJ 1990; (300): 780-3
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11. Lin HW, Wang KH, Lin HC et al. Increased risk of acute myocardial infarction in patients with psoriasis: a 5 year population-based study in Taiwan. J Am Acad Dermatol. 2011; (64): 495-501
12. Reich K. The concept of psoriasis as a systemic inflammation: implications for disease management. J Eur Acad Dermatol Venereol. 2012; (26): 3-11
13. Fredriksson T, Pettersson U. Severe psoriasis – oral therapy with a new retinoid. Dermatologica 1978; (157): 238-44
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15. Smith CH, Anstey AV, Barker JNWN et al. British Association of Dermatologists’ guidelines for biologic interventions for psoriasis 2009. Br J Dermatol. 2009; (160): 987-1019
16. Papp KA, Leonardi C, Menter A et al. Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N Engl J Med. 2012; 366: 1181-9
17. Leonardi C, Matheson R, Zachariae C et al. Anti-interleukin-17 monoclonal antibody Ixekizumab in chronic plaque psoriasis. N Engl J Med. 2012; 366: 1190-9
18. Papp K, Cather JC, Rosoph L et al. Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised control trial. Lancet 2012; June 28