Psoriasis: an updated overview

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 psoriasis, including a number of genes called PSORS 1-9.² Psoriasis can be divided into types I and II depending on the age of onset. Patients with type I 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 I 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. These include psoriatic arthritis, premature cardiovascular disease, obesity, type II 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 the epidemiological findings.¹²   

The role of the general practitioner

Given the significantly increased 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 (BP), body mass index (BMI), 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 counselled about reducing alcohol intake and smoking cessation, which, if adhered to, can both benefit their skin disease and help to reduce their cardiac risk. At every consultation patients should be assessed for the development of psoriatic arthritis (PsA).

Advances in the management of psoriasis

A stepwise approach to treatment of patients with psoriasis is used, cognisant of disease severity and its associated impact on the quality of life of its sufferers. Those with less extensive disease with minimal impact on quality of life may benefit from topical treatment. Phototherapy is the next option for more extensive disease or disease which impacts significantly on quality of life. A number of systemic treatments for moderate-to-severe psoriasis have been available for some years, including methotrexate, fumaric acid esters, acitretin and ciclosporin. The individual patient profile, lifestyle factors, associated arthritis, drug cost and patient preference influence the choice of drug used.

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 the patient’s day-to-day 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-α, 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 that is partly derived from mouse antibodies and is given by intravenous infusion. The dose is based on body weight (5mg/kg) and initiated at 0, 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 subunit common to both interleukins 12 and 23, is the most recently approved biologic agent that is currently in use in Ireland for the treatment of psoriasis.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. As mentioned, 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 20 or 30mg po daily.¹⁸

Discussion

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 PsA is crucial for optimal long-term outcomes. Appropriate screening and treatment of cardiovascular risk factors is also important in the management of this multi-faceted disease. 

References

1. Gelfand JM, Weinstein R, Porter SB et al. Prevalence and treatment of psoriasis in the United Kingdom: a population-based study. Arch Dermatol 2005; 141: 1537-1541 
2. Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature 2007; 445: 866-873 
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: 183-186 
4. Higgins E. Alcohol, smoking and psoriasis. Clin Exp Dermatol 2000; 25: 107-110 
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: 780-783
6. Fortune DG, Richards HL, Main CJ et al. What patients with psoriasis believe about their condition. J Am Acad Dermatol 1998; 39: 196-201 
7. Lee E, Treppichio WL, Ostreicher JL et al. Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J Exp Med 2004; 199: 125-130  
8. Kaye J, Li L, Jick S. Incidence of risk factors for myocardial infarction and other vascular diseases in patients with psoriasis. Br J Dermatol 2008; 159: 895-902
9. Gelfand J, Neimann A, Shin D et al. Risk of myocardial infarction in patients with psoriasis. JAMA 2006; 296 (14): 1735-1741
10. Brauchli YB, Jick SS, Miret M et al. Psoriasis and risk of incident myocardial infarction, stroke or transient ischaemic attack: an inception cohort study with a nested case-control analysis. Br J Dermatol 2009; 160: 1048-1056
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: 238-244 
14. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI): A simple practical measure for routine clinical use. Clin Exp Dermatol 1994; 19: 210-216 
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: 1181-1189 
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: 1190-1199 
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 Jun 28 [Epub ahead of print]