Psoriasis: from gene to clinic A satellite symposium held at the Royal College of Physicians, London, United Kingdom, in December 2005 investigated the associations between psoriasis, comorbid diseases and concomitant therapy and their significance for long-term patient treatment. The programme generated substantial debate and raised some clinically significant issues, which are further outlined here. Introduction 26 53 19 31 83 41 83 54 5 37 82 P  P  P  P  26 53 53 73 60 30 44 86 2 1 26 Table 1 65 Condition n  RKI sample OR (95% CI) Diabetes mellitus type I 11 (1.9) 3.99 (1.30–12.2)* 6.34 (2.80–14.3)*** Diabetes mellitus type II 68 (11.7) 2.48 (1.70–3.61)** 2.07 (1.50–2.85)*** Arterial hypertension 127 (21.9) 3.27 (2.41–4.43)*** 1.39 (1.09–1.77)* Hyperlipoproteinemia 30 (5.2) 2.09 (1.23–3.54)** f Coronary heart disease 32 (5.5) 1.77 (1.07–2.93)* f Metabolic syndrome 25 (4.3) 5.92 (2.78–12.8)*** 2.20 (1.41–3.43)** Alcohol consumption none vs. moderate 246 (42.3) 2.78 (2.14–3.62)*** 2.03 (1.62–2.55)*** None vs. regularly 75 (12.9) 3.33 (2.20–5.05)*** 2.00 (1.45–2.77)*** a 24 (4.1) 3.61 (1.85–7.07)*** 8.50 (5.28–16.8)*** Cigarette smoking 264 (45.4) 2.96 (2.27–3.84)*** 2.49 (2.00–3.10)*** n n n f a P  P  P  39 22 46 48 P  P  27 22 48 22 22 21 These identified diseases associated with psoriasis have led clinicians to look at underlying mechanisms that might be involved and start considering how managing comorbid conditions may impact treatment selection and outcome for the psoriasis patient. Common inflammatory pathways in psoriasis and associated diseases 7 51 1 Fig. 1 50  24 37 82 14 79 Atherosclerosis and rheumatoid arthritis 3 10 11 16 64 75 P  10 32 75 24 38 78 28 Atherosclerosis and psoriasis 39 44 42 55 62 26 42 56 42 80   The increased cardiovascular risk in psoriasis may result from • The increased prevalence of associated risk factors, such as smoking, obesity, hypertension and alcohol misuse. • The use of dyslipidaemic therapies, such as corticosteroids, acitretin and ciclosporin. • An associated unfavourable lipid profile (high triglycerides, low HDL). • Endothelial dysfunction. • Uncontrolled inflammation.  • Combination of some or all of the above. Unfortunately, there is a shortage of published studies corrected for traditional risk factors and no published study has formally assessed systemic vasculature inflammation in psoriasis. 9 12 14 15 15 81 1 4 12 4 Genetic basis of comorbidities 69 70 6 58 76 25 47 77 47 26 26 20 17 20 20 Chlamydia pneumoniae 36 63 Clinical importance of comorbidities in psoriasis 2 68 56 39 56 Fig. 2 67  39 44 42 55 62 68 55 Implications of comorbidities 33 74 40 83 59 59 13 85 34 Focus on inflammation control. Consider impact on patient as a whole. Monitor all associated diseases. Drug interactions in psoriasis 72 84 2 Table 2 84 Drug class n ACE inhibitors 12.3 Oral anticoagulants 11.3 Diuretics 12.4 Thyroid drugs 9.9 Beta blockers 7.9 Psycholeptics 5.6 NSAIDs 7.0 Lithium salts 0.70 Interferon-alpha 0.25 Risk of interactions with psoriasis therapies 67 Effect of psoriasis treatment on comorbidities The importance of considering the impact of treatment of diseases associated with psoriasis cannot be stressed enough. Working with physicians in different specialties (e.g., rheumatology, gastroenterology and cardiology) would allow physicians an opportunity to ensure that the psoriatic treatments do not worsen the associated condition and where possible provide additional benefits. Benefits of psoriasis therapy on comorbid conditions 2 18 31 45 45 Crohn’s disease 50 66 23 61 52 35 Cardiovascular disease 57 29 P  24 43 49 P  P  P  P  43 71 49 Potential drawbacks of psoriasis therapy on comorbid conditions 8 8 Drug interactions and precipitating disease in psoriasis A diagnosis of psoriasis also has implications regarding treatment for physicians from specialities other than dermatology. The potential of some drugs (eg, angiotensin-converting enzyme inhibitors, beta blockers, NSAIDs) to ‘trigger’ psoriasis means that these drugs should be avoided where possible and awareness of this potential should be raised. The potential for drug interactions with some psoriasis drugs is high and this should also be considered when designing therapeutic regimens. Furthermore, the increased risk of cardiovascular events associated with psoriasis should be considered when conducting global cardiovascular risk assessments. If possible, lower cut-off points for treatment should be used in psoriasis patients in an effort to take into consideration their overall cardiovascular risk. Discussion and conclusions Psoriasis is a multifaceted systemic condition that is not restricted to cutaneous symptoms. There is a need for further research to fully understand the reasons for comorbidities and their implications on treatment and management of psoriasis patients. Data are required to fully characterise risk of cardiovascular disease in psoriasis patients and whether treatment can impact this level of risk. Could effective (systemic) treatment of psoriasis reduce the risk of comorbidities or, conversely, could effective treatment of comorbidities improve psoriasis? Investigation of the genetics of psoriasis and related inflammatory conditions may provide insight into their pathogenesis and points of commonality, which could reveal novel drug targets However, while research is conducted, there is a pressing need for education about comorbidities in psoriasis. Dermatologists need to be aware of the likelihood of comorbid conditions to ensure their detection and that psoriasis is managed with consideration of the possible impact on associated comorbid inflammatory conditions. Similarly, physicians from other specialities should be aware of the potential impact of their management strategies on psoriasis and take care not to exacerbate psoriasis when treating associated conditions. A focus on rapid and profound systemic control of inflammation in psoriasis may have added benefits by controlling inflammation associated with comorbid conditions. It is clear that TNFα is a central mediator in psoriasis and many of the recognised associated diseases. Knowledge and awareness of the common inflammatory processes involved should provide the opportunity to more effectively treat the common causes of inflammatory conditions benefitting both physicians and patients. Managing the psoriasis patient as a whole with integrated therapy is likely to maximise outcomes.