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Keywords:

  • biological agents;
  • cardiovascular risk;
  • comorbidity;
  • inflammation;
  • plaque psoriasis

Summary

  1. Top of page
  2. Summary
  3. Long-term impact of psoriasis comorbidities
  4. Management of long-term inflammation and associated comorbidities
  5. Conclusions
  6. Acknowledgments
  7. References

Psoriasis is a chronic, inflammatory, immune-mediated skin disease associated with substantial comorbidity. Traditional comorbid conditions include psychological/psychiatric disorders, psoriatic arthritis and inflammatory bowel disease. Increasingly, an association with metabolic dysfunction, including obesity and the metabolic syndrome, and cardiovascular disease, with consequent effects on morbidity and mortality, has been recognized in psoriasis. The underlying inflammatory mechanisms of both psoriasis and psoriasis-associated comorbidities involve mediation by proinflammatory T-helper type 1 cytokines. For effective management of psoriasis and related comorbidities, an integrated approach targeting both cutaneous and systemic inflammation may be beneficial, and strategies to improve overall management of the patient should be encouraged to reduce the disease burden. This paper discusses the emerging role of biological agents in this approach, and offers an appreciation of the role of existing anti-psoriasis and adjunctive therapies.

Psoriasis is a common, immune-mediated, inflammatory skin condition of unknown aetiology that requires life-long treatment once the disease has progressed to an advanced stage.1,2 Prevalence varies with geographical area and race/ethnicity, and in Europe and the USA approximately 1–3% of the population is affected.1,3,4 In patients with psoriasis, comorbidities have been identified that occur more frequently than in the general population, which appear to be associated with the presence of psoriasis.5 Well-recognized comorbidities include immune-mediated disorders, such as inflammatory joint disease and inflammatory bowel disease (IBD). Psychiatric disorders are also over-represented.6 Further, there is an increasing awareness of a link between psoriasis and obesity, although the causal nature of this association remains uncertain.7,8 More recently, attention has focused on the relation between psoriasis and metabolic dysfunction and cardiovascular risk factors, with consideration of common underlying pathogenic mechanisms, which suggests that a more integrated approach to therapy may be beneficial.9

Long-term impact of psoriasis comorbidities

  1. Top of page
  2. Summary
  3. Long-term impact of psoriasis comorbidities
  4. Management of long-term inflammation and associated comorbidities
  5. Conclusions
  6. Acknowledgments
  7. References

Traditional comorbidities

The best-recognized comorbidity in patients with psoriasis is psoriatic arthritis, with a prevalence of 10–30%,10,11 although some patients report joint-related symptoms without meeting the diagnostic criteria for psoriatic arthritis.12 Indeed the severity of psoriasis may affect the prevalence13 but not the severity14 of joint disease.

IBD, most notably Crohn’s disease, is also over-represented in patients with psoriasis, with an increased relative risk of 2·9 [95% confidence interval (CI), 1·1–7·9],15 and patients with IBD are up to seven times more likely than the normal population to develop psoriasis.5,16

In addition, there is an apparent increased risk of malignancy associated with psoriasis, although the supporting data are inconsistent. This increased risk may stem from the underlying immune mechanisms involved in the pathogenesis of psoriasis, but some treatments, notably high-dose methotrexate and psoralen ultraviolet A (PUVA) therapy, may also be associated with carcinogenesis. In a large retrospective observational study of 153 197 patients with psoriasis, an increased risk of Hodgkin’s lymphoma [relative risk (RR) = 3·18; 95% CI, 1·01–9·97] and of cutaneous T-cell lymphoma (RR = 10·75; 95% CI, 3·89–29·76) was reported in patients with severe psoriasis who were receiving systemic treatments.17 The absolute risk of malignancy in this study, however, remained low at 7·9/100 000 patients per year. A similar but smaller study of 1380 patients with psoriasis who had been treated initially with PUVA found that the increased incidence of lymphoma was apparent only in those who had also been treated with high-dose methotrexate.18 For patients who had not received methotrexate, the incidence was comparable with that expected in the general population. In Caucasian patients with psoriasis, extended treatment with PUVA (more than 200 courses) has been associated with a 14-fold increase in the risk of non-melanoma skin cancer.19

Psoriasis is strongly associated with a significant reduction in health-related quality of life (QoL), with the prevalence of joint involvement associated with lower QoL scores.20 Indeed, the effects of psoriasis on QoL are comparable with those observed with other major chronic diseases, such as cancer, arthritis and depression.21 The psychological burden of psoriasis should not be underestimated.22 Indeed, moderate-to-severe psoriasis is associated with marked physical and psychological morbidity, with up to 40% of patients reporting that their disease has negative effects on daily functioning.23 Psychiatric comorbidity is also apparent, with higher anxiety scores reported in over one-third of patients.6,22 In addition, clinical depression is prevalent and has been reported in as many as 60% of cases.24 Moreover, disease severity can influence the severity of psychological comorbidities. In one study of 217 patients with psoriasis, active suicidal ideation was reported in 7·2% of patients requiring inpatient care compared with 2·5% of those treated as outpatients.25

There also appears to be an association between psoriasis and lifestyle choices that can have a negative impact on patients’ general health, which can contribute directly to both medical and psychological comorbidities. Numerous studies in different countries have shown a link between psoriasis and cigarette smoking; patients with psoriasis are at least twice as likely to smoke cigarettes than is the general population.7,26–29 In one such study,7 the Utah Psoriasis Initiative, in which information from 557 patients with psoriasis was compared with that from a local control population, 37% of patients with psoriasis were current smokers compared with 13% of the general population [prevalence odds ratios (OR), 4·02; 95% CI, 3·31–4·88]; the majority of patients (78%) started smoking before the onset of psoriasis. Heavy tobacco intake also confers an increased risk of more clinically severe disease. A study involving 818 patients treated as hospital inpatients for psoriasis found that smoking more than 20 cigarettes per day was associated with a greater than twofold increased risk of more clinically severe psoriasis (OR, 2·2; 95% CI, 1·2–4·1).29 A particularly strong association has been shown between smoking and palmoplantar pustular psoriasis, and in one case–control study of 560 patients with psoriasis, smokers were five times more likely to suffer from this form of the disease than were non-smokers (OR, 5·3; 95% CI, 2·1–13·0).27

The likelihood of alcohol abuse is increased in patients with psoriasis.6,30 A German retrospective cohort study of 581 patients with chronic plaque psoriasis found that increased alcohol consumption was seen twice as frequently in patients with moderate-to-severe psoriasis compared with hospital-based controls.26 Compared with patients treated surgically for localized stage I melanoma, the ORs indicated that patients with psoriasis were more likely to have a regular or heavy alcohol intake [ORs (95% CIs) for moderate intake, 2·78 (2·14–3·62); regular intake, 3·33 (2·20–5·05); heavy intake, 3·61 (1·85–7·07)].26 In a study of 144 patients with psoriasis and 285 unmatched controls with other skin diseases, greater alcohol consumption before the onset of disease was reported for those with psoriasis compared with the control group.31

Both smoking and excessive alcohol consumption can contribute directly to increased mortality in patients with psoriasis.32 A retrospective cohort study of 5687 patients admitted as inpatients for psoriasis treatment reported an excess in all-cause mortality directly related to alcohol consumption.32 The standardized mortality ratio (SMR) for men was 4·46 (95% CI, 3·60–5·45) and for women, 5·60 (95% CI, 2·98–8·65). Smoking was also associated with excess mortality, with the SMR for men being 1·44 (95% CI, 1·33–1·56) and for women, 1·61 (95% CI. 1·45–1·77).

Emerging comorbidities

The association of obesity with psoriasis has been demonstrated in large case–control studies.7,26,28 In the German retrospective study mentioned above,26 obesity was also more prevalent in patients with psoriasis (OR, 2·3), with higher rates of obesity seen in females. Similar findings were reported in the Utah Psoriasis Initiative,7 which found obesity to be more prevalent in patients with psoriasis compared with the control population (OR, 2·39; 95% CI, 1·98–2·90), particularly in women (OR, 3·24; 95% CI, 2·48–4·23). In the largest study on obesity in psoriasis reported thus far,28 Neimann and colleagues analysed data from the UK General Practice Research Database (UK GPRD), which contains data from more than 130 000 patients with psoriasis and is validated for retrospective population studies,33–35 and found that obesity was more prevalent in patients with psoriasis of any severity than in the general population. In addition, after adjusting for age, sex and person-years, obesity was more prevalent in patients with severe psoriasis than in those with milder forms of the disease (OR, 1·47; 95% CI, 1·32–1·63).

Although the causal nature of the relation between psoriasis and obesity remains unclear, a process mediated by proinflammatory cytokines derived from helper type 1 T cells (Th1) is common to both psoriasis and obesity, and is considered central to the underlying pathogenesis of these two conditions.36,37 In particular, proinflammatory cytokines produced in the skin may directly contribute to inflammation within adipose tissue, promoting obesity. Conversely, inflammatory mechanisms considered central to the metabolic dysfunction found in obesity may contribute directly to the ongoing dermal inflammation seen in psoriasis. As has been proposed,28 the presence of obesity correlates with disease severity in psoriasis, and some data even suggest that obesity is a consequence of psoriasis.7 Such inflammatory mechanisms that are common to both diseases, and their clinical and therapeutic implications for patients with psoriasis, are discussed in further detail later in this article.

The metabolic syndrome, which comprises a cluster of risk factors, including obesity, dyslipidaemia, hypertension and glucose intolerance, is a strong predictor of cardiovascular disease, conferring a cardiovascular risk greater than that for the individual components.38 As discussed above, obesity is more prevalent in patients with psoriasis, and data reported by Neimann et al.28 indicate that other components of the metabolic syndrome are also more prevalent, as is the syndrome itself. Using the UK GPRD, these investigators found that individuals with psoriasis of any severity had an increased prevalence of a variety of cardiovascular risk factors. Compared with controls, patients with mild psoriasis had higher adjusted odds of diabetes (OR, 1·13; 95% CI, 1·08–1·18), hypertension (OR, 1·03; 95% CI, 1·01–1·06) and hyperlipidaemia (OR, 1·16; 95% CI, 1·12–1·21). Further, patients with severe psoriasis had a higher adjusted odds of diabetes (OR, 1·62; 95% CI, 1·3–2·01), and diabetes was more prevalent in patients with severe psoriasis compared with those with mild disease (OR, 1·39; 95% CI, 1·22–1·58).28

Two case–control studies have demonstrated an increased prevalence of the metabolic syndrome and its contributing components in patients hospitalized for severe or treatment-refractory psoriasis.26,39 In the German retrospective cohort study,26 a recognizable pattern of comorbid conditions was found, all of which were associated with the metabolic syndrome: the increased prevalence of obesity in psoriasis, type 2 diabetes (OR, 2·48; 95% CI, 1·70–3·61), arterial hypertension (OR, 3·27; 95% CI, 2·41–4·43), hyperlipidaemia (OR, 2·09; 95% CI, 1·23–3·54) and coronary heart disease (OR, 1·77; 95% CI, 1·07–2·93) were all reported as significant comorbidities, with increased prevalence compared with hospitalized control patients. Moreover, the combined presence of these conditions, which was considered to represent the metabolic syndrome, was also significantly more prevalent in patients with severe psoriasis (OR, 5·92; 95% CI, 2·78–12·8). In fact, there was a consistent trend towards an increased risk of the metabolic syndrome with greater severity of psoriasis. It should be noted, however, that the overall prevalence of the metabolic syndrome in the study population was low (4·3% in patients with psoriasis vs. 1·1% in controls)26 compared with other studies.40

A hospital-based study in Italy involving 338 patients found that, after the age of 40 years, the metabolic syndrome was more prevalent in patients with psoriasis than in those with other skin diseases (30·1% vs. 20·6%; OR, 1·65; 95% CI, 1·16–2·35). Specific components are also significantly more common, most notably abdominal obesity and hypertriglyceridaemia.39 Additionally, in the Italian study, the increased prevalence of the metabolic syndrome in patients with psoriasis was independent of obesity. Unlike in the German study,26 other components of the metabolic syndrome, such as plasma glucose level and hypertension, were not independently associated with psoriasis. Although no correlation was seen between the prevalence of the metabolic syndrome and disease severity, prevalence was associated with disease duration and onset past the age of 40 years.

The association of an increased prevalence of cardiovascular risk factors and the metabolic syndrome in patients with psoriasis, in particular in those with severe disease, has led to suggestions that psoriasis itself may be an independent risk factor for cardiovascular events, including myocardial infarction (MI). Supporting evidence, however, has been conflicting, with one study finding a 50% increase in the risk of cardiovascular mortality in patients hospitalized for psoriasis41 but an earlier study finding no such association.42 More recently, using the UK GPRD, Gelfand and colleagues demonstrated that, after correction for conventional cardiovascular risk factors, psoriasis remained an independent risk factor for MI.43 The relative risk of MI, though, was dependent on age and disease severity, with younger patients and those with more severe disease having a higher relative risk of MI. After adjustment for major risk factors, the relative risk of MI for a 30-year-old patient with psoriasis compared with the control population was 1·29 (95% CI, 1·14–1·26) with mild psoriasis and 3·10 (95% CI, 1·98–4·86) with severe psoriasis, and for a 60-year-old patient the adjusted relative risk was 1·08 (95% CI, 1·03–1·13) with mild disease and 1·36 (95% CI, 1·13–1·64) with severe disease.43

Clinical factors associated with psoriasis may explain some of the findings discussed above. Abnormal lipid profiles (elevated very-low-density lipoprotein and high-density lipoprotein fractions) are present at disease onset in patients with mild psoriasis, even after adjustment for cardiovascular risk factors. Such predisposition may contribute to future metabolic dysfunction.44 Patients with psoriasis have a significantly increased prevalence of coronary artery calcification, which predisposes to atherosclerosis, and psoriasis itself is an independent risk factor for atherosclerosis.45 Thus, as has been reported with rheumatoid arthritis (RA),46 independent features associated with the disease may contribute to cardiovascular comorbidity.

Although the studies outlined above suggest that an increase in overall mortality may be expected in patients with psoriasis, data to support this suggestion have been lacking. However, in a recent retrospective study by Gelfand et al.,47 again using the UK GPRD, although no association between mortality and mild disease was found, severe disease conferred a significantly greater risk of mortality (hazard ratio, 1·5; 95% CI, 1·3–1·7), which remained significantly increased after adjustment for other risk factors. This equates to a 50% increased risk of mortality in patients with severe psoriasis. Compared with the normal population, men with severe psoriasis died an average of 3·5 years earlier, and women 4·4 years earlier. Another recent population study involving a cohort of patients with psoriasis among 50 000 individuals from Newfoundland and Labrador, Canada, evaluated comorbidities in patients with psoriasis, and found that the prevalence of diabetes was increased in patients with severe (12%) or mild-to-moderate (10%) psoriasis, compared with the general population (4%).48 In addition, 44% of deaths in patients with psoriasis were due to cardiovascular causes, compared with 36% in the general population. Patients with psoriasis had a reduced lifespan, 10 years shorter than the Canadian average, with early disease onset (<25 years of age) reducing life expectancy by 25–30 years.48

The conventional and emerging comorbidities associated with plaque psoriasis are summarized in Table 1.

Table 1.   Comorbidities in psoriasis
Comorbidities related to systemic inflammationObesity7,26,28,39
Metabolic syndrome26,28,39
Atherosclerosis26,28
Myocardial infarction43
Hypertension26,28
Diabetes and insulin resistance26,28
Comorbidities or lifestyle risk factors related to impaired quality of lifeAnxiety6,22
Depression6,24
Suicidal ideation6,25
Smoking7,26–29
Alcohol abuse6,26,30
Comorbidities related to treatment [with the use of traditional systemic agents in particular, and possibly with some of the tumour necrosis factor blockers (e.g. infliximab)]Nephrotoxicity49,50
Hepatotoxicity50,51
Non-melanoma skin cancer19,49,50

Role of common inflammatory processes in both psoriasis and comorbid conditions

The underlying pathogenesis of psoriasis is characterized by T-cell activation and subsequent immune/inflammatory cell trafficking within the skin, promoting keratinocyte proliferation and epidermal hyperplasia leading to psoriatic plaque formation.36 Consequent to T-cell activation, proinflammatory cytokines are released by Th1 cells [including tumour necrosis factor (TNF)-α, interleukin (IL)-2 and interferon-γ], which induce an inflammatory cascade. In the skin, stimulated keratinocytes produce additional cytokines (including IL-6, IL-8 and transforming growth factor-α and -β), which drive keratinocyte proliferation and immune cell trafficking. A role of TNF-α in this chain of events has been demonstrated in both immunological studies and clinical studies investigating the effects of blocking TNF-α activity.52–54 Through activation of the transcription factor nuclear factor κβ, TNF-α induces a proinflammatory cytokine response (including IL-1, IL-8 and IL-6), vascular adhesion molecule upregulation and an increase in inducible nitric oxide synthase.55,56 These mechanisms result in activation of keratinocytes and stimulation of their proliferation, as well as driving inflammatory cell activation, migration and action in the skin. The central role of the inflammatory process in the pathogenesis of psoriasis has led to the therapeutic use of agents acting against T-cell activation (e.g. efalizumab and alefacept) and agents acting against mediators of the subsequent inflammatory cascade (e.g. the anti-TNF-α agents infliximab, adalimumab and etanercept).

The processes that lead to the persistent, low-grade inflammation characteristic of psoriasis are also common to the comorbidities discussed above.8,9 Obesity is associated with chronic low-grade inflammation, with circulating levels of TNF-α, IL-2, IL-6 and C-reactive protein (CRP) positively correlated to body mass index, possibly under the influence of macrophages that infiltrate adipose tissue.37,57 Similarities also exist among psoriasis, the metabolic syndrome and atherosclerosis, with all three conditions characterized by an inflammatory process driven by Th1 cytokines.8,9,28,58 The association between smoking and psoriasis may also be explained partly by the action of nicotine in promoting Th1-mediated inflammation.58 Still, the exact nature of such common mechanisms across different disease states is uncertain,8,9 and remains a focus of ongoing investigation.

Management of long-term inflammation and associated comorbidities

  1. Top of page
  2. Summary
  3. Long-term impact of psoriasis comorbidities
  4. Management of long-term inflammation and associated comorbidities
  5. Conclusions
  6. Acknowledgments
  7. References

Undoubtedly, the presence of comorbid conditions in patients with psoriasis affects the clinical management of the disease. As we now understand that psoriasis and its associated comorbidities share common inflammatory mechanisms, we can also suggest that therapies targeting the underlying inflammation may be effective in treating both psoriasis and these comorbidities.9 Thus, normalization of levels of inflammatory mediators and the subsequent reduction in inflammation may be an important mechanism in the long-term control of psoriasis, which could in turn lead to a reduction in metabolic dysfunction and cardiovascular risk. Additionally, effective treatment of comorbidities may also decrease psoriasis disease activity and severity.

In RA, for which a similar relation between primary disease and systemic comorbidities has been established, clinical guidelines have been developed to address the management of the primary disease and its associated cardiovascular comorbidities.59 Data from studies of patients with RA, and more limited data in patients with psoriasis, support the development of such guidelines for the treatment of psoriasis.

Statins

Recent studies indicate that statins may reduce both the general inflammatory burden and disease activity in RA. Statin therapy effectively reduces CRP levels in patients with acute coronary syndrome60 and, in RA, the use of statins results in a significant reduction in CRP and TNF-α levels as well as significant improvements in RA disease activity and disease scores.61,62 Statins can also reduce low-density lipoprotein levels and arterial stiffness.63 Thus, the use of statins in patients with psoriasis may also be beneficial in reducing the inflammatory burden and cardiovascular risk in patients with elevated cholesterol levels. Further investigation is required to ascertain if statin use may have the dual purpose of reducing cardiovascular risk and psoriasis disease activity, similar to that seen in RA.64

Methotrexate

It is recognized that methotrexate may protect against cardiovascular mortality in patients with RA. A longitudinal prospective study65 and a large retrospective study66 both found that methotrexate treatment significantly reduced cardiovascular mortality. Although there are no data currently available indicating a reduction in mortality in patients with psoriasis, a protective effect of methotrexate on the vasculature has been demonstrated. A retrospective study of more than 7000 patients with psoriasis and 6707 patients with RA found that individuals treated with methotrexate had a significantly reduced risk of vascular disease compared with those receiving other therapies: for patients with psoriasis, the relative risk was 0·73 (95% CI, 0·55–0·98).67 Risk reduction was also greater for patients with psoriasis than for those with RA (RR = 0·83; 95% CI, 0·71–0·96), and was greatest in those receiving a low cumulative dose of methotrexate or folic acid supplementation. However, morbidity associated with methotrexate treatment should also be considered in patients with psoriasis. Methotrexate is hepatotoxic50,51 and, in patients with psoriasis receiving treatment with PUVA, methotrexate use confers an increased risk of lymphoma.18

An increased risk of lymphoma was not observed during treatment with ciclosporin, but the increased risk of non-melanoma skin cancer seen in patients exposed to more than 2 years of ciclosporin was reported to be influenced by prior exposure to methotrexate.68

TNF-α blockers

Studies in patients with RA have suggested that treatments that block TNF-α activity may also have cardioprotective effects. A small comparative study found that treatment with adalimumab significantly increased levels of protective high-density lipoprotein compared with placebo.69 A retrospective study involving 992 patients with RA treated with TNF-α blockers or standard therapies found that TNF-α blockers significantly reduced the risk of a first cardiovascular event (standardized incidence ratio, 0·6; 95% CI, 0·3–1·1).70 More recently, it was reported that patients who responded to treatment with TNF-α blockers had a two-fold reduction in the risk of MI, compared with patients treated with traditional therapies, with non-responders showing no such benefit.71 Another study found that TNF-α blockers reduced the risk of cardiovascular-related death in patients with RA.72 As yet, no studies evaluating such effects in patients with psoriasis have been reported. It may be anticipated that reducing TNF-α production and/or using TNF-α blockade in psoriasis may have a similar effect, but caution should be exercised when extrapolating effects in patients with RA to those with psoriasis, and investigations in patients with psoriasis are required. In addition, limitations apply to the use of TNF-α blockers in psoriasis. TNF-α blockers are contraindicated in patients with severe heart failure and those with a history of demyelinating disease, and may be associated with reactivation of hepatitis B virus infection and latent tuberculosis.73 Other complications related to TNF-α blockade include increased risk of serious infection. There are conflicting data regarding a possible increased risk of lymphoma and solid tumours.74–77 In addition, treatment with TNF-α blockers may directly contribute to weight gain, which is particularly problematic in patients at risk of cardiovascular comorbidities.78 Furthermore, the efficacy of long-term use of TNF-α blockers in the treatment of psoriasis is uncertain; there is evidence to suggest that the efficacy of TNF-α blockade may decrease over time.79

T-cell-modulating biologicals

In psoriasis, there are biological agents other than the TNF-α blockers that act on the inflammatory process, upstream of TNF-α activitation.52 These include efalizumab and alefacept. In patients with moderate-to-severe psoriasis, treatment with efalizumab has been shown to reduce the levels of TNF-α and inducible nitric oxide synthase in lesional skin.80 There are data to demonstrate the efficacy of efalizumab acting upstream of TNF-α and its influence on the inflammatory cascade without direct TNF-α blockade. As well as abrogating the effects of TNF-α, efalizumab acts at multiple stages in the inflammatory cascade involved in the pathogenesis of psoriasis by binding to the α subunit (CD11a) of leukocyte function-associated antigen type 1 on T cells, and blocking its interaction with intercellular adhesion molecule-1 and subsequent T-cell migration to sites of inflammation.52 In skin lesions, efalizumab may block in situ production of proinflammatory cytokines. Indeed, efalizumab has now been shown to be effective in long-term use in patients with moderate-to-severe psoriasis.81 All patients who had achieved at least a 50% reduction in their baseline Psoriasis Area and Severity Index (PASI-50) score after 3 months of treatment were entered into a continuous treatment regimen and 73% of these patients showed at least a 75% reduction in their baseline PASI score after 3 years of continuous therapy; almost all had maintained a PASI-50 response (as-treated analysis). The efficacy and favourable safety profile of efalizumab in long-term use81 suggest that this agent may offer a long-term reduction in the chronic inflammatory burden seen in psoriasis, with possible benefits extended across associated comorbidities.

Considerations in treatment selection

When considering management of the patient who has psoriasis, it should be remembered that comorbidities can influence the treatment choices available and their efficacy. For example, alcohol misuse or psychiatric disorders may reduce adherence to medication.82 Obesity may affect the efficacy of biological agents and, given the prevalence of obesity in the population with psoriasis, should be a consideration in treatment selection. Both efalizumab and infliximab are administered on a per kilogram of body weight basis and are consistently effective across weight ranges, whereas fixed-dose agents, including etanercept and alefacept, may be less effective in obese patients.83 Further, treatment with TNF-α blockers may directly contribute to weight gain, which is particularly important given the strong association between psoriasis and obesity. The pharmacokinetics and adverse effects of therapies may also impact on comorbidity.9 Methotrexate is contraindicated in patients with hepatic impairment,50,51 and may adversely affect glucose metabolism in patients with diabetes.84 Ciclosporin is associated with renal dysfunction,49,50 and a range of drugs (including beta-blockers, lithium, non-steroidal anti-inflammatory drugs and tetracyclines) are implicated in the initiation or exacerbation of psoriasis.9,85 It is clear that, in the future management of psoriasis, treatment must be tailored towards the individual patient, accommodating existing medical conditions as well as prior and current therapies. An integrated approach by the dermatologist, along with clinicians in cardiology, internal medicine and other specialties, as appropriate, will help to ensure an optimal outcome for the patient.

Conclusions

  1. Top of page
  2. Summary
  3. Long-term impact of psoriasis comorbidities
  4. Management of long-term inflammation and associated comorbidities
  5. Conclusions
  6. Acknowledgments
  7. References

Comorbid conditions linked with psoriasis are associated with increasing rates of morbidity and mortality.9 They include both long-recognized conditions (e.g. psoriatic arthritis, IBD, psychiatric conditions) and conditions that can adversely affect overall survival and QoL, such as obesity, metabolic dysfunction and cardiovascular disease. Psoriasis and many of its associated comorbidities share common underlying disease mechanisms. A reduction in disease activity and/or severity of one or more concomitant conditions may reduce the severity of others. Thus, strategies to improve the management of both psoriasis and its related comorbidities should be encouraged, in order to reduce overall disease burden. In particular, the increased risk of cardiovascular disease in patients with psoriasis means that measures to modify risk factors such as cigarette smoking, dyslipidaemia, hypertension, alcohol abuse and a sedentary lifestyle should be included in the clinical management programme of the patient with psoriasis.

Our increasing knowledge of the pathogenesis of psoriasis and its associated comorbidities should allow for early investigation and diagnosis of these comorbidities and, consequently, improve outcomes for the patient. If genetic links between psoriasis and associated comorbidities can be identified, then genetic screening programmes and preventive strategies may be feasible.5,48 There is a need for better education of patients and dermatologists about comorbidities in psoriasis, and about strategies to correct modifiable risk factors.8,9,58 Psoriasis can be considered to be a systemic inflammatory condition, with the underlying inflammatory processes being key to psoriasis and the associated metabolic dysfunction and cardiovascular disease. The use of biological therapies that modify the inflammatory process to treat psoriasis offers a promising approach to reducing both cutaneous and systemic inflammation, and to reducing the burden of morbidity and mortality seen in this condition. The development of clinical guidelines to address this aspect of psoriasis disease management would be welcome.

Acknowledgments

  1. Top of page
  2. Summary
  3. Long-term impact of psoriasis comorbidities
  4. Management of long-term inflammation and associated comorbidities
  5. Conclusions
  6. Acknowledgments
  7. References

The author takes full responsibility for the content of the paper, but thanks Iain O’Neill (supported by Merck Serono International S.A., Geneva, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany) for assistance in preparing the initial draft of the manuscript and collating comments.

References

  1. Top of page
  2. Summary
  3. Long-term impact of psoriasis comorbidities
  4. Management of long-term inflammation and associated comorbidities
  5. Conclusions
  6. Acknowledgments
  7. References