Clinical Update on Psoriasis Comorbidities
Psoriasis is a chronic inflammatory disease that is estimated to affect more than 7.5 million individuals in the United States.1 The main comorbid disease conditions associated with psoriasis include psoriatic arthritis, cardiometabolic disease, obesity, and mood disorders.2 The comorbid disease conditions associated with psoriasis can significantly impact the quality of life for these patients. This article evaluates the current understanding of the association between psoriasis and cardiovascular disease (CVD) as well as the association between psoriasis and mental health conditions. In addition, the impact of treatment of psoriasis on these 2 comorbid conditions is discussed.
Psoriasis and Cardiovascular Disease
Compared with the general population, patients with severe psoriasis appear to be at an increased risk of major adverse cardiovascular events (MACE) after adjustment for traditional cardiovascular risk factors.3 Common pathophysiologic pathways between psoriasis and CVD may help explain the potentially increased CVD risk among patients with psoriasis.2 As a result, the association between psoriasis and cardiovascular events may be due to an enhanced baseline burden of subclinical coronary artery disease among patients with psoriasis compared with the general population.4 Lerman and colleagues performed a study that compared total coronary plaque burden, noncalcified coronary plaque burden (NCB), and high-risk plaque (HRP) prevalence among patients with psoriasis, patients with hyperlipidemia, and healthy controls.5 Compared with an older population of patients with greater traditional risk and hyperlipidemia, patients with psoriasis had higher NCB and similar HRP prevalence. In comparison with healthy controls, patients with psoriasis had elevated total coronary plaque burden, NCB, and HRP prevalence above traditional risk. Moreover, among patients with psoriasis followed for 1 year, improvement in disease severity was associated with improvement in total coronary plaque burden and NCB beyond traditional risk factors. Thus, regulation of inflammation through treatment of psoriasis may correspond with lower coronary artery disease risk in this patient population.5
Based on studies using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), psoriasis appears to be associated with vascular inflammation.6-8 A study by Youn and colleagues used FDG-PET/CT to demonstrate that mild psoriasis is associated with arterial and hepatic inflammation.6 Furthermore, severity of skin disease has been associated with vascular inflammation independent of cardiovascular risk factors.7 Egeberg and colleagues performed a study with FDG-PET/CT to evaluate the impact of psoriasis duration on vascular disease and cardiovascular events.8 For young patients with a high prevalence of cardiometabolic diseases and low cardiovascular risk by traditional risk scores, vascular inflammation by FDG-PET/CT was significantly associated with disease duration. Additionally, psoriasis duration was strongly associated with the risk of MACE.8 Thus, chronic inflammation observed with extended psoriasis disease duration may contribute to the development of vascular disease and MACE.
A nationwide study demonstrated an association between psoriasis and risk of aortic aneurysm (AA) beyond traditional cardiovascular risk factors.9
Khalid and colleagues demonstrated an association between psoriasis and risk of abdominal AA independent of cardiovascular risk factors.10 In both of these studies, the reported risk increased with psoriasis severity.9,10 On the other hand, a retrospective cohort study that evaluated 11,223 patients with psoriasis and 48,264 matched controls did not determine a significant association between psoriasis severity and AA.11 In addition, patients with psoriasis were not significantly more likely to develop an AA vs controls.11 Therefore, future studies would help determine the potential association of psoriasis and risk of AA.
The association of psoriasis and CVD may be attributed to a family history of CVD. Specifically, a family history of CVD may serve as an independent risk factor for the occurrence of MACEs in young adults with psoriasis.12 Egeberg and colleagues demonstrated that the associated impact of psoriasis and CVD risk was no longer apparent after accounting for a family history of CVD.12 Therefore, it is important to evaluate psoriasis patients for a family history of CVD when determining their cardiovascular risk assessment.
It is also important to determine the potential impact of psoriasis treatment on risk of CVD and MACE. A prospective study evaluated the effect of adalimumab (Humira) on endothelial function and arterial stiffness in patients with moderate to severe psoriasis.13 Patients with a history of cardiovascular events, diabetes mellitus, kidney disease, and hypertension were excluded from the study. By 6 months, adalimumab therapy was associated with a significant improvement in endothelial function and a significant reduction in carotid arterial stiffness in patients with moderate to severe psoriasis. Given the impact of endothelial dysfunction and arterial stiffness in the development of CVD, tumor necrosis factor-alpha (TNF-α) inhibitor therapy may offer a protective effect against the development of CVD for patients with psoriasis.
A retrospective study compared cardiovascular event risk among psoriasis patients receiving TNF-α inhibitors vs methotrexate.14 After 1 year, patients with psoriasis receiving TNF-α inhibitors experienced significantly fewer cardiovascular events compared with patients receiving methotrexate. Furthermore, the hazard ratio of cardiovascular event was significantly lower among patients receiving TNF-α inhibitors compared with methotrexate. In addition, cumulative exposure to TNF-αinhibitors was correlated with a lower risk of MACE.14 TNF-α inhibitor therapy has also been associated with improvement in left and right ventricular echocardiographic parameters in patients with psoriasis.15 Based on the data from these studies, TNF-α inhibitor therapy may help prevent the development of MACE in psoriasis patients.
Psoriasis and Mental Health Conditions
Compared with other dermatologic conditions, depression appears to be more common in patients with psoriasis.16 A population-based cohort study evaluated the risk of depression, suicidal ideation, and suicide attempt in patients with psoriasis, psoriatic arthritis, or ankylosing spondylitis.17 The risk of depression, yet not suicidal ideation or suicide attempt, was significantly higher in patients with psoriasis, psoriatic arthritis, and ankylosing spondylitis, respectively, compared with a general population cohort.
Egeberg and colleagues evaluated the association among patients with psoriasis and risk of self-harm, suicide attempts, and suicides.18 In this study, patients with severe psoriasis had a significantly increased risk of self-harm or suicide attempts, yet this finding was no longer significant after adjusting for presence of psoriatic arthritis. In addition, the risk of suicide was not increased in patients with mild or severe psoriasis and there was no increased risk of self-harm or suicide attempts in patients with mild psoriasis.
The prescribing information for brodalumab (Siliq) includes a warning regarding use in patients with suicidal ideation and behavior.19 Four completed suicides were reported in psoriasis clinical trials for brodalumab.20,21 However, a causal relationship has not been identified between suicidal behavior and brodalumab treatment.20
Notably, all 4 cases of completed suicides were in patients with underlying psychiatric disorders or stressors. Moreover, clinical trials on systemic treatments for psoriasis frequently incorporate specific exclusion criteria regarding history of psychiatric disorders or known suicidal risk factors. The brodalumab trials did not incorporate such criteria, thus patients with risk factors for suicidal ideation or behavior at baseline were allowed to enroll in these trials.20
Nonetheless, physicians should discuss the risks and benefits of treatment with brodalumab before use in patients with a history of depression or suicidal ideation or behavior.
Improvement of psoriasis may help improve symptoms of mental health conditions. A systematic review demonstrated that adalimumab, etanercept (Enbrel), and ustekinumab (Stelara) were associated with statistically significant reduction in depressive symptom scores among patients with moderate to severe psoriasis.22
Also for psoriasis patients monitored in the Psoriasis Longitudinal Assessment and Registry (PSOLAR), biologic agents were associated with a reduced incidence of depressive symptoms compared with systemic therapy.23
Conclusion
Psoriasis is associated with comorbid disease conditions that can significantly impact the quality of life for these patients. Studies using FDG-PET/CT have demonstrated an association between psoriasis and vascular inflammation. In addition, given that psoriasis duration has been associated with the risk of MACE, chronic inflammation may contribute to the development of vascular disease and MACE. Therefore, physicians should discuss with psoriasis patients the reported association of psoriasis with CVD and MACE.
It would also be beneficial to determine cardiovascular risk factors or a family history of CVD in patients with psoriasis. Considering that TNF-α inhibitor therapy may help prevent the development of MACE in psoriasis patients, cardiovascular risk factors should be taken into consideration when selecting treatment for patients with psoriasis.
Future studies that evaluate the potential impact of different classes of biologic agents for psoriasis on CVD would be beneficial.
Additionally, a diagnosis of psoriasis can significantly impact the quality of life for patients. Given the reported association between psoriasis with depression and suicidal ideation and behavior, it is important to discuss any history of psychiatric conditions with patients before initiating treatment for psoriasis, especially biologic agents.
Current evidence suggests that biologic agents may help reduce the incidence of depressive symptoms in patients with psoriasis. Further research should be conducted to help determine the potential effect of treatment of psoriasis on mental health conditions.
Ms Amin is a student at University of California, Riverside, School of Medicine in Riverside, CA.
Ms Lee is a student at University of Hawaii, John A. Burns School of Medicine in Honolulu, HI.
Dr Wu is director of dermatology research in the department of dermatology at Kaiser Permanente Los Angeles Medical Center in Los Angeles, CA.
Disclosure: Ms Amin and Ms Lee report no potential conflicts of interest. Dr Wu is an investigator for AbbVie, Amgen, Eli Lilly, Janssen, Novartis, and Regeneron.
References
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