Psoriasis is an immune-mediated chronic inflammatory skin disease that affects approximately 2%-4% of adults in Western countries. Over the past decade, discovery of the pathogenic pathways in psoriasis has led to a greater understanding of the role psoriasis plays in systemic inflammation and associated comorbidities. Several recent studies have shown that patients with psoriasis have higher rates of comorbid conditions, and for many of these comorbidities, the rates increase as psoriasis disease severity increases. Psoriasis-associated comorbidities can have a significant impact on a patient’s quality of life and overall life expectancy. Clinicians should be aware of these co-existing conditions for screening and co-management with adjunctive systemic medications.

Here are five things to know about psoriasis and associated comorbidities.

1. Psoriatic arthritis (PsA) is often unrecognized in patients with psoriasis but co-occurs in up to one third of patients.

PsA is a heterogeneous chronic, inflammatory disease of the joints that generally starts around 10 years after onset of psoriasis but can also develop first or independently of skin disease. Clinical domains of PsA include peripheral arthritis, axial disease, enthesitis, and dactylitis. Owing to delays in diagnosis, patients may develop structural damage to cartilage and bone leading to loss of physical function and reduced quality of life.

Annual arthritis screening is recommended in adults with psoriasis. Although several validated screening tools exist, the user-friendly PSA, an acronym mnemonic tool developed by experts, can be quickly applied in clinic to assess for:

• Pain in the joints;
• Stiffness for more than 30 minutes after a period of inactivity and/or sausage digits (dactylitis); and
• Axial spine involvement/back pain associated with stiffness and pain that improved with activity. 

Patients with psoriasis or with a strong family history of psoriasis who score ≥ 2 on the PSA tool are more likely to have PsA. 

In addition, the five-question, validated Psoriasis Epidemiology Screening Tool can be completed by patients to screen for PsA.

For patients with psoriasis who have symptoms of PsA, it is important that treatments address both skin and joint disease. In 2018, the American College of Rheumatology and the National Psoriasis Foundation created a broad guideline for the treatment of PsA. The guideline recommends tumor necrosis factor (TNF) inhibitors as first-line therapy for treatment-naive patients. However, conditional recommendations note that interleukin (IL)-17 inhibitors may be used as first-line therapy in patients with severe psoriasis or in whom TNF inhibitors are contraindicated (eg, those with congestive heart failure). Studies have shown that TNF inhibitors and IL-17 inhibitors improve PsA symptoms and inhibit radiographic disease progression. Research is ongoing to understand the long-term radiographic outcomes of newer biologics. 

2. Depression is common and often underdiagnosed in adults with psoriasis. 

Patients with psoriasis have been found to have higher rates of depression and anxiety. As in other comorbidities, the risk of developing depression increases with disease severity, and patients with moderate to severe psoriasis at greater risk for depression than are patients with mild psoriasis. The US Preventive Services Task Force recommends (Grade B) screening for depression in the general adult population. Additionally, the American Academy of Dermatology-National Psoriasis Foundation (AAD-NPF) guidelines of care for psoriasis state that addressing mental health is an essential part of comprehensive care for patients with psoriasis, but depression screening rates in the dermatologic and primary care setting remain low. Validated screening instruments such as the Patient Health Questionnaire (PHQ)-9 and PHQ-2 can be used in the dermatology clinic to help identify more patients with depression and refer them for the appropriate mental health care.

3. Patients with psoriasis have a higher prevalence of metabolic syndrome. 

Metabolic syndrome is a cluster of classic cardiovascular (CV) risk factors including central obesity, dyslipidemia, glucose intolerance, and hypertension, and it is identified as a predictor of atherosclerotic cardiovascular disease (CVD) and major adverse cardiovascular events (MACEs). Patients with psoriasis have approximately a twofold increased risk of developing metabolic syndrome compared with the general population. Some studies have demonstrated a link between severity of psoriasis and risk of developing metabolic syndrome. This is probably due to the interplay of a similar genetic predisposition, cytokine profiles, and environmental exposures among these conditions. 

Since most signs and symptoms of metabolic syndrome are not obvious, and early diagnosis and treatment can significantly impact longevity and health-related quality of life, clinicians should educate patients on the connection between psoriasis and metabolic syndrome. The AAD-NPF guidelines of care recommend that in addition to being encouraged to adopt healthy lifestyle modifications, patients with psoriasis should be screened and referred for treatment of abnormalities in blood pressure, blood glucose, A1c, and lipid levels.

4. Psoriasis, an independent risk factor for myocardial infarction (MI), has been recognized as a risk-enhancing factor for CVD by the American Heart Association. 

In addition to the strong association between psoriasis and CV risk factors, psoriasis has been shown to be an independent risk factor for MI and stroke. A meta-analysis of nine observational studies found an increased risk for MI (relative risk [RR], 1.70; 95% CI, 1.32-2.18) in patients with psoriasis (particularly those with severe disease), with several studies adjusting for traditional risk factors including social demographics, obesity, smoking, diabetes, hypertension, hyperlipidemia, and history of MI. The analysis also estimated that severe psoriasis was associated with significantly increased risk for CV mortality (RR, 1.39; 95% CI, 1.11-1.74). Owing to increased awareness of this link, the guidelines on management of blood cholesterol by the American College of Cardiology/American Heart Association include psoriasis as a risk-enhancing factor for atherosclerotic CVD.

Given the strong relationship between psoriasis and CVD, the effect of psoriasis treatment on markers of CVD and subsequent CV events has been explored. A retrospective study looking at claims data of almost 10,000 psoriasis patients showed a statistically significant lower number of CV events in patients on TNF inhibitors (1.45%) compared with patients on methotrexate (4.09%) by 12 months (P < .01). In this study, every 6 months of cumulative exposure to TNF inhibitors were associated with an 11% CV event risk reduction (P = .02) over a median of 24 months of follow-up. 

In randomized controlled trials (RCTs), however, the treatment effect of TNF inhibitors on MACEs is less clear. Two well-powered RCTs, one by Bissonnette and colleagues and the other by Mehta and colleagues, assessed the impact of TNF inhibitors on vascular inflammation as a surrogate for MACEs. Both RCTs did not demonstrate an effect of TNF inhibitors on aortic vascular inflammation but did show improvement in some inflammatory CV risk biomarkers such as C-reactive protein and glycoprotein acetylation at 52 weeks. Longer-term trials may be needed to understand the effects of psoriasis treatments on CVD.

5. Although there is an association between psoriasis and inflammatory bowel disease, several treatment nuances exist. 

Increased rates of Crohn’s disease and ulcerative colitis are seen in psoriasis, probably owing to a shared genetic susceptibility and inflammatory profile. Patients with psoriasis should be educated on this connection and monitored for new gastrointestinal symptoms that may warrant further evaluation.

There is an overlap in biologic therapies between psoriasis and inflammatory bowel disease (IBD), but several nuances in treatment exist. TNF inhibitors, particularly adalimumab and infliximab, are first-line biologic therapies for IBD. These TNF inhibitors can also be used to treat psoriasis but also rarely cause paradoxical psoriasiform eruptions. Some psoriasiform eruptions can be managed with topical steroids as a “treat through” strategy, but treatment may require discontinuation of the TNF inhibitor and transition to another biologic medication, such as ustekinumab (IL-12/23 inhibitor) or risankizumab (IL-23 inhibitor). For patients with psoriasis and a personal or family history of IBD, IL-17 inhibitors should be avoided because these agents have been associated with induction or exacerbation of IBD.