Comorbidities

A number of conditions are associated with psoriasis, so effective management must take these into consideration. Psoriasis disease-related comorbidities include hypertension and cardiovascular diseases, obesity, type 2 diabetes, non-alcoholic fatty liver disease, anxiety, depression, and inflammatory bowel disease.

Are comorbidities actually part of the systemic disease? Find out more from Professor Ulrich Mrowietz.

This section of the Psoriasis Learning Zone will provide an overview of some of the comorbidities associated with psoriasis, their impact on mortality and address the link between psoriatic arthritis and comorbidities.

Incidence and impact of psoriasis comorbidities 

Psoriasis is ‘more than skin deep’ and shares systemic manifestations with other chronic inflammatory diseases such as Crohn’s disease (Benson et al., 2015).

A number of conditions are associated with psoriasis and are hypothesised to be the result of chronic inflammation associated with the skin disease (Takeshita et al., 2017).  Patients with severe disease are more affected by comorbid conditions than those with milder disease (Edson-Heredia et al., 2015a; 2015b).

It is believed that 73% of psoriasis patients have at least one comorbidity (Machado-Pinto et al., 2016).

Such comorbidities include (Boehncke & Boehncke, 2014):

• metabolic syndrome (type 2 diabetes, hypertension, obesity and dyslipidaemia)
• cardiovascular diseases
• lymphoma
• anxiety and depression 

Other emerging comorbidities of psoriasis include chronic obstructive pulmonary disease, peptic ulcer disease, sexual dysfunction, and obstructive sleep apnea (Takeshita et al., 2017). 

Find out the importance of considering vascular inflammation as an important comorbidity in psoriasis from Professor Ulrich Mrowietz.

Psoriatic arthritis and comorbidities

Patients with Psoriatic Arthritis (PsA) are more affected by comorbidities than psoriasis patients without PsA (Edson-Heredia et al., 2015a; 2015b). 

Find out the incidence of psoriatic arthritis in Professor Andrew Blauvelt’s patients. 

A real-world survey of comorbidities in 94,302 US patients with psoriatic arthritis revealed the prevalence and incidence rates of the most common comorbidities, listed in Table 4.

Table 4. Prevalence and incidence of common comorbidities in patients with psoriatic arthritis (Shah et al., 2017).

It was also identified that compared to patients with psoriasis, patients with PsA had notably higher incidence rates of uveitis, fibromyalgia, osteoporosis, Crohn’s disease and non-alcoholic liver disease (Shah et al., 2017).

Psoriasis comorbidities and mortality 

Patients with psoriasis have a 5-year shorter life expectancy, than those without psoriasis most frequently due to cardiovascular disease (CVD) (Siegel et al., 2013).

Comorbidities are associated with increased mortality in patients with both mild and severe psoriasis and whilst cardiovascular disease is the primary factor contributing to excess mortality, other causes of death are markedly elevated in psoriasis, including (Svedbom et al., 2015):

• kidney disease
• liver disease
• chronic lower respiratory disease
• severe infection 
• neurological diseases

Psoriasis is associated with a chronic inflammatory state. As a result, elevated levels of CRP and other inflammatory cytokines play a role increasing the risk of CVD (Siegel et al., 2013).

Find out more about psoriasis as a systemic inflammatory condition from Professor Ulrich Mrowietz.

The impact of psoriasis comorbidities on patient-related outcomes

As well as increasing mortality risk, psoriasis comorbidities contribute to morbidity, disease burden and reduced quality of life (QoL) (Cohen et al., 2012; Boehncke et al., 2011; Boehncke & Boehncke, 2014; Edson-Heredia et al., 2015a). 

Data from 3,821 patients with moderate-to-severe psoriasis in the multinational Growth from Knowledge Disease Atlas Global Real-World Evidence programme revealed that patients with additional comorbidities were significantly more likely to (Griffiths et al., 2018a):

• experience skin pain
• have a lower QoL 
• experience greater work impairment
• utilise medical resources more often (except patients with comorbid obesity and type 2 diabetes)

The study also highlighted that patients suffering from itch and those whose disease affects visible and sensitive areas of the body had greater impairment of their QoL than those without these aspects (Griffiths et al., 2018).

Cardiometabolic comorbidities

Psoriasis has now been identified as an independent risk factor for cardiovascular disease, possibly due to the systemic inflammation that drives psoriasis, and has led to the concept of the psoriatic march (see Figure) (Boehncke, 2018). 

Figure 8. Psoriasis and cardiovascular disease: the psoriatic march (Boehncke, 2018).
CRP, c-reactive protein; HOMA-IR, homeostatic model assessment of insulin resistance; VEGF, vascular endothelial growth factor.

Cardiometabolic comorbidities, psoriasis and other risk factors

Could other factors, such as smoking or obesity, be responsible for cardiometabolic comorbidities in psoriasis rather than psoriasis itself?  A Danish study followed 2,435 pregnant women with psoriasis and 81,388 controls for 11-years. Self-reported hypercholesterolaemia at the 11-year follow-up was significantly associated with psoriasis after adjusting for confounders (adjusted OR 1.31, 95% CI 1.01–1.70) (Blegvad et al., 2019).

Strong associations were found between severe psoriasis and:

• hypercholesterolaemia (adjusted OR 2.71, 95% CI 1.41–6.41) 
• metabolic syndrome (adjusted OR 4.63, 95% CI 1.38–15.47) 

However, hypertension, thrombosis, type 2 diabetes, and metabolic syndrome didn’t show significant associations with psoriasis.

Smoking, obesity and age were all linked with comorbidities, with the effect of age being the most important confounder for hypertension, followed by smoking status. In addition, an increased risk of type 2 diabetes was found in overweight women with psoriasis (adjusted HR 4.50, 95% CI 1.12–18.07) (Blegvad et al., 2019).

Major Adverse Cardiovascular Events (MACE)

In a cohort study of severe psoriasis patients in the UK, Mehta et al. found a 6.2% attributable risk of severe psoriasis on MACE over a 10-year period (Mehta et al., 2011). Furthermore, in a study to determine the impact of psoriasis on the Framingham Risk Score (FRS), adding psoriasis to the FRS resulted in reclassification of most patients to a higher CV risk category (Mehta et al., 2012).

Inflammatory diseases

Inflammatory bowel disease 

Inflammatory diseases have often been reported as comorbid conditions of psoriasis, including inflammatory bowel disease (IBD). The link between the two conditions may not be so surprising due to the shared nature of relapsing inflammation; previous studies have demonstrated that the two conditions share genetic and immunologic features, including chromosomal locus 6p21 and the IL23R and IL12B genes (Cargill et al., 2007; Capon et al., 2007; Cho, 2008; Skroza et al., 2013), and an increase in levels of IL-17 (Fujino et al., 2003; Maddur et al., 2012; Chiricozzi & Krueger, 2013).

A meta-analysis of 5 case-control or cross-sectional studies and 4 cohort studies including a total of 7,794,087 participants found a significant association between psoriasis and Crohn’s disease (pooled OR 1.70, 95% CI 1.20–2.40) and ulcerative colitis (pooled OR 1.75, 95% CI 1.49–2.05) (Fu et al., 2018).

The gut microbiome is relevant in both psoriasis and IBD. Many biological therapies such as anti-tumour necrosis factor (TNF) and anti-interleukin 23 are effective in both conditions, highlighting common immunological mechanisms (Cottone et al, 2019).

Hepatic disease

Non-alcoholic fatty liver disease (NAFLD) is often found in patients with metabolic syndrome (Elmets et al., 2019a).

Confirmation that psoriasis patients are at a higher risk of developing non-alcoholic fatty liver disease (NAFLD) was provided by a study in which the prevalence of psoriasis was twice as high in patients with NAFLD compared to healthy controls (65% vs. 35%, p<0.01) (Abedini et al., 2015). A study of 333 patients with severe psoriasis found that 14.1% showed advanced liver fibrosis on transient elastography. Patients with central obesity, insulin resistance and active psoriasis were at the highest risk of fibrosis. Moreover, inflammation generally and the IL-17 pathway in particular seem to drive the development and progression of liver fibrosis (Maybury et al, 2019).

Peridontitis

Another inflammatory condition that could occur as a comorbidity of psoriasis is periodontitis; the infectious-inflammatory condition causes destruction of dental supporting structures and affects more the 50% of adults worldwide. A higher prevalence of periodontitis among patients with psoriasis was confirmed in a case-control study finding 46.1% of patients with psoriasis had periodontitis, compared to 33.1% of controls. Interestingly, the prevalence of periodontitis significantly increased with severity of psoriasis (mild 44.4%, moderate 46.3%, severe 47.1%) (Mendes et al., 2019).

Malignancy

Compared with unaffected patients, psoriasis patients in Taiwan aged 0-79 years had a greater overall risk for malignancy than non-psoriatic controls (Chen et al., 2011).

In patients with a first-time diagnosis of psoriasis, the following cancer types were significantly elevated relative to nonpsoriatic patients (Chen et al., 2011):

• skin cancer (HR = 3.10, 95% CI 1.24–7.71),
• malignancies of the oropharynx and larynx (HR = 2.16, 95% CI 1.17–3.96),
• digestive tract malignancies (HR = 2.02, 95% CI 1.33–3.07)
• malignancies of the colorectum (HR = 1.70, 95% CI 1.01–2.86)

In an observational study using the UK General Practice Research Database, among 67,761 patients, 1,703 patients had incident cancer; of whom 54% had a history of psoriasis. Patients with psoriasis had a higher incidence rate of lymphohematopoietic malignancies and pancreatic cancer relative to unaffected controls (Brauchli et al., 2009).

Depression and anxiety

Investigators conducting the National Health and Nutrition Examination Survey (2009–2012) concluded that all patients with psoriasis, regardless of severity, may be at risk for major depression (Cohen et al., 2016). Furthermore, depression is an independent risk factor for incident ischaemic heart disease and cerebrovascular disease in patients with psoriasis (Hu et al., 2019). 

Psoriasis-specific therapy is recommended by The American Academy of Dermatology to improve psoriasis-associated anxiety and depression in individuals with psoriasis (Elmets et al., 2019a).

Implications for patient management

Presence and risk of comorbidities in psoriasis patients can have implications for clinical management. For example, obesity's association with dyslipidaemia, hypertension, and increased liver enzymes could be worsened by acitretin, cyclosporine and methotrexate, respectively. Therefore, therapeutic targets who have positive effects on both psoriasis and mechanisms regulating body weight homeostasis may be of great importance to such patients (Chiricozzi et al., 2019). Another example is in the case of patients with or at risk of renal disease, which should be considered when over-the-counter and/or systemic medications are used in psoriatic patients (Elmets et al., 2019a).

In addition, screening patients with psoriasis for comorbidites may constitute an important part of management. For example, patients with moderate to severe psoriasis should be screened and aggressively treated for CVD risk factors (Siegel et al., 2013).

Find out from Professor Mrowietz the importance of comprehensive screening for patients with psoriasis.

To help health care professionals address these challenges, new guidelines have been introduced in response to important clinical questions regarding:

• Undertaking risk assessments
• Screening requirements
• Collaborative working and timely referral to other care providers as necessary
• Patient education around comorbidities
• Psoriasis management and treatment for those with or at risk of comorbidities
• Treatment of comorbidities

To view these guidelines, follow this link.

Despite differences in the mechanism of action, use of immunobiologicals reduces inflammatory burden observed in psoriasis which, in turn, appears to relate to the occurrence of different comorbidities associated with these diseases. Thus, use of immunobiologicals could inhibit their onset or aggravation. However, like any other medication, adverse events that negatively interfere with these comorbidities should also be taken into consideration (de Carvalho et al., 2017).

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