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 including metabolic syndrome (type 2 diabetes, hypertension, obesity and dyslipidaemia), cardiovascular diseases, lymphoma, anxiety and depression (Boehncke & Boehncke, 2014). These disorders may be due to underlying systemic inflammatory processes and contribute to morbidity and mortality, disease burden and reduced QoL (Cohen et al., 2012; Boehncke et al., 2011; Boehncke & Boehncke, 2014; Edson-Heredia et al., 2015a). In fact, 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 (Figure 7) (Boehncke, 2018). However, could cardiometabolic comorbidities be due to other factors such as smoking or obesity, rather than psoriasis? A study of the Danish national birth cohort investigated this question by interviewing 83,823 pregnant women, identifying 2,435 with psoriasis (2.9%), and conducting an 11-year follow-up questionnaire answered by 38,903 women, of which 1,047 had psoriasis, and 52 were considered to have severe psoriasis. 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). Strong associations between severe psoriasis and hypercholesterolaemia (adjusted OR 2.71, 95% CI 1.41–6.41) and metabolic syndrome (adjusted OR 4.63, 95% CI 1.38–15.47) were also observed. 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., 2018).
Patients with severe disease are more affected by comorbid conditions than those with milder disease, and patients with Psoriatic Arthritis (PsA) are more affected by comorbidities than psoriasis patients without PsA (Edson-Heredia et al., 2015a; Edson-Heredia et al., 2015b). A real-world survey of comorbidities in 94,302 US patients with psoriatic arthritis, the prevalence and incidence rates of the most common comorbidities were 47.5% and 35.0% for hyperlipidaemia, respectively; 47.3% and 31.3% for hypertension; 21.2% and 15.4% for depression; 20.2% and 13.5% for type 2 diabetes; and 16.6% and 12.4% for fibromyalgia. It was also identified that patients with PsA had notably higher incidence rates of uveitis, fibromyalgia, osteoporosis, Crohn’s disease and non-alcoholic liver disease compared to patients with psoriasis (Shah et al., 2017).
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 (including kidney disease, liver disease, chronic lower respiratory disease, severe infection and neurological disease) are markedly elevated in psoriasis (Svedbom et al., 2015). 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).
Although it has previously been suggested that psoriasis is a risk factor for depression, and that depression may trigger/exacerbate psoriasis, these relationships have until recently remained poorly understood. Results from the National Health and Nutrition Examination Survey (2009–2012) indicate that psoriasis is independently associated with major depression regardless of severity and led the authors to conclude that all patients with psoriasis, regardless of severity, may be at risk for major depression (Cohen et al., 2016).
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).
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., 2018).