Severe Psoriasis Linked to Higher Risk of Death From Liver, Esophageal, Pancreatic Cancers

Patients with severe psoriasis have an increased risk of dying from liver, esophageal, and pancreatic cancers, and people with psoriasis have an overall increased risk of a variety of other cancers, according to a meta-analysis and review published Wednesday in JAMA Dermatology.

The authors said the findings indicate that dermatologists and psoriasis guidelines should pay more attention to the notion of cancer as a comorbidity of psoriasis, in the same way that cardiovascular, psoriatic arthritis, and other diseases are viewed.

This is the first meta-analysis of the mortality risk of cancer for these patients; the study also attempted to stratify the risk by psoriasis severity. While psoriasis severity is typically measured through Psoriasis Area and Severity Index improvement scores, obtaining that information was not possible in this review of 58 unique observational studies from 6 databases. Instead, the researchers used other measures as proxies, such as types of treatment and whether or not the patient had been hospitalized.

Of the 58 studies, 50 reported on cancer incidence and 15 on cancer mortality, with 7 overlapping both categories. Quality varied for both the incidence and the mortality studies, the researchers said. They separately analyzed study estimates restricted to people with severe psoriasis and those including people with all psoriasis severities. Systemic treatment for psoriasis (including methotrexate sodium, cyclosporin, acitretin, etretinate, phototherapy, or biologics) or hospitalization for psoriasis was included in the severe category.

Studies were also grouped into 2 categories according to the level of adjustment for potential confounding. Level 1 studies adjusted for age and sex; level 2 studies adjusted for age, sex, and at least 1 other confounding factor, such as smoking status, alcohol consumption, or body mass index.

The outcome and measures of the study were the pooled relative risk (RR) estimates for cancer incidence and cancer mortality comparing people with and without psoriasis; results showed that severe psoriasis (RR, 1.22; 95% CI, 1.08-1.39 [9 studies]) and all severities of psoriasis (RR, 1.18; 95% CI, 1.06-1.31 [7 studies]) were associated with an increased risk of cancer.

Overall cancer mortality risk was highest in patients with severe psoriasis (RR, 1.22; 95% CI, 1.08-1.38 [4 studies]), specifically:

• Liver cancer (RR, 1.43; 95% CI, 1.09-1.88)
• Esophageal cancer (RR, 2.53; 95% CI, 1.87-3.41)
• Pancreatic cancer (RR, 1.31; 95% CI, 1.02-1.69)

In addition, psoriasis was linked to colon, colorectal, kidney, laryngeal, lymphoma, non-Hodgkin lymphoma, oral cavity, and keratinocyte cancers.

Chronic inflammation has previously been linked to increased cancer risk, and the idea that psoriasis is also linked to cancer stems from inflammation’s role in the development of psoriasis. In addition, psoriasis treatments, including the use immune system modifiers, may also increase the risk of developing cancer.

Complicating matters further, smoking, excessive alcohol consumption and obesity are both risks for cancer and have also been reported to occur more often in patients with psoriasis, which causes a good deal of psychosocial stress as well as physical discomfort, noted lead author Alex Trafford, MSc, a PhD candidate at the University of Manchester, in an email to The American Journal of Managed Care^®.

“Obviously a number of studies have suggested elevated levels of smoking, alcohol consumption, and obesity in people with psoriasis—given the association between these lifestyle factors and cancer, this complicates our understanding of the mechanisms that underlie the link between psoriasis and cancer,” he said.

Simply adjusting for these factors “may be an oversimplification of the issue. For example, consider a study that finds an association between psoriasis and cancer, but the association is lost when these lifestyle factors are taken into account (adjusted for). Although the adjusted results may suggest there is no association, another message that could be taken from the results is that cancer risk in people with psoriasis is influenced by modifiable lifestyle factors that could be improved through appropriate care.”

Besides giving cancer more focus in psoriasis treatment guidelines, Stafford said “these results give further support to the notion of a holistic approach to psoriasis care, including lifestyle behavior change.”

In addition, further studies with longer follow-up times are needed to fully understand any possible link between certain psoriasis treatments, such as methotrexate, cyclosporine, phototherapy, and biologics, with cancer, he said. In addition, Stafford said the association between the 2 diseases is still not entirely clear, "evidenced not least by the heterogeneity, so further study is required. Studies considering the mechanisms underlying the association would also be beneficial."

Reference

Trafford AM, Parisi R, Kontopantelis E, Griffiths CEM, Ashcroft DM. Association of psoriasis with the risk of developing or dying of cancer: A systematic review and meta-analysis [published online October 16, 2019]. JAMA Dermatol. doi:10.1001/jamadermatol.2019.3056.