Psoriasis Comes With Comorbidities

Like other inflammatory conditions, psoriasis often comes with concurrent systemic comorbidities, and physicians should be aware of symptoms that suggest associated conditions.

Comorbidities include metabolic syndrome, cardiovascular disease (CVD), and inflammatory bowel disease (IBD). The inflammatory cytokines elevated in psoriatic skin are also elevated in the bloodstream, and these same mediators underlie the development of internal lesions such as atherosclerotic plaques.

Other psoriasis-associated conditions include diabetes mellitus, obesity, osteoporosis, autoimmune eye disease, metabolic dysfunction-associated steatotic liver disease (formerly nonalcoholic fatty liver disease), fibromyalgia, and rheumatic disorders. Psoriasis may also slightly raise the risk of some malignancies, and concurrent psychological disorders such as depression and anxiety are common.

"We haven't ironed out the chicken-or-the-egg question as to whether the psoriasis or the comorbidities come first, but we do know comorbidities and psoriasis often run together," said dermatologist Chris Adigun, MD, of the Dermatology & Laser Center of Chapel Hill in North Carolina. "And when psoriasis is treated, markers of cardiovascular risk, for example, can improve."

Some treatments may adversely impact other risks. "Anti-tumor necrosis factor therapy may increase the risk of multiple sclerosis, and interleukin-17 therapy may raise the risk for IBD," said Adigun. "And all treatments that lower the immune response put patients at greater risk for infections, so we have to pre-screen them for latent TB and hepatitis, which may be reactivated during treatment."

Conversely, drugs used for other conditions may exacerbate psoriasis. "For example, beta blockers commonly used to treat hypertension can cause psoriasis to flare," she noted.

Adigun said it is important that primary care physicians know what medications their patients with psoriasis are on, and should watch for psoriasis-related joint problems.

"These patients are at high risk for psoriatic arthritis, so if a patient has concurrent joint pain in the absence of injury, psoriatic arthritis should be top of mind," she said. "It's also important to be aware how much this condition can adversely affect a patient's overall quality of life."

Nicholas Brownstone, MD, of Temple University Hospital in Philadelphia, agreed. "Depression and anxiety can be worse in psoriasis patients than cancer patients. And the unsightly plaques and itching in awkward places like the groin and buttocks can make daily life miserable."

Primary care doctors should monitor internal markers such as blood pressure and blood lipids in patients being treated for psoriasis, Brownstone stressed. In his view, this systemic inflammatory condition may be undertreated. "Some may consider it to be more of a cosmetic condition not requiring systemic therapy," he said. Moreover, the goals of treatment are not as clear as in blood pressure or cholesterol control. "A doctor might say to a patient, 'Hey, your skin looks pretty good. See you later.'"

Comorbidity Risks

Psoriatic arthritis

The most common comorbidity with psoriasis is psoriatic arthritis (PsA), which affects an estimated 6% to 41% of patients. In one study, the U.S. prevalence rate of PsA in psoriasis patients was 36%.

Because PsA is progressive and can cause irreversible joint damage, early diagnosis and treatment are critical.

Most cases start with the skin condition and within 7 to 10 years, joint pain symptoms start to develop, said rheumatologist Elaine Husni, MD, MPH, of the Cleveland Clinic.

"About 30% of patients with psoriasis will get PsA, but it can vary," she said. "We usually tell our psoriasis patients, 'For every 10 of you, about three or four will also develop PsA.' In 10% to 15%, the two could occur simultaneously, and in a likely smaller percentage, the joint symptoms could precede the psoriasis."

According to a Swedish population study, nearly two incident cases of PsA will occur across 100 psoriasis patients per year. The authors advised physicians to screen patients with newly diagnosed psoriasis for important risk factors for PsA, paying special attention to those receiving biologics or apremilast (Otezla), who likely have more severe skin disease and may have rheumatic involvement.

As for mutually effective treatments, Husni said, "we only have observational data so we are still not sure we can say definitively that treating psoriasis will prevent joint symptoms, but many of the drugs used to treat psoriasis will also treat PsA."

Cardiovascular disease

Cutaneous and systemic inflammation coupled with traditional CVD risk factors are thought to be behind an up to 50% greater risk of CVD, and this susceptibility increases with skin severity. Major society guidelines now advocate incorporating a psoriasis diagnosis into CVD risk prediction and prevention strategies, according to cardiologist Michael Garshick, MD, of NYU Langone Health in New York City.

In one meta-analysis of psoriasis patients, the risk ratio relative to the general population was 1.37 for CVD mortality, 3.04 for myocardial infarction (MI), and 1.59 for stroke.

The relative risk was highest in the younger, severe psoriasis population, with a relative risk for MI of 3.10 at 30 years. Severe disease was also linked to a 60% higher risk of stroke and a 40% higher risk of CVD death.

Another meta-analysis including more than 500,000 individuals reported up to 50% increased odds of CVD in those with psoriasis versus those without psoriasis.

Psoriasis was associated with an odds ratio of 1.5 for ischemic heart disease, 1.5 for peripheral vascular disease, 1.10 for atherosclerosis, 1.9 for diabetes, 1.8 for hypertension, and 1.5 for dyslipidemia. Other increased odds ratios were observed for obesity and metabolic syndrome, but not cerebrovascular disease.

Cancer

Psoriasis is also linked to cancer risk. One meta-analysis reported an increase in cancer incidence and mortality over a range of site-specific malignancies, especially with severe disease.

All severities of psoriasis carried a relative risk of 1.18, and associations were found especially for the following cancer types: oral (2.80), esophageal (2.05), liver (1.83), laryngeal (1.79), keratinocyte (1.71), and kidney (1.58). Smaller associated risks emerged for other malignancies as well.

Psychological disorders

The burden of psychiatric comorbidity is elevated in psoriasis patients and this may be explained by shared inflammatory pathways, according to a recent overview, which showed that affected patients were 1.5 times more likely to have depressive symptoms and experienced a higher prevalence of anxiety (20-50%) than their unaffected counterparts.

Schizophrenia and suicidal ideation were also observed to be more prevalent than in the general population, at 2.82% and 12.7%, respectively. Pro-inflammatory markers, which play a key role in the pathophysiology of psoriasis, are also elevated in people with depression and anxiety.

Inflammatory bowel disease

A meta-analysis found that those with psoriasis had up to a 2.53-fold increased odds of Crohn's disease, and up to a 1.75-fold increased odds of ulcerative colitis. The authors noted that patients with psoriasis have been found to have a similar decrease in the diversity and abundance of gut microbiota as patients with IBD. Gastroenterology consultation is in order for psoriasis patients with bowel symptoms.

The thing to bear in mind is that the inflammatory pathways that underlie psoriasis leave patients vulnerable to the above and other conditions, and physicians should be watchful for comorbidities.

Future research should shed more light on the mutual etiologies and risk factors of comorbidities.

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