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Psoriatic Disease Affects More Than Skin and Joints

The systemic inflammation that drives symptoms of psoriatic disease can raise your risk for other health problems.

If you have psoriasis or psoriatic arthritis (PsA), you may know that these diseases raise your risk for some other conditions as well. When one disease is triggered by or linked to another, the related condition is called a “comorbidity.” PsA, for example, is a common comorbidity of psoriasis, affecting up to 33 percent of people with psoriasis. [1]

According to the recent Joint AAD-NPF Guidelines of Care for the Management and Treatment of Psoriasis with Awareness and Attention to Comorbidities, other comorbidities for which psoriatic disease raises risk include: [1]

  • Cardiovascular disease (CVD)
  • Metabolic syndrome
  • Obesity
  • High blood pressure
  • High cholesterol
  • Insulin resistance
  • Mental health impacts, including depression and anxiety
  • Inflammatory bowel disease
  • Malignancy
  • Chronic kidney disease
  • Sleep apnea
  • Chronic obstructive pulmonary disease
  • Uveitis
  • Nonalcoholic fatty liver disease

Just how this elevated risk happens for each comorbidity isn’t fully understood. One underlying factor that likely plays an important role in triggering or contributing to development of many comorbidities, however, is systemic (bodywide) inflammation, explains dermatologist Paul S. Yamauchi, M.D., Ph.D.

“There’s a misperception among some that psoriasis is ‘just’ a cosmetic skin disease. But it’s actually a disorder that’s driven by an overly active immune system that can attack many areas of the body,” says Dr. Yamauchi, clinical assistant professor of dermatology at the David Geffen School of Medicine at the University of California, Los Angeles.

The weapons the immune system uses for this attack are inflammatory immune cells that normally defend the body from injury and infection.

“In psoriatic disease, inflammatory immune cells and the factors they release are overly produced,” says Dr. Yamauchi. “They spread through the body in the bloodstream, causing extensive inflammation that can lead to the development of comorbidities.”   

The Body’s Defenses Gone Rogue

Researcher Nehal N. Mehta, M.D., MSCE, is a senior investigator in the Section of Inflammation and Cardiometabolic Diseases at the National Heart, Lung, and Blood Institute (NHLBI) in Bethesda, Maryland. For the past six years, he and other scientists in his NHLBI lab have followed a group of 350 people with plaque psoriasis, looking into how chronic inflammation affects their risk of heart disease and metabolic conditions such as diabetes.

“Inflammation is simply a collection of immune cells trying to put out a fire, and that fire is usually an infection or some sort of virus,” says Dr. Mehta, a cardiologist and internist.

Setting off this inflammatory response, infiltration of immune cells and release of factors, is what the immune system evolved to do. In psoriatic disease, however, this primal defense has gone awry.

“In psoriasis, immune cells attack places they shouldn’t,” Dr. Mehta says. “They go to the skin and cause psoriatic plaques, but they can also go to the joints and cause psoriatic arthritis. When they infiltrate blood vessels of the heart, they inflame the cells that line blood vessels. These fill with immune cells that don’t belong there and cause inflammation. That’s the beginning of cardiovascular disease.”

Cardiovascular disease (CVD) is the comorbidity of psoriatic disease that scientists have linked most clearly to systemic inflammation, says rheumatologist Alexis Ogdie, M.D., MSCE, associate professor of medicine and epidemiology at the University of Pennsylvania in Philadelphia.

Eventually, Dr. Ogdie says, inflammation in blood vessels can lead to potentially fatal events like heart attack and stroke. Here’s how it may happen: “We have lipid, or fat, particles circulating in our blood all the time,” she says. “When you have inflammation, it’s probably easier for those particles to ‘lie down’ in key areas, like the aorta [the main artery that carries blood from your heart to other areas of the body].”

Once there, she says, the particles gather into atherosclerotic plaques. “These are fatty deposits that build up in the arteries and that can eventually break off, block the vessel, and cause a heart attack or stroke. Inflammation makes these plaques less stable, so that process happens more easily,” Dr. Ogdie says.  

When you understand your risk for CVD and other comorbidities of psoriatic disease, you can take steps to help prevent them. And if you’ve already developed problems, it’s important to identify them. That way, you and your doctor can treat the comorbidities to potentially stave off the most serious consequences.

The Impact of Psoriatic Disease Comorbidities

Psoriasis and PsA, and the comorbidities they lead to, can shorten your life. “People with psoriasis tend to live a few years less than those without the condition. This is particularly true for those with severe disease,” says Dr. Yamauchi. “It’s not the psoriasis that’s shortening life span, but the heart attacks, strokes and other comorbidities it can cause.”

Let’s look at how some common comorbidities of psoriatic disease can affect your life and health.

Cardiovascular Disease

CVD is by far the deadliest comorbidity of psoriatic disease, says Dr. Mehta, who notes that CVD risk begins early on in people with psoriasis.

“People with severe disease have a two-fold increase in the rate of first heart attack between the ages of 40 and 50, and a 44 percent increase in stroke compared to people without psoriasis,” he says.

People with mild or moderate disease have lower but still heightened risks.

“There’s a linear relationship between psoriasis severity and the amount of vascular inflammation and subsequent risk for events such as heart attack and stroke, but even those with mild psoriasis are at risk,” Dr. Mehta says.

The risks, he says, are driven by a combination of the harmful effects of systemic inflammation and the fact that people with psoriatic disease often have other CVD risk factors, such as obesity and high blood pressure. Many of these risk factors are at least partly driven by inflammation.

Obesity, Metabolic Syndrome and Diabetes

Obesity is the most common comorbid condition in people with both psoriasis and PsA, says Dr. Ogdie. It sets the stage for insulin resistance and type 2 diabetes.

Insulin resistance means the body is less able to move glucose, a type of sugar your body uses for energy, from the blood into cells. Glucose builds up in the blood and begins the processes that cause type 2 diabetes, another risk factor for heart disease and stroke.

“In addition, in people with psoriatic disease, obesity is linked to not responding well to treatment and to worse quality of life and function,” Dr. Ogdie says. “In people with psoriasis, it’s the single greatest risk factor for development of psoriatic arthritis. For those with psoriatic arthritis, obesity creates an extra burden for joints already affected by disease.”

The relationship among inflammation, obesity and related comorbid conditions is complicated, says Dr. Mehta.

“We think inflammation from the overactive immune system is getting into the adipose, or fat, tissue,” he says. “Our bodies have insulin receptors on adipose tissue, and when you have more fat, you’re more likely to become insulin resistant – and that’s prediabetes.”

Once you become insulin resistant, he says, other metabolic functions get unbalanced. “Your cholesterol goes up, your blood pressure goes up, and then you get diagnosed with something called the metabolic syndrome,” Dr. Mehta says. It’s a cluster of conditions that includes obesity (particularly excess fat around the waist), high blood pressure, and elevated cholesterol and blood sugar, all of which are risk factors for CVD.

Depression and Anxiety

People with psoriasis and PsA have high rates of depression and anxiety. Up to 62 percent of people with psoriasis and 20 percent of people with PsA have depression, according to some studies. [2] [3] The number of individuals with mental health concerns for psoriasis and PsA is likely even larger over a lifetime due to the impact of the condition and because often many do not seek treatment or care.

“Depression undermines quality of life, can make it harder to engage in a healthy lifestyle, and is a well-recognized trigger for psoriatic disease flares,” Dr. Yamauchi says.

Dr. Mehta adds that people who are more anxious and depressed have more heart disease, as well as more overactive immune systems. “Scientists in my lab are studying the effect of anxiety and depression on atherosclerosis and weight gain,” he says.

There’s some early evidence that systemic inflammation contributes to these mood disorders. Treating psoriasis with inflammation-lowering biologics, for example, often improves depression. [3] [4]

Dr. Ogdie suspects that inflammation may add to depression and anxiety in those with psoriatic disease but noted that many other factors likely play a role too. 

“Having visible skin disease can cause people to limit their social life and other activities,” she says. “When appropriate treatment clears their skin, people often feel better and are more physically active and socially engaged.”

Treating Psoriatic Disease Is Key

Untreated inflammation is dangerous, stresses Dr. Mehta.

“You need to treat psoriasis no matter what its severity,” he says. “If you’re ignoring it, your body is doing things on the inside that you don’t know about until later. People who don’t treat severe disease, for example, are growing coronary plaque at an alarmingly fast rate.”

Those with mild disease also need treatment, says Dr. Mehta. “It’s my personal opinion, and not yet part of the guidelines, but I think even one psoriatic plaque is too much,” he says.

There’s evidence that treatment with biologics reduces incidences of heart disease and heart attacks, says Dr. Mehta. [5] [6] [7] He, Dr. Yamauchi and Dr. Ogdie say they also suspect treatments that control systemic inflammation may lower the risk of other comorbidities of psoriasis, including PsA.

“We think it’s probably true that if you treat your psoriasis, you’re more likely to prevent psoriatic arthritis, delay its onset or reduce its severity if it does develop,” Dr. Ogdie says. “But we still don’t yet have the data to say that definitively.” 

Undertreatment of Psoriasis Is Common

Dr. Yamauchi points out that many patients with moderate-to-severe psoriasis are undertreated. This may be less true of people with PsA, who now often begin therapy with a biologic; however, diagnosis is often delayed, which is also an issue.

“In psoriasis, undertreatment may happen because patients or providers aren’t comfortable with biologics,” Dr. Yamauchi says. “Some think biologics are dangerous because there’s the perception that they suppress the immune system. I explain that these agents target immune system pathways that contribute to psoriasis and its comorbidities and that biologics normalize them to control psoriatic disease and inflammation.”   

Dr. Ogdie also emphasizes that treating psoriatic disease improves quality of life. “Many patients assume they’re fine, but until their inflammation is under control, they don’t know how good they can feel,” she says.

If your skin isn’t clear or nearly clear, or you continue to have joint symptoms or fatigue from PsA that interferes with your daily life, your systemic inflammation may not be well-controlled, says Dr. Yamauchi.

Talk with your health care provider about medications that can bring your psoriatic disease – and the inflammation associated with it – under control. 

Screen for and Treat Comorbidities

If you have psoriasis, your dermatologist or primary care physician should screen you regularly – at least once a year – for PsA, says Dr. Ogdie.

“The earlier you catch it and start treatment, the more likely you are to respond to therapy,” she says, noting that early treatment also potentially lowers the chances of permanent joint damage.

Dr. Ogdie advises people with psoriasis to understand the signs and symptoms of PsA. These include joint pain, swelling and tenderness – particularly in fingers and toes – and enthesitis, or inflammation at the points where tendons insert into bones. In addition, having psoriasis in the nails, scalp or skinfolds should raise suspicion for PsA, as should a family history of the disease. 

“If you have new symptoms, tell your doctor,” Dr. Ogdie says. “Remind them you have psoriasis and ask if these changes could mean you have psoriatic arthritis.”

Comorbidities such as CVD and metabolic syndrome can start developing at young ages in people with psoriasis and PsA, and sometimes health care providers aren’t looking for them, Dr. Mehta says.

“People with psoriasis should ask their doctors to screen them for heart and metabolic disease. They can do this by checking the three ‘Bs,’ which are blood pressure, body mass index (BMI) and blood levels of glucose and cholesterol,” he says. 

He notes that the risks of CVD in people with psoriatic disease were recognized by the American College of Cardiology and the American Heart Association in their 2019 guideline for CVD prevention, of which Dr. Mehta is a coauthor. [8] For the first time, the guideline recommends that health care providers consider using preventive medications – like cholesterol-lowering statin drugs – earlier in people with psoriatic disease, to help lower their CVD risk.

Lifestyle Changes Can Help Too

Eating a healthy diet that includes limiting alcohol consumption, quitting smoking, getting regular exercise, maintaining or reaching a normal weight, and managing stress with yoga, meditation or other mindbody practices may also help reduce inflammation and your risk of psoriatic disease comorbidities.

“Many of these comorbid conditions can be reversed by treating psoriasis and making the right lifestyle changes,” says Dr. Mehta, who emphasizes that taking small steps each day can lead to better heath.

“I tell my patients, ‘Each day, please do one thing for your psoriasis, one thing for your mind and one thing for your body,’” he says.  

References:

1.     Elmets CA, Leonardi CL, Davis DMR, Wu JJ, Hariharan V, Menter A, et al. Joint AAD-NPF Guidelines of Care for the Management and Treatment of Psoriasis with Awareness and Attention to Comorbidities. Published February 13, 2019.  J Am Acad Dermatol. Doi.org/10.1016/j.jaad.2018.11.058

2.     Takeshita J, Grewal S, Langan SM, Mehta NN, Ogdie A, Van Voorhees A, Gelfand JM. Psoriasis and Comorbid Disease Part I. Epidemiology. March 2017. J Am Acad Dermatol. Doi.org/10.1016/j.jaad.2016.07.064

3.     Mathew AJ, Chandran V. Depression in Psoriatic Arthritis: Dimensional Aspects and Link with Systemic Inflammation. Published April 22, 2020. Rheumatology and Therapy. Doi.org/10.1007/s40744-020-00207-6

4.     Kohler O, Krogh J, Mors O, Benros ME. Inflammation in Depression and the Potential for Anti-Inflammatory Treatment. Published 2017. Curr Neuropharmacol. Doi.org/10.2174/1570159x14666151208113700

5.     Joshi AA, Mehta NN. Biologic therapy to treat Psoriasis: A Dual Benefit? Published June 1, 2019. Eur Heart J. doi.org/10.1093/eurheartj/ehz349

6.     Ridker PM, Bavry AA, Bhatt DL Canakinumab Anti-Inflammatory Thrombosis Outcomes Study – CANTOS. Published September 28, 2020. J Am Col Card. acc.org/latest-in-cardiology/clinical-trials/2017/08/26/08/35/cantos

7.     Teklu M, Zhou W, Kapoor P, Playford MP, Gelfand JM, Mehta NN, et al. Metabolic Syndrome and its Factors are Associated with Non-Calcified Coronary Plaque Burden in Psoriasis: An Observational Cohort Study. Published December 28, 2020. J Am Acad Dermatol. Doi.org/10.1016/j.jaad.2020.12.044

8.     Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, Himmelfarb CD, Khera A, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Published March 2019. ahajournals.org/doi/full/10.1161/CIR.0000000000000677

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