Inflammation to blame for psoriatic disease

| Melissa Leavitt

The list of treatments that Marsha Hall had tried was dizzying. From biologics to methotrexate to phototherapy, she would sometimes see results at first, but nothing delivered lasting relief from her psoriasis and psoriatic arthritis.

"I went on this roller coaster, on, off, on, off," she said.

As Hall stopped and started different therapies, her condition continued to worsen. At one point, she said, she had so much psoriasis coverage on her legs and feet that she had trouble putting shoes on. On top of that, she was carrying too much weight, had developed high blood pressure and had other cardiovascular problems — all related conditions, or comorbidities, that are frequently seen in patients with psoriatic disease.

"I weighed 260 pounds," said Hall, now 60.

Hall's dermatologist helped her understand that many of her health problems could be traced to one thing: inflammation.

Inflammation causes the red, flaky plaques seen in psoriasis and the joint pain of psoriatic arthritis. Research is now showing that inflammation is also tied to a host of other conditions, such as diabetes, heart disease and depression. On the surface, these conditions don't seem to be tied to psoriatic disease, but in fact, they're some of the most common psoriatic disease comorbidities.

"Immune cells are like a security officer going around the facility with a torch at night, checking to see if everything is OK."
Dr. Iain McInnes, University of Glasgow

"A lot of the symptoms that have been making me not feel well over the years have been related to my psoriasis, and I just didn't know it," Hall said.


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    Some inflammatory proteins involved in psoriatic disease, like tumor necrosis factor-alpha (TNF-alpha), can also be increased in people with depression. That might explain why people with psoriasis and psoriatic arthritis can have higher rates of depression than the general population.

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    People with psoriasis and psoriatic arthritis can have higher rates of hearing loss. One explanation could be that psoriatic disease and some forms of hearing loss can both be caused by an overactive immune system.

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    Inflammatory proteins that start in psoriasis plaques can travel through the bloodstream to the liver, changing the way the liver processes glucose and cholesterol. These changes can increase your risk for conditions like metabolic syndrome and type 2 diabetes.

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    Everybody has hormones inside their fat that play an important role in metabolism. But in people with psoriatic disease, fat hormones can function differently, changing your metabolism in a way that can make you susceptible to developing diabetes.

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    Skin inflammation in psoriasis leads to the formation of itchy red plaques. Underneath the plaque, new blood vessels form to carry immune cells and inflammatory proteins throughout the body.

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    People with psoriatic disease may be at increased risk for developing uveitis, an inflammatory eye disorder that can lead to vision loss.

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    Just like psoriasis and psoriatic arthritis, gum disease can also be the result of an overactive immune system.

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    In people with psoriatic disease, immune cells and inflammatory proteins traveling throughout the body can damage the blood vessels, making it easier for vessels to get clogged with cholesterol and other substances. Clogged arteries, known as atherosclerosis, can lead to heart attacks or stroke.

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    In people with psoriatic disease, immune cells and inflammatory proteins traveling throughout the body can damage the blood vessels, making it easier for vessels to get clogged with cholesterol and other substances. Clogged arteries, known as atherosclerosis, can lead to heart attacks or stroke.

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    Some of the same inflammatory proteins that are involved in psoriatic disease are also involved in the development of osteoporosis. Research shows that people with psoriatic disease have higher rates of osteopenia, an early form of osteoporosis.


When a good thing goes bad

Inflammation starts as part of a body's normal healing process, said Dr. Nehal Mehta, a cardiologist at the National Institutes of Health and a member of the National Psoriasis Foundation Medical Board who researches inflammation and psoriatic disease.

When you cut yourself, you likely experience acute, or short-term, inflammation around the wound for about week. During that time, blood vessels near the cut grow, allowing more blood to the area, and immune cells, known as white blood cells, flood in to repair the wound. That's why the skin around the cut is red and puffy. And usually, that's it, Mehta said — unless you have an inflammatory disease such as psoriasis.

"In a psoriatic patient, that acute inflammation doesn't have a stopping point," Mehta said.

Eventually, a white blood cell called a T cell gets into the mix, turning acute inflammation into chronic inflammation, Mehta said. T cells secrete proteins called cytokines, which leads to even more inflammation, like that seen in psoriatic disease.

"The white blood cells are the master controllers of the immune response, and the proteins that they release are the foot soldiers," said Dr. Iain McInnes, a rheumatologist at the University of Glasgow in Scotland.

It doesn't end there. Beneath the surface of a psoriasis plaque, a number of processes are being set in motion to allow inflammation to spread throughout the body.

"The psoriatic plaque knows to create blood vessels," Mehta said.

The plaque sends cytokines into these new vessels, which carry them in the blood throughout the body. And in people with psoriatic arthritis, these immune cells end up in the joints.

Immune cells are constantly moving through the body, always vigilant for a threat — which is what they're supposed to do to defend the body against infection. But sometimes they stay too long in a certain area, and that can cause problems.

"Immune cells are like a security officer going around the facility with a torch at night, checking to see if everything is OK," McInnes said. "If everything is not OK, they'll stop and phone some friends — immune cells that migrate out of the bloodstream and into the tissue. It may be that more cells than are needed will turn up."

McInnes said scientists don't fully understand what tells the immune cells to gather in the joint tissue or why sometimes too many show up. But one thing's for certain — if immune cells overstay their welcome, it can lead to psoriatic arthritis.

"Then they start to cause mayhem and damage," McInnes said.

Immune cells release cytokines that lead to the breakdown of joint tissue, and enzymes that break down the tissues that protect the joint. The immune cells also cause fluid to build up in the joints, which leads to swelling, he said. As in skin psoriasis, the inflammation causes blood vessels to expand and multiply, which in turn allows more immune cells to arrive in the area from the bloodstream.

"There is a vicious circle set up," McInnes said.

And the skin and joints aren't the only body parts caught up in it. Chronic inflammation can also lead to conditions including metabolic syndrome and heart disease.

It turns out that inflammation might also be the culprit behind atherosclerosis, clogged arteries that can lead to heart attacks and strokes. The immune cells and cytokines flowing through the blood can damage the protective layer of the blood vessel called the endothelium, Mehta said. This damage allows cholesterol and sugar into the vessel wall. When these substances accumulate, they form the plaques that can clog arteries, leading to heart attacks and stroke.

Why weight loss can help

Fat can also be a source of inflammation, a source that could be even more active in people with psoriasis and psoriatic arthritis. Fats secrete hormones called adipokines, which usually help with metabolism, Mehta said. However, recent research shows that adipokines change in people with psoriasis and resemble what is seen in diabetes. Further, according to a study published in August 2014 in Frontiers in Immunology, adipokines can change the way that fat processes sugars, which could make someone susceptible to diabetes.

For Marsha Hall, losing weight was the key to reducing inflammation. After she had bariatric surgery, she lost 110 pounds. She also was able to decrease her psoriasis treatment, free herself of joint pain and become nearly plaque-free.

Bariatric surgery is not the solution for everyone. But staying active and maintaining a healthy body weight are important ways to tackle chronic inflammation, Mehta said.

There are also studies showing that some psoriatic disease treatments could reduce inflammation all over the body, not just in the skin and joints. A study published in April in the Journal of the European Academy of Venereology and Dermatology, for instance, found that taking biologics for psoriasis may improve heart health.

Ongoing clinical trials are also looking at the effects of systemic psoriatic disease treatment on cardiovascular health. Dr. Joel Gelfand, a dermatologist at the University of Pennsylvania, and his colleagues are conducting studies testing whether the biologic drugs Stelara (ustekinumab) and Humira (adalimumab) or phototherapy could strengthen heart health by reducing vascular inflammation and improving the health of the aorta.

Understanding the role of inflammation in her psoriasis and psoriatic arthritis helped Hall have a vision for everything that was happening in her body and helped her take control, she said.

"I have my energy back, and I'm guarding my body," Hall said. "I think of my disease a whole lot differently."

Infographic sources

Nehal Mehta, interview, April 9, 2015; Iain McInnes, interview, May 1, 2015; Amor-Dorado, J.C., et al. "Investigations into audiovestibular manifestations in patients with psoriatic arthritis." Journal of Rheumatology. October 2014; Azfar, R.S., et al. "Increased risk of diabetes mellitus and likelihood of receiving diabetes mellitus treatment in patients with psoriasis." Archives of Dermatology. September 2012; Burden-Teh, E., Murphy R. "Psoriasis and uveitis—should we be asking about eye symptoms?" British Journal of Dermatology. March 2014; D'Epiro, S., et al. "Psoriasis and bone mineral density: implications for long-term patients." Journal of Dermatology. September 2014; Mehta, N.N., et al. "Attributable risk estimate of severe psoriasis on major cardiovascular events." American Journal of Medicine. August 2011; McDonough E., et al. "Depression and anxiety in psoriatic disease: prevalence and associated factors." Journal of Rheumatology. May 2014; Raison, C.L., et al. "Cytokines sing the blues: inflammation and the pathogenesis of depression." Trends in Immunology. January 2006; Skudutyte-Rysstad, R., et al. "Association between moderate to severe psoriasis and periodontitis in a Scandinavian population." BMC Oral Health. November 2014; Toussirot, É., et al. "Relationships between adipose tissue and psoriasis, with or without arthritis." Frontiers in Immunology. August 2014; Yen, Y.C., et al. "Risk of sudden sensorineural hearing loss in patients with psoriasis: a retrospective cohort study." American Journal of Clinical Dermatology. February 2015.

Driving discovery, creating community

For more than 50 years, we’ve been driving efforts to cure psoriatic disease and improve the lives of those affected. But there’s still plenty to do! Learn how you can help our advocacy team shape the laws and policies that affect people with psoriasis and psoriatic arthritis – in your state and across the country. Help us raise funds to support research by joining Team NPF, where you can walk, run, cycle, play bingo or create your own fundraising event. If you or someone you love needs free, personalized support for living a healthier life with psoriatic disease, contact our Patient Navigation Center. And keep the National Psoriasis Foundation going strong by making a donation today. Together, we will find a cure.

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