In the biomedical world, skin conditions can suffer from disrespect by association. Dermatology treatments, even of the medical kind, are often driven as much by vanity as health concerns.
But skin is the largest organ of the body, with important functions including sensation, thermoregulation and host defense.
Skin disorders can compromise all those functions. And they can also have effects on general physiology, noted Nehal Mehta.
At a recent lecture at the U.S. National Institutes of Health, Mehta, who is chief of the laboratory of inflammation and cardiometabolic diseases at the National Heart Lung and Blood Institute and an adjunct professor of medicine at George Washington University, described his insights into the links between psoriasis, inflammation and cardiometabolic disease.
Psoriasis is an autoimmune disorder that usually affects the skin, but can also manifest as psoriatic arthritis in the joints. An acute psoriatic flare can activate more than a billion immune cells.
Psoriasis patients also have an increased risk of cardiometabolic diseases, such as atherosclerosis, insulin resistance, adipose dysfunction and high cholesterol -- disorders that were once collectively called metabolic syndrome.
Their risk of cardiovascular disease is also increased. In middle age, their risk of a heart attack is twice that of the general population, and their overall life expectancy is shortened by roughly 5 years, with cardiovascular events being the most prominent culprit.
Those epidemiological data, Mehta said, first brought him to "the idea that inflammation at a young age could drive later cardiovascular events."
By conducting long-term studies of psoriatic patients, both while their disease is active and while it is in remission, his team's work at the NHLBI has provided experimental support for that idea, and also shown that psoriasis is "a model to study inflammation and cardiometabolic diseases." The team now has about 5,000 years worth of follow-up data on psoriasis patients, which enables them to look at the physiological states that precede heart attacks ad strokes.
Using imaging studies to trace activated macrophages, Mehta and his team have shown that the cells show up not just in skin lesions, but in joints -- even in patients with no other symptoms of psoriatic arthritis -- and the liver, and lead to vascular inflammation.
"From an imaging standpoint, psoriasis is a systemic inflammatory disease," Mehta said.
In other studies, Mehta and his team have discovered that systemic inflammation in psoriasis resembles acute coronary syndrome, which the pro-inflammatory cytokines TNF-alpha and IL-1beta increased ninefold and fivefold, respectively, over baseline levels.
The team has also shown that psoriasis decreases the efflux capacity of high-density lipoprotein (HDL cholesterol) -- the ability of HDL to "go to a loaded cholesterol macrophage and pull out the LDL," cholesterol which then can be secreted as bile.
Psoriasis also leads to thicker coronary walls through increased plaque burden that is not calcified, which is the "the most common cause of myocardial infarction," Mehta said.
His team has developed a method to image such plaque, and demonstrated that high-risk coronary plaque occurs 14 years earlier in psoriasis patients than hyperlipidemia patients.
The team has also looked at inflammation markers in psoriasis patients that were treated with biologics, and showed that starting anti-TNF, anti-IL-12/23 or anti IL-17 biologics all decreased inflammation markers, with anti IL-17 therapy having the strongest effect.
Mehta stressed that he "would not conclude from these data," which came from an open-label observational study, that using those biologics is warranted for the prevention of heart attacks and strokes. For one thing, there is no direct demonstration yet that tamping down inflammation ultimately reduces the risk of heart attack and strokes in psoriasis patients, though epidemiological data does suggest this is the case. Mehta's team is currently looking at this question.
But the work does support the idea that looking at patients with psoriasis can give clues to how to identify high-risk patients as well as possible preventive strategies.