By Darcy Lewis
The skin and the joints are seemingly unrelated organs. Yet about a third of the 8 million Americans with the skin condition psoriasis will eventually develop psoriatic arthritis. In this disease, the body’s immune system causes painful inflammation in the joints in addition to the overproduction of skin cells that creates itchy, scaly psoriasis plaques. But how?
This seeming paradox has intrigued Alexis Ogdie-Beatty, MD, MSCE, since early in medical residency at Penn, when she met her mentor, the renowned rheumatologist H. Ralph Schumacher, Jr., MD. Then, during fellowship (also at Penn), she met dermatologist Joel Gelfand, MD, MSCE. “As he talked about psoriatic arthritis, I realized this was the perfect focus of study to help me understand inflammatory joint disease because, unlike other people with arthritis, some of these patients were destined to develop this condition,” said Ogdie, who is now director of the Penn Psoriatic Arthritis and Spondyloarthritis Program and the Center for Clinical Epidemiology and Biostatistics. “We know there is some connection, but why and for whom?”
Preventing Escalation of Psoriasis
“The fact that psoriasis is so common gives us a unique opportunity to learn to prevent psoriatic arthritis, or at least achieve early diagnosis, before joint damage occurs,” Ogdie said.
While she’s driven by the deeper question of how skin and joint issues are connected in psoriatic arthritis, for now, the goal is to help patients achieve a low-disease state. That means having no more than one joint that is tender or swollen and a low score on the 0-to-10 pain scale, Ogdie said. “Through our research, we want to get a larger portion of our patients to low-disease activity and [have them] stay there longer so they can function better in daily life,” she explained.
Studying the role of obesity in psoriatic arthritis is one way she hopes to help. “If your body mass index (BMI) is greater than 30, you're only half as likely to respond to biologic therapy as someone who is not overweight,” she says. “But when patients lose around 10% of their body weight, they have nearly seven times the likelihood of responding to that therapy.”
To that end, one of Ogdie’s research projects is a dietary trial that pairs patients with one of two scientifically supported eating plans—Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet—along with dietitian support and various behavioral incentives. “The idea is that both these diets are mainstream and easy to follow, and both focus on healthy eating,” she says. “The DASH diet is also aimed at lowering calories, so we hope to see if it turns out to be healthy eating or actual weight loss that most benefits people with psoriatic arthritis.”
Systematic Study of an Autoimmune Disease
Arthritis and psoriasis are both immune-mediated diseases. “The immune system gets turned on for reasons that we don't fully understand, and then we can't really turn it off,” Ogdie said. “We have therapies that suppress the immune system, but they never fully reverse the inflammatory process.”
Now, through these related but distinct conditions which comprise psoriatic arthritis, scientists are starting to understand how different parts of the immune system “talk” to each other. “It turns out there are cells that communicate with both the skin and the joints and may even travel between them,” Ogdie said. “It's a fascinating interaction between very different cell populations that has broader implications.”
Her team’s discoveries in this area benefit from the collaborations, resources, and expertise of colleagues from Dermatology and Rheumatology at Penn, collaborators across the country, and the Center for Clinical Epidemiology and Biostatistics (CCEB), which Ogdie has directed since 2022.
Taking an epidemiological approach, Ogdie has been researching whether dermatologists should treat psoriasis more aggressively in patients who have other conditions that might contribute to the development of psoriatic arthritis in collaboration with Jose Scher, MD from New York University, Joseph Merola from Brigham and Women’s Hospital, and others. The team has since launched a randomized clinical trial to address this question. Understanding the patterns of the risk factors and which ones seem to precede the psoriatic arthritis diagnosis is the key way that epidemiology informs this research.
These studies have been exploring whether the electronic medical record (EMR) can be used to alert the provider when a patient with psoriasis comes in with depression, anxiety, obesity, or other known risk factors of psoriatic arthritis. “The EMR can then prompt the provider to ask the patient about any joint pain or swelling,” Ogdie said. “That way, the provider can start the patient on an effective therapy for psoriasis that could potentially delay or prevent the onset of clinical joint symptoms.”
The CCEB’s multidisciplinary approach—and its focus on research questions that improve patient outcomes—have broader implications for medical research than just psoriatic arthritis, Ogdie said. “We focus on risk, why people develop diseases and how these complex pieces can fit together to create a clinical symptom for a patient sitting in front of you,” she said. “We’re also designing new types of trials to help us get the right therapy for the right patient by incorporating what patients and clinicians actually need.”