 Hello, I’m Mark Lebwohl. I’m at the Icahn School of Medicine at Mount Sinai in New York, New York. I am joined today by Dr Philip Mease, from the University of Washington School of Medicine and Swedish Medical Center/Providence St Joseph Health, in Seattle, Washington, to discuss management of plaque psoriasis and the importance of a multidisciplinary approach in treating this disease state.

Welcome, everyone. Let’s begin. Phil, let’s discuss together the clinical manifestations of plaque psoriasis and psoriatic arthritis. I’ll start with plaque psoriasis, which as you know, is characterized by sharply demarcated, erythematous, scaling plaques. In fact, I teach my residents that if they can say the words 

, then that’s the diagnosis. Often patients will present it with that manifestation on just 1 area, like the glans of the penis, for example. The diagnosis is missed all the time when it’s not on the elbows and knees, not on the scalp, which are the classic locations. But when you can say those words, think of psoriasis. Tell us about the many manifestations in the joints of psoriatic arthritis.

 Mark, as you know, patients typically first have psoriasis sometimes up to 10 years before they will develop manifestations of musculoskeletal disease. In various studies, we have seen that somewhere around 30% of patients with psoriasis will ultimately develop some manifestation of psoriatic arthritis. In some settings, it seems to be less, in some, more, but that’s a reasonable figure, about a third.

Interestingly, when the patients are first presenting, it will often be with a swollen joint or what we call a dactylitic digit, where the whole digit is swollen and looks like a sausage, but when you probe the patient, it’s interesting to hear that really, that’s probably not the first manifestation. Sometimes, instead of arthritis as the first experience, they may have what we call enthesitis, where a tendon inserts in the bone, or a ligament inserts in the bone—anywhere in the body, really. It could be an Achilles tendon insertion, it could be the plantar fascia, could be around the kneecap, or it could be around the rib cage. The gristle of the rib cage in this case is the entheseal organ, where inflammation is occurring. They’ll go back and they’ll say, “I had problems with chest pain or Achilles tendinitis a year ago, 2 years ago, and it was quite stubborn and difficult to improve.”

On rare occasions, the person will have a history of back pain, which was part of the inflammatory arthritis of psoriatic arthritis. The key domains that we focus on from a musculoskeletal point of view are arthritis, tender and swollen joints; dactylitis, a sausage digit; enthesitis, wherever a tender ligament inserts in the bone and can be painful because of inflammation; and axial disease, or spinal disease. When I see a patient with psoriatic arthritis for the first time, I will tell them there is no one who is going to be just like you because no one is going to have the same mix of skin disease being mild or severe, joint disease being mild or severe, and entheseal inflammation being mild or severe. And it’s going to vary from time to time. It is like when you’re sitting in the symphony orchestra performance, and you hear, at times, the whole orchestra is profundo. We have everybody playing at once, and the audience is getting stirred out of their seats. Other times, when you can barely hear the piccolo section playing, or the cellos have a little solo going on. That will be how a person with psoriatic arthritis can perform.

 I love the analogy, and it makes me think of the piece that we’re missing, which is the nail involvement, which occurs in diseases and very commonly is a marker of psoriatic arthritis. That also has many manifestations. You can get nail bed disease, so that’s usually subungual hyperkeratosis. You can get nail matrix disease. That’s usually pinning in the nail, but you can also get salmon spots and crumbling of the nail, splinter hemorrhages, and a variety of other changes that occur, which are manifestations of nail psoriasis.

The other thing that I would say is, as you described in arthritis, there are patients who have minor plaques on the elbows or minor plaques in the scalp and some patients who carried them for years as seborrheic dermatitis, because all they have is some scalp scale. When they suddenly develop plaques on the elbows and knees, you realize that all those years, what you were calling seborrheic dermatitis is, in fact, psoriasis. By the way, I don’t consider it an error to have called it seborrheic dermatitis for all those years; it’s a very mild form of psoriasis.

Clinical Manifestations of Psoriatic Diseases 

 I am curious to hear what you say about triggers for joint disease, because triggers for skin disease are well known.

There is the withdrawal of summer sun. When we hit November—the season we’re recording this in—when we hit December or even late October, patients start to come back with an exacerbation of the psoriasis, which is related to having less sun exposure. On the other hand, guttate psoriasis can be triggered by a strep throat. Other infections contribute to the development of guttate psoriasis, and then various forms of psoriasis can be triggered by medications.

For example, the withdrawal of systemic steroids is the most common precipitating cause of pustular and erythrodermic psoriasis. Lithium can generate plaque psoriasis and pustular psoriasis. Antimalarials have been associated with erythrodermic and pustular psoriasis and just a flare of general plaque psoriasis, so there are different triggers for different forms of psoriasis. Are there triggers for psoriatic arthritis?

 Absolutely. One of the things that is interesting about the disease and makes a difference from rheumatoid arthritis, for example, is that there is more activity of the innate immune system activation initial phases. The frontline defense is warning signals saying that we’ve got an infection going on in the skin surface or an infection somewhere in the body, we’ve got an alteration in the gut microbiome that is triggering disease activity, we’ve got microtrauma to the tendon attachment, which leads to dendritic cell activation, the production of interleukin-23, the stimulation of other cells in the genetically predisposed individual. All those things can contribute through innate immune system activation.

Oftentimes the disease is either monoarticular or oligoarticular, meaning 1 or less than 5 joints are being involved initially, and sometimes, the sentinel joint, as we call it, may be a joint that has previously had damage to it. The microdamage leads to activation of the immune system.

Eventually, what happens with psoriatic arthritis is that it becomes polyarticular: More parts of the body are involved, it’s progressive in nature, the spine can get involved later on in the disease. The other thing that we see is associated manifestation. Other diseases that may be present in a genetically related fashion, including not only psoriasis and the musculoskeletal aspects but inflammatory bowel disease and uveitis are associated conditions that can become inflamed and activated along with a certain comorbidity that’s including cardiovascular disease and metabolic syndrome. There’s a whole canopy of issues that will ensue after that initial inciting event.

 The 1 thing I didn’t hear you say that I know you’ve seen and we’ve seen is that the withdrawal of systemic steroids can result in a massive flair of not just psoriasis but also psoriatic arthritis.

Triggers of Joint Disease 

 I’ll tell you what we use in the skin, but what physical, psychological, and social burdens does psoriatic disease have on patients, and how are these linked? I’m sure you’re aware of an old SF-36 study. SF-36 is a measure of the impact of physical function or psychological function of different diseases. It turns out, when you look at physical functioning, psoriasis had more impact on physical functioning than conditions like cancer and diabetes. Only congestive heart failure had a more negative impact on physical functioning and on psychological functioning, and only depression had a worse impact than psoriasis.

Again, psoriasis had a worse impact on psychological functioning than cancer, diabetes, and many other diseases that, on the face of it, we would think are more sever. Psoriatic arthritis has to be debilitating. What are the psychological, physical, and social burdens of psoriatic arthritis on patients?

 Mark, it’s all that you’ve just described and more, and I’ve seen those same SF-36 data, which rank psoriasis and psoriatic arthritis right up there at the top in terms of impairment for quality of life. When you have the double whammy of embarrassing and emotionally distressing skin lesions—especially, for example, if someone has grown up as an adolescent or in their 20s—when they’ve got this social stigma, they’re embarrassed to go to the swimming pool or to the beach. You combine that with the physical disability of painful joints, painful back, and difficulty getting about. It can lead to a severe state of depression, and it’s something we clinicians just never really address adequately, in my opinion.

We are in a bit of a hurry. We realize that if we start to probe with questions about emotional well-being that we can open up a whole can of worms in the discussion with the patient. When we really need to, and they need to share their emotional burden with us as part of the trusting process with us, with the clinician, all I can do is just exhort people who are listening to take the time to inquire, and sometimes—fortunately, rarely in my experience—you’ll pick up suicidal ideation, and 1 of the things that can happen with these 2 diseases or these 2 aspects of 1 disease is that there can be increased suicide rate. That’s something we just don’t want to see.

 I know you must face some of the same challenges we face in the management of patients, but in some cases, because of the cost of treatments, they think any treatment is bad for them.

Psoriatic Arthritis: Physical and Social Burdens

 Can you talk to us about some of the challenges you face in managing patients with psoriatic arthritis?

 The obvious 1 is what you’ve alluded to, which is patients are worried and anxious —especially during the pandemic—about taking medications that have immune-moderating or immune modulating properties. They have the word 

 in their minds when they’re using the various effective medicines, like biologics or targeted synthetic disease-modifying antirheumatic drugs, so 1 of the first things we need to address is what’s the reality behind that concern or fear. I won’t diminish that severe infections can occur, but I will also try to put in perspective that the rates are low and that the rates of other adverse effects besides infection are also very low but not nonexistent. We have to talk about them, but they are very low. When you balance that against the value of using medicines to diminish inflammations, to diminish pain, to improve function, to improve quality of life, to improve work status, and also potentially to diminish some of the downwind effects of chronic inflammation in the body, including cardiovascular disease. These are all things that we have conversations about, and we do our best, and our staff does its best in trying to find the most modest expense for the patient. That’s thinking through what’s going to be effective yet not cost a home mortgage for the patients to take, and there are many programs that the pharmaceutical companies now offer for non-Medicare patients to try to reduce the cost of co-pays and to reduce the cost of medicines. Hopefully, you can start to take that out of the discussion and focus on the seesaw of cost benefit for potential adverse effects that you’re trying to put in perspective.

 It’s interesting that when I have the conversation with patients about the adverse effects, and they all hear these ads on TV about infection and malignancy, and that really stays in their mind. I’ll point out to them that older drugs, specifically tumor necrosis factor [TNF] blockers and certainly the very old drugs, like methotrexate and cyclosporine, were unequivocally associated with infections and malignancy. They have black box warnings about infections and malignancies; new drugs don’t.

In fact, if you look at the package insert for the new drugs, the word 

 does not appear, and if you look at some of the new drugs in the oral realm, apremilast is a phosphodiesterase inhibitor; so is caffeine. The adverse effects that occur with apremilast are diarrhea and weight loss. The diarrhea is temporary and generally resolved within a couple of weeks. The weight loss, most of our patients want. And headache are usually mild to moderate and self-limited.

With the IL-17 blockers, there are people born with that IL-17, and they get yeast infections, they get chronic mucocutaneous candidiasis. They don’t get more malignancies, they don’t get more heart attacks, and all the data look like they’re not going to get more malignancies or heart attacks. For the patients on the IL-23 blockers, the closest example we have to that is people born deficient in p40, or people who have been treated for years with ustekinumab.

They get salmonella. People born deficient in p40, that’s IL-12 and IL-13, get salmonella infections, which has not been reported in patients on these drugs, and they get microbacterial infections. We’re going to get a tuberculin test once a year, and I say to patients, “We could have predicted that our patients on the latter 2 drugs would do well with COVID-19 [coronavirus disease 2019] because there’s not an increase in viral infections.

If you look at TNF blockers, the picture is not as clear, but it’s interesting. When you look at published studies that review pivotal trial data, they look at it very differently. Some of them make a mistake because you can’t count yeast infections as viral infections. Some of them make that mistake. Sure enough, when you look at registries of patients who have been infected with COVID-19, it looks as though patients on all the biologics, if anything, do better. They don’t do worse, and for methotrexate, that might not be the case, but they also might do better. That’s controversial.

Low-dose steroids at the outset are probably not great, but certainly late in the disease, steroids appear to be beneficial, so certainly, you can’t paint with 1 brush. The biologics appear to be good, not bad, in that setting, and I have managed to calm my patients down about that, and they’ve been accepting of the biologics.

Multidisciplinary Perspectives on the Management of Plaque Psoriasis

Clinical Manifestations of Psoriatic Diseases

Triggers of Joint Disease

Psoriatic Arthritis: Physical and Social Burdens

Challenges in the Management of Psoriatic Arthritis