Raj Chovatiya, MD, PhD; and Boni Elewski, MD, reviews the many pathways of generalized pustular psoriasis (GPP), focusing on individualizing therapy for patients with GPP and treatment options.
Raj Chovatiya, MD, PhD: The patient journey of GPP (generalized pustular psoriasis) is interesting, right? So, we know that it’s a pretty rare disease, 1 in maybe 1000, 100,000. I mean, our epidemiologic studies aren’t amazing given the fact that GPP could sometimes lie dormant for long periods of time. It can flare sort of without setting a warning and then kind of go quiet. Again, other people have a bit more of a relapsing remitting course. It can really depend. But in general, not the most common. So, from the data that we have, there’s probably 2 big ways that you’re really going to be thinking about a GPP patient presenting. So there’s kind of the one that Boni alluded to where they might be coming to the emergency [department], or urgent care, or inpatient setting. And you’re hoping that there’s a dermatologist nearby that can really sort of put a lot of those pearls together to make that diagnosis. There’s others that may not have necessarily reached that point of being very, very sick and almost seeming septic in that sense. And those might be ones that are actually coming through the outpatient arm. [The] tricky part here is, given that differential diagnosis we talked about, they may end up with a primary care doctor’s office or they may be at a dermatologist, and it may not be apparent that GPP is the diagnosis. [It’s] the reason why some of these other ancillary clues can be helpful to really try to stop things from getting to that point where they’re going to have to necessitate an actual inpatient admission itself. And…that’s biggest problem for misdiagnosis and delay of treatment. The harm here is the fact that a downstream occurrence of really bad GPP can be that essentially. And so that is what you are trying to stop when it comes to thinking about that.
Boni Elewski, MD: And we know that people with GPP may, but not all, some have a mutation in the receptor antagonist gene. And that was kind of a new development. And when that was found, we now have been finding treatments to treat [GPP] effectively. But not all patients do, and if they have the mutation, they probably have only pustular psoriasis. But if they don’t have the mutation, they may have plaque psoriasis and pustular psoriasis.
Raj Chovatiya, MD. PhD: Important. And I think that oftentimes there’s this, I feel like dilemma of, well, can somebody have both? Is it really one? Do you need to have one to have the other? And I think you kind of heard it here, but I feel like in our experience, we’ve seen patients who have a history of flaps, right? But have it, but by no means is that a requisite given the fact that there’s actually very different pathways. Well, the fact that you actually delve into the epidemiologic data, it would suggest that more often than not, the patient’s actually don’t have a history of plaque psoriasis even though those are kind of the ones that we end up kind of seeing a lot from a day-to-day clinical standard.
Boni Elewski, MD: I don’t think we brought up the patient who may be on a TNF [tumor necrosis factor] blocker for some non-psoriasis problem like IBD [inflammatory bowel disease] of some sort, and then develop a pustular psoriasis eruption from the TNF blocker. Which is kind of its own bucket tier, it’s not one of the ones we mentioned.
Raj Chovatiya, MD, PhD: Great point. And I think that sort of leads me to my next question for you, Boni, how do you individualize that treatment plan for GPP? And really think about the symptoms, the signs, the history, and try to put this together in a package where you’re going to come up with the best therapeutic options and journey for that patient who you’ve seen that you feel like as GPP.
Boni Elewski, MD: So, I think the first thing in managing a patient with GPP appropriately is to make the diagnosis as fast as possible. Because this is life-threatening and up to 25% of people will die. Generally, cause [of death] is sepsis, it’s not good. So, you have to make a diagnosis quickly. There’s only one drug now approved for GPP, which is spesolimab which blocks the IL-36 pathway. Other options could be cyclosporine. And I have done cyclosporine numerous times, but it’s not appropriate for everybody. That has its own side effects. And I generally dose [cyclosporin] at 3 to 5 mg/kg for a short period of time while you try to get someone stable and then you might put them on another biologic. Interestingly, in Japan, there are several biologics based on limited studies that are approved for GPP. In Japan, the disease is more common than here. It’s more common in people of Asian descent for reasons I don’t know. So, the first part of managing a patient is make a diagnosis. If they have GPP and they’re in the intensive care unit as they probably are, if they’re acute flare, the IL-36 blockers spesolimab would be the treatment of choice if you can get that. Cyclosporine would be a backup plan depending on the situation, and the patient’s insurance, and everything else you have to consider. And then you manage their other problems. The usual topical steroids might be helpful to calm their skin down. Patients I’ve talked to with GPP have laid in the hospital for a while…before they’re transferred to our center, and they tell me that the stressful part of their disease was they’re lying there and no one knows what they have. And they are given probably vancomycin for a presumed infection. And then when that’s not working, they get transferred to a major medical center where we make the diagnosis. So again, we need to educate people on this disease and know how to treat it appropriately and quickly.
Raj Chovatiya, MD, PhD:Great point. And I think that it’s amazing that even just in your short description of treatment how different that is from if you had asked me last year or 2 years ago, given the fact that we didn’t necessarily have a targeted biologic … disease base. And really the treatment that we were thinking about were largely general immunosuppressants or therapies that were approved for plaque psoriasis that had some anecdotal data for GPP. So much like yourself, cyclosporine, I think is sort of a one that we classically think about using in terms of the ones that have at least cases anecdotal data, the IL-17 pathway blockers are one that people…will use. But speed is really a major issue of some of these therapies. Cyclosporine is not the fastest, but we know that not every patient is correct. A lot of labs, you have to monitor for cyclosporine limitations on how long you can use it, it doesn’t agree with every patient. And then from the conventional sort of subcutaneous biologic therapies we have, again, that may not necessarily be sort of taking a chunk out of that disease as quickly as possible as we want. And some of those other therapies that we may consider for inflammatory diseases, [such as] phototherapy, [is] not going to be quick enough and practical enough for a patient here. Even though this is not what I use for my patients with psoriasis, oral steroids, which are used quite a bit. In general, withdrawal of steroids actually can be a problem exacerbating GPP and so not what we’re going to be going for there as well. And then TNF blockers and others…have their own issues in terms of potentially causing other issues in somebody too. So really, our options have been quite limited for a very, very long time. And I think that really highlights some of the risks we’ve had to deal with in terms of treating our patients because many of these tests were not completely appropriate, but we didn’t have really great options.
Transcript edited for clarity.