Comorbidities of Generalized Pustular Psoriasis


Aaron Farberg, MD, and Mark G. Lebwohl, MD, discuss the common comorbidities seen in patients with generalized pustular psoriasis (GPP) and some potential future developments in the management of GPP.

Ryan Haumschild, PharmD, MS, MBA: One thing that was mentioned earlier was comorbidities with generalized pustular psoriasis [GPP]. Dr Farberg, can you describe some of the comorbidities you commonly see with GPP? I know in the psoriasis landscape, those with metabolic syndrome sometimes can be impacted more, but I’m not sure what comorbidities associated with GPP you see the most.

Aaron Farberg, MD: Something I always look for with my patients is oftentimes they’ll come in with what I call their cheerleader, another family member oftentimes, and they’re the best canary in the coal mine, the litmus test to tell me how this patient is doing. When it comes to comorbidities for GPP, well, thankfully I don’t have to read too far. It’s literally in the title of the name, psoriasis. That’s probably one of the biggest comorbidities. I don’t think there’s anything particularly out there, the data are very limited, as Dr Lebwohl mentioned, in terms of the actual numbers. It’s also, regional across the globe. I would say that the most important things to recognize are the medications that could potentially cause this, and again, highlight that it’s oftentimes steroids, and you’re coming off the steroids, as the stories have been told. Even some of the treatments for psoriasis have been implicated with causing GPP as well. It’s always important to keep an open mind and a wide yet important differential.

Mark G. Lebwohl, MD: I will say I agree with Aaron. The comorbidities are the comorbidities of psoriasis. If you listen to the stories, I told you about Erin E. Boh’s, [MD, PhD, FAAD,] patient who had diabetes and obesity. Those are both comorbidities of psoriasis. I told you about Crohn disease being treated. Crohn disease is a comorbidity of psoriasis. Psoriasis is increased about 5-fold in patients with Crohn disease. The first patient I saw had psoriatic arthritis, a known comorbidity of psoriasis, but it was the withdrawal of steroids that triggered her pustular psoriasis. The comorbidities are really the comorbidities of psoriasis.

Ryan Haumschild, PharmD, MS, MBA: That’s very helpful. One last question, when we talk about the future, we talk about it as an exciting time in the treatment and care of these patients, and I think that’s so true, but I’d love to give additional context there. Dr Lebwohl, can you help us add more context to that question? What are some potential future developments, what can we expect to see in the management of generalized pustular psoriasis?

Mark G. Lebwohl, MD: Right now we’ve identified IL-36 [interleukin-36] as the key cytokine in the treatment of pustular psoriasis, the key target. There will be other treatments that come out. Right now we have a treatment that’s given intravenously. Hopefully one day it will be available subcutaneously. Hopefully, one day we’ll have a pill that does the same. There is a second drug in development that is targeting IL-36, imsidolimab, also an antibody to IL-36. Right now we are dealing with biologics, and the advantage of biologics, frankly, which is hard to overcome and doesn’t look like we will in the near future, but their advantage is they are so targeted that pretty much you can treat a patient and get rid of what you need to get rid of without creating other problems.

When we use smaller molecules like methotrexate, we hit the liver, and we hit the bone marrow. When we use molecules like cyclosporin, we hit the kidneys. The targeted antibodies so far have been very safe and very effective. That’s not to say that there aren’t any signals. I believe the package insert talks about infections, and we did see a few infections in the patients who got imsidolimab. One of the dilemmas in quantifying infections is the placebo group had lots of infections because GPP makes you prone to infections. While it may not have seemed like it was that much, when you’re making the patient better right away, and then over a period of time you see infections, you have to be concerned or be on the lookout. Unfortunately, we don’t have another choice. There’s no question that this is the fastest working drug and also the most effective drug we have for GPP, which potentially can kill you.

Transcript edited for clarity.

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