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Differential Diagnosis of GPP

Opinion
Video

Raj Chovatiya, MD, PhD; and Boni Elewski, MD, define what differentiates generalized pustular psoriasis (GPP) from other forms of psoriasis and discuss tools for diagnosing GPP.

Raj Chovatiya, MD, PhD: Hello, and thank you for joining me for this Dermatology Times Case-Based Peer Perspectives series titled “Exploring the Complexities of Generalized Pustular Psoriasis (GPP).” My name is Dr Raj Chovatiya. I’m an assistant professor of dermatology, director for the Center of Eczema and Itch and Medical Director of the clinical trials unit at the Northwestern University Feinberg School of Medicine in Chicago, Illinois. Joining me today is Dr Boni Elewski, who is the James Elder Professor and chair of the Department of Dermatology at the University of Alabama at Birmingham, in Birmingham, Alabama. In this series, Boni and I will talk about the nuances of diagnosis and treatment of GPP. We’ll also present a challenge case study on behalf both of us to discuss clinical and practical components and managing patients with GPP. With that being said, let’s get started.

…[With] this type of discussion, often the question that always comes up, what is generalized pustular psoriasis? It has the word psoriasis in it; is it similar to what we think about in plaque psoriasis? Is it distinct? And I think a really good place to start this discussion sometimes would be underpinning of pathophysiology. And we really think about generalized pustular psoriasis as a neutrophilic disease, which is slightly different when you think about more conventional types of psoriasis like plaque psoriasis. So, one important difference is, pathophysiologic mechanism. In the case of generalized pustular psoriasis, there’s a feedback loop consisting of keratinocytes producing IL-36, recruitment of neutrophils and other immune cells, and production of pustular which one sees very overtly on the scale. In many ways, it’s the innate immune-driven disease. In the case of plaque psoriasis, we think about this more classically as an adaptive immune-driven disease, one that depends a lot on T cells, particularly Th17 cells and the actual production of soluble IL-23. Boni, any thoughts on how you should attempt to differentiate generalized pustular psoriasis from plaque psoriasis or any other forms of psoriasis?

Boni Elewski, MD: Yes, the key word is pustules. Patients with generalized pustular psoriasis [have] pustules. And the pustules are generally fairly large, we call them pustular lakes. And interestingly, if you see the patient dependent, the neutrophils kind of settle at the bottom of the pustular and you see the serum at the top. There’s different types of pustular psoriasis, I think you’re alluding to. We have the generalized pustular psoriasis, of von Zumbusch, which is kind of what we’re talking about. But there’s a more benign process, the annular pustular psoriasis, which is similar, but you have an annular arcuate lesions. And then we have the palmoplantar pustular psoriasis, where patients may or may not have plaque psoriasis and they have pustules on the palms and soles. It’s a benign process, but definitely can be painful and affect the quality of life. And then there’s acrodermatitis continua of Hallopeau where you get pustules on the fingertips with dystrophic nails [and] can also occur on the toes. But I believe in our session today we’re talking about GPP, the von Zumbusch type, which is regulated by the IL-36 pathway, which gets overregulated, causing downstream cytokine production and resulting all these pustules. I think we should also talk about things that might trigger this too as we move forward.

Raj Chovatiya, MD, PhD: Very good point. And I think that another one that I like to think about particularly when having this discussion with my residents or students is systemic symptoms. They are an important part to think about in disease. And of course, one can have systemic symptoms truly with any inflammatory skin disease. But it is very characteristic of the von Zumbusch, of generalized pustular psoriasis type of disease where people can be having nausea, fever, chills, malaise, really a lot of those systemic symptoms that you classically associate with when somebody has a rip-roaring infection. And in the case of plaque psoriasis or even some of the more localized pustular variant, those are not really necessarily the most common thing that we see. And so it’s another important differentiating factor that really separates GPP from some of these other diseases. And that really kind of feeds into another question I have for you, Boni. In terms of making that diagnosis, what kind of tools in the armamentarium are you tapping into when somebody is coming in or you’re looking at a patient case to say, this person definitely has GPP or there potentially could be something else going on here?

Boni Elewski, MD: So most patients with GPP are pretty toxic, as you mentioned. And they may or may not have had a history previously of plaque psoriasis, but it’s easy if they did. Most patients I’ve seen have had plaque psoriasis in the distant or recent past. And then they may have had something triggering effect that caused them to develop GPP. For example, withdrawal of steroids might be something you might look for. Starting antimalarial hydroxychloroquine is a big trigger of GPP and so can beta blockers. So you can look for triggering events, you can look for a past history of psoriasis. A biopsy may help differentiate it, but it’s not necessary before you start treating because if you don’t treat, [the patient] can die. So you can’t do a biopsy and sit on it [until] you get it back, and wait till the patient gets further and further sick and dies. So, you have to call the diagnosis before you get the biopsy back. So it’s really a clinical diagnosis based on patients being toxic, they’re probably erythrodermic. If they have really [severe] GPP, they’re pretty red, they’re probably edematous and they’re symptomatic toxic with tachycardia, they may at the end, [have] high output heart failure.

Raj Chovatiya, MD, PhD: Really, really good point. And I think that, obviously we think about GPP as sort of this thing where it’s 0 to 100 and things just sort of quite dire. But there are instances as well where it may not necessarily be at the point of full toxicity. And sometimes, those can be the really tricky ones for diagnosis. Because we do have other conditions where people can have pustular outbreaks. So, think about AGEP, or acute generalized exanthematous pustulosis. Think about Sneddon-Wilkinson disease [subcorneal pustular dermatosis], which is sort of a different type of pustular disease as well. These are all, wouldn’t say mimickers, but they’re definitely in a differential diagnosis that you want to consider in terms of what’s going on. And to your point about medication flaring disease, AGEP is oftentimes down to the medication sometimes too. So that’s sort of a really important one when someone has widespread involvement, you really want to think about. I oftentimes think about lab workup too. Now it’s not necessary, but if someone is getting labs, there are a few things that oftentimes can help push you in the right direction. Your classic and monitoring markers like an erythrocyte sedimentation rate or C-reactive protein, sometimes people show them low levels of calcium or protein. Those might be sort of helpful markers, you may end up seeing a leukocytosis as well with a shift in terms of the distribution of cells. Again, for everyone’s take-home point, you don’t need to [order] labs [for] every single person, but those are all helpful clues that can go with that clinical diagnosis.

Boni Elewski, MD: But you brought AGEP because that would be what you might consider in the differential because they both might have generalized pustules. But my experience with AGEP is. [the patients are] not as toxic. And the pastorals are generally monomorphous and smaller. I call them pustular puddles vs GPP or pustular lakes because they’re bigger, and the patients generally are not toxic.

Transcript edited for clarity.

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