The Many Considerations of Managing Generalized Pustular Psoriasis

Mark G. Lebwohl, MD, joined Erin E. Boh, MD, PhD, to discuss difficult generalized pustular psoriasis (GPP) cases during a recent Dermatology Times Case-Based Peer Perspectives custom video series titled “GPP Case-Based Perspectives: Dermatology Experts Explore Complex Cases.” Lebwohl is dean for clinical therapeutics and chairman emeritus of the Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai in New York, New York. Boh is the Joseph Chastain Endowed Chair of Clinical Dermatology at Tulane University School of Medicine in New Orleans, Louisiana.

Protective Functions of the Skin

Lebwohl emphasized that patients with generalized pustular psoriasis lose the protective functions of the skin. “[Patients are] often febrile or even hypothermic because you never think about your skin controlling your body temperature, but it has a big role in controlling your body temperature and you lose the integrity of the skin when you get generalized pustular psoriasis,” he said. He went on to explain the role of the skin in kidney function. “Your skin is a barrier against fluid loss. And when you lose a lot of fluid, you can go into shock. Renal failure is not rare,” Lebwohl said.

He added, “All the patients who have generalized pustular psoriasis have low albumin because they lose protein through the skin. They almost always have microcytic anemia because they lose iron through the skin. They can develop electrolyte abnormalities. Hypocalcemia is common, but loss of other electrolytes is common, too, which can lead to arrhythmias, cardiac arrhythmias.”

Spesolimab in Emergencies

Spesolimab-sbzo (Spevigo; Boehringer Ingelheim) generally works quickly. “The patients we’ve seen have actually turned around in hours. Literally the next day they look dramatically better. So this is a lifesaving drug, and we should try as much as possible to speed the delivery of it to patients,” Lebwohl said.

Referring to a case that Boh presented of a 60-year-old Black woman with a more than 20-year history of psoriasis and psoriatic arthritis, Lebwohl said, “You don’t need a skin biopsy to make that diagnosis. And to withhold a lifesaving treatment for a patient who literally could be dead in 2 days or 1 day and withhold that treatment when you know the treatment’s there waiting to be given to them, [that] is just a crime,” Lebwohl said.

However, Boh said, “I do want to point out that in this case, at least for spesolimab, when you’re treating, it blocks IL-36. The cool thing about it is that there are no comorbidity restrictions. So it doesn’t matter that the patient has significant renal disease. My patient’s creatinine went up to 4.6, and it was 1.7 on admission…. There [are] no contraindications in kidney disease, liver disease, even technically in infection. It doesn’t really work through that pathway.”

In 24 to 36 hours, Boh’s patient began to get better, which took longer than many of the referenced cases. “I do think part of the slow resolution was the fact that she had some very significant comorbidities that had been sort of jostled. She had chronic renal disease, but when you go into acute renal failure, we were talking about dialysis, all of these confounders I think made [it] a little bit more difficult to clear any toxins, to clear things that would have maybe gotten her a much quicker response,” Boh said. The patient was cleared in 2 weeks and continued to be clear 7 to 8 months later while on psoriasis medicine.

Access to Spesolimab

When an insurance company requires testing or skin biopsies that will take time that a dying patient does not have, clinicians often need to be persistent. Boh said, “This drug works very fast, it’s very effective, but you’ve got to get it to the patient. So you really sometimes need to stick with it and be a little bit of a bulldog to get it if you don’t have the luxury of time.”

Added Lebwohl, “The patient is dying. In 2 days the patient could be dead, but their TB [tuberculosis] test could be negative, or they ask for a skin biopsy. This is really a clinical diagnosis.”

Boh also emphasized the importance of a team approach in caring for patients with GPP. “We don’t think about high output failure. We don’t think about arrhythmias. I think you have to be on your guard. And soit’s good to have a team approach when it’s a medical emergency like that,” she said.

Determining Triggers

Lebwohl and Boh highlighted the importance of understanding what triggers pustular psoriasis. “Some people will just flare with pustular psoriasis, but there are triggers other than steroids,” Boh said. “Steroids are the very biggest trigger. But sometimes infections can do it. And in my patient, one of the confounders was she had just gotten the COVID-19 vaccine and she had gotten it at the same time as the Pneumovax [pneumococcal vaccine]. And when you think about, especially I think the COVID-19 vaccine, it’s in part mediated by T cells. We do see a lot of immune dysfunction and dysregulation transiently after these infections.”

A patient Lebwohl saw after treatment from other doctors was originally thought to have rheumatoid arthritis and was treated with hydroxychloroquine and then developed GPP. The first doctor to treat the patient for GPP prescribed prednisone, and each time that the dose was lowered, the GPP worsened. “And, of course, she started going through this sequence of events where she was getting worse every time it was lowered. Ultimately, she ended up getting spesolimab and cleared,” he said.

Treating Chronic GPP

The treatment plan for patients in an outpatient setting is different than for patients in the hospital. “For now, I keep them like your patient on maintenance therapy. I do use a lot of oral retinoids,” Lebwohl said. “And that really speaks to how difficult it is to treat pustular psoriasis with the old drugs that we have. But until we had spesolimab, what I would use was often an IL-17 blocker and often in conjunction with acitretin.”

Lebwohl and Boh agreed that spesolimab works well but that accessing the drug for patients requires persistence.

Raj Chovatiya, MD, PhD, assistant professor of dermatology, director of the Center for Eczema and Itch, and medical director of the clinical trials unit at the Northwestern University Feinberg School of Medicine in Chicago, Illinois, and Dermatology Times Editorial Advisory Board member, then joined Boni E. Elewski, MD, the James E. Elder MD, Endowed Professor for Graduate Education and chair of the Department of Dermatology at the University of Alabama Heersink School of Medicine in Birmingham, to discuss identifying and treating patients with GPP.

“Most patients I’ve seen have had plaque psoriasis in the distant or recent past,” Elewski said. “And then they may have had some 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. You can look for triggering events, you can look for a history of psoriasis.”

Testing to Determine GPP

Although biopsies are sometimes performed, a clinical diagnosis often has to be made before the biopsy results are returned. “You have to call the diagnosis before you get the biopsy back. It’s really a clinical diagnosis based on patients being toxic. They’re probably erythrodermic. If they really have, 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,” Elewski said.

As patients are often in the hospital, lab workups can help in making a diagnosis. “[They may show] your classic inflammatory markers like an erythrocyte sedimentation rate or C-reactive protein. Sometimes [patients] have low levels of calcium or protein,” Chovatiya said. “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 be ordering labs on every single person, but those are all helpful clues that can go with that clinical diagnosis.”

Chovatiya added, “We do have other conditions where [patients] can have pustular outbreaks so, think about AGEP, or acute generalized exanthematous pustulosis. Think about Sneddon-Wilkinson disease, which is a different type of pustular disease as well. These are all, I wouldn’t say mimickers, but they’re definitely a differential diagnosis that you want to consider in terms of what’s going on.”

Presentation of Patients With GPP

Patients with GPP often present when the disease has reached a critical point, but sometimes the patient is not yet exhibiting severe symptoms. “[The patient] might be coming to the emergency [department] or urgent care or inpatient setting. And you’re hoping that there’s a dermatologist nearby who can…put a lot of those pearls together to make that diagnosis. There are others who may not have necessarily reached that point of being very, very sick and almost seeming septic in that sense,” Chovatiya said. “And the tricky part here is, given that differential diagnosis we talked about, they may end up in a primary care doctor’s office or they may be at a dermatologist, and it may not be apparent that GPP is the diagnosis. 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.”

Examining GPP Cases

Chovatiya presented a case of a 61-year-old woman who said she had experienced fluid-filled bumps on her feet years before and they had spread to other parts of her body. The bumps would last a few days and then burst, leaving her skin scaly. The patient said that a previous biopsy had shown pustular psoriasis. She was treated with several drugs, topicals and systemics, before spesolimab, which cleared her.

“One of the teaching pearls here…was that when you really thought about the totality of [her] history, it allowed us to go forward with treatment. And this is just a general point for us in dermatology all the time. We see cross sections, so [patients come] to see us at one point in time, and that tells us very little about the longitudinal course of disease. And unless you act, you may not see what you’re looking for, and therefore your conclusion may be totally different unless you actually get that information,” Chovatiya said.

Elewski presented a case of a 60-year-old woman who was transported to the hospital for GPP most likely triggered by steroids. In her case, spesolimab cleared her GPP quickly. The patient worried about a recurrence, and the issue for Elewski was how to treat her moving forward. Rather than another dose of spesolimab, the patient was treated with guselkumab (Tremfya; Janssen) and has remained clear.

Pearls to Put Into Practice

The cases presented by Lebwohl, Boh, Chovatiya, and Elewski depict the different settings in which dermatologists encounter patients with generalized pustular psoriasis. It’s important to consider the patient’s history, sometimes going back decades, to make an accurate diagnosis and develop the best treatment plan.