Patients with GPP present with an abrupt onset of pustules all over the skin. The pustules are itchy, painful, and uncomfortable. There are also systemic symptoms that can include fever and fatigue, and individuals with GPP often appear unwell. Often, these patients will first present to an Emergency Department or Urgent Care, but health care providers in these settings may not be familiar with GPP and may misdiagnose patients with a skin infection based on the pustules.

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In the past, there were no specific treatments for GPP, so treatment overlapped with that of plaque psoriasis and included cyclosporine, methotrexate, acitretin, and traditional psoriasis biologics. Although these therapies work, they are not optimal and often do not lead to the rapid improvements that we would like to see. Therefore, it was very exciting when spesolimab, an IL-36R antagonist, received US Food and Drug Administration (FDA) approval for GPP in 2022. Spesolimab confers rapid improvement, with pustules clearing up as quickly as a few days after starting treatment in some patients. It is now also FDA approved for maintenance therapy, and it may decrease the likelihood of flares and overall disease severity in the long-term.

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Some patients with GPP also have plaque psoriasis, and these individuals may need background therapy for their plaque psoriasis. In my own practice, I often prescribe an IL-17 or IL-23 inhibitor. Then, if patients develop a flare of GPP, I use spesolimab to treat the flare rather than keeping them on it long-term. Patients with GPP and plaque psoriasis might also have psoriatic arthritis or other comorbidities associated with plaque psoriasis, such as cardiovascular disease, diabetes, and obesity. Further, GPP has its own comorbidities, as patients are at an increased risk for serious infections such as sepsis. They may also develop end-organ damage, including kidney failure, liver failure, and even heart failure if their disease is severe enough, so we need to control GPP as quickly as possible.

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Finally, there are some factors that can contribute to treatment delays. For example, insurance coverage can be a challenge and may require extra review or authorization. Additionally, spesolimab is administered intravenously for GPP flares, but, depending on where a patient lives, they might not have easy access to a large academic hospital or an infusion center.