Rosanne Paul, DO, is a dermatologist and assistant professor of dermatology at Case Western Reserve University in Cleveland, Ohio. Her areas of practice include general dermatology, medical dermatology, cosmetic dermatology, and dermatologic surgery.
Generalized pustular psoriasis (GPP) is a chronic autoimmune condition. It’s the rarest form of psoriasis, affecting 1 in 10,000 people in the U.S. — around 33,000 people. By comparison, about 7.5 million adults in the U.S. have chronic plaque psoriasis.
GPP is a skin disease. It causes recurring pus-filled blisters (pustules) on red, painful skin, but it also causes systemic symptoms, like fevers, chills, and fatigue. The condition can be severe, even life-threatening, so treatment for flares is urgent.
There’s no cure for GPP, but there are medications that can shorten how long the flares last and how severe they are. The drugs can also lengthen remission, which is the amount of time between flares or symptoms. We spoke with Rosanne Paul, DO, a dermatologist at Case Western Reserve University in Cleveland, Ohio, about GPP, its symptoms, triggers, treatment, and more.
Q: Who gets GPP?
A: GPP is very rare and there’s no typical GPP patient, although more women do get it than men. We don’t know what causes GPP or what might predispose somebody to getting the disease. Someone who has chronic plaque psoriasis might be more likely to get it. Although GPP can happen at any age, it often appears in people in their 20s or 50s, with the 50s being more common. Generalized pustular psoriasis may also occur in the third trimester of pregnancy.
Q: What are the signs and symptoms of GPP? How is it diagnosed?
A: First, there’s the clinical appearance of GPP. The psoriasis that most people think of appears as dry, flaky patches or plaques, usually on the scalp, elbow, and knees. GPP is different. Usually GPP appears as little red bumps, or pustules, but that’s not always the case. Sometimes there’s just a general redness on the skin. Another thing is that the pustules aren’t always on a large area of skin. You can have the pustules just on your hands and feet, for example, and they can spread. In addition to the pustules and skin redness, patients often will have fever, chills, and other abnormalities, like fatigue. Dehydration can occur as well.
Typically, GPP is diagnosed with a biopsy. A small skin sample is sent to a lab for examination. A doctor might already have a strong feeling that the patient has GPP because of what they see, but those symptoms could also be caused by other conditions like a reaction to a medication, for example. That’s why the biopsy is important. There’s no blood test for psoriasis.
If the patient has symptoms such as fever and chills, then we need a thorough workup to rule out any infections that could be causing this. This includes a CBC (complete blood count), a CMP (comprehensive metabolic panel), and other tests.
Once the patient is diagnosed with GPP, if they need treatment with drugs that will suppress their immune system (immunosuppressants), we need to know if they have any other types of infections before we start. So we test for that. The infections could be acute (temporary), latent (existing but not showing any signs or symptoms), or chronic (infection that is chronically present). Testing includes screening for tuberculosis, HIV, and hepatitis B and C.
Q: What kind of damage and complications does GPP cause?
A: The most serious complication caused by GPP is sepsis, the body’s inflammatory response to an infection. It causes fever, chills, and abnormal white blood cell counts, and it can be fatal. Another complication from GPP is dehydration. Your skin is a large barrier organ. When it’s extensively inflamed and disrupted, you can lose large amounts of fluid through the skin. This is what leads to dehydration. Dehydration could also end up affecting the kidneys and, if it’s not treated, this can be life-threatening as well.
Other complications from GPP include recurrent (repeat) flares of the skin disease and higher rates of cardiovascular disease, including heart attacks. Patients whose kidney, liver, respiratory system, or cardiovascular system are affected need to be treated by other specialists as well. But if flares are treated and respond to treatment, these other health issues can go into remission, too.
Other reported complications from GPP include uveitis (inflammation of the eye’s middle layer, the uvea), fever, and arthritis. Patients with GPP might be admitted to the hospital frequently. This can have a significant impact on a patient's overall quality of life, both mentally and physically. The mortality rate of GPP is reported to be from 2% to 15%.
Q: How is GPP treated?
A: IL-36 is an immune system protein that we believe plays a key role in GPP. A new biologic drug called spesolimab (Spevigo) targets this pathway and it works quickly and effectively, clearing the skin. Spesolimab is given by IV for acute flares. After the flare is over, patients can take a maintenance dose when the skin is clear. The goal is to help prevent or reduce further flares. This drug is a major advance that makes the future bright for people with GPP.
In the past, GPP was treated with immunosuppressant cyclosporine, methotrexate, and drugs in the oral retinoid category, like acitretin (Soriatane). This was the standard of care before the newer options became available. The older agents, like cyclosporine, were helpful for some people with GPP, but when patients took them, they required close lab and blood pressure monitoring. These drugs weren’t good long-term solutions and there’s not a lot of data to support how well they work. Another drug, infliximab (Remicade), for acute flares and maintenance, can be used, too, but it has to be given at an infusion center.
Oral methotrexate and drugs like acitretin take longer to work, and given that GPP flares are an emergency, we need to treat the GPP quickly to prevent complications. Therefore, we don’t often choose to use drugs that take so long. They also have more side effects and patients need to be monitored closely. Neither of these should be used in pregnant patients or people of childbearing potential.
Other biologics, such as bimekizumab (Bimzelx), ixekizumab (Taltz), and secukinumab (Cosentyx), which block IL-17, and guselkumab (Tremfya) and risankizumab (Skyrizi), which block IL-23, may be appropriate for some patients. Oral corticosteroids might be an option in some cases, but they have to be used carefully because when the patient stops taking them, they may rebound and have more severe flares.
If someone with GPP is not responding to any type of treatment, their doctor might try medications such as anakinra, apremilast, or mycophenolate. Some doctors have published case reports of using these drugs for their patients with some success.
Q: How can you manage the symptoms? Are there any lifestyle changes that can help?
A: Unfortunately, there’s not much someone can do safely on their own during a GPP flare. The important thing at home is to apply any prescribed topical medicine and follow your treatment plan. There aren’t any at-home self-care steps that could safely control a GPP flare. If you have GPP, it’s very important that you are followed by a dermatologist because GPP is an emergency that requires prompt, urgent medical care rather than at-home management.
As for lifestyle changes, some lifestyle modifications like changing your diet may help with plaque psoriasis, but not for GPP. This isn’t a condition where lifestyle changes are likely to have an immediate effect because it appears and progresses so fast.
Q: What does the future hold for people with GPP?
A: We’re optimistic about the future. Spesolimab has shown that it works quickly and well, and its effects last. This new drug gives people with GPP something that is at their fingertips when it comes to treating flares and preventing them.
Whether it’s plaque psoriasis or GPP, researchers have identified specific inflammatory proteins that led to more targeted drugs, and there are more in development. This is huge given that in the past, we only had cyclosporine and methotrexate, and then broader biologics. I anticipate even more precision in treatment in the future. For example, doctors might be able to use genetic profiles to determine which drugs would be best to start with rather than trying one and then moving on to another if the first one doesn’t work.
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