“In psoriasis, there are microscopic little collections of pus cells, but in generalized pustular psoriasis (GPP), which is a very abrupt and severe flare, people get the psoriasis all over their body and those little microscopic pus cells get so large they are visible with the naked eye,” says Steven Feldman, MD, PhD, a dermatologist who specializes in psoriasis at Atrium Health Wake Forest Baptist in Winston-Salem, North Carolina. In contrast to GPP, a related condition called localized pustular psoriasis causes rashes and pustules confined to one area of the body. According to a 2022 article in the American Journal of Clinical Dermatology, there are two subtypes of GPP. One is subacute annular GPP, which generally occurs in children and is milder than the adult form of the disease, and the other is pustular psoriasis of pregnancy (previously called impetigo herpetiformis). During these episodes, a person with GPP may develop symptoms associated with systemic inflammation. According to the National Psoriasis Foundation, these symptoms may include:
FeverChills and shiversIntense itchingRapid pulseFatigueHeadacheNauseaMuscle weaknessJoint pain
If a person thinks they may have GPP, they should see a healthcare provider immediately, because the condition can lead to potentially life-threatening complications. There are basically two forms of GPP, says Dr. Feldman. One is more prevalent in Japanese people, involving a mutation in certain genes that regulate inflammation. “For these people, the immune system gets out of control and the signaling pathways that promote inflammation are overly active,” Feldman says. In the United States, GPP is typically an extraordinarily intense psoriasis flare. “People have psoriasis in part due to their genetics, and so they’ll be predisposed to having psoriasis, but then they’ll get an infection or be exposed to some drug that activates their immune system and causes the psoriasis to severely flare up,” Feldman says. A urinary tract infection or pneumonia, for instance, could cause somebody who has psoriasis to experience a GPP flare. In addition to infections, stress and pregnancy are frequent causes of GPP flares, according to the National Psoriasis Foundation. Systemic IV corticosteroid treatment withdrawal could also trigger a GPP flare during the tapering process. So could the use of certain medications, including antibiotics and antifungals, says Feldman. Doctors unfamiliar with GPP may misdiagnose symptoms as an infection, especially in patients experiencing a flare for the first time. Just like GPP, “infections cause pus and fevers and chills,” Feldman explains. Often when patients come to the doctor with GPP, they are very sick. In addition to making a diagnosis, their healthcare provider may also need to decide whether or not the person needs to be admitted to the hospital, according to the National Psoriasis Foundation.
Prognosis of Generalized Pustular Psoriasis
There is no cure for GPP. The condition can be relapsing, meaning it recurs — either for no known reason (idiopathic) or because of exposure to a trigger. In some cases GPP can be persistent, with symptoms lasting for months. A GPP flare usually requires aggressive treatment, although in some unusual cases the rash and pustules may go away on their own. GPP is unpredictable and highly variable. Some people may experience a flare every few years; others may have multiple flares per year. About 50 percent of GPP flares require hospitalization, and a person with GPP will require hospitalization for a flare at least once every five years, according to a paper published in January 2022 in the American Journal of Clinical Dermatology. GPP and GPP treatment (specifically the use of systemic steroids) can cause life-threatening complications, leading to a mortality rate between 2 and 16 percent. But advancements in psoriasis treatment as well as a new drug for GPP are improving the outlook. Without treatment, the flares may come and go throughout a person’s lifetime. But treatment will greatly reduce the likelihood of a flare.
Spesolimab (Spevigo) for GPP
The U.S. Food and Drug Administration (FDA) approved spesolimab (Spevigo) in September 2022, making it the first and only treatment approved specifically for GPP in adults. Delivered by injection, the drug blocks the activation of the interleukin-36 receptor (IL-36R), a key part of a signaling pathway within the immune system shown to be involved in causing GPP. In the clinical trial, more than half of people treated with Spevigo showed no visible pustules within a week. “It’s exciting to have an approved drug for GPP. Because it is a rare form of psoriasis, finding enough people to test the medication in a clinical trial can be difficult,” says Feldman.
Psoriasis Medications
Doctors also treat GPP with medications developed for severe psoriasis. According to the American Academy of Dermatology (AAD), options include the following:
Oral retinoid Oral retinoids are a class of medication derived from vitamin A. The FDA approved one kind, acitretin, to treat severe psoriasis. It is one of the more effective treatments but comes with more serious side effects.Biologics Biologics are drugs that target the part of the immune system that is overactive because of psoriasis, decreasing inflammation (and bumps) quickly. Infliximab (Remicade) often begins calming GPP flares very rapidly. Adalimumab (Humira) or etanercept (Enbrel) are other choices.Apremilast (Otezla) This drug works by controlling inflammation in the immune cells.Methotrexate This very strong medication suppresses the overactive immune system.Cyclosporine This reliable and fast-acting medication also works by suppressing the immune system, says Feldman.
Physicians may find it necessary to administer two medications at once — for example, both etanercept and cyclosporine, or infliximab and methotrexate, or infliximab followed by etanercept, according to the AAD. In addition to these systemic treatments that focus on the immune system, physicians also need to address specific skin issues. “Often the skin of someone with GPP is treated in the same way that a person with severe burns would be treated — with special kinds of bandages, special emollients, and antibiotics,” Feldman says. If infections are a trigger, that’s more difficult: You can’t always avoid getting them, but if you do, your healthcare team should monitor you closely, says Feldman. Because tapering systemic steroids can trigger a GPP flare, people with plaque psoriasis should avoid oral or IV steroids like prednisone if possible, according to the National Psoriasis Foundation. Experts believe that alcohol and smoking make GPP worse, says Feldman. Now that there are more advanced medications for managing psoriasis as well as a drug approved to treat GPP, these complications are becoming less common, says Feldman. GPP can affect people of any skin color, says Feldman. Women are more likely to develop GPP: 62.5 percent of people with the condition are female, according to a study published in the March 2019 Atopic Dermatitis and Inflammatory Skin Disease. The average age of onset of the disease is 31 years old. Plaques are raised, inflamed, and scaly patches of skin that can be painful and itchy. In white skin, they usually look red with a silvery white buildup of scales, and on skin of color the plaques may appear thicker, and more of a purple/grayish or darker brown color. Plaques can appear anywhere on the body, but occur most often on the scalp, knees, elbows, and torso. The AAD represents most practicing dermatologists in the United States, but the organization also provides lots of resources and information for people living with skin conditions, including GPP. Its website includes a tool that allows you to search its database to find dermatologists in your area. National Psoriasis Foundation (NPF) As the leading patient advocacy group for people living with psoriatic disease, the NPF hosts an online support community for people dealing with different types of psoriasis, including GPP. It provides a wealth of patient resources, including personalized guidance on lifestyle, medications, and living with the disease. Psoriasis Cure Now This patient advocacy group specializes in raising awareness about the seriousness of psoriasis and the need for additional medical research. It also provides resources and information to encourage people with psoriasis to advocate for themselves when seeking medical care.
