Generalized pustular psoriasis (GPP) is a serious and rare form of psoriasis that can cause systemic symptoms. Because GPP can be life threatening, hospitalization may be necessary when a flare occurs.

Generalized pustular psoriasis (GPP) is a rare type of psoriasis. It is a chronic inflammatory skin condition that features the sudden appearance of small, pus-filled blisters (pustules) across large patches of red, inflamed skin.

GPP also causes systemic (body-wide) inflammation that can lead to symptoms such as fever, chills, dehydration, and a drop in blood pressure. If a person does not receive treatment, the inflammation can spread to vital organs. Also, the inflamed skin can peel, contributing to severe dehydration and dangerous infections, among many other possible complications.

This article provides an overview of GPP and the current guidelines on its treatment and management.

GPP is a type of psoriasis — an immune-mediated skin disorder that causes rapid skin cell turnover, redness or other skin color changes, and inflammation.

It differs from other types of psoriasis in its specific clinical presentation, severity, and underlying causes.

GPP involves the widespread formation of pustules, which appear suddenly across large areas of red, inflamed skin and can peel similarly to a burn.

More common forms of psoriasis feature thick, scaly patches of skin called plaques. GPP can cause plaques, but they are often studded with pustules.

The effects of GPP are not limited to a person’s skin. GPP causes significant systemic inflammation that can have life threatening consequences.

  • von Zumbusch variant
  • impetigo herpetiformis
  • annular GPP
  • chronic acral GPP
  • mixed presentation

The hallmark symptom of GPP is the sudden appearance of small, pus-filled blisters on inflamed skin. These pustules can be white or yellowish and may form in clusters that develop into large blistered areas.

During a GPP flare, a person can experience skin inflammation that feels similar to a severe sunburn. Tightness, tenderness, and itching or burning sensations are also possible. Flares can vary in severity and frequency but may last weeks to months.

As a flare progresses, pustules dry up and eventually form layers of brownish scabs that slowly peel off, leaving raw, tender skin exposed.

However, GPP affects more than just the skin. This type of psoriasis also causes by systemic inflammation that triggers immune and stress responses. Symptoms that can develop as a result of systemic inflammation in GPP include:

  • fever
  • chills
  • nausea
  • diarrhea
  • headache
  • extreme fatigue
  • muscle weakness
  • joint pain
  • rapid pulse
  • low blood pressure
  • leg swelling
  • eye inflammation
  • jaundice (yellowing of the skin and eyes)

If a GPP flare is severe or if a person does not receive treatment for it, widespread skin breakdown can increase the risk of infection. This can lead to sepsis, a life threatening condition in which systemic inflammation causes the body to attack its own tissues, resulting in organ damage and possible organ failure.

Health experts do not yet fully understand the exact underlying causes of GPP.

In some people, GPP has a link to a genetic change in the IL36RN gene, which is responsible for blocking certain inflammatory signals. Having a variant of IL36RN can make a person more susceptible to inflammatory skin conditions such as GPP and has an association with earlier onset of this condition.

Variants of the CARD14 gene have also been associated with GPP.

Other known triggers of GPP flares include:

  • use of certain topical medications
  • vaccines
  • withdrawal from systemic corticosteroids
  • use of anti-TNF drugs and other biologics
  • infections
  • certain medical conditions, such as hypoparathyroidism
  • pregnancy and menstruation
  • stress
  • skin injury
  • sunlight
  • smoking
  • electrolyte imbalances, such as hypocalcemia (low calcium levels)

At the physiological level, GPP occurs when dysfunction in the immune system causes the overproduction of interleukin-36 (IL-36) cytokines. IL-36 cytokines are typically involved in wound healing and immune activity.

In GPP, however, high levels of IL-36 cytokines trigger an inflammatory reaction that causes the rapid growth of immature cells within the outermost layers of skin.

The inflammatory process in the skin summons neutrophils, a type of immune cells that collect and release other substances to form the fluid in GPP pustules. The overactive immune response then sends inflammatory substances such as IL-36 into the bloodstream, affecting the rest of the body.

Doctors use a combination of a person’s clinical symptoms, medical history, and test results to diagnose GPP.

While widespread skin inflammation and pustules are classic features of GPP, this type of psoriasis can vary significantly in presentation and severity.

GPP has several subtypes, and the skin symptoms can mimic those of other conditions, such as acute generalized exanthematous pustulosis, which is a drug reaction.

To help rule out other potential conditions and to support a GPP diagnosis, healthcare professionals may perform a skin biopsy and evaluate skin samples under a microscope.

Blood work can also contribute to a GPP diagnosis by showing changes in a person’s levels of white blood cells, calcium, enzymes, and antibodies.

Treatment of GPP depends on the severity of a flare, but the goal is always the rapid and sustained clearance of pustules, skin inflammation, and systemic symptoms.

For people who are experiencing mild flares, conservative treatment with topical products and proper hydration may be enough. Doctors may prescribe antibiotics if a person has obvious signs of an infection.

When a GPP flare is severe or acute, hospitalization is often necessary to provide immediate attention for symptoms such as abnormal heart rate, low blood pressure, or sepsis.

Traditionally, doctors administer systemic medications such as cyclosporine, infliximab, and methotrexate when GPP is severe.

In 2022, the Food and Drug Administration (FDA) approved spesolimab (Spevigo), the first medication to directly target the IL-36 inflammatory pathway in GPP. A person can receive spesolimab intravenously during a GPP flare to help break the inflammatory cycle. Some people may also receive this drug as an ongoing maintenance treatment if necessary.

While Spevigo was the first FDA-approved IL-36 targeting medication, researchers are currently developing other drugs to target the IL-36 pathway, including:

  • imsidolimab (ANB019)
  • HB0034
  • zasocitinib

GPP can lead to a variety of serious and potentially life threatening complications, such as:

  • secondary bacterial skin infections
  • scarring and hyperpigmentation
  • dehydration and electrolyte imbalances
  • hyperthermia
  • multi-organ dysfunction or failure
  • sepsis

It can also contribute to secondary mental health conditions such as depression and anxiety. Additionally, some people with GPP are at an increased risk of developing co-occurring conditions such as cardiovascular disease or diabetes.

GPP is a type of psoriasis that causes sudden flares of widespread skin pustules and inflammation. Widespread skin breakdown can increase the risk of infection, which can lead to sepsis and affect organ function.

While GPP can vary in presentation and severity, treatment focuses on stabilizing vital signs and eliminating skin pustules and inflammation.

New and emerging treatments for GPP target the IL-36 inflammatory pathways that underlie this chronic condition.