Generalized pustular psoriasis in Adult
Alerts and Notices
SynopsisGeneralized pustular psoriasis (GPP) is a rare and severe form of psoriasis that presents as a widespread eruption of sterile superficial pustules with background erythema, with or without systemic inflammation. Pustular psoriasis, particularly in the acute setting, can be a severe inflammatory disease that requires hospitalization and aggressive therapy. Untreated disease can also progress to erythroderma.
There are 3 subtypes of GPP:
- von Zumbusch type (GPP) – Acute onset of generalized erythema and pustules with systemic manifestations including fever, skin tenderness, malaise, arthralgias, headache, and nausea. After several days, the pustules resolve to become confluent, scaling plaques.
- Exanthematic type – Acute onset of small pustules that are triggered by an infection or a drug. This subtype usually lacks systemic symptoms.
- Annular subtype – Erythematous, annular lesions that have pustules at the advancing edge of a lesion and is associated with fever, malaise, and other systemic manifestations. The annular variant is the most common form of pustular psoriasis in children.
GPP can also present in infants and children, and these patients may have a known genetic mutation. Genetic associations involving interleukin-36 receptor antagonist (IL36RN); the keratinocyte nuclear factor κB adaptor protein, CARD14; and adaptor protein 1 complex, subunit 3 (AP1S3) have been discovered in European, Asian, and Pakistani populations. These may be inherited in a homozygous compound or simple heterozygous state. IL36RN mutations are most frequently associated with early-onset pustular psoriasis. Mutations in SERPINA1 and SERPINA3 have also been associated with pustular psoriasis.
Pustular psoriasis may be preceded by or may coexist with plaque psoriasis. Pustular flares can be induced by infection (Trichophyton rubrum, cytomegalovirus, Streptococcus spp, varicella-zoster, and Epstein-Barr virus), a rapid withdrawal of corticosteroids, pregnancy, medications (NSAIDs, lithium, potassium iodine, trazodone, penicillin, interferon, and hydroxychloroquine), and topical irritants such as tar and anthralin. More recently, COVID-19 infection has been shown to trigger pustular flares of psoriasis.
While tumor necrosis factor (TNF)-alpha antagonists such as infliximab and adalimumab are used to treat pustular psoriasis, they have also been reported, paradoxically, to induce it.
Patients may experience relapses and remissions over a period of years. It may be precipitated by use and withdrawal from systemic corticosteroids.
Extracutaneous manifestations of pustular psoriasis may be severe and are associated with a great deal of morbidity and mortality. The most common extracutaneous manifestations of pustular psoriasis include cholestasis, cholangitis, arthritis, intestinal pneumonitis, oral lesions, and acute renal failure. Electrolyte disturbances such as hypocalcemia may occur and can be life-threatening. Lesions may also become superinfected.
L40.1 – Generalized pustular psoriasis
238612002 – Generalized pustular psoriasis
Differential Diagnosis & Pitfalls
- AGEP – Clinically indistinguishable from pustular psoriasis. Time of onset and a drug history may help differentiate AGEP from pustular psoriasis. Antibiotics are the likely causative agents in AGEP. Histology can also help differentiate between those diagnoses. Also look for high fever, edema of the face, pustular eruption that occurs shortly after drug administration (fewer than 2 days), marked serum leukocytosis with neutrophilia, and associated petechiae, purpura, and vesicles in AGEP.
- Toxic epidermal necrolysis (TEN)
- Drug reaction with eosinophilia and systemic symptoms (DRESS) – Look for marked eosinophilia, visceral involvement (most commonly hepatitis), less acute onset, facial edema, and atypical lymphocytosis.
- Subcorneal pustular dermatosis (Sneddon-Wilkinson disease) – Associated with immunoglobulin A (IgA) paraproteinemia and is very responsive to dapsone. Pustular psoriasis is not responsive to dapsone and does not have an IgA paraproteinemia.
- Erythema annulare centrifugum – To be considered when annular-type psoriasis is observed. No associated systemic findings. Individual lesions can last for months.
- Disseminated herpes simplex infection
- Eczema with secondary infection
Drug Reaction DataBelow is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.
Patient Information for Generalized pustular psoriasis in Adult
OverviewGeneralized pustular psoriasis (GPP) is an uncommon and severe type of psoriasis where many pustules (pus-filled bumps) develop on red, inflamed skin. Individuals with GPP often have other symptoms associated with their skin disease, such as a general unwell feeling, fever, itching, or skin pain. GPP may occur as a single episode or as a long-term condition that comes and goes for many years.
While the exact cause of GPP is unclear, it appears to be the result of an overactive immune system that attacks the skin. This subtype of psoriasis may occur in individuals with or without a prior history of plaque psoriasis. It may also occur in families, as several genetic causes of GPP have been identified. Flares of GPP can be triggered by infections, stopping topical steroids or other psoriasis medications, pregnancy, low calcium levels, certain medications, and other irritants to the skin, such as sunburns.
Who’s At RiskGPP can affect people of any age, but it is most common in middle-aged adults, and it is more common in women.
Signs & SymptomsGPP commonly appears as many similarly sized pustules covering large areas of skin, such as the trunk and arms and legs. Individual pustules may begin to merge into larger collections, sometimes referred to as "lakes of pus." Pustules are often within red patches (flat areas of skin larger than a thumbnail) and may be more prominent around the edges of redness. The redness may be difficult to see in darker skin colors, where the patches may appear more purple, gray, or darker brown. The lining of the mouth can also be affected in GPP.
GPP differs from other types of localized pustular psoriasis, such as palmoplantar pustulosis. Nevertheless, people with GPP may have a personal history of plaque psoriasis. In this case, there may be pustules along with plaques (raised areas of skin larger than a thumbnail) covered by silvery scales, especially on the scalp, trunk, buttocks, genitals, elbows, or knees.
The lesions of GPP can become infected, and this condition may affect other organs in the body, such as the liver, joints, lungs, and kidneys.
Self-Care GuidelinesGPP is a severe type of psoriasis that can lead to serious complications if inadequately managed or treated. For this reason, there are no self-care measures that are adequate for treating GPP.
The National Psoriasis Foundation is an excellent resource for individuals with psoriasis, including GPP. Additional disease information can be found on their website (https://www.psoriasis.org/).
When to Seek Medical CareConcerning skin changes include widespread inflamed areas of skin and/or pus-filled lesions over patches of red skin or skin color changes. It is important to visit a dermatologist or seek urgent medical attention if you suspect you may have GPP.
TreatmentsThe widespread redness and pus-filled bumps of GPP may mimic or resemble other pustular conditions or infections. Your medical provider may do a biopsy and skin culture along with some blood tests to rule out these similar conditions.
If you have severe GPP, your medical professional may recommend hospitalization to ensure appropriate care, including hydration, nutrition, temperature regulation, and treatment of any infection.
Initial management and general care from your medical professional may include:
- Topical steroids applied to the skin with damp dressings.
- Fluid replacement.
- Screening for infection.
- Other laboratory blood tests.
- Medications for pain management.
- There is only one FDA-approved medication for GPP: spesolimab (Spevigo), which is an intravenous (IV) medication given for flares of GPP.
- Biologic medications such as infliximab (eg, Remicade), ustekinumab (Stelara), secukinumab (Cosentyx), ixekizumab (Taltz), brodalumab (Siliq), guselkumab (Tremfya), or risankizumab (Skyrizi).
- Retinoid medications such as acitretin (eg, Soriatane).
- Immunosuppressant medications such as methotrexate (eg, Trexall) or cyclosporine (eg, Neoral).
- Ultraviolet therapy, also known as phototherapy.
Generalized pustular psoriasis in Adult