Generalized pustular psoriasis

Generalized pustular psoriasis (GPP), also known as von Zumbusch psoriasis in its acute form, is a rare and potentially life-threatening autoinflammatory skin disorder characterized by widespread eruptions of sterile (non-infectious) pustules on erythematous (reddened) skin. Unlike the more common plaque psoriasis, GPP primarily involves the innate immune system and can occur with or without a history of plaque psoriasis. The disease presents with sudden onset of widespread painful, sterile pustules that may coalesce into lakes of pus, accompanied by systemic symptoms including high fever, malaise, and elevated inflammatory markers. Flares can be triggered by infections, withdrawal of corticosteroids, pregnancy, or certain medications. GPP predominantly affects the skin but has significant systemic implications. During acute flares, patients may develop leukocytosis, hypocalcemia, hypoalbuminemia, and liver dysfunction. Severe complications can include secondary bacterial infection, sepsis, acute respiratory distress syndrome, and cardiovascular shock, which can be fatal if not promptly treated. The disease follows a relapsing-remitting course in many patients, with flares of variable frequency and severity. Some patients experience a chronic subacute form with persistent pustulation. The genetic basis of GPP has been increasingly elucidated, with loss-of-function mutations in the IL36RN gene (encoding the interleukin-36 receptor antagonist, also known as DITRA — Deficiency of Interleukin-36 Receptor Antagonist) identified as a major cause, particularly in familial cases. Mutations in CARD14 and AP1S3 have also been implicated. Treatment of acute flares historically relied on acitretin, cyclosporine, methotrexate, and infliximab. A major therapeutic advance occurred with the approval of spesolimab, an anti-interleukin-36 receptor monoclonal antibody, specifically indicated for the treatment of GPP flares in adults. Supportive care including fluid management, infection prevention, and monitoring for systemic complications is essential during acute episodes.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Generalized pustular psoriasis