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Research Article: Long-term comorbidities and mortality associations with treatment in generalized pustular psoriasis: a multi-institutional cohort study

Date Published: 2026-09-03

Abstract:
Generalized pustular psoriasis (GPP) is a rare, severe inflammatory disease with limited evidence on long-term prognosis and treatment–mortality associations. To compare mortality and major comorbidities in GPP, psoriasis vulgaris (PV), and non-psoriatic individuals, and treatment–mortality associations in GPP. Adults with GPP, psoriasis vulgaris (PV) without pustular psoriasis, and non-psoriatic controls were identified. GPP patients were 1:1 propensity score–matched to PV and non-psoriatic controls by age, sex, and race. Among GPP patients, those receiving biologics, conventional anti-psoriatic drugs, or small-molecule inhibitors were separately matched to patients treated with systemic corticosteroids alone. Primary outcome was all-cause mortality; secondary outcomes included major mortality-related comorbidities based on the ten leading causes of death per US CDC. Kaplan–Meier and Cox models estimated cumulative incidence and hazard ratios. After matching, 6,959 GPP–PV and 28,459 GPP–non-psoriatic pairs were analyzed. Over 5 years, GPP patients had higher 5-year mortality than PV (HR, 1.83; 95% CI, 1.28–2.59) and non-psoriatic controls (HR, 2.42; 95% CI, 1.99–2.94). Major comorbidity risks were higher in GPP than in PV, notably ischemic heart disease (HR, 1.34; 95% CI, 1.01–1.78), cerebrovascular disease (HR, 1.62; 95% CI, 1.06–2.47), and neurodegenerative disease (HR, 2.94; 95% CI, 1.47–5.89), and were elevated across all evaluated comorbidities compared with non-psoriatic controls. Mortality risks were particularly pronounced in patients >60 years and males. Among GPP patients, biologic therapy was associated with lower mortality than systemic corticosteroids alone (HR, 0.71; 95% CI, 0.52–0.96), whereas conventional anti-psoriatic drugs and small-molecule inhibitors were not. GPP is associated with higher mortality and comorbidity risk than PV and non-psoriatic individuals. Biologic therapy was associated with lower mortality.

Introduction:
Generalized pustular psoriasis (GPP) is a rare, severe inflammatory disease with limited evidence on long-term prognosis and treatment–mortality associations.

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