Generalized Pustular Psoriasis: Current Treatment and Innovative Therapies

TL;DR

This study examines treatment outcomes for generalized pustular psoriasis, highlighting spesolimab's effectiveness and the need for better access and standardized protocols.

Contribution

The paper presents the largest Latin American cohort for GPP and proposes a tiered treatment algorithm prioritizing IL-36 blockade.

Findings

Spesolimab achieved 100% flare-free status at 12 months compared to 50-75% recurrence with other therapies.

Complications like ARDS and acute cholangitis were observed in 33.3% of patients.

A tiered treatment algorithm prioritizing rapid IL-36 blockade was proposed for severe flares.

Abstract

Background: Generalized pustular psoriasis (GPP) is a rare, life-threatening auto-inflammatory disease driven by IL-36 pathway dysregulation leading to recurrent flares of widespread erythema, sterile pustules, and systemic symptoms. Real-world data on spesolimab - the first U.S. Food and Drug Administration (FDA)/European Medicines Agency (EMA)-approved GPP therapy - remains scarce, particularly outside Europe.

Methods: We performed a retrospective case series with prospective follow-up (2010-2025) following Consensus-based Clinical Case Reporting (CARE) guidelines. Nine patients diagnosed according to European Rare and Severe Psoriasis Expert Network (ERASPEN) criteria by board-certified dermatologists were included. Data on demographics, triggers, clinical features, complications, and treatments were collected from electronic medical records.

Results: Nine patients (100%) aged 3-61 years, including five (55.6%) female patients, were included. Obesity was the most common comorbidity (n=6, 66.7%). Steroid withdrawal was the most common trigger (n=5, 55.6%). All patients presented with generalized erythema, sterile pustules, and pain; complications observed were acute respiratory distress syndrome (ARDS) in two patients (22.2%) and acute cholangitis in one patient (11.1%). Six flares required inpatient care. Spesolimab achieved 100% flare-free status at 12 months versus 50-75% recurrence with non-IL-36 agents. A tiered treatment algorithm was proposed, prioritizing rapid IL-36 blockade in severe flares.

Conclusion: This largest Latin American GPP cohort reveals an earlier onset in pediatric patients and high complication rates. Spesolimab shows superior flare control, but access barriers persist. Standardized protocols and genetic studies in diverse populations are urgently needed.

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