INTRODUCTION
Generalized pustular psoriasis (GPP) is a rare, chronic, severe autoinflammatory dermatosis distinguished by abrupt flares of sterile pustulation, systemic inflammation, and substantial morbidity and mortality.1-4 Once viewed as a variant of plaque psoriasis, accumulating epidemiologic, clinical, and mechanistic evidence now establishes GPP as a distinct disease entity with unique diagnostic challenges, extracutaneous manifestations, and therapeutic priorities. Patients may require hospitalization during flares, exhibit marked laboratory evidence of systemic inflammation, and experience recurrent disease associated with significant health care utilization and excess morbidity and mortality.4-8 In addition, GPP is associated with substantial economic burden, with average annual direct healthcare costs of approximately USD 23,675 per patient, driven primarily by inpatient care, and with all-cause hospitalization rates ranging from 12.6% to 44%, underscoring the high healthcare utilization associated with GPP.9 Advances in disease biology have identified dysregulated innate immune signaling, centered on the interleukin-36 pathway, as the principal driver of neutrophilic inflammation and pustule formation, reshaping contemporary treatment paradigms.10-12 This review synthesizes consensus guidance, realworld evidence, randomized clinical trials, and meta-analyses to define the clinical spectrum of GPP, clarify diagnostic and management frameworks, and highlight IL-36 pathway inhibition as the cornerstone of modern, diseasespecific therapy.6,13-16
Generalized Pustular Psoriasis Epidemiology and Cutaneous Manifestations
Epidemiology
GPP is rare compared with plaque psoriasis, with population-based prevalence estimates ranging from approximately 1 to 180 cases per million, depending on geographic region and case definition.2 By contrast, psoriasis overall affects approximately 2–4% of the population in many Western countries (equivalent to 20,000–40,000 cases per million).17,18 Marked geographic variability has been reported in GPP, including higher prevalence estimates in US (~90 per million), South Korea (88–124 per million), and China (~140 per million), intermediate estimates in Sweden (15.3 per million) and Japan (7.46 per million), and lower estimates in France (1.76 per million), suggesting contributions from genetic background, environmental factors, and diagnostic practices.1,2 Several epidemiologic studies also suggest that GPP occurs more frequently in females than in males, although the magnitude of this difference varies across populations.3 National data further highlight methodological heterogeneity; for example, in Spain, the 5-year prevalence and incidence of GPP have been estimated at ~13 and ~7 per million, respectively, whereas hospitalization-based analyses report an incidence of ~3.18 per million/year, reflecting capture of more severe disease.4
Generalized Pustular Psoriasis Epidemiology and Cutaneous Manifestations
Epidemiology
GPP is rare compared with plaque psoriasis, with population-based prevalence estimates ranging from approximately 1 to 180 cases per million, depending on geographic region and case definition.2 By contrast, psoriasis overall affects approximately 2–4% of the population in many Western countries (equivalent to 20,000–40,000 cases per million).17,18 Marked geographic variability has been reported in GPP, including higher prevalence estimates in US (~90 per million), South Korea (88–124 per million), and China (~140 per million), intermediate estimates in Sweden (15.3 per million) and Japan (7.46 per million), and lower estimates in France (1.76 per million), suggesting contributions from genetic background, environmental factors, and diagnostic practices.1,2 Several epidemiologic studies also suggest that GPP occurs more frequently in females than in males, although the magnitude of this difference varies across populations.3 National data further highlight methodological heterogeneity; for example, in Spain, the 5-year prevalence and incidence of GPP have been estimated at ~13 and ~7 per million, respectively, whereas hospitalization-based analyses report an incidence of ~3.18 per million/year, reflecting capture of more severe disease.4
