An update on genetic basis of generalized pustular psoriasis (Review)

Abstract

Generalized pustular psoriasis (GPP) is a rare and severe auto-inflammatory skin disease that is characterized by recurrent, acute onset, and generalized pustular eruptions on erythematous, inflamed skin. GPP is traditionally classified as a variant of psoriasis vulgaris, even though recent clinical, histo- logical and genetic evidence suggests that it is a heterogeneous disease and requires a separate diagnosis. In recent years, vari- ants of IL36RN, CARD14, AP1S3 and MPO genes have been identified as causative or contributing to genetic defects in a proportion of patients affected by GPP. These disease-related genes are involved in common inflammatory pathways, in particular in the IL-1/IL-36-chemokines-neutrophil patho- genic axis. At present, no standard therapeutic guidelines have been established for GPP management, and there is a profound need for novel efficacious treatments of GPP. Among them, biological agents antagonizing the IL-36 pathway are prom- ising therapeutics. The aim of the present review is to provide the most recent updates on the genetics, genotype-phenotype correlation and pathological basis of GPP, as well as on biologic treatments available for GPP and relative clinical courses.