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, histological and genetic evidence suggests that it is a heterogeneous disease and requires a separate diagnosis. In recent years, variants 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 pathogenic 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 promising 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.

Permeability glycoprotein (P-gp) is an active efflux membrane transporter that has been researched extensively due to its ability to confer multidrug resistance in a wide range of cancers. P-gp has an impressively broad substrate specificity and is known to interact with hundreds of compounds, including drugs and toxins. This substrate promiscuity is the key to its physiological role, and P-gp is thought to be responsible for extruding xenobiotics and cellular metabolites, as well as maintaining tissue barriers at the blood-brain interface and gastrointestinal epithelium. In addition, P-gp is thought to be involved in regulating immune responses and is able to influence the secretion of cytokines and chemokines. This role as an immunomodulator links P-gp activity in the sinonasal epithelium with chronic rhinosinusitis (CRS), and a series of studies have provided evidence suggesting that P-gp may be a potential therapeutic target for treating CRS. Here, we highlight key knowledge about this intriguing protein, which may offer an important advancement in our understanding of CRS pathogenesis.