Generalized pustular psoriasis: immunological mechanisms, genetics, and emerging therapeutics

Chih-Chun Lee; Yu-Huei Huang; Ching-Chi Chi; Wen-Hung Chung; Chun-Bing Chen

doi:10.1016/j.it.2024.12.001

Generalized pustular psoriasis: immunological mechanisms, genetics, and emerging therapeutics

Trends Immunol. 2024 Dec 27:S1471-4906(24)00303-X. doi: 10.1016/j.it.2024.12.001. Online ahead of print.

Authors

Chih-Chun Lee¹, Yu-Huei Huang², Ching-Chi Chi², Wen-Hung Chung³, Chun-Bing Chen⁴

Affiliations

¹ Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Chang Gung Memorial Hospital, Keelung, Taiwan.
² College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Dermatology, Chang Gung Memorial Hospital, Taipei, Taiwan.
³ College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Chang Gung Memorial Hospital, Keelung, Taiwan; Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Dermatology, Chang Gung Memorial Hospital, Taipei, Taiwan; Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan; Cancer Vaccine and Immune Cell Therapy Core Laboratory, Department of Medical Research, Chang Gung Memorial Hospital, Linkou, Taiwan; Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China; Xiamen Chang Gung Allergology Consortium, Xiamen Chang Gung Hospital, Xiamen, China; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan; Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan; Department of Dermatology, Beijing Tsinghua Chang Gung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China; Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan; School of Medicine, National Tsing Hua University, Hsinchu, Taiwan.
⁴ College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Chang Gung Memorial Hospital, Keelung, Taiwan; Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Dermatology, Chang Gung Memorial Hospital, Taipei, Taiwan; Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan; Cancer Vaccine and Immune Cell Therapy Core Laboratory, Department of Medical Research, Chang Gung Memorial Hospital, Linkou, Taiwan; Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China; Xiamen Chang Gung Allergology Consortium, Xiamen Chang Gung Hospital, Xiamen, China; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan; Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan; Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan; School of Medicine, National Tsing Hua University, Hsinchu, Taiwan. Electronic address: [email protected].

PMID: 39732527
DOI: 10.1016/j.it.2024.12.001

Abstract

Generalized pustular psoriasis (GPP) is a rare human autoinflammatory disorder with life-threatening systemic effects. Keratinocyte-derived interleukin (IL)-36 signaling has been identified as a key mediator of immune response in the skin of affected individuals. Recognition of various mutations along the IL-36 axis and the downstream nuclear transcription factor κB (NF-κB) signaling have established GPP as genetically, immunologically, and histopathologically distinct and amenable to immunomodulation, which is epitomized by the recent success of IL-36 antagonism. This review covers recent discoveries of the genetic and immunological underpinnings of GPP, which have proved fertile ground for improving the quality of care of this clinically challenging and debilitating condition.

Keywords: CARD14; autoinflammation; generalized pustular psoriasis; genetics; interleukin-36; neutrophils; nuclear transcription factor κB; spesolimab.

Publication types

Review