Abstract
Generalized pustular psoriasis (GPP) is a rare, severe neutrophilic skin disorder characterized by sudden widespread eruption of superficial sterile pustules with or without systemic inflammation. GPP flares can be life-threatening if untreated due to potential severe complications such as cardiovascular failure and serious infections. Currently, there are no GPP-specific therapies approved in the USA or Europe. Retinoids, cyclosporine, and methotrexate are the most commonly used non-biologic therapies for GPP. The evidence that supports the currently available treatment options is mainly based on case reports and small, open-label, single-arm studies. However, recent advances in our understanding of the pathogenic mechanisms of GPP and the identification of gene mutations linked to the disease have paved the way for the development of specific targeted therapies that selectively suppress the autoinflammatory and autoimmune mechanisms induced during GPP flares. Several biologic agents that target key cytokines involved in the activation of inflammatory pathways, such as tumor necrosis factor-α blockers and interleukin (IL)-17, IL-23, and IL-12 inhibitors, have emerged as potential treatments for GPP, with several being approved in Japan. The evidence supporting the efficacy of these agents is mainly derived from small, uncontrolled trials. A notable recent advance is the discovery of IL36RN mutations and the central role of IL-36 receptor ligands in the pathogenesis of GPP, which has defined key therapeutic targets for the disease. Biologic agents that target the IL-36 pathway have demonstrated promising efficacy in patients with GPP, marking the beginning of a new era of targeted therapy for GPP. Graphical abstract: [Figure not available: see fulltext.].
| Original language | English |
|---|---|
| Journal | American Journal of Clinical Dermatology |
| Volume | 23 |
| Pages (from-to) | 51-64 |
| Number of pages | 14 |
| ISSN | 1175-0561 |
| DOIs | |
| Publication status | Published - 01.2022 |
Funding
James Krueger has received grants from and been an investigator for Boehringer Ingelheim; received personal fees from AbbVie, Baxter, Biogen Idec, Delenex Therapeutics, Kineta, Sanofi, Serono, and XenoPort; and received grants from Amgen, Bristol Myers Squibb, Dermira, Innovaderm Research, Janssen, Kadmon, Kyowa Kirin, Eli Lilly, Merck, Novartis, Parexel, and Pfizer. Lluís Puig has received grants/research support or participated in clinical trials (paid to institution) from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB; received honoraria or consultation fees from AbbVie, Almirall, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Fresenius-Kabi, Janssen, JS BIOCAD, LEO Pharma, Lilly, Mylan, Novartis, Pfizer, Regeneron, Roche, Sandoz, Samsung-Bioepis, Sanofi, and UCB; and participated in company-sponsored speaker’s bureau for Celgene, Janssen, Lilly, Novartis, and Pfizer. Diamant Thaçi has served as a consultant, advisory board member, and/or investigator for Pfizer, AbbVie, Almirall, Amgen, Beiersdorf, Bristol Myers Squibb, Boehringer Ingelheim, Dainippon Sumitomo Pharma, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Maruho, Medac, MorphoSys, Novartis, Regeneron, Samsung, Sandoz, Sanofi, Sun Pharma, and UCB. This article has been published as part of a journal supplement wholly funded by Boehringer Ingelheim.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
- Centers: Center for Research on Inflammation of the Skin (CRIS)
DFG Research Classification Scheme
- 2.22-19 Dermatology
