gms | German Medical Science

Introduction: Psoriasis is a major risk factor regarding the development of spondyloarthritis. The most common type is Psoriasis vulgaris which is understood to be driven mainly by increased Interleukin (IL) 23 and 17 levels. However, there are rare, pustular forms of psoriasis in which neutrophils play a dominant role: The potentially life-threatening Generalized pustular psoriasis (GPP), Palmoplantar psoriasis (PPP) and Acrodermatitis continua suppurativa Hallopeau (ACH) which merely affects fingers and toes.

Treatment of these conditions with the established psoriasis armamentarium of immunomodulating therapies is more or less a trial-and-error game because pathophysiology of these entities has not been decoded properly yet.

Methods: Focusing on differential transcriptomic differences in GPP vs. PPP bulk RNA sequencing of affected skin and healthy skin of 3 GPP and 3 PPP patients was performed and results were compared to each other and to matching healthy skin samples.

Results: PCA (Principal Component Analysis) showed 3 distinct clusters of differential gene expression profiles (lesional GPP, lesional PPP and unaffected skin). Detailed analysis of heatmaps confirmed the expected up-regulation of IL 17, IL 23 and IL 36 pathway related genes, especially in GPP. The latter has been highlighted recently in the pivotal study of Spesolimab (anti–IL-36R mAb) indicated for acute flares of GPP. Surprisingly, IL 1 signaling in PPP was lower than in healthy controls. In PPP-patients the above immune signatures, although differentially regulated, struck with a notable heterogeneity. Unexpectedly, in GPP a marked atopic milieu with an upregulated Th2 profile was detected.

Conclusion: From a translational point of view these findings explain the unsatisfying results of classical psoriasis bDMARD therapies in pustular psoriasis.

As the number of patients of this study is small further research is required to get clearer insights of pustular psoriasis to make personalized medicine in clinical immunology more likely.