Based on Molecular Profiling of Gene Expression, Palmoplantar Pustulosis and Palmoplantar Pustular Psoriasis Are Highly Related Diseases that Appear to Be Distinct from Psoriasis Vulgaris

Abstract

IntroductionThere is a controversy surrounding the existence of palmoplantar pustulosis (PPP) and palmoplantar pustular psoriasis (PPPP) as separate clinical entities or as variants of the same clinical entity. We used gene expression microarray to compare gene expression in PPP and PPPP.Methodology/Principal findingsSkin biopsies from subjects with PPP (3), PPPP (6), psoriasis vulgaris (10) and acral skin from normal subjects (7) were analyzed using gene expression microarray. Principal component analysis showed that PPP and PPPP were different from psoriasis vulgaris and normal acral skin. However gene expression of PPP and PPPP clustered together and could not be used to differentiate PPP from PPPP. Gene-wise comparison between PPP and PPPP found no gene to be differentially expressed at a false discovery rate lower than 0.05. Surprisingly we found a higher expression of several genes involved in neural pathways (e.g. GPRIN and ADAM23) in PPP/PPPP as compared to psoriasis vulgaris and normal acral skin. Immunohistochemistry confirmed those findings and showed a keratinocyte localization for those proteins.Conclusion significancePPP and PPPP could not be differentiated using gene expression microarray suggesting that they are not distinct clinical entities. Increased expression of GPRIN1, and ADAM23 in keratinocytes suggests that these proteins could be new therapeutic targets for PPP/PPPP.

Six-transmembrane epithelial antigens of the prostate comprise a novel inflammatory nexus in patients with pustular skin disorders

“…Histology staining confirmed the presence of intra-epidermal pustules (Figure 1A). In addition, we compared our PPP results with published transciptome profiles obtained from fresh tissues(6). The majority of genes altered in PPP (82% of PPP-increased genes and 76% of PPP-decreased genes) were confirmed by our study (see Figure E1 in the Online Repository).…”

“…The same mutations were detected in PPP and AGEP, leading to speculation that similar molecular alterations may underlie these disorders (4, 5). Interestingly, gene expression study on PPP provided evidence that select neural genes were increased, raising the possibility that unique pathways are activated in this disease(6). However, the molecular abnormalities associated with GPP, PPP and AGEP have not been systematically compared on a transcriptome-wide level, and common and/or distinct mechanisms driving these inflammatory conditions have thereby remained largely elusive.…”

Efficacy of ixekizumab compared to etanercept and placebo in patients with moderate‐to‐severe plaque psoriasis and non‐pustular palmoplantar involvement: results from three phase 3 trials (UNCOVER‐1, UNCOVER‐2 and UNCOVER‐3)

“…[1][2][3] These patients may have localized palmoplantar psoriasis [3][4][5] or generalized psoriasis in addition to the palms and soles. 6 The relationship between palmoplantar types and subtypes is an area of significant interest and research especially relating to genetic similarities and differences and therapeutic options. 5 Pure palmoplantar pustulosis is recognized as a subtype of palmoplantar psoriasis.…”

Treatment of Palmoplantar Pustulosis with the Combination of Ustekinumab and Apremilast: A Case Report

“…PPP can present by itself, or along with plaque psoriasis where it is considered Palmoplantar pustular psoriasis (PPPP) [1,2]. Genetic studies indicate that PPP may not be related to psoriasis, possibly accounting for their different responses to certain treatments, namely TNF-α antagonists [3].…”

“…Genetic studies indicate that PPP may not be related to psoriasis, possibly accounting for their different responses to certain treatments, namely TNF-α antagonists [3]. Gene expression microarray analysis has shown that PPP and PPPP are not distinct clinical entities and differ from psoriasis based on increased expression of GPRIN1 and ADAM23 at the gene and protein level [2]. PPP is more common in middle-aged women, diabetics and smokers [1].…”