F1000ResearchF1000Research2046-1402F1000 Research LimitedLondon, UK10.12688/f1000research.159565.1CorrespondenceArticlesComments about the comparative bulk RNA sequencing between palmoplantar pustulosis and dyshidrotic palmoplantar eczema
[version 1; peer review: 2 approved]
YatsuzukaKazukiConceptualizationValidationWriting – Original Draft PreparationWriting – Review & Editinghttps://orcid.org/0000-0001-7747-0551a1MutoJunConceptualizationValidationWriting – Review & Editing1MurakamiMasamotoConceptualizationSupervisionWriting – Review & Editing2
Department of Dermatology, Ehime University, Toon, Ehime Prefecture, 791-0295, Japan
Department of Anatomy, Miyazaki University, Miyazaki, Miyazaki Prefecture, 889-1692, Japandoctorkynt@gmail.com
Competing interests: K.Y. has received speaker's fees from Abbvie, Eli Lilly, Janssen, Maruho, Novartis, Sun pharma, Taiho, and UCB outside the submitted work. K.Y. has received research grants from Sun pharma outside the submitted work. J. M. has received speaker's fees from Abbvie, Eli Lilly, and Maruho outside the submitted work. J.M. has received research grants from Rohto outside the submitted work. M.M. has received speaker's fees from Abbvie, Amgen, Eli Lilly, Janssen, Kyowa Kirin, Maruho, Novartis, and Taiho outside the submitted work. M.M. has received research grants from Abbvie outside the submitted work. M.M. has received consulting fees from Amgen outside the submitted work.
This correspondence discusses the recent findings by Straalen et al., highlighting molecular similarities and distinctions between palmoplantar pustulosis (PPP) and dyshidrotic palmoplantar eczema (DPE). The study emphasizes shared proinflammatory pathways and T-cell–related gene upregulation while detailing unique features such as neutrophil involvement in PPP and lipid antigen processing in DPE. We elaborate on histopathological differences, especially intraepidermal vesicle formation in PPP linked to IL–1–mediated pathways and the absence of hyaluronan expression, contrasting with Th2 cytokines-driven spongiosis in DPE. By addressing IL-4, hyaluronan synthases, and keratinocyte adhesion molecules, this correspondence aims to deepen understanding of PPP and DPE pathophysiology.
palmoplantar pustulosisdyshidrotic eczemapsoriasisRNA sequencingintraepidermal vesicleThe author(s) declared that no grants were involved in supporting this work.
To the Editor:
We read with great interest the recent report by Straalen et al.
1 describing molecular overlap among inflammatory palmoplantar diseases, including palmoplantar pustulosis (PPP), palmoplantar psoriasis (palmPP), and dyshidrotic palmoplantar eczema (DPE). Their findings highlight shared upregulation of proinflammatory cytokines, chemokines, and T-cell–associated genes. Research in this field often lacks rigorous inclusion criteria, such as consistent diagnostic and sampling standards, making studies such as theirs—which has high reproducibility—extremely valuable for advancing global clinical trials. We sincerely commend their work. In addition to identifying shared molecular characteristics, the study elucidated unique features of each disease, such as enriched neutrophil processes in PPP (and, to a lesser extent, in palmPP) and lipid antigen processing in DPE.
1 These findings further clarify the histological and pathophysiological differences between PPP and DPE, which are of particular interest to us.
PPP is a persistent pustular skin condition that primarily affects the palms and soles. It is marked by the presence of erythema, pustules, and irregular peeling of the skin with or without psoriasis vulgaris.
2 In Japan, PPP rarely co-occurs with psoriasis, whereas in Western countries, it is frequently associated with psoriasis. Our group has proposed subdividing PPP into type A (rarely associated with psoriasis) and type B (frequently associated with psoriasis).
2 Type A PPP is distinguished by the clinical feature of intraepidermal vesicles preceding pustule formation.
2 We recently demonstrated that interleukin (IL)-1 present in eccrine sweat could infiltrate the epidermis via the acrosyringium, impairing E-cadherin expression on keratinocytes and contributing to the development of intraepidermal vesicles in type A PPP.
3 Conversely, the mechanisms underlying intraepidermal vesicle formation in DPE remain poorly understood. Spongiosis, a hallmark of eczema, is associated with hyaluronan production and reduced E-cadherin expression, driven by IL-4, IL-13, and interferon-γ (IFN-γ)-stimulated keratinocytes.
4 Notably, we previously observed that keratinocytes around PPP-associated vesicles lack hyaluronan expression, unlike those in DPE.
5 These findings strongly suggest that the mechanisms of intraepidermal vesicle formation differ between PPP and DPE.
Straalen et al. confirmed and redefined clinical diagnoses of PPP and DPE using biopsy samples, diagnosing PPP based on “intraepidermal vesicles” without spongiosis and with potential microabscesses at the edges.
1,
6 These criteria align with type A PPP, increasing our interest in their study. The authors reported higher expression of IL-13 and IFN-γ in DPE than in PPP,
1 which aligns with our understanding and represents an intriguing confirmation of these findings.
To elucidate further the pathophysiology of PPP and DPE, we invite the authors to share their opinions and any detailed findings regarding IL-4 expression, hyaluronan synthases 1 to 3, and intercellular adhesion factors of epidermal keratinocytes, such as cadherins and desmogleins.
Ethics and consent
Ethical approval and consent were not required.
Acknowledgements
None.
Data availability
No data are associated with this article.
ReferencesStraalenKRvanKirmaJYeeCM:
Disease heterogeneity and molecular classification of inflammatory palmoplantar diseases.J. Allergy Clin. Immunol.2024;154(5):1204–1215.e9.
3908933410.1016/j.jaci.2024.07.017MurakamiMTeruiT:
Palmoplantar pustulosis: Current understanding of disease definition and pathomechanism.J. Dermatol. Sci.2020;98(1):13–19.
3220108510.1016/j.jdermsci.2020.03.003YatsuzukaKKawakamiRNikoY:
A fluorescence imaging technique suggests that sweat leakage in the epidermis contributes to the pathomechanism of palmoplantar pustulosis.Sci. Rep.2024;14(1):378.
3817232710.1038/s41598-023-50875-xPMC10764317OhtaniTMemezawaAOkuyamaR:
Increased hyaluronan production and decreased E-cadherin expression by cytokine-stimulated keratinocytes lead to spongiosis formation.J. Invest. Dermatol.2009;129(6):1412–1420.
1912265010.1038/jid.2008.394MurakamiMMutoJMasuda-KurokiK:
Pompholyx vesicles contain small clusters of cells with high levels of hyaluronate resembling the pustulovesicles of palmoplantar pustulosis.Br. J. Dermatol.2019;181(6):1325–1327.
3125439010.1111/bjd.18261Masuda-KurokiKMurakamiMKishibeM:
Diagnostic histopathological features distinguishing palmoplantar pustulosis from pompholyx.J. Dermatol.2019;46(5):399–408.
3091946310.1111/1346-8138.1485010.5256/f1000research.175314.r352003Reviewer response for version 1CarneiroSueli1Referee
Federal University of Rio de Janeiro, RJ, Brazil
Competing interests: No competing interests were disclosed.
The authors agree with the findings of Straalen et al. and confirm that the redefinition of the clinical diagnoses of PPP and DPE were of great clinical and histopathological value. The authors further state that such findings, criteria and definitions align with their type A PPP criteria, including in relation to greater expression of IL-13 and IFN-γ in DPE than in PPP.
They close the communication by inviting authors to share their opinions and any other detailed findings on the expression of interleukins and cell aggregation factors.
Are arguments sufficiently supported by evidence from the published literature or by new data and results?
Yes
Is the conclusion balanced and justified on the basis of the presented arguments?
Yes
Is the rationale for commenting on the previous publication clearly described?
Yes
Are any opinions stated well-argued, clear and cogent?
Yes
Reviewer Expertise:
Dermatology, Rheumatology and Immunodermatology and Immunorheumatology
I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.
YatsuzukaKazukiDermatology, Ehime University, Toon, Ehime Prefecture, Japan
Competing interests: No competing interests were disclosed.
1312025
Thank you for taking your valuable time to review our paper.
Sincerely,
Kazuki Yatsuzuka
10.5256/f1000research.175314.r352002Reviewer response for version 1SunYulong1Refereehttps://orcid.org/0000-0002-6811-5926LiHuijuan2Co-referee
Northwestern Polytechnical University, Xi'an, Shaanxi, China
School of Electrical Engineering, Shaanxi Polytechnic Institute, Xianyang, Shaanxi, China
Competing interests: No competing interests were disclosed.
The advent of high-throughput omics technologies, particularly bulk transcriptome sequencing, has revolutionized our understanding of complex diseases over the past two decades. This innovative approach has been crucial for elucidating disorders with overlapping clinical presentations, such as palmoplantar pustulosis (PPP), non-pustular palmoplantar psoriasis (palmPP), and wet palmoplantar eczema (DPE). In this context, the work of Straalen et al. offers valuable insights into the transcriptomic profiles of these closely related conditions. Their study includes a comprehensive analysis of disease samples, comprising lesion samples from PPP (n = 533), palmPP (n = 555), and DPE (n = 528), alongside skin samples from 10 healthy individuals and 5 healthy non-acral sites. This systematic mapping enhances our understanding of these three diseases and highlights the distinctive features of their immune microenvironments
1.
Kazuki Yatsuzuka et al. have provided a comprehensive summary of the work by Straalen et al., effectively analyzing the clinical characteristics and challenges associated with diagnosing and treating three specified skin diseases
2. They articulate the clinical significance of this research, emphasizing its relevance for improving diagnostic and therapeutic strategies in this field. The authors recommend a more nuanced molecular classification of Palmoplantar Psoriasis (PPP), particularly considering the frequent co-occurrence of psoriasis, which may enhance awareness and understanding of this condition. Furthermore, the authors elucidate the differing mechanisms underlying intraepidermal vesicle formation in each disorder by examining the pathophysiological and histological distinctions between PPP and Dyshidrotic Eczema (DPE). This insight offers a valuable foundation for accurately diagnosing and treating these often-confused conditions. Overall, this work has significant implications for advancing our understanding of dermatological research and clinical practice.
Are arguments sufficiently supported by evidence from the published literature or by new data and results?
Yes
Is the conclusion balanced and justified on the basis of the presented arguments?
Yes
Is the rationale for commenting on the previous publication clearly described?
Yes
Are any opinions stated well-argued, clear and cogent?
Yes
Reviewer Expertise:
psoriasis
We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.
References:
Disease heterogeneity and molecular classification of inflammatory palmoplantar diseases.J Allergy Clin Immunol.2024;154(5) :
10.1016/j.jaci.2024.07.0171204-1215.e93908933410.1016/j.jaci.2024.07.017YatsuzukaKazukiDermatology, Ehime University, Toon, Ehime Prefecture, Japan
Competing interests: No competing interests were disclosed.
1312025
Thank you for taking your valuable time to review our paper.