Advancing Precision Medicine in Inflammatory Skin Disease - PubMed (original) (raw)

Review

Advancing Precision Medicine in Inflammatory Skin Disease

Michelle Yuan et al. Am J Clin Dermatol. 2025 Nov.

Abstract

The growing availability of targeted immunomodulatory therapies has transformed the treatment landscape for chronic inflammatory skin diseases. However, treatment selection remains largely empirical, often guided more by trial-and-error and insurance mandates than by an individual patient's underlying disease biology. This disconnect between therapeutic strategy and the need to address and calibrate for patient molecular heterogeneity undermines clinical outcomes and contributes to inefficiency in care delivery. Precision medicine offers a solution by tailoring diagnosis and treatment to the molecular and cellular features of each patient's skin disease. In this Current Opinion, we outline key clinical contexts where precision approaches can be transformative: diagnostic ambiguity, selecting treatments for an established diagnosis, and selecting treatments without a defined diagnosis or disease mechanism. We highlight advances in precision techniques such as single-cell RNA sequencing and spatial transcriptomics that enable more refined skin disease classification and accurate prediction of drug response. Although several challenges remain before these techniques can be widely adopted, such as limited biomarker validation, high costs, and a lack of breadth in research cohorts, we argue that their potential benefits, for patients, clinicians, and the broader field of dermatologic care, substantially outweigh the associated costs. We advocate for expanded funding, population-based research, and scalable diagnostics to successfully integrate precision medicine into dermatology. By combining molecular phenotyping with traditional clinicopathologic diagnosis, precision medicine can reduce therapeutic inefficiency, improve patient outcomes, and redefine care paradigms in chronic inflammatory skin disease.

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Conflict of interest statement

Declarations. Funding: J.BC. is supported by a grant from the LEO Foundation and a Merit Review Award from the Veterans Health Administration Office of Research and Development (I01CX002608). Conflict of interest: Jeffrey B. Cheng and Raymond J. Cho received grants from BMS, Janssen, Regeneron, Sanofi, and Sun Pharma outside the submitted work. Michelle Yuan, Jinwoo Lee, and Mark Taylor have no conflicts of interest that are directly relevant to the content of this article. Ethics approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Availability of data and material: No data were created in this publication. Code availability: No code was created in this publication. Author contributions: MY, MT, JL, JBC, and RJC wrote the manuscript. All authors have read and agreed to the published version of the manuscript.

Figures

Fig. 1

Inflammatory skin disease categories that would benefit from precision medicine approaches. (A) Cases suggesting more than one possible disease state, for example atopic dermatitis/psoriasis overlap conditions. (B) Selecting targeted treatments for an established diagnosis, for example psoriasis. The majority of patients (green overlap) will respond to both tumor necrosis factor (TNF) and/or interleukin (IL)-23 inhibition, with a larger percentage responding to IL-23 over TNF inhibition. A minority of patients are non-responders to neither IL-23 nor TNF inhibition, and utilization of precision medicine approaches would be critical to identify these patients before starting treatment. (C) For conditions without a diagnosis or diseases with unclear mechanisms, precision medicine approaches can identify overactivity of specific inflammatory pathways that can be therapeutically targeted. JAK Janus kinase, STAT signal transducer and activator of transcription

Fig. 2

Transcriptomic profiling of skin-resident T-cell signatures stratifies patients with overlapping features of psoriasis and atopic dermatitis. Depicted here is a UMAP (Uniform Manifold Approximation and Projection) representation of whole transcriptomes of skin-resident T cells from patients with psoriasis vulgaris (dark red clusters), atopic dermatitis (dark blue clusters), and overlapping features of both diseases (yellow clusters), as shown by their three-dimensional proximity (adapted from data in Liu et al. [13]). UMAP is a dimensionality reduction technique that simplifies complex data with many features into just several dimensions. The axes (UMAP components 1–3) are abstract dimensions that capture major patterns in the data and do not correspond to specific genes. Here, each dot represents a single cell, and clusters of dots indicate groups of cells with similar gene expression profiles visualized in a reduced three-dimensional space. While cases (B) and (C) show molecular features intermediate between psoriasis and atopic dermatitis, case (A) segregates much more closely with psoriasis

References

1. Mulcahy AW, Hlavka JP, Case SR. Biosimilar cost savings in the United States: initial experience and future potential. Rand Health Q. 2018;7(4):3. -PMC -PubMed
1. Cohen JN, Bowman S, Laszik ZG, North JP. Clinicopathologic overlap of psoriasis, eczema, and psoriasiform dermatoses: a retrospective study of T helper type 2 and 17 subsets, interleukin 36, and β-defensin 2 in spongiotic psoriasiform dermatitis, sebopsoriasis, and tumor necrosis factor α inhibitor-associated dermatitis. J Am Acad Dermatol. 2020;82(2):430–9. 10.1016/j.jaad.2019.08.023. -DOI -PubMed
1. Schäkel K, Reich K, Asadullah K, Pinter A, Jullien D, Weisenseel P, et al. Early disease intervention with guselkumab in psoriasis leads to a higher rate of stable complete skin clearance (‘clinical super response’): week 28 results from the ongoing phase IIIb randomized, double-blind, parallel-group, GUIDE study. J Eur Acad Dermatol Venereol. 2023;37(10):2016–27. 10.1111/jdv.19236. -DOI -PubMed
1. Javaid K, Andruszka C. Early disease intervention with guselkumab in psoriasis leads to a higher rate of stable complete skin clearance (‘clinical super response’): week 28 results from the ongoing phase IIIb randomized, double-blind, parallel-group, GUIDE study: an analysis with considerations for future studies. J Eur Acad Dermatol Venereol. 2024;38(4):e302–3. 10.1111/jdv.19599. -DOI -PubMed
1. Gargiulo L, Ibba L, Malagoli P, Amoruso F, Argenziano G, Balato A, et al. A risankizumab super responder profile identified by long-term real-life observation-IL PSO (Italian landscape psoriasis). J Eur Acad Dermatol Venereol. 2024;38(1):e113–6. 10.1111/jdv.19464. -DOI -PubMed

Advancing Precision Medicine in Inflammatory Skin Disease - PubMed (original) (raw)