Genomic Profiling of the Overlap Phenotype between Psoriasis and Atopic Dermatitis

Clinical overlaps between psoriasis and atopic dermatitis (AD) are sometimes undiscernible, and there is no consensus on whether to treat the overlap phenotype as psoriasis or AD. We enrolled 41 patients diagnosed with either psoriasis or AD and clinically re-stratified them into classic psoriasis (n = 11), classic AD (n = 13), and the overlap phenotype between psoriasis and AD (n = 17). We compared the gene expression profiles of lesional and nonlesional skin biopsy tissues and the proteomic profiles of blood samples among the three comparison groups. Global mRNA expression and T-cell subset cytokine expression in the skin and protein biomarker elevation in the blood of the overlap phenotype were consistent with the profiles of psoriasis and different from the profiles of AD. Unsupervised k-means clustering indicated that the best number of distinct clusters for the total population of the three comparison groups was two, and the two clusters of psoriasis and AD were differentiated by gene expression. Our study suggests that the clinical overlap phenotype between psoriasis and AD has dominant molecular features of psoriasis, and genomic biomarkers can differentiate psoriasis and AD at molecular levels in patients with a spectrum of psoriasis and AD. Clinical overlaps between psoriasis and atopic dermatitis (AD) are sometimes undiscernible, and there is no consensus on whether to treat the overlap phenotype as psoriasis or AD. We enrolled 41 patients diagnosed with either psoriasis or AD and clinically re-stratified them into classic psoriasis (n = 11), classic AD (n = 13), and the overlap phenotype between psoriasis and AD (n = 17). We compared the gene expression profiles of lesional and nonlesional skin biopsy tissues and the proteomic profiles of blood samples among the three comparison groups. Global mRNA expression and T-cell subset cytokine expression in the skin and protein biomarker elevation in the blood of the overlap phenotype were consistent with the profiles of psoriasis and different from the profiles of AD. Unsupervised k-means clustering indicated that the best number of distinct clusters for the total population of the three comparison groups was two, and the two clusters of psoriasis and AD were differentiated by gene expression. Our study suggests that the clinical overlap phenotype between psoriasis and AD has dominant molecular features of psoriasis, and genomic biomarkers can differentiate psoriasis and AD at molecular levels in patients with a spectrum of psoriasis and AD. Back to Broad? How Molecular Profiling Facilitates Targeted Therapies of Overlapping PhenotypesJournal of Investigative DermatologyVol. 144Issue 1PreviewPsoriasis and eczema are noncommunicable inflammatory skin diseases (ncISDs) that may present with overlapping clinical and histopathological features, making their differential diagnosis a pertinent challenge for clinicians. Treatments with highly effective mAbs for psoriasis and eczema are increasingly replacing broadly acting immunosuppressant drugs such as methotrexate and cyclosporine. However, because antibodies targeting the IL-23/T helper (Th)17 axis in psoriasis and the IL-4/Th2 axis in eczema address fundamentally distinct modes of action, misdiagnosed patients may not only receive ineffective but even harmful therapies (Casale et al., 2022; Nakamura et al., 2017). Full-Text PDF