RESUMO
Prurigo nodularis (PN) is an intensely pruritic, inflammatory skin disease with a poorly understood pathogenesis. We performed single-cell transcriptomic profiling of 28,695 lesional and nonlesional PN cells. Lesional PN has increased dysregulated fibroblasts (FBs) and myofibroblasts. FBs in lesional PN were shifted toward a cancer-associated FB-like phenotype, with POSTN+WNT5A+ cancer-associated FBs increased in PN and similarly so in squamous cell carcinoma. A multicenter cohort study revealed an increased risk of squamous cell carcinoma and cancer-associated FB-associated malignancies (breast and colorectal) in patients with PN. Systemic fibroproliferative diseases (renal sclerosis and idiopathic pulmonary fibrosis) were upregulated in patients with PN. Ligand-receptor analyses demonstrated an FB neuronal axis with FB-derived WNT5A and periostin interactions with neuronal receptors melanoma cell adhesion molecule and ITGAV. These findings identify a pathogenic and targetable POSTN+WNT5A+ FB subpopulation that may predispose cancer-associated FB-associated malignancies in patients with PN.
Assuntos
Moléculas de Adesão Celular , Fibroblastos , Prurigo , Análise de Célula Única , Proteína Wnt-5a , Humanos , Proteína Wnt-5a/metabolismo , Proteína Wnt-5a/genética , Moléculas de Adesão Celular/metabolismo , Moléculas de Adesão Celular/genética , Prurigo/patologia , Prurigo/metabolismo , Prurigo/genética , Fibroblastos/metabolismo , Fibroblastos/patologia , Feminino , Masculino , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Perfilação da Expressão Gênica , Análise de Sequência de RNA , AdultoRESUMO
Atopic dermatitis (AD) is a pruritic inflammatory skin disease that disproportionately affects skin of color patients. African American, Asian, and Hispanic patients carry disproportionate disease burdens, with increased prevalence, disease severity, and health care utilization. AD has a unique clinical presentation in skin of color patients, often with greater extensor involvement, dyspigmentation, and papular and lichenified presentations. Erythema is also more difficult to appreciate and can result in an underappreciation of disease severity in skin of color patients. In this review, we highlight the important manifestations of AD across all skin types, including nuances in treatment.
