Cytokine Networks in Lichen Sclerosus: A Roadmap for Diagnosis and Treatment?

Abstract

Lichen sclerosus (LS) is a chronic inflammatory skin disorder primarily affecting the anogenital region, leading to symptoms such as itching, pain, and sexual dysfunction, all of which significantly impact patients' quality of life. Due to the non-specific nature of its early symptoms, diagnosis is often delayed. This review examines the cytokine networks involved in LS, with a focus on immune activation, the role of T-helper (Th)1 cells, and the interaction between inflammatory mediators and the extracellular matrix, particularly in fibrosis. By providing an updated understanding of LS immunopathogenesis, this review highlights key mediators involved in disease progression and offers insights into personalized treatment strategies that may improve patient outcomes. Additionally, current therapeutic approaches and future directions in LS management are discussed.

Keywords: ECM1; TGFβ; chemokines; cytokines; lichen sclerosus; pathogenesis.

Figure 1

Dermoscopic and clinical pictures of vulvar LS. Dermoscopy (left panel) shows white structureless areas, chrysalis-like structures, and linear and/or reticular vessels. Clinically (right panel), advanced LS presents with fusion of the labia minora and labia majora, clitoral hooding, and a reduction of the vaginal introitus.

Figure 2

Schematic representation of the main pathogenetic mechanisms in LS. The complex interplay between genetic, immunological, mechanical, physical, and infectious agents leads to the development of LS-specific changes in affected skin: interface dermatitis with inflammatory cells at the dermal–epidermal junction level, derma sclerosis (especially in the upper dermis), epidermal atrophy (blue square), hyperkeratosis (pink square), basal degeneration (yellow square). Created with BioRender.com.

Figure 3

Schematic representation of the main interactions of ECM1 in the upper dermal compartment. In the dermis, ECM1 is mostly present in the upper dermis and at the DEJ (dermal–epidermal junction) level. ECM1 functions as a glue for dermal proteins, including collagen and proteoglycans. ECM1 is also crucial for maintaining DEJ integrity through binding with perlecan and integrins on basal keratinocytes. Lastly, ECM1 also colocalizes with collagen V and shares with this molecule a key role in modulating the activation and the release of pro-fibrotic growth factors hidden in the dermis. KC: keratinocyte; PDGF: platelet-derived growth factor; FGF: fibroblast growth factor; ECM1: extracellular matrix protein 1; LTGF: latent transforming growth factor β. Created with BioRender.com.