The Distribution of Innervation and Immune Cell Infiltration Is Different in Genital and Extragenital Variants of Lichen Sclerosus

Abstract

Lichen sclerosus (LS) is a progressive skin disease that is characterized by chronic inflammation of either genital or extragenital skin, and it disproportionately affects women. We analyzed the distribution of nerve fibers, vanilloid receptors, cell proliferation, mast cells and macrophages in genital and extragenital LS samples, as well as in healthy skin, by using immunohistochemistry. The total amount of intraepidermal nerve fibers was lower in LS samples compared to healthy controls, while the total amount of subepidermal nerve fibers and calcitonin gene-related peptide (CGRP) positive fibers was higher in genital LS samples compared to both extragenital LS and healthy controls. Cell proliferation, macrophage and mast cell density were increased in LS samples compared to healthy controls. Genital LS had a higher macrophage density compared to the extragenital variant. Mast cell distribution significantly differed between genital and extragenital LS samples, even though their total mast cell densities were similar. These findings could explain the differences between pruritic symptoms of genital and extragenital LS and provide targets for the research of novel therapeutic strategies for LS management.

IL-17: a novel player in the pathogenesis of vulvar lichen sclerosus

“…The hallmarks of late-stage VLS lesions are superficial dermal sclerosis with an inflammatory infiltrate and atrophic epidermis. The inflammatory infiltrate in VLS is composed mainly of lymphocytes, but some other cells may be present including mast cells and macrophages [1][2][3][12][13][14]. Genital LS has been shown to have a higher number of macrophages as compared to the extragenital variant [12].…”

“…The inflammatory infiltrate in VLS is composed mainly of lymphocytes, but some other cells may be present including mast cells and macrophages [1][2][3][12][13][14]. Genital LS has been shown to have a higher number of macrophages as compared to the extragenital variant [12]. An abnormal activation of Th1 cells and overexpression of some Th1-type proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), IL-2 and interferon-γ (INF-γ) have been found in LS [2,3,10,15].…”

“…Both the primary and acquired immune response appear to be involved in the pathogenesis of this disease [1][2][3]10]. The histological features of VLS comprise a dermal inflammatory infiltrate around the dilated capillaries composed mostly of lymphocytes (CD8+ T cells and to a lesser extent, CD4+ T cells) [2,3,12,14]. In the inflammatory infiltrate in VLS, some other cells may be present e.g.…”

“…The link with other autoimmune diseases have been reported in LS [ 2 , 11 ]. The histological features of VLS comprise an inflammatory, mainly lymphocytic infiltrate around dilated capillaries and homogenized collagen in an upper, papillary dermis as well as basement membrane thickening and epidermal changes [ 1 – 3 , 12 ]. Although the histological picture of epidermis in VLS may vary, early lesions often show: vacuolar degeneration of the epidermal basal layer; hyperkeratosis; mild, irregular, occasionally psoriasiform acanthosis and epidermal oedema or thinning [ 1 , 13 ].…”