Cytokine profiles in localized scleroderma and relationship to clinical features

Abstract

Localized scleroderma (LS) is a disfiguring autoimmune disease of the skin and underlying tissue that mainly affects the pediatric population. Inflammation of the tissue leads to fibrosis and atrophy, causing physical and psychological disability that can continue throughout childhood into adulthood. Available therapies for LS have had variable effects and are associated with morbidity themselves. A better understanding of the pathophysiology of LS, especially during the active inflammatory phase, would lead to more directed and efficacious therapies. As in systemic sclerosis (SSc), the other form of scleroderma, T-helper (Th) cells and their associated cytokines have been suggested to contribute significantly to the pathophysiology of LS supported by the presence of cytokines from these lineages in the sera and tissue of LS patients. It is postulated that the imbalance between Th1/Th2/Th17 cell subsets drives inflammation in the early stages of disease (Th1 and Th17 predominant) and fibrosis in the later stages of scleroderma (Th2 predominant). We review the available experimental data regarding cytokines in LS and compare them to available clinical disease severity and activity features. This provides the platform to launch further investigations into the role of select cytokines in the pathogenesis of LS and to provide directed therapeutic options in the future.

Overlap between linear scleroderma, progressive facial hemiatrophy and immune-inflammatory encephalitis in a paediatric cohort

“…In one of our patients, the discrete scleroderma lesion had disappeared when his hemifacial atrophy was fully developed. The skin biopsy in our patient with clinical PFH showed histological signs typical for LSCS: fibrosis associated with a lymphocytic perivascular infiltrate and IgG and IgM deposits [9]. The spectrum of extracutaneous manifestations is similar for LSCS and PFH, but they seem to be more frequent in PFH.…”

“…By studying cytokine profiles in serum and skin biopsy specimens of scleroderma patients, Th1-responses seem to play an important role in the active state of the disease, whereas Th2-responses are more important in fibrosis extent and disease damage. Th17-cells may be instrumental in the transition between these two phases as they can modulate the propagation of inflammation and the transition to the fibrotic state of the disease [9].…”

Coexistence of Ankylosing Spondylitis With Morphea: A Case Report

“…15 Similar to morphea, AS is an inflammatory disease with immune activation and recent studies have described the role of Th17 and cytokines as being involved in their development, as interleukin 17 and interleukin 23 can play a role in the pathogenesis of the disease. 16 The similarity of immunity of the two diseases may have a role for co-existence in the same patient.…”

A vitamin D analog inhibits Th2 cytokine- and TGFβ -induced periostin production in fibroblasts: a potential role for vitamin D in skin sclerosis

“…Th1 and Th17 cells are predominant in the early stages of inflammation, and Th2 cells are predominant in the late fibrosing stage,. 23 IL-4, IL-13, and IL-6, which are secreted by Th2 cells, work as profibrotic mediators. 24 IL-6 produced from dermal fibroblasts also contribute to fibrosis by activating fibroblasts to myofibroblasts, which are known to produce collagen.…”