calcipotriene and Scleroderma--Systemic

Localized scleroderma refers to a diverse spectrum of disorders that involve fibrosis of the skin. Children are more likely than adults to develop localized forms of scleroderma. This condition may have devastating effects on growth and development such as limb asymmetry, flexion contractures, and psychological disability. The pathogenesis of localized scleroderma is unknown but its possible relation to Borrelial infection is discussed. This article reviews associated laboratory and radiologic abnormalities, and discusses implications for monitoring disease activity. There is no universally effective therapy for this idiopathic condition and therapy is limited. A rationale for treatment based on disease subtype and severity is provided.

Topics: Adrenal Cortex Hormones; Biomarkers; Calcitriol; Child; Dermatologic Agents; Humans; Immunosuppressive Agents; Methotrexate; Scleroderma, Localized; Scleroderma, Systemic; Skin; Ultraviolet Therapy

Vitamin D analogues can reduce TGF-β pro-fibrotic signaling in dermal fibroblasts, but they may also induce a potentially pro-fibrotic thymic stromal lymphopoietin (TSLP)-dependent Th2 cytokine local response. We have analyzed the net effect of topical vitamin D analogue calcipotriol (CPT) on the cytokine profile and the development of fibrosis in experimental model of bleomycin-induced fibrosis. Mice were simultaneously treated with topical CPT or vehicle cream and skin fibrosis was measured by collagen deposition, Masson's trichrome staining and hydroxyproline content. Cytokine and TSLP gene expression was evaluated by quantitative RT-PCR. We showed that in bleomycin injected skin, CPT administration significantly enhanced TSLP and IL-13 gene expression, but did not modify the expression of other cytokines. Skin fibrosis and hydroxyproline content were significantly reduced in CPT compared to vehicle-treated mice. In normal skin, topical administration of CPT lacked a direct pro-fibrotic effect. Our results demonstrate that topical CPT superinduces the expression of the TSLP/IL-13 Th2 axis in fibrotic skin, but it has a net anti-fibrotic effect. These data support the therapeutic use of topical vitamin D analogues for skin fibrosis.

Topics: Administration, Topical; Animals; Bleomycin; Calcitriol; Collagen; Cytokines; Dermatologic Agents; Disease Models, Animal; Female; Fibrosis; Humans; Hydroxyproline; Interleukin-13; Mice; Mice, Inbred C3H; Scleroderma, Systemic; Skin; Thymic Stromal Lymphopoietin; Up-Regulation

A 53-year-old woman with systemic sclerosis developed numerous cutaneous nodules, resembling keloids, on her anterior chest wall. The nodules failed to respond to therapy with topical steroid, calcipotriol, or extended photochemotherapy. This is a rare, disfiguring variant of scleroderma, unresponsive to treatment, and poorly understood.

Topics: Administration, Topical; Anti-Inflammatory Agents; Beclomethasone; Calcitriol; Dermatologic Agents; Female; Glucocorticoids; Humans; Keloid; Middle Aged; PUVA Therapy; Scleroderma, Systemic; Treatment Failure