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Pathogenesis and therapeutic approaches for improved topical treatment in localized scleroderma and systemic sclerosis Badea I; Taylor M; Rosenberg A; Foldvari MRheumatology (Oxford) 2009[Mar]; 48 (3): 213-21SSc is a chronic progressive disorder of unknown aetiology characterized by excess synthesis and deposition of collagen and other extracellular matrix components in a variety of tissues and organs. Localized scleroderma (LS) differs from SSc in that with LS only skin and occasionally subcutaneous tissues are involved. Although rarely life threatening, LS can be disfiguring and disabling and, consequently, can adversely affect quality of life. There is no known effective treatment for LS, and various options, including, as examples, corticosteroids and other immunomodulatory agents, ultraviolet radiation and vitamin D analogues, are of unproven efficacy. Clinical trials evaluating combination therapy such as corticosteroids with MTX or UVA1 exposure with psoralens have not been established as consistently effective. New immunomodulators such as tacrolimus and thalidomide are also being evaluated. A better understanding of the molecular and cellular mechanisms of LS has led to evaluation of new treatments that modulate profibrotic cytokines such as TGF-beta and IL-4, regulate assembly and deposition of extracellular matrix components, and restore Th1/Th2 immune balance by administering IL-12 or IFN-gamma. IFN-gamma acts by directly inhibiting collagen synthesis and by restoring immune balance. In this review, we evaluate current and future treatment options for LS and cutaneous involvement in SSc. Recent advances in therapy focus mainly on anti-fibrotic agents. Delivery of these drugs into the skin as the target tissue might be a key factor in developing more effective and safer therapy.|Animals[MESH]|Cytokines/immunology[MESH]|Drug Delivery Systems[MESH]|Genetic Therapy/methods[MESH]|Humans[MESH]|Immunologic Factors/therapeutic use[MESH]|Mice[MESH]|Scleroderma, Localized/*etiology/immunology/therapy[MESH]|Scleroderma, Systemic/*etiology/immunology/therapy[MESH] |
