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  • Title: Elephantiasic pretibial myxedema: insight into and a hypothesis regarding the pathogenesis of the extrathyroidal manifestations of Graves' disease.
    Author: Rapoport B, Alsabeh R, Aftergood D, McLachlan SM.
    Journal: Thyroid; 2000 Aug; 10(8):685-92. PubMed ID: 11014313.
    Abstract:
    The basis for the extrathyroidal manifestations of Graves' ophthalmopathy (GO) and dermopathy are not well understood. We describe immunohistochemical studies on the skin of a patient with an extreme, elephantiasic form of Graves' dermopathy that developed after periods of prolonged standing with dependent edema. Excision of part of the lesion with subsequent skin grafting from a normal donor site resulted in recurrence of the disease at the original site as well as in development of disease at the donor site. A murine monoclonal antibody reacted with the thyrotropin receptor (TSHR) or a cross-reacting protein in fibroblast-like cells in the patient's upper dermis and, surprisingly, with dermal cells from unaffected individuals. The patient's dermis containing lymphoid follicles comprising B cells and CD3+, CD4+ T cells, with few CD8+ T cells. CD21+ cells (most likely follicular dendritic cells) were also present in the dermis. Based on past and present observations, we raise an unifying hypothesis to explain the diverse extrathyroidal manifestations of Graves' disease and their apparent lack of association with TSHR autoantibodies. As opposed to the present concept that these phenomena relate to site-specific properties on preadipocytes or fibroblasts, we suggest that clinically evidence GO and dermopathy are primarily caused by local factors (particularly in the orbit) superimposed on a systemic, low-grade connective tissue inflammation.
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