IS GRAVES DERMOPATHY A GENERALIZED DISORDER

The pathogenesis of the extrathyroidal manifestations of Graves' disea se-ophthalmopathy and pretibial myxedema (Graves' dermopathy)-involves fibroblast activation and increased mucin (glycosaminoglycan) product ion. It is unclear why fibroblasts are activated at these sites and ev idence for site-specific and generalized fibroblast activation is conf licting. One previous report has demonstrated an increase in glycosami noglycan deposition in the forearm skin of patients with Graves' disea se but without pretibial myxedema. We have sought to confirm the exist ence of subclinical dermopathy in the forearm tissue from patients wit h untreated (UG) and treated (TG) Graves' disease and compared the his tological changes with normal controls (C), treated toxic nodular goit er (MNG) and Graves' dermopathy specimens (PTM), using stains for muci n, elastin, glycosaminoglycans (GAGs), and HLA-DR molecules. Four of 4 PTM specimens stained positive for mucin, with varying sparse, fragme nted, or dense elastin fibers. Four of 5 PTM specimens stained heavily for GAGs using colloidal iron and 2 of 5 stained heavily using colloi dal gold. None of the patients in groups UG, TG, MNG, or the controls, showed mucin deposition or elastin changes. Mild staining with colloi dal gold for GAGs was seen in 1 each of the UG, the TG, and MNG groups , and 4 of 8 controls. Heavy staining with colloidal iron for GAGs was seen in 1 TG patient and 1 control, while moderate staining was found in several TG, UG, and controls. In 2 of 4 PTM specimens the monoclon al antibody CR3/43 (against HLA-DR) stained frequent dermal fibroblast -like cells and in 2 a lymphocytic infiltrate was seen. Only 1 of 8 UG patients had multiple CR3/43 staining cells present in the dermis: 3 of 8 TG and 1 of 8 controls had a few CR3/43 stained cells. Overall we found no evidence of dermal mucin deposition in the forearms of 16 pa tients with Graves' disease and a similar GAG distribution to normal c ontrols. HLA-DR expression by fibroblast-like cells in the dermis sugg ests activation of these cells in the dermis of the PTM specimens, but no evidence of widespread fibroblast activation was found in the fore arms of patients with Graves' disease.