Is Graves' dermopathy a generalized disorder?

The pathogenesis of the extrathyroidal manifestations of Graves' disease-ophthalmopathy and pretibial myxedema (Graves' dermopathy)-involves fibroblast activation and increased mucin (glycosaminoglycan) production. It is unclear why fibroblasts are activated at these sites and evidence for site-specific and generalized fibroblast activation is conflicting. One previous report has demonstrated an increase in glycosaminoglycan deposition in the forearm skin of patients with Graves' disease but without pretibial myxedema. We have sought to confirm the existence of subclinical dermopathy in the forearm tissue from patients with untreated (UG) and treated (TG) Graves' disease and compared the histological changes with normal controls (C), treated toxic nodular goiter (MNG) and Graves' dermopathy specimens (PTM), using stains for mucin, elastin, glycosaminoglycans (GAGs), and HLA-DR molecules. Four of 4 PTM specimens stained positive for mucin, with varying sparse, fragmented, or dense elastin fibers. Four of 5 PTM specimens stained heavily for GAGs using colloidal iron and 2 of 5 stained heavily using colloidal gold. None of the patients in groups UG, TG, MNG, or the controls, showed mucin deposition or elastin changes. Mild staining with colloidal 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 monoclonal 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 patients with Graves' disease and a similar GAG distribution to normal controls. HLA-DR expression by fibroblast-like cells in the dermis suggests activation of these cells in the dermis of the PTM specimens, but no evidence of widespread fibroblast activation was found in the forearms of patients with Graves' disease.