Pretibial myxedema (thyroid dermopathy) in autoimmune thyroid disease
- Terry F Davies, MD, FRCP, FACE
Terry F Davies, MD, FRCP, FACE
- Baumritter Professor of Medicine
- Icahn School of Medicine at Mount Sinai
Pretibial myxedema (also called localized myxedema, thyroid dermopathy, or infiltrative dermopathy) is an infrequent manifestation of Graves' disease. It forms the third component of the classical triad of Graves' disease (goiter, ophthalmopathy, pretibial myxedema). It is not restricted to the pretibial area but may spread to the ankle and dorsum of the foot and may present on the elbows, knees, upper back, and neck . Pretibial myxedema used to occur in up to 5 percent of patients with Graves' disease and 15 percent of patients with Graves' disease and ophthalmopathy [2,3], but the incidence of pretibial myxedema has declined considerably, probably because the diagnosis of Graves' hyperthyroidism is now established much earlier and antithyroid therapy is initiated sooner.
Pretibial myxedema also occurs, very rarely, in patients with no past or present thyroid dysfunction and in patients with chronic autoimmune thyroiditis (Hashimoto's thyroiditis). The clinical manifestations, diagnosis, and treatment of pretibial myxedema will be reviewed here. Other clinical manifestations of hyperthyroidism are reviewed separately. (See "Overview of the clinical manifestations of hyperthyroidism in adults".)
PATHOLOGY AND PATHOGENESIS
Pretibial myxedema results from the accumulation in the dermis of glycosaminoglycans (GAG), especially hyaluronic acid, secreted by fibroblasts under the stimulation of cytokines. The cytokines arise from the lymphocytic infiltration, which is best seen in early lesions. The resulting characteristic pathologic changes are mucinous edema and the fragmentation of collagen fibers with deposition of acid mucopolysaccharides (hyaluronic acid) in the papillary and reticular dermis, with subsequent extension into deeper tissue [1,4]. An increased number of fibroblasts have been reported . Clinically, one sees nonpitting edema of the dermis, due both to the hydrophilic nature of these substances and secondarily to compression of dermal lymphatics  and fragmentation of dermal collagen fibers.
The etiology of pretibial myxedema is not proven. These patients characteristically have very high serum concentrations of thyroid-stimulating hormone (TSH) receptor antibodies when compared with patients with fewer manifestations of Graves' disease.
The demonstration of TSH receptor protein expression by normal dermal fibroblasts raises the possibility that TSH-receptor antibodies and/or antigen-specific T cells initiate the inflammatory response, which stimulates the production of GAG by these cells, as seen in the accompanying Graves' orbitopathy [6,7]. Cytokines such as tumor necrosis factor alpha and gamma interferon induce GAG release from fibroblasts and may be secreted by Th1 type T cells activated by TSH receptor antigen [6-8].
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