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].To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Doshi DN, Blyumin ML, Kimball AB. Cutaneous manifestations of thyroid disease. Clin Dermatol 2008; 26:283.
- Fatourechi V, Pajouhi M, Fransway AF. Dermopathy of Graves disease (pretibial myxedema). Review of 150 cases. Medicine (Baltimore) 1994; 73:1.
- Fatourechi V. Thyroid dermopathy and acropachy. Best Pract Res Clin Endocrinol Metab 2012; 26:553.
- Shishido M, Kuroda K, Tsukifuji R, et al. A case of pretibial myxedema associated with Graves' disease: an immunohistochemical study of serum-derived hyaluronan-associated protein. J Dermatol 1995; 22:948.
- Bull RH, Coburn PR, Mortimer PS. Pretibial myxoedema: a manifestation of lymphoedema? Lancet 1993; 341:403.
- Ajjan RA, Watson PF, Weetman AP. Cytokines and thyroid function. Adv Neuroimmunol 1996; 6:359.
- Kahaly G, Förster G, Hansen C. Glycosaminoglycans in thyroid eye disease. Thyroid 1998; 8:429.
- Bahn RS, Heufelder AE. Pathogenesis of Graves' ophthalmopathy. N Engl J Med 1993; 329:1468.
- Harvey RD, Metcalfe RA, Morteo C, et al. Acute pre-tibial myxoedema following radioiodine therapy for thyrotoxic Graves' disease. Clin Endocrinol (Oxf) 1995; 42:657.
- Rapoport B, Alsabeh R, Aftergood D, McLachlan SM. Elephantiasic pretibial myxedema: insight into and a hypothesis regarding the pathogenesis of the extrathyroidal manifestations of Graves' disease. Thyroid 2000; 10:685.
- Davies TF. Trauma and pressure explain the clinical presentation of the Graves' disease triad. Thyroid 2000; 10:629.
- Syed AA, Jones NA, Perros P. Medical image. Acute pretibial myxoedema following thyroidectomy for Graves' disease. N Z Med J 2008; 121:108.
- Ai J, Leonhardt JM, Heymann WR. Autoimmune thyroid diseases: etiology, pathogenesis, and dermatologic manifestations. J Am Acad Dermatol 2003; 48:641.
- Schwartz KM, Fatourechi V, Ahmed DD, Pond GR. Dermopathy of Graves' disease (pretibial myxedema): long-term outcome. J Clin Endocrinol Metab 2002; 87:438.
- Pujol RM, Monmany J, Bagué S, Alomar A. Graves' disease presenting as localized myxoedematous infiltration in a smallpox vaccination scar. Clin Exp Dermatol 2000; 25:132.
- Takasu N, Higa H, Kinjou Y. Treatment of pretibial myxedema (PTM) with topical steroid ointment application with sealing cover (steroid occlusive dressing technique: steroid ODT) in Graves' patients. Intern Med 2010; 49:665.
- Kriss JP, Pleshakov V, Rosenblum A, Sharp G. Therapy with occlusive dressings of pretibial myxedema with fluocinolone acetonide. J Clin Endocrinol Metab 1967; 27:595.
- Volden G. Successful treatment of chronic skin diseases with clobetasol propionate and a hydrocolloid occlusive dressing. Acta Derm Venereol 1992; 72:69.
- Lang PG, Sisson JC, Lynch PJ. Intralesional triamcinolone therapy for pretibial myxedema. Arch Dermatol 1975; 111:197.
- Engin B, Gümüşel M, Ozdemir M, Cakir M. Successful combined pentoxifylline and intralesional triamcinolone acetonide treatment of severe pretibial myxedema. Dermatol Online J 2007; 13:16.
- Heyes C, Nolan R, Leahy M, Gebauer K. Treatment-resistant elephantiasic thyroid dermopathy responding to rituximab and plasmapheresis. Australas J Dermatol 2012; 53:e1.
- Mitchell AL, Gan EH, Morris M, et al. The effect of B cell depletion therapy on anti-TSH receptor antibodies and clinical outcome in glucocorticoid-refractory Graves' orbitopathy. Clin Endocrinol (Oxf) 2013; 79:437.
- Antonelli A, Navarranne A, Palla R, et al. Pretibial myxedema and high-dose intravenous immunoglobulin treatment. Thyroid 1994; 4:399.