- Author: Ranjodh Singh Gill, MD, FACP, CCD; Chief Editor: Dirk M Elston, MD more...
Pretibial myxedema (PTM) or, more appropriately, thyroid dermopathy is a term used to describe localized lesions of the skin resulting from the deposition of hyaluronic acid, usually as a component of thyroid disease. Thyroid dermopathy occurs rarely. Although PTM is most often confined to the pretibial area, it may occur anywhere on the skin, especially the ankle, dorsum of the foot, knees, shoulders, elbows, upper back, pinnae, nose, and neck. It is nearly always associated with autoimmune thyroid disease (ie, Graves Disease for more information).
Pretibial myxedema (PTM) occurs as a result of the deposition of hyaluronic acid in the dermis and subcutis. The precise cause of this phenomenon remains uncertain. A leading theory proposes that fibroblasts are stimulated to produce abnormally high amounts of glycosaminoglycan under the influence of cytokines due to exposure to thyrotropin receptor antibody (TRAB) and antigen-specific T cells. TRAB-binding sites are found in the plasma membranes of fibroblasts derived from the skin of patients with PTM. TRAB is present in the serum of most patients with PTM (80-100%), but it has also been found in the serum of patients without PTM.
Research published in 2006 suggests that it may not be just the high level of glycosaminoglycans, but the change in percentage of the constituents of the glycosaminoglycans in the blood that leads to the development of PTM. Thyroid hormones, by means of their influence on prostaglandin metabolism, alter the synthesis and degradation of glycosaminoglycans. Prostaglandin degradation may be what is changed in the course of Graves disease, based on findings that glycosaminoglycan synthesis is reduced, as is extracellular matrix assembly in vitro with exposure to T3 excess.
Cell-mediated immunity, using differentially expressed T-cell surface receptors in localized PTM, has also been proposed as having a causative role. The fact that PTM frequently develops in areas of injury suggests that trauma may contribute to local fibroblast activation. In addition, extrathyroid manifestations of Graves disease often occur in the skin and eyes—fibroblasts within the orbits and skin were found to have phenotypic differences from other fibroblasts throughout the body.
Pretibial myxedema (PTM) occurs in 0.5-4.3% of patients with Graves disease. PTM has also been reported, but much less frequently, in patients with Hashimoto thyroiditis, primary hypothyroidism, and euthyroidism. Peak incidence occurs in the fifth to sixth decades of life.
Women are affected more frequently than men, with a female-to-male ratio of 3.5:1.
PTM may occur in children and young adults, but most cases occur in older adults, with a peak age at onset in the fifth to sixth decades of life.
Doshi DN, Blyumin ML, Kimball AB. Cutaneous manifestations of thyroid disease. Clin Dermatol. 2008 May-Jun. 26 (3):283-7. [Medline].
Kamath C, Young S, Kabelis K, Sanders J, Adlan MA, Furmaniak J, et al. Thyrotrophin receptor antibody characteristics in a woman with long-standing Hashimoto's who developed Graves' disease and pretibial myxoedema. Clin Endocrinol (Oxf). 2012 Sep. 77(3):465-70. [Medline].
Komosinska-Vassev K, Winsz-Szczotka K, Olczyk K, Kozma EM. Alterations in serum glycosaminoglycan profiles in Graves' patients. Clin Chem Lab Med. 2006. 44(5):582-8. [Medline].
Heufelder AE, Bahn RS, Scriba PC. Analysis of T-cell antigen receptor variable region gene usage in patients with thyroid-related pretibial dermopathy. J Invest Dermatol. 1995 Sep. 105(3):372-8. [Medline].
Subramanyam S, Lohiya V, Stahl EJ. Pretibial Myxedema Without Ophthalmopathy: An Initial Presentation of Graves' Disease. Am J Med Sci. 2013 Mar 19. [Medline].
Sendhil Kumaran M, Dutta P, Sakia U, Dogra S. Long-term follow-up and epidemiological trends in patients with pretibial myxedema: an 11-year study from a tertiary care center in northern India. Int J Dermatol. 2015 Aug. 54 (8):e280-6. [Medline].
Schwartz KM, Fatourechi V, Ahmed DD, Pond GR. Dermopathy of Graves' disease (pretibial myxedema): long-term outcome. J Clin Endocrinol Metab. 2002 Feb. 87(2):438-46. [Medline].
Fatourechi V, Bartley GB, Eghbali-Fatourechi GZ, Powell CC, Ahmed DD, Garrity JA. Graves' dermopathy and acropachy are markers of severe Graves' ophthalmopathy. Thyroid. 2003 Dec. 13(12):1141-4. [Medline].
Missner SC, Ramsay EW, Houck HE, Kauffman CL. Graves' disease presenting as localized myxedema in a thigh donor graft site. J Am Acad Dermatol. 1998 Nov. 39(5 Pt 2):846-9. [Medline].
Ai J, Leonhardt JM, Heymann WR. Autoimmune thyroid diseases: etiology, pathogenesis, and dermatologic manifestations. J Am Acad Dermatol. 2003 May. 48 (5):641-59; quiz 660-2. [Medline].
Lan C, Li C, Chen W, Mei X, Zhao J, Hu J. A Randomized Controlled Trial of Intralesional Glucocorticoid for Treating Pretibial Myxedema. J Clin Med Res. 2015 Nov. 7 (11):862-72. [Medline].
Ramos LO, Mattos PC, Figueredo GL, Maia AA, Romero SA. Pre-tibial myxedema: treatment with intralesional corticosteroid. An Bras Dermatol. 2015 Jun. 90 (3 Suppl 1):143-6. [Medline].
Pineda AM, Tianco EA, Tan JB, Casintahan FA, Beloso MB. Oral pentoxifylline and topical clobetasol propionate ointment in the treatment of pretibial myxoedema, with concomitant improvement of Graves' ophthalmopathy. J Eur Acad Dermatol Venereol. 2007 Nov. 21(10):1441-3. [Medline].
Türke B, Balázs C. [Treatment of pretibial myxoedema with pentoxifylline]. Orv Hetil. 2012 Oct 28. 153(43):1719-22. [Medline].
Engin B, Gümüsel M, Ozdemir M, Cakir M. Successful combined pentoxifylline and intralesional triamcinolone acetonide treatment of severe pretibial myxedema. Dermatol Online J. 2007 May 1. 13(2):16. [Medline].
Antonelli A, Navarranne A, Palla R, Alberti B, Saracino A, Mestre C, et al. Pretibial myxedema and high-dose intravenous immunoglobulin treatment. Thyroid. 1994 Winter. 4(4):399-408. [Medline].
Priestley GC, Aldridge RD, Sime PJ, Wilson D. Skin fibroblast activity in pretibial myxoedema and the effect of octreotide (Sandostatin) in vitro. Br J Dermatol. 1994 Jul. 131(1):52-6. [Medline].
Shinohara M, Hamasaki Y, Katayama I. Refractory pretibial myxoedema with response to intralesional insulin-like growth factor 1 antagonist (octreotide): downregulation of hyaluronic acid production by the lesional fibroblasts. Br J Dermatol. 2000 Nov. 143(5):1083-6. [Medline].
Rotman-Pikielny P, Brucker-Davis F, Turner ML, Sarlis NJ, Skarulis MC. Lack of effect of long-term octreotide therapy in severe thyroid-associated dermopathy. Thyroid. 2003 May. 13(5):465-70. [Medline].
Felton J, Derrick EK, Price ML. Successful combined surgical and octreotide treatment of severe pretibial myxoedema reviewed after 9 years. Br J Dermatol. 2003 Apr. 148(4):825-6. [Medline].
Deng A, Song D. Multipoint subcutaneous injection of long-acting glucocorticid as a cure for pretibial myxedema. Thyroid. 2011 Jan. 21(1):83-5. [Medline].
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(7):665-9. [Medline].