Introduction
Background
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. Although the condition is most often confined to the pretibial area, it may occur anywhere on the skin. It is nearly always associated with Graves disease (see Graves Disease for more information).
Additionally, a Medscape CME course related Graves disease is Therapy Insight: Management of Graves' Disease During Pregnancy.
Pathophysiology
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 due to exposure to thyroid hormones. Both thyrotropin and thyrotropin receptor antibody binding sites are found in the plasma membranes of fibroblasts derived from the skin of patients with PTM. Long-acting thyroid stimulator (LATS), an immunoglobulin G (IgG) antibody, is present in the serum of almost all patients with PTM, but it has also been found in the serum of patients without PTM. LATS was later demonstrated to represent thyrotropin receptor autoantibodies.
Research published in 2006 suggests that it may be more than 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.1
Cell-mediated immunity, using differentially expressed T-cell surface receptors in localized PTM, has also been proposed as having a causative role.2 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.
Frequency
United States
PTM occurs in 0.5-4.3% of patients with Graves disease. PTM has also been reported in patients with Hashimoto thyroiditis, primary hypothyroidism, and euthyroidism. Peak incidence occurs in the fifth to sixth decades of life.
Mortality/Morbidity
PTM is primarily of cosmetic concern and rarely causes significant morbidity. Local discomfort and difficulty wearing shoes are expected.
Sex
Women are affected more frequently than men, with a female-to-male ratio of 3.5:1.
Age
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.
Clinical
History
- The onset of PTM most commonly occurs 1-2 years after the diagnosis of Graves disease, but it may occur earlier or later. PTM in the absence of Graves disease is uncommon. Most patients who develop PTM also have Graves ophthalmopathy, with the onset of dermopathy typically following the onset of ophthalmopathy by 6-12 months. The natural history of PTM is not well defined. Available data indicate that about 10-26% of patients eventually experience complete remission, and about 24% have partial remission.
- Skin lesions or areas of nonpitting edema appear on the anterior or lateral aspects of the legs or in sites of old or recent trauma in patients with Graves disease.
- Otherwise unexplained skin lesions or areas of nonpitting edema occur in patients with thyroid disease.
Physical
Pertinent physical findings of PTM are limited to the skin. However, physical findings consistent with Graves thyrotoxicosis are significant because they are indicative of PTM as the etiology of the skin lesions. This observation is especially true regarding the finding of proptosis because nearly all patients who develop PTM have thyroid ophthalmopathy. Ophthalmopathy usually occurs prior to dermopathy.3 Thyroid acropachy occurs in 1% of patients with Graves disease. It is clinically characterized by clubbing of the fingers and the toes, periosteal proliferation of the shafts of the phalanges and other distal long bones, and swelling of the soft tissues overlying affected bony structures. When present, acropachy usually follows dermopathy. Graves dermopathy and acropachy appear to be markers of severe ophthalmopathy.
- Primary lesion
- Early lesions are bilateral, firm, nonpitting, asymmetrical plaques or nodules.
- Hair follicles are sometimes prominent, giving a peau d'orange texture.
- Areas of nonpitting edema may develop.
- In the elephantiasic form of PTM, lesions may coalesce to give the entire extremity an enlarged, verruciform appearance.
- Overlying hyperhidrosis or hypertrichosis may be present in these cases.
- Distribution
- Lesions characteristically appear on the lateral or anterior aspect of the legs, but they may occur on the thighs,4 the shoulders, the hands, the forehead, or any other skin surface.
- Lesions often occur in areas of recent or prior trauma or skin graft donor sites.
- Color: Lesions are characteristically shiny pink to purple-brown.
Causes
- The cause is unknown.
- PTM is generally considered a cutaneous manifestation of thyroid disease.
More on Pretibial Myxedema |
 Overview: Pretibial Myxedema |
| Differential Diagnoses & Workup: Pretibial Myxedema |
| Treatment & Medication: Pretibial Myxedema |
| Follow-up: Pretibial Myxedema |
| Multimedia: Pretibial Myxedema |
| References |
| Next Page » |
References
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. Sep 1995;105(3):372-8. [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. Dec 2003;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. Nov 1998;39(5 Pt 2):846-9. [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. Nov 2007;21(10):1441-3. [Medline].
Engin B, Gümüsel M, Ozdemir M, Cakir M. Successful combined pentoxifylline and intralesional triamcinolone acetonide treatment of severe pretibial myxedema. Dermatol Online J. May 1 2007;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. Winter 1994;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. Jul 1994;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. Nov 2000;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. May 2003;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. Apr 2003;148(4):825-6. [Medline].
Fatourechi V, Pajouhi M, Fransway AF. Dermopathy of Graves disease (pretibial myxedema). Review of 150 cases. Medicine (Baltimore). Jan 1994;73(1):1-7. [Medline].
Heymann WR. Advances in the cutaneous manifestations of thyroid disease. Int J Dermatol. Sep 1997;36(9):641-5. [Medline].
Kriss JP. Pathogenesis and treatment of pretibial myxedema. Endocrinol Metab Clin North Am. Jun 1987;16(2):409-15. [Medline].
Malkinson FD, Furey N. Pretibial myxedema. Arch Dermatol. Dec 1967;96(6):737-8. [Medline].
Schwartz KM, Fatourechi V, Ahmed DD, Pond GR. Dermopathy of Graves' disease (pretibial myxedema): long-term outcome. J Clin Endocrinol Metab. Feb 2002;87(2):438-46. [Medline].
Smith TJ, Bahn RS, Gorman CA. Connective tissue, glycosaminoglycans, and diseases of the thyroid. Endocr Rev. Aug 1989;10(3):366-91. [Medline].
Somach SC, Helm TN, Lawlor KB, Bergfeld WF, Bass J. Pretibial mucin. Histologic patterns and clinical correlation. Arch Dermatol. Sep 1993;129(9):1152-6. [Medline].
Further Reading
Keywords
PTM, thyroid dermopathy, Graves disease, hyaluronic acid, thyroid ophthalmopathy, thyroid disease
