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Pretibial myxedema
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Pretibial myxedema (PM), more accurately termed thyroid dermopathy, is characterized by non-pitting edema and skin-colored to violaceous nodules or plaques. These are most commonly distributed pretibially but can sometimes be seen over the arms, shoulders, head, and neck. The differential diagnosis of thyroid dermopathy includes lymphedema, lipodermatosclerosis, and the newly described obesity-associated lymphedematous mucinosis .
Management Strategy
PM is an autoimmune response to the expression of thyrotropin (TSH)-receptor antigen in skin fibroblasts, resulting in secretion and accumulation of glycosaminoglycans in the dermis and subcutaneous tissue. Autoantibodies inhibiting the binding of TSH to its receptor (TBII) has also been described. Usually occurring after treatment of Graves disease, PM may develop in hypothyroid and euthyroid patients. Exophthalmos is the commonest association. Other clinical signs of thyroid disease, including thyroid acropachy (characterized by clubbing of the fingers and toes, periosteal proliferation of the phalanges and long bones, and swelling of the soft tissue overlying bony structures) and the presence of a goiter may occur. Goals of treatment include cosmesis and the prevention of long-term sequelae such as elephantiasis, decreased range of motion, or foot drop from neural entrapment. Resolution may occur without treatment.
Patients with significant thyroid dermopathy should start a trial of high-potency topical corticosteroids , alone or under occlusion, for at least 2 months. If symptoms persist, intralesional corticosteroids may be effective. A combination of these methods in conjunction with compression bandages can be beneficial when monotherapy proves inadequate. Both oral and intravenous corticosteroids have also been shown to improve lesions in several patients. However, their use is limited by systemic side effects.
Pentoxifylline has shown efficacy and can also be used in conjunction with topical and/or intralesional corticosteroids. Despite conflicting data, intravenous immunoglobulin ( IVIG ) may improve PM. Subcutaneous or intralesional octreotide , a somatostatin analog, yields conflicting results. Intralesional hyaluronidase has emerged as a promising treatment option. Plasmapheresis has been reported to be beneficial in improving severe cases, especially when combined with rituximab.
Temporary improvement with cytotoxic agents has been observed. PM is not a life-threatening condition, and so the use of such agents should be limited to severe, debilitating cases. Surgical excision has been shown to be effective in a minority of cases. The high risk of recurrence makes surgical intervention an infrequently used modality; however, postoperative intralesional steroids can minimize this risk. Complete decongestive physiotherapy has shown some success in treating the elephantiasic form of PM.
Pretibial ultrasonography, with or without digital infrared thermal imaging, to measure skin thickness may be useful in assessing treatment response. Measuring serum hyaluronic acid levels to follow therapeutic response may also be of value.
Specific Investigations
Pretibial myxedema
Fatourechi V. In: Heymann WR, ed. Thyroid Disorders with Cutaneous Manifestations. London: Springer Verlag, 2008; 103–19.
Pretibial myxedema: case presentation and review of treatment options
Kim WB, Mistry N, Alavi A, et al. Int J Low Extrem Wounds 2014; 13: 152–4.
A classic case of PM in a 57-year-old woman treated for Graves disease is presented.
This article details how to differentiate PM from lymphedema and lipodermatosclerosis.
Pretibial myxedema as the initial manifestation of Graves’ disease
Georgala S, Katoulis AC, Georgala CJ. Eur Acad Dermatol Venereol 2002; 16: 380–3.
A 28-year-old woman presented initially with asymptomatic PM, which ultimately led to a diagnosis of Graves disease. This patient had elevated anti-TSH-receptor antibodies.
An assessment of thyroid function is warranted because most patients with PM have clinical or laboratory evidence of autoimmune thyroid disease.
Observing pretibial myxedema in patients with Graves’ disease using digital infrared thermal imaging and high-resolution ultrasonography: for better records, early detection and further investigation
Shih SR, Lin MS, Li HY, et al. Eur J Endocrinol 2011; 164: 605–11.
Digital infrared thermal imaging (DITI) detects surface temperature, and sonography reflects composition changes in soft tissue. In all patients with PM, DITI showed abnormally low focal temperatures over the lesions. In Graves disease patients with mild diffuse non-pitting edema and in Graves disease patients with normal appearance of the lower legs, DITI showed abnormally low focal temperature in 90.9% and 65.2% of the patients, respectively. Areas of clinically visible PM and low focal temperature detected by DITI were sonographically characterized with increased skin thickness, hypoechoic substance deposition in the cutaneous tissue, and blurred boundary lines between dermis and subcutaneous tissue.
Dermopathy of Graves disease (pretibial myxedema): review of 150 cases
Fatourechi V, Pajouhi M, Fransway AF. Medicine 1994; 73: 1–7.
Treatment with topical 0.05–0.1% triamcinolone acetonide cream under occlusion for 2–10 weeks led to partial remission in 29 of 76 patients in this retrospective study; 1% had complete remission.
Intralesional triamcinolone therapy for pretibial myxedema
Lang PG, Sisson JC, Lynch PJ. Arch Dermatol 1975; 111: 197–202.
Seven of nine patients treated with monthly injections of 8 mL or less of intralesional triamcinolone acetonide solution (5 mg/mL, 1 mL per injection site) had complete remission of PM after three to seven visits. The other two patients showed a partial improvement.
Pretibial myxedema: a review of the literature and case report
Frisch DR, Roth I. J Am Podiatr Med Assoc 1985; 75: 147–52.
A 29-year-old woman with PM was treated with rest, elevation, and weekly intralesional Celestone Soluspan injections followed by topical 0.05% fluocinonide cream under occlusion and compression dressings with an Unna boot left on for a week. After 2 months the lesions were greatly improved.
Compression stockings may also be beneficial. Unless contraindicated, compression should be used in conjunction with any therapeutic approach for this disorder.
Treatment of pretibial myxedema with intralesional immunomodulating therapy
Ren Z, He M, Deng F, et al. Ther Clin Risk Manag 2017; 13: 1189–94.
A group of 32 PM patients were treated prospectively with intralesional compounded betamethasone solution (betamethasone sodium phosphate 2 mg and betamethasone dipropionate 5 mg mixed with 5 mL of 5% lidocaine) injected at 1-cm intervals (total volume of 0.5–1 mL per treatment). All 32 patients achieved clinical remission at different intervals; 21.7% patients after one treatment, 34.8% with two treatments, 17.4% with three treatments, 4.3% with four treatments, and 4.3% with five treatments.
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