Pretibial Myxedema Masquerading as a Venous Leg Ulcer

The authors report a case of pretibial myxedema (PTM) masquerading as a venous leg ulcer to alert wound care clinicians to this diagnostic possibility. Pretibial myxedema is a localized form of mucin cutaneous deposition characterized by indurated plaques most commonly on anterior legs. It is more likely to present in patients with Graves’ disease, but it can be found in euthyroid patients as well. The physiopathology of PTM is complex, and there is an accumulation of highly hydrophilic glycosaminoglycans in the dermis. Minimal morbidity is associated with PTM, but the pruritus related to mucin deposition can be intense. The skin around venous leg ulcers and the skin changes related to PTM can have a similar clinical presentation, which may be a reason PTM is under-recognized.

This is a report on a dermatologic condition that can mimic the skin changes caused by venous insufficiency to alert clinicians about an under-recognized yet treatable comorbidity. The topics discussed involve dermatology and wound care (venous leg ulcer in an unusual setting). 

An 85-year-old woman presented to the University of Miami Hospital Wound Center (Miami, FL) with a 4-month history of painful, nonhealing leg ulcers. For several years, she had relapsing ulcers on her lower extremities. She had been treated with compression therapy using multilayered bandages without improvement. Her past medical history was significant for hypertension, and she had been hospitalized previously for pain and secondary bacterial infection. She was taking amlodipine, metoprolol, and gabapentin. There was no history of thyroid disease.

On physical examination, both legs had several well-demarcated ulcers varying in size. The left leg had 2 ulcers ranging in size from 1 cm² to 4 cm², and 6 ulcers on the right leg between 1 cm² to 10 cm² (Figures 1, 2).  All ulcers had a yellow fibrinous base. Edema was present on both legs, and the skin around the ulcers showed islands of hyperpigmentation admixed with areas of hypopigmentation. The skin also was notably tender and indurated with loss of hair and atrophy of the subcutaneous fat. In addition, she had evident bilateral nonpitting edema of the dorsum of her feet and toes. The skin of the dorsum of the feet and toes was thickened and hardened with distortion of the normal architecture of the foot. Distal pulses were palpable. Patient refused venous reflux studies.

A 4-mm biopsy of the border of the most distal ulcer of the left leg border was performed and showed a thickened epidermis with slight spongiosis. There was an edematous appearance to the upper dermal collagen. Colloidal iron stain was positive for mucin consistent with myxedema. Her thyroid-stimulating hormone (TSH) level was 1.17 (normal range 0.35–5.5). The patient was treated with Optifoam (Medline, Oklahoma City, OK) absorbing foam dressings and Fourflex (Medline, Oklahoma City, OK) elastic compression as well as 1 intramuscular injection of 40 mg triamcinolone acetonide per month for 4 months with improvement of the pruritus and decreased hardness of her skin.

Pretibial myxedema (PTM) is a localized form of mucin cutaneous deposition that presents as indurated plaques, most commonly on bilateral anterior legs. It is uncommon, occurring in approximately 1.5% of patients with Graves’ disease.^1,2 Ophthalmopathy is more frequent than PTM, and both can correlate with disease activity level.^3-5 Pretibial myxedema can appear following treatment of thyroid disease and occur in euthyroid patients² with chronic venous dermatitis.

Graves’ disease is an autoimmune hyperthyroid state caused by circulating immunoglobulin G antibodies that bind to and activate the G protein-coupled thyrotropin receptor on thyroid cells.^3,6,7 The activation of these receptors induces follicular hypertrophy and hyperplasia, increasing thyroid hormone production.³ It is possible that these circulating autoantibodies directed against TSH receptor in patients with Graves’ disease can also increase orbital adipose tissue volume, which also may be the mechanism by which PTM develops. In addition, there are antibodies directed against the insulin-like growth factor 1 receptor that may recruit and activate T cells, stimulating hyaluronan production.⁴ Pretibial myxedema consists of an accumulation of glycosaminoglycans and edema,⁸ and it is believed that the pathogenesis of PTM is complex; humoral and cellular immunity through cytokine-mediated mechanisms are implicated in the proliferation and activation of fibroblasts, expansion of adipose tissue, and fibroblast production of glycosaminoglycans that are highly hydrophilic.^3,6,9

Lesions of PTM are localized to the anterolateral aspect of the legs in the pretibial area but can also be seen elsewhere.^10,11 This typical localization of PTM may be explained by position (elevated pressure due to gravity),¹² lymphatic obstruction due to accumulation of mucin, and by the possibility that fibroblasts in the affected area may have different characteristics than fibroblasts in other areas of the body.^13,14 Pretibial myxedema lesions are nodular, coalescent, skin-colored, or pink. They have a peau d’orange appearance¹⁵ and usually are asymptomatic but can evolve into elephantiasis-like lesions. Pretibial myxedema lesions are firm and nonpitting. There is minimal morbidity related to PTM. Occasionally, more complicated presentations arise with peroneal nerve entrapment by mucinous connective tissue that can cause foot drop or faulty dorsiflexion.¹⁶ 

Myxedema treatment is instituted to achieve symptomatic relief from pruritus and avoid progression of the disease. Therapeutic options include topical application of mid- to high-potency steroids under occlusion^1,16,17 and locally injected steroids.¹⁶ Other therapies have been tried with variable degrees of success such as plasmapheresis, gradient pneumatic compression, intravenous immunoglobulin, and octreotide.^16,18 One important consideration is that therapies employed to treat the hyperthyroidism do not have an effect on cutaneous lesions; however, in some instances, the myxedema may regress spontaneously (on average after 3.5 years).¹⁶

This case is presented to familiarize wound care clinicians with an uncommon comorbidity they may encounter in patients who clinically may have venous disease. Several conditions that may go undiagnosed, such as PTM, can impact a patient’s quality of life and add to the burden of a wound. Given the similar presentation of myxedema and chronic venous leg ulcers skin changes, increasing awareness of PTM is warranted.

From the Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL