Pretibial myxedema (PM), also known as thyroid dermopathy, is a localized skin condition caused by the abnormal accumulation of complex carbohydrate molecules called glycosaminoglycans in the deep layers of the skin. Hyaluronic acid, the main component of this buildup, leads to swelling and thickening of the affected skin. This rare, extrathyroidal manifestation, meaning it occurs outside of the thyroid gland, is almost always seen in people with underlying autoimmune thyroid disease.
Clinical Presentation and Appearance
Pretibial myxedema most often affects the skin on the front and sides of the lower legs (the pretibial area). The lesions usually present as firm plaques or nodules displaying non-pitting edema, meaning pressing on the area does not leave an indentation. Common forms include diffuse swelling or distinct raised, thickened plaques.
The skin surface may appear waxy or shiny, sometimes resembling the dimpled surface of an orange peel (peau d’orange). Color changes are common, with lesions often appearing pink, purple, yellow-orange, or brownish. In rare, advanced cases, the lesions may coalesce into a larger, warty, or elephantiasic form associated with significant lymphedema.
The Underlying Cause
Pretibial myxedema is a manifestation of severe autoimmune thyroid disease, overwhelmingly associated with Graves’ disease. The cause is an immunological process where the immune system targets its own tissues. Specifically, the skin’s fibroblasts, which produce connective tissue components, are stimulated inappropriately.
This stimulation is driven by Thyroid Stimulating Hormone Receptor Antibodies (TRAbs), the same autoantibodies that cause hyperthyroidism. TRAbs bind to and activate TSH receptors on the fibroblasts. The activated fibroblasts then produce excessive amounts of glycosaminoglycans, primarily hyaluronic acid, which accumulates in the dermis and subcutis.
The condition can arise even after hyperthyroidism has been treated and the patient is in a euthyroid state (normal thyroid hormone levels). This highlights that the primary driver is the lingering autoimmune process, indicated by high TRAb concentrations, rather than current thyroid hormone levels. Localization to the lower legs is thought to be influenced by mechanical factors such as gravity and prior trauma.
Diagnosis and Differentiation
Diagnosis is often made clinically, based on the characteristic appearance of the lesions in a patient with a history of Graves’ disease. Evaluation includes thyroid function tests (TFTs), measuring TSH, free T3, and free T4 levels, to assess current thyroid status. Testing for the presence and concentration of TRAbs is also performed, as high levels strongly support the autoimmune nature of the condition.
The condition must be differentiated from other causes of lower leg swelling and skin changes, such as venous stasis, lymphedema, and cellulitis. If the clinical presentation is atypical or uncertain, a skin biopsy may be used for confirmation. The biopsy specimen characteristically shows extensive deposition of mucin (glycosaminoglycans) throughout the dermis and subcutis.
Management and Treatment Options
Treatment focuses on managing the localized skin lesions, as resolving the underlying thyroid condition does not always resolve the skin changes. The mainstay of local therapy is high-potency topical corticosteroids. These are often applied under occlusion, such as a plastic wrap dressing, to enhance absorption and effectiveness.
Compression therapy, utilizing stockings or socks that apply 20–40 mmHg pressure, helps reduce associated swelling and improve appearance. For thick lesions resistant to topical treatment, corticosteroids may be injected directly into the nodules (intralesional injection).
If the condition is severe and unresponsive to local measures, systemic treatments may be considered, though evidence for long-term efficacy is less conclusive. Systemic options include octreotide, a somatostatin analog, or immunomodulating therapies like plasmapheresis. The goal of treatment is to slow glycosaminoglycan production and reduce skin inflammation and thickness.