A 63-year-old woman presents for evaluation of unsightly erythematous-brown plaques on her anterior shins. The lesions appeared approximately 6 months ago and are occasionally itchy. She reports that she has delightfully but unintentionally lost 30 lb in the past year and her friends tell her she always looks “startled.” On examination her skin is warm and flushed and her palms are sweaty, while her eyes are bulging with scleral show and proptosis of the upper eyelid. Examination reveals firm, nonpitting nodular red-brown plaques on her anterior shins and dorsal feet. She is diagnosed with hyperthyroidism with thyroid dermopathy. She is referred to endocrinology for further evaluation and definitive management of her hyperthyroidism and treated topically with daily application of a class 1 corticosteroid under occlusion; her skin lesions gradually resolve. Figures 69-1 and 69-2 show typical cases of pretibial myxedema (PTM), which is classically associated with Graves disease but can occur with other thyroid diseases.

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  Localized myxedema or thyroid dermopathy is classically localized to the anterior shins; hence, it is more commonly known as PTM.

  
  
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  PTM is rare and occurs in approximately 4.3% of patients with Graves disease.¹

  
  
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  PTM is nearly always associated with Graves disease but has been reported with Hashimoto thyroiditis as well as primary hypothyroidism and euthyroidism.²

  
  
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  One-half of cases of thyroid dermopathy occur after the patient becomes euthyroid with treatment.³

  
  
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  Peak incidence is in the fifth to sixth decades of life, but it can occur in children or at any age.²

  
  
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  Females are more likely to be affected with a female-to-male ratio of 3.5:1.²

  
  
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  The disease may regress spontaneously after months to years, persist indefinitely, or evolve into the most severe variant: elephantiasis nostras verrucosa (ENV).

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  The exact cause and mechanism have yet to be determined.

  
  
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  PTM is technically a misnomer, as edema is not a prominent feature of the disorder. Rather, the deposition of dermal mucin composed of glycosaminoglycans (GAGs), including hyaluronic acid and chondroitin sulfate, leads to the characteristic skin lesions.

  
  
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  GAG deposition is thought to be due to fibroblast stimulation via activation by thyroid hormones or long-acting thyroid stimulator (LATS), an immunoglobulin G (IgG) antibody pathogenic in Graves disease.²

  
  
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  Pretibial and periorbital fibroblasts have been shown to share antigenic sites pathogenic in Graves disease, thus accounting for the development of myxedema even after destruction of the thyroid and establishment of euthyroidism.³

  
  
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  Another theory proposes that thyroid hormones alter the metabolism of GAGs primarily through decreased degradation, thus accounting for their accumulation.⁴

  
  
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  Mechanical trauma may contribute as well, given that localized myxedema may develop in areas of repetitive trauma.^5,6

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  The diagnosis is typically clinical in the setting of the characteristic pretibial skin lesions with concurrent ophthalmopathy and a history of thyrotoxicosis.⁷

  
  
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  A biopsy may be needed for confirmation in atypical cases, where the history is less clear, or when the patient has other confounding disease processes.

  
  
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  The diagnosis is unlikely to be thyroid dermopathy if ophthalmopathy is not present.

  
  
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  Patients with Graves disease will almost always have serologic evidence of autoimmune thyroid disease.⁸

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  While lesions may be morphologically variable (see Figures 69-1,69-2,69-3,69-4,69-5, and 69-6), the classical presentation consists of waxy, indurated, nonpitting, pebbly plaques that may have a peau d’orange appearance (Figure 69-3) on the anterior shins and dorsal feet. Alternatively, PTM may present as just a few skin-colored to purple-brown papules or nodules or appear as brawny nonpitting edema as in Figure 69-1. Pronounced infiltration of the dorsal toes with exaggerated skin creases is very characteristic of the disorder (see Figure 69-5).

  
  
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  Less than 1% of cases evolve into ENV, which is characterized by coalescence of plaques and marked thickening and induration of the skin with a verruciform appearance (Figure 69-4).⁹

  
  
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  PTM is often asymptomatic and only of cosmetic importance, but large plaques may be painful or pruritic.

  
  
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  Rarely hypertrichosis or hyperhidrosis is present (limited to myxedematous skin).

  
  
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  Patients often have other stigmata of Graves disease such as goiter, exophthalmos, and thyroid acropachy. Other signs of hyperthyroidism include cutaneous vasodilation causing facial flushing and palmar erythema, warm moist skin, fine soft hair, diffuse nonscarring scalp alopecia, nail changes including Plummer nails (onycholysis), or diffuse hyperpigmentation.

  
  
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  PTM is found in up to 25% of patients with concurrent exophthalmos.¹⁰

  
  
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  Patients typically manifest thyrotoxicosis first, followed by ophthalmopathy, and finally PTM (in cases where all three manifestations are present).⁹