69: PRETIBIAL MYXEDEMA

PATIENT STORY

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.

EPIDEMIOLOGY

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

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

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

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

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

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

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

ETIOLOGY AND PATHOPHYSIOLOGY

• The exact cause and mechanism have yet to be determined.

• 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.

• 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

• 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 ...