Department of Dermatology, New York University
PATIENT: 75-year-old woman
DURATION: One month
DISTRIBUTION: Left shin
The patient noticed a non-tender, erythematous nodule on the left shin approximately one month ago. The lesion grew slowly in size, and new lesions developed near the original nodule. She denied a history of trauma to the leg, fevers, chills, sore throat, cough, night sweats, or weight loss. Indomethacin 25 mg three times daily for two weeks was administered with no resolution of the lesions. She has been taking levothyroxine since radiation treatment to the thyroid for Grave's disease.
On the left lateral and anterior aspect of the shin, there were three, erythematous, indurated nodules and plaques with no ulcers. The lesions were neither warm nor tender to the touch. Bilateral exophthalmos was noted but there was no appreciable thyromegaly or nodularity in the thyroid.
Complete blood count showed a white cell count of 7.5 x 109/L, hemoglobin 12.5 gm/dl, hematocrit 37.6%, and platelets 251x 109/L. Streptozyme test was negative; thyroid function tests and free T4 levels were normal. There were no infiltrates noted on a chest radiograph, however a purified protein derivative test was positive at 48 hours.
The upper dermis was thickened by extensive deposits of mucin that separated the collagen fibers. The epidermis and papillary dermis were spared.
Pretibial myxedema can be present in either Grave's disease or hypothyroidism. Pretibial myxedema is an infiltrative dermopathy that most frequently appears symmetrically on the anterior tibia and dorsa of the feet. The lesions can be morphologically variable, but commonly they consist of pink, flesh-colored to violaceous nodules. The skin can also present with a diffuse brawny edema without the nodules or in rare cases with elephantiasis nostras . In Grave's disease, myxedema tends to occur in the presence of ophthalmopathy at a later stage in the disease. One half of the cases of myxedema occur after the patient becomes euthyroid with treatment. Other manifestations of thyrotoxicosis include warm, moist and smooth skin, often accompanied by persistent flushing of the face, redness of the elbows, and palmar erythema. Other presentations can include chronic urticaria, alopecia areata, generalized pruritus, and hyperpigmentation.
Primary hypothyroidism or Hashimoto's thyroiditis can have similar myxedematous involvement in a diffuse or acral distribution. Facial changes can be characteristic with a broad nose, thick lips, large tongue, sticky secretions on the eyelids, and droopy eyelids.
Myxedema in both hyperthyroid and hypothyroid conditions results from the accumulation of increased amounts of hyaluronic acid and chondroitin sulfate in the dermis in both lesional and normal skin. The mechanism that causes myxedema is unclear although animal model studies suggest that thyroid hormones affect the synthesis and catabolism of mucopolysaccharides and collagen by dermal fibroblasts.[2,3] The fibroblasts in the orbital and pretibial dermis share antigenic sites that underlie the autoimmune process that causes Grave's disease. This cross-reaction may contribute to the development of myxedema occurring long after euthyroid status is achieved through treatment.
Treatment for myxedema is difficult. Systemic or intralesional glucocorticoids, topical glucocorticoids under occlusion or high-dose intravenous immunoglobulin have been reported to offer some relief.[4,5]
References1. Fatourechi V, Pajouhi M, Fransway AF. Dermopathy of Graves disease (pretibial myxedema).Review of 150 cases. Medicine (Baltimore). 1994 Jan;73(1):1-7. PubMed
2. Chang TC, Wu SL, Hsiao YL, Kuo ST, Chien LF, Kuo YF, Change CC, Chang TJ. TSH and TSH receptor antibody-binding sites in fibroblasts of pretibial myxedema are related to the extracellular domain of entire TSH receptor. Clin Immunol Immunopathol 1994;71(1):113-20. PubMed
3. Stadlmayr W, Spitzweg C, Bichlmair AM, Heufelder AE. TSH receptor transcripts and TSH receptor-like immunoreactivity in orbital and pretibial fibroblasts of patients with Graves' ophthalmopathy and pretibial myxedema. Thyroid. 1997 Feb;7(1):3-12. PubMed
4. Volden G. Successful treatment of chronic skin diseases with clobetasol propionate and a hydrocolloid occlusive dressing. Acta Derm Venereol 1992;72(1):69-71. PubMed
5. Antonelli A, Navarranne A, Palla R, Alberti B, Saracino A, Mestre C, Roger P, Agostini S, Baschieri L. Pretibial myxedema and high-dose intravenous immunoglobulin treatment. Thyroid 1994;4(4):399-408. PubMed
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