Pretibial myxedema E03.8

Pretibial (more rarely also in the area of the forearms or shoulders) deposits of glucosamine glycans in the cutis and subcutis in the case of an underlying thyroid dysfunction (usually in hyperthyroidism, especially in immunogenic hyperthyroidism of the Graves' type.

As in endocrine orbitopathy (Graves' endocrinopathy), there is an increase in the synthesis of hyaluronic acid by fibroblasts in the subcutaneous tissue of the pretibial regions. TSH-R is considered as a target antigen in Graves' dermatopathy. Thyroid hormone receptors have been found in skin fibroblasts, sebaceous glands, smooth muscle cells and Schwann cells. Similar to Graves' orbitopathy, this rare manifestation is associated with high titers of TSHRAbs and is characterized by a large amount of glycosaminoglycans distributed in the reticular part of the dermis. TSH-R immunoreactivity has been detected in the prepuce of patients with Graves' dermatopathy.

In individual cases, there is no endocrinological reference.

In patients with immunogenic hyperthyroidism(Graves' disease). Also in Hashimoto's thyroiditis, after thyroidectomy or after treatment with thyrostatic drugs.

f>m; preferably in patients >35 LJ.

1-5% of patients with Graves ' disease develop pretibial myxedema, and about 25% of patients with exophthalmos.

Circumscribed pretibial, yellowish-brownish or whitish-gray, firm, difficult or impossible to depress, otherwise asymptomatic swellings, usually occurring as dermatologic subsymptoms of Graves`disease. Often due to retractions of the follicular ostia, orange peel-like surface. Pretiabial edema may also occur in Hashimoto thyroiditis, but also without recognizable thyroid disease.

Rarely, acropachy (club-shaped distension of the finger or toe extremities) is seen. Doughy swellings may also occur on the backs of the lower legs, face, and shoulder region. Onycholysis (often ring finger) occurs in about 10% of patients.

If prolonged, elephantiasis-like swellings of the entire lower legs also occur. These are usually associated with verrucous epidermal hyperplasia with hyperkeratosis, pruritus, and hypertrichosis.

Less commonly, myxedema may also occur on the face, shoulders, and upper extremities (see myxoedema circumskriptes below).

Epidermis is slightly acanthotic; orthokeratotic or orthohyperkeratotic keratinization. Massive mucin depots in the middle and deep dermis; these appear as optically empty spaces (fixation artifact) in HE section, between collagenous fiber bundles that have been pushed apart (detection of mucin is best achieved in Alcian blue staining). Fibroblasts only slightly increased. Low diffuse or perivascular lymphocytic infiltrate. In isolated cases, changes reminiscent of a spindle cell lipoma are found (Bolton E et al 2022).

Treatment is difficult. Relatively good success is achieved by consistent compression therapy (especially segmental compression; see lymphatic drainage below).

If moderate or unsuccessful, glucocorticoid crystal suspension such as triamcinolone (e.g., Volon A diluted 1:1 with LA such as scandicaine), external potent glucocorticoids under occlusion such as clobetasol (e.g., Dermoxin cream), surgical removal of the offending tissue if necessary. Recurrences often occur after discontinuation of therapy.

Promising success (and recommended as a therapeutic option), local radiotherapy was shown in a casuistry (Elsayad K et al. 2015).

Spontaneous healing may occur (after 3.5 years on average).

Plasmapheresis has been reported to have variable results.

The term "pretibial myxedema" is a confusing term, as"myxedema" refers to hypothyroidism.

A 72-year-old Ethiopian patient with a very rare case of biopsy-proven pretibial myxedema in a euthyroid state with no history of thyroid disease and no thyroid autoimmune markers. The skin lesion regressed after topical application of corticosteroids. (see Fig./Ambachew R et al. 2021)

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2. Anderson CK et al (2003) Triad of exophthalmos, pretibial myxedema, and acropachy in a patient with Graves' disease. J Am Acad Dermatol 48: 970-972.
3. Bartalena L et al (2014) Extrathyroidal manifestations of Graves' disease: a 2014 update. J Endocrinol Invest 37:691-700
4. Bolton E et al (2022) Localized myxedema histologically mimicking spindle cell lipoma. Dermatol Online J 28.
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8. Heise P et al (1992) Myxoedema circumscriptum symmetricum praetibiale. Dermatol Mon 178: 205-206
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10. Lan C et al (2015) A Randomized Controlled Trial of Intralesional Glucocorticoid for Treating Pretibial Myxedema. J Clin Med Res 7:862-872.
11. Mir M et al (2011) Pretibial mucinosis in a patient without Graves disease. Cutis 88:300-302
12. Nair PA et al (2014) Pretibial myxedema associated with Euthyroid Hashimoto's thyroiditis: A Case Report. J Clin Diagn Res PubMed PMID: 25121051
13. Schleicher SM et al (1994) Treatment of pretibial mucinosis with gradient pneumatic compression. Arch Dermatol 130: 842-844.
14. Schwartz KM et al (2002) Dermopathy of Graves' disease (pretibial myxedema): long-term outcome. J Clin Endocrinol Metab 87: 438-446.
15. Susser WS et al (2002) Elephantiasic pretibial myxedema: a novel treatment for an uncommon disorder. J Am Acad Dermatol 46: 723-726.