Myxedema pretibiales E03.8

Pretibial (more rarely also in the area of the forearms or shoulders) deposits of glucosamine glycans in the subcutaneous tissue in the case of an underlying thyroid dysfunction (mostly in hyperthyroidism, especially in immunogenic hyperthyroidism of the Graves' type, more rarely in hypothyroidism, e.g. after thyroidectomy).

As in endocrine orbitopathy, there is an increase in the synthesis of hyaluronic acid by fibroblasts in the subcutaneous tissue of the pretibial regions. The cause of this is ultimately unclear. TSH (thyrotropic anterior pituitary hormone) and ESF (exophthalmus stimulating factor) as well as LATS (long acting thyroid stimulating hormone) or the "insulin-like growth factor" are discussed as triggering factors.

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 after the 35th LJ

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

Circumscribed pretibial, yellowish-brownish or whitish-grey, firm, difficult or impossible to depress, otherwise asymptomatic swellings which usually occur as dermatological partial symptoms of Graves' disease. Often due to retractions of the follicular ostia, orange peel-like surface. However, pretiabial edema may also occur in Hashimoto thyroiditis or without identifiable 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, also elephantiasis-like swelling of the entire lower legs. Then also epidermal hyperplasia with hyperkeratosis, pruritus and hypertrichosis.

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

The epidermis is slightly acanthotic; orthokeratotic or orthohyperkeratotic keratinization. Massive mucin deposits in the middle and deep dermis; these appear in HE section as optically empty spaces (fixation artefact), between collagenous fibre bundles which are pushed apart (detection of the mucin is best achieved with the alcian blue stain). Fibroblasts only slightly increased. Low diffuse or perivascular lymphocytic infiltrate.

The treatment is difficult. Relatively good results can be achieved by a consistent compression therapy (especially segmental compression; see lymph drainage below).

In case of moderate or no success glucocorticoid crystal suspensions such as triamcinolone (e.g. Volon A diluted 1:1 with LA such as scandicain), external potent glucocorticoids under occlusion such as clobetasol (e.g. dermoxin cream), if necessary surgical removal of the disturbing tissue. After discontinuation of the therapy, recurrences often occur.

Promising (and recommendable as a therapeutic option), local radiotherapy has been shown in one case study (Elsayad K et al. 2015).

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

The results of plasmapheresis have been reported to vary.

1. 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
2. Bartalena L et al (2014) Extrathyroidal manifestations of Graves' disease: a 2014 update. J Endocrinol Invest 37:691-700
3. Cho S et al (2001) Graves' disease presenting as elephantiasic pretibial myxedema and nodules of the hands. Int J Dermatol 40: 276-277
4. Elsayad K et al (2015) Radiation therapy as part of the therapeutic regimen for extensive multilocularmyxedema
   in a patient with exophthalmos, myxedema and osteoarthropathy syndrome:
   A case report. Oncol Lett9:2404-2408.
5. Georgala S et al (2002) Pretibial myxedema as the initial manifestation of Graves' disease. J Eur Acad Dermatol Venereol 16: 380-383
6. Heise P et al (1992) Myxoedema circumscriptum symmetricum praetibiale. Dermatol Mon 178: 205-206
7. Lan C et al (2015) A Randomized Controlled Trial of Intralesional Glucocorticoid for Treating Pretibial Myxedema. J Clin Med Res 7:862-872.
8. Mir M et al (2011) Pretibial mucinosis in a patient without Graves disease. Cutis 88:300-302
9. Nair PA et al (2014) Pretibial Myxedema Associated with Euthyroid Hashimoto's Thyroiditis: A Case Report. J Clin Diagn Res PubMed PMID: 25121051
10. Schleicher SM et al (1994) Treatment of pretibial mucinosis with gradient pneumatic compression. Arch Dermatol 130: 842-844
11. Schwartz KM et al (2002) Dermopathy of Graves' disease (pretibial myxedema): long-term outcome. J Clin Endocrinol Metab 87: 438-446
12. Susser WS et al (2002) Elephantiasic pretibial myxedema: a novel treatment for an uncommon disorder. J Am Acad Dermatol 46: 723-726