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• W2091273162 abstract "Only 3% of patients with pretibial myxoedema present with grotesque swelling of the lower legs, described as the elephantiasic form of pretibial myxoedema. This variant of the disease results from excessive dermal and subcutaneous accumulation of glycosaminoglycans as a result of a yet unknown mechanism.1, 2 In most patients, the disorder is associated with Graves' disease. Several hypotheses, which have been substantiated in vitro, suggest the involvement of both humoral and cellular mechanisms.3, 4 Specifically, in the pathogenesis of the disease, antibodies to the thyroid‐stimulating hormone (TSH) receptor, directed against thyroid antigens expressed on pretibial skin fibroblasts and preadipocytes, may stimulate these cells to produce large amounts of glycosaminoglycans. Prompted by a report that high‐dose intravenous immunoglobulin (IVIG) therapy produced favourable results in elephantiasic pretibial myxoedema,5 we treated a patient with long‐standing disease using IVIG. The 36‐year‐old female patient presented with a 2‐year history of slowly enlarging bluish erythematous plaques on the distal shins. Twelve years previously, Graves' disease had been diagnosed. Subtotal thyroidectomy was performed 6 years ago, and, subsequent to a carbimazole refractory relapse of hyperthyroidism, she was treated with radio‐iodine. Subsequently, thyroid function was maintained within the normal range with replacement thyroxine. The patient received a course of oral corticosteroids and compression therapy of the lower legs without any improvement. On physical examination, there were confluent flesh‐coloured waxy nodules forming large tumours with deep furrows and mild hyperkeratosis involving almost the complete circumference of the distal portions of the lower legs (Fig. 1a). The patient underwent repeated surgical resection of myxoedematous skin (Fig. 1b), but the skin changes recurred (Fig. 1c). Therefore, we initiated treatment with six cycles of IVIG monotherapy at 4‐week intervals over a period of 6 months. Immunoglobulin (2 g/kg body weight, Intraglobin® F, Biotest, Dreieich, Germany) was given on two consecutive days (1 g/kg daily) at a rate of 5 g/100 mL/h. Side‐effects included headaches, lack of appetite, nausea (all cycles) and vomiting (three cycles) starting within 4 h of completion of the infusions. These symptoms were not thought to reflect aseptic meningitis, a known side‐effect of IVIG therapy. The patient was advised to continue wearing compressive stockings during the course of therapy. At the time of initiation of therapy, pretibial myxoedema had existed for 6 years. Although our treatment did not lead to a significant reduction of myxoedematous masses, the previously progressive disease was stabilized (Fig. 1d). Measurements of the circumference of the lower legs revealed no change compared to the pretreatment circumference. Repeated biopsies showed a minimal reduction of dermal hexuronic acid content after therapy, i.e. 715 µg/g tissue before and 663 µg/g tissue 1 month after cessation of therapy. During treatment, serum levels of anti‐TSH‐receptor antibodies substantially decreased, reaching a 50% reduction after five cycles (178 IU/mL before and 95 IU/mL at the end of therapy). In contrast, serum anti‐thyroid peroxidase (TPO) antibody levels changed only marginally (195 IU/mL before therapy, 247 IU/mL after 10 days and 185 IU/mL at the end of therapy). Similarly, serum titres of anti‐nuclear antibodies were not altered during therapy. With continuation of compression therapy, after a follow‐up period of 1 year, the myxoedematous changes have remained stable. Anti‐TSH‐receptor antibody levels increased again and are now at higher levels than before the initiation of treatment (200 IU/mL)." @default.
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• W2091273162 date "2003-03-01" @default.
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• W2091273162 title "Lack of response of elephantiasic pretibial myxoedema to treatment with high-dose intravenous immunoglobulins" @default.
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• W2091273162 doi "https://doi.org/10.1046/j.1365-2230.2003.01232_3.x" @default.
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