[Pretibial myxedema after Graves' disease: A differential diagnosis of lymphedema]. / Myxœdème prétibial pseudo-tumoral après une maladie de Basedow : un diagnostic différentiel du lymphœdème.

INTRODUCTION: Pretibial myxedema is a rare manifestation of Graves' disease, and pseudotumoral forms may be confused with lower limb lymphedema. OBSERVATIONS: We reported 3 cases of pretibial myxedema in 2 women and 1 man, aged 72, 66, and 49 years, treated for Graves' disease 3, 25 and 32 years previously. Two patients were active smokers. Lymphedema diagnosis of the lower limbs was suspected in the presence of bilateral pseudotumoral lesions of the feet, toes and ankles and the presence of a Stemmer's sign (skin thickening at the base of the 2nd toe, pathognomonic of lymphedema). Lymphoscintigraphy in one case was normal, not confirming lymphedema. CONCLUSION: Pretibial pseudotumoral myxedema is a differential diagnosis of lower limb lymphedema. This diagnosis is confirmed by questioning the patient about preexisting Graves' disease, the underlying etiology, to decide the appropriate treatment and to encourage cessation of smoking, which is a risk factor for pretibial myxedema.

Bilateral breast myxedema caused by Graves' disease and responsive to multipoint subcutaneous injection of long-acting glucocorticoid: Case report.

RATIONALE: With the absence of ophthalmopathy, thyroid dermopathy especially lesions at atypical locations is a very rare presentation. We herein report an original case of bilateral breast myxedema caused by Grave's disease. PATIENT CONCERNS: A 21-year-old unmarried woman presented with a 4-month history of Grave's disease and a 1-month history of progressive bilateral breast enlargement. She had symmetrical bilateral breast enlargement with redness and nonpitting thickening of the skin, diffusely enlarged thyroid glands, and no exophthalmos. DIAGNOSIS: Ultrasonography, magnetic resonance imaging scan, and skin biopsy confirmed the diagnosis of bilateral breast myxedema. INTERVENTIONS: The patient was treated with multipoint subcutaneous injections of triamcinolone acetonide in each breast every month. OUTCOMES: The bilateral breast returned approximately to its normal size after therapy for 6 months. CONCLUSIONS: Our case illustrates that multipoint subcutaneous injection of glucocorticoids is beneficial for bilateral breast myxedema.

Local immune microenvironment of skin may play an important role in the development of pretibial myxedema.

Pretibial myxedema (PTM), characterized by the accumulation of glycosaminoglycans in dermis is an autoimmune skin disorder, which is almost always associated with Graves' disease (GD). Although fibroblast stimulated by thyroid-stimulating hormone receptor (TSHR) antibody, cytokines and growth factors have been postulated as target of the autoimmune process in the dermopathy, the pathogenesis of PTM remains unclear. We hypothesize that the local immune microenvironment of the skin including the antigens and antibodies, T cells, B cells, plasma cells and fibroblasts may play an important role in the development of PTM. Results obtained on PTM patients indicate increased thyroid-stimulating hormone receptor antibodies (TRAb) in the blood positively correlate with the dermal thickness of the lesions. Further analysis shows that there were more CD3+ T cells and CD20+ B cells in the skin lesions. These T and B cells are in close contact, indicating that inducible skin-associated lymphoid tissue (iSALT) may be formed in the area. In addition, we found that the infiltrating plasma cells can secrete TRAb, proving that B cells in the skin other than the thyroid are an additional source of TSHR antibodies. Meanwhile, the T and B cells in the skin or skin homogenate of patients can promote the proliferation of pretibial fibroblasts. In conclusion, our results provide evidence that the local immune microenvironment of the skin may play an important role in the development of PTM.

Mixedema pretibial en enfermedad de Graves / Pretibial myxoedema in Graves' disease

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Electrosurgical debulking of pretibial myxedema of the foot.

Pretibial myxedema or thyroid dermopathy constitutes dermal deposition of mucin, primarily hyaluronic acid and chondroitin sulfate. It is a manifestation of autoimmune thyroiditis, seen more in Graves disease than in Hashimoto thyroiditis. The time delay from treatment of hyperthyroidism to appearance of localized myxedema varies from one month to 16 years (mean 5.13 years). Despite a variety of therapeutic options, failure and relapse rates are high. Therapeutic options reported in the literature include compression, topical and intralesional corticosteroids, oral pentoxifylline, octreotide, rituximab, plasmapheresis, and high-dose intravenous immunoglobulin. We share our experience in two patients who were treated with electrosurgical debulking of selected longstanding myxedematous lesions, with one positive result and one negative result.

Pretibial myxedema in a euthyroid patient.

Pretibial myxedema (PM) is a rare extrathyroidal manifestation of Graves' disease (GD), usually during the hyperthyroid state, coexisting with orbitopathy. We describe a rare case of a biopsy-proven PM in a euthyroid patient, without history of GD or Hashimoto's thyroiditis. Assessment of commonly reported thyroid autoantibodies, such as thyroid peroxidase and thyroglobulin autoantibodies, thyroid stimulating immunoglobulins and thyroid binding inhibitory immunoglobulins, was negative. Resolution of skin pathology was achieved after topical application of corticosteroids and was sustained 1 year later.

Pretibial Myxedema Masquerading as a Venous Leg Ulcer.

The authors report a case of pretibial myxedema (PTM) masquerading as a venous leg ulcer to alert wound care clinicians to this diagnostic possibility. Pretibial myxedema is a localized form of mucin cutaneous deposition characterized by indurated plaques most commonly on anterior legs. It is more likely to present in patients with Graves' disease, but it can be found in euthyroid patients as well. The physiopathology of PTM is complex, and there is an accumulation of highly hydrophilic glycosaminoglycans in the dermis. Minimal morbidity is associated with PTM, but the pruritus related to mucin deposition can be intense. The skin around venous leg ulcers and the skin changes related to PTM can have a similar clinical presentation, which may be a reason PTM is under-recognized.

A rabbit model of fatal hypothyroidism mimicking "myxedema coma" established by microscopic total thyroidectomy.

Myxedema coma (MC) is a life-threatening endocrine crisis caused by severe hypothyroidism. However, validated diagnostic criteria and treatment guidelines for MC have not been established owing to its rarity. Therefore, a valid animal model is required to investigate the pathologic and therapeutic aspects of MC. The aim of the present study was to establish an animal model of MC induced by total thyroidectomy. We utilized 14 male New Zealand White rabbits anesthetized via intramuscular ketamine and xylazine administration. A total of 7 rabbits were completely thyroidectomized under a surgical microscope (thyroidectomized group) and the remainder underwent sham operations (control group). The animals in both groups were monitored without thyroid hormone replacement for 15 weeks. Pulse rate, blood pressure, body temperature, and electrocardiograms (ECG) were recorded and blood samples were taken from the jugular vein immediately prior to the thyroidectomy and 2 and 4 weeks after surgery. The thyroidectomized rabbits showed a marked reduction of serum thyroxine levels at 4 weeks after the surgical procedure vs. controls (0.50±0.10 vs. 3.32±0.68 µg/dL, p<0.001). Additionally, thyroidectomized rabbits exhibited several signs of hypothyroidism such as hypothermia, systolic hypotension, bradycardia, and low voltage on ECGs, compared with controls. Of the 7 rabbits with severe hypothyroidism, 6 died from 4 to 14 weeks after the thyroidectomy possibly owing to heart failure, because histopathologic examinations revealed a myxedema heart. In summary, we have established a rabbit model of fatal hypothyroidism mimicking MC, which may facilitate pathophysiological and molecular investigations of MC and evaluations of new therapeutic interventions.

Pre-tibial myxedema: treatment with intralesional corticosteroid.

The pretibial myxedema is a manifestation of Graves' disease characterized by accumulation of glycosaminoglycans in the reticular dermis. The dermopathy is self-limiting but in some cases may cause cosmetic and functional damage. Conventional treatment is use of topical steroids under occlusive dressing, however the intralesional application has shown good results. We present a case of pretibial myxedema treated with single injection of intralesional corticosteroid.