Cases reported "Leg Dermatoses"

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1/9. Elephantiasic pretibial myxedema: insight into and a hypothesis regarding the pathogenesis of the extrathyroidal manifestations of Graves' disease.

    The basis for the extrathyroidal manifestations of Graves' ophthalmopathy (GO) and dermopathy are not well understood. We describe immunohistochemical studies on the skin of a patient with an extreme, elephantiasic form of Graves' dermopathy that developed after periods of prolonged standing with dependent edema. Excision of part of the lesion with subsequent skin grafting from a normal donor site resulted in recurrence of the disease at the original site as well as in development of disease at the donor site. A murine monoclonal antibody reacted with the thyrotropin receptor (TSHR) or a cross-reacting protein in fibroblast-like cells in the patient's upper dermis and, surprisingly, with dermal cells from unaffected individuals. The patient's dermis containing lymphoid follicles comprising B cells and CD3 , CD4 T cells, with few CD8 T cells. CD21 cells (most likely follicular dendritic cells) were also present in the dermis. Based on past and present observations, we raise an unifying hypothesis to explain the diverse extrathyroidal manifestations of Graves' disease and their apparent lack of association with TSHR autoantibodies. As opposed to the present concept that these phenomena relate to site-specific properties on preadipocytes or fibroblasts, we suggest that clinically evidence GO and dermopathy are primarily caused by local factors (particularly in the orbit) superimposed on a systemic, low-grade connective tissue inflammation.
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ranking = 1
keywords = ophthalmopathy
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2/9. Evidence for thyrotropin receptor immunoreactivity in pretibial connective tissue from patients with thyroid-associated dermopathy.

    Pretibial myxedema (PTM), mainly characterized by the accumulation of glycosaminoglycans in the dermis and subcutaneous tissue, is an extrathyroidal manifestation of autoimmune Graves' disease (GD), almost always associated with Graves' ophthalmopathy (GO). The thyrotropin receptor (TSH-R) has been proposed as the common target antigen in GD, GO and PTM, with evidence for receptor transcripts and/or protein in these locations. The aim of this study has been to investigate whether receptor protein is present in the pretibial tissues. skin biopsies were obtained from two patients with PTM and two normal subjects without thyroid disease. A portion of each sample was fixed to produce semi-thin sections for Toluidine Blue or periodic acid Schiff (PAS) staining. The remainder was snap frozen to generate cryostat sections for immunohistochemical analysis using three monoclonal antibodies against TSH-R. In the skin from the two patients suffering from PTM, the dermis was infiltrated by inflammatory cells (lymphocytes, B cells, macrophages, mast cells) and adipocytes. The collagen fibers were dissociated by edema and by the accumulation of a PAS-positive material. Immunodetection of TSH-R produced positive staining on cells localized in the dermis, beneath the epidermis or close to the hypodermis. These cells were elongated and resembled fibroblasts. No immunoreactivity was observed in the dermis from control patients without thyroid disease. In conclusion, we have evidence for TSH-R immunoreactivity in the pretibium of patients with GD, GO and PTM. Further studies are needed to unambiguously identify the positive cells and determine whether the reactivity is due to the receptor itself or to a cross-reacting protein.
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ranking = 3.4537599695172
keywords = ophthalmopathy, thyroid-associated
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3/9. Lack of effect of long-term octreotide therapy in severe thyroid-associated dermopathy.

    Severe thyroid associated dermopathy (TAD), a rare complication of Graves' disease, currently lacks effective treatment. Mediators of growth and inflammation, including insulin-like growth factor-1 (IGF-1) and somatostatin (SST) have been implicated in its pathogenesis. octreotide, a potent SST analogue, has been used in TAD with anecdotal success. Therefore, we evaluated the efficacy of long-term octreotide therapy in moderate to severe TAD. Three obese women with TAD were studied. Baseline treatment included levothyroxine, methimazole, fluocinonide ointment under occlusive dressing, and physiotherapy for lymphedema. After establishing baseline clinical status, octreotide was started (300 microg subcutaneously daily) for 10 to 28 months. Studies obtained at baseline and every 3 months included: leg circumference, skin examination, clinical photography, self-reported clinical status, body mass index (BMI), serum thyrotropin (TSH) and free thyroxine, titers of antithyroidal and anti-TSH receptor antibodies. Minimal changes in the edema, erythema, skin texture and size of nodules were observed. The minor changes seen followed significant decreases in the patients' BMI, and hence, cannot be specifically attributed to octreotide administration. No clinically significant benefit from long-term octreotide therapy was demonstrated in three patients with moderate to severe TAD. weight loss and measures such as compression bandaging and topical corticosteroid application still remain the most cost effective treatment modalities for TAD.
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ranking = 2.4537599695172
keywords = thyroid-associated
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4/9. Euthyroid pretibial myxedema.

    Pretibial myxedema is typically associated with clinical hyperthyroidism, diffuse goiter, and ophthalmopathy in patients with Graves' disease. A case of biopsy-proved pretibial myxedema was encountered in a clinically euthyroid woman who had neither diffuse goiter nor exophthalmos. Although serum total and free thyroxine hormone concentrations were normal, the thyroid-stimulating hormone response to thyrotropin-releasing hormone was absent. This case illustrates that pretibial myxedema may present without other more common manifestations of Graves' disease. In patients with suspect pretibial skin lesions, the thyrotropin-releasing hormone stimulation test may be required to establish the presence of subtle underlying thyroid gland autonomy and the diagnosis of euthyroid pretibial myxedema.
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ranking = 1
keywords = ophthalmopathy
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5/9. Successful treatment of exophthalmos and pretibial myxoedema with plasmapheresis.

    A patient with Graves's disease with acute progressive exophthalmos and pretibial myxoedema was treated twice with plasmapheresis. Two weeks after the first treatment the symptoms recurred, but 20 weeks after the second treatment the exophthalmos was much improved and the pretibial myxoedema had disappeared. Analysis of sequential serum IgG concentrations and the thyroid-stimulating immunoglobulin index suggested that the two conditions were caused by specific IgGs. The results suggest that plasmapheresis has a useful place in the treatment of acute and rapidly progressive ophthalmopathy and pretibial myxoedema in patients with Graves's disease.
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ranking = 1
keywords = ophthalmopathy
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6/9. Acute pre-tibial myxoedema following radioiodine therapy for thyrotoxic Graves' disease.

    A 54-year-old woman was treated with an oral dose of 555MBq of 131I radioiodine for thyrotoxicosis. She had no clinically detectable extrathyroidal manifestations of Graves' disease at the time, but within two months developed moderately severe ophthalmopathy and very extensive thyroid dermopathy affecting her face, arms, hands and feet, in addition to the classic pre-tibial area. Although she developed mild post radioiodine hypothyroidism, this was detected at an early stage and its treatment had no effect on the extrathyroidal signs. Thyrotrophin receptor antibodies (TRAb) were positive before treatment (22% inhibition of TSH binding in neat serum), rose to very high levels following radioiodine (97.6% inhibition), and fell progressively over the following year during treatment with prednisolone. thyroglobulin autoantibodies became detectable following radioiodine but thyroid peroxidase antibodies were undetectable throughout. serum and purified IgG from blood samples obtained prior to steroid therapy and over the subsequent year were tested on a dermal fibroblast cell line in vitro for the stimulation of synthesis of glycosaminoglycans, protein and dna, but no increase in radiolabel incorporation was apparent for any sample when compared to controls. The temporal relation between the radioiodine and the acute onset of dermopathy and ophthalmopathy, together with the abrupt rise in TRAbs, indicates a probable causal association. However, the absence of in-vitro fibroblast stimulation would suggest that the pathogenesis of Graves' dermopathy is not dependent solely on any simple humoral factor.
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ranking = 2
keywords = ophthalmopathy
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7/9. Patient with monoclonal gammopathy, thyrotoxicosis, pretibial myxedema and thyroid-associated ophthalmopathy; demonstration of direct binding of autoantibodies to the thyrotropin receptor.

    We describe a patient with monoclonal gammopathy who subsequently developed thyrotoxicosis, pretibial myxedema and thyroid-associated ophthalmopathy. The pathogenesis of thyrotoxicosis in Graves' disease is due to the presence of autoantibodies that mimic the action of thyrotropin (TSH), called thyroid-stimulating antibodies (TS-ab); these antibodies may or may not inhibit the binding of TSH to the receptor (thyroid-binding inhibiting immunoglobulin, TBII). The patient's immunoglobulins were TS-ab positive and TBII negative when measured on cho cells expressing the human TSH receptor. The pathogenetic link between the thyroid, orbit and skin is yet to be established but several candidate shared antigens have been proposed, including the TSH receptor itself. The monoclonal immunoglobulins were in evidence before the symptoms of pretibial myxedema, thyrotoxicosis and ophthalmopathy. In addition, the patient had no autoantibodies to thyroglobulin or thyroperoxidase, which are classic markers of thyroid autoimmunity. This combination led us to postulate that the monoclonal gammopathy could be the cause of all the observed pathology. One method to test this hypothesis would be to show that the monoclonal immunoglobulin is a TS-ab. Various methods were used to separate the monoclonal from the polyclonal components of the patient's serum. Preparative isoelectric focusing enabled us to obtain fractions containing only the monoclonal (as revealed by polyacrylamide gel electrophoresis), which were devoid of TS-ab activity (measured as cAMP accumulation in cho cells expressing the human TSH receptor in a hypotonic bioassay). Subsequently, different oligoclonal fractions were shown to have varying degrees of TS-ab activity, with one fraction having faint biological activity and able to recognize a recombinant TSH receptor preparation in a Western blot. In conclusion, the monoclonal antibody does not seem to be responsible for the thyrotoxicosis, pretibial myxedema and ophthalmopathy. We confirm previous data showing that TSH receptor antibodies in patients with Graves' disease are heterogeneous in nature and we present the first demonstration of autoantibodies capable of binding the TSH receptor but devoid of TBII activity.
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ranking = 10.067199961896
keywords = ophthalmopathy, thyroid-associated
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8/9. Concomitant Graves' disease and Hashimoto's thyroiditis, presenting as primary hypothyroidism.

    hypothyroidism in patients with Graves' disease is usually the result of ablative treatment. We describe a 58 year old man with Graves' ophthalmopathy and pre-tibial myxoedema, who presented with spontaneous primary hypothyroidism. Circulating TSH receptor antibody activity was increased, while thyroid microsomal antibody was detectable in titres greater than one in one hundred thousand. It is likely that the TSH receptor antibody of Graves' disease was ineffective in stimulating hyperthyroidism because of concomitant thyroid destruction due to Hashimoto's disease. Alternatively, primary hypothyroidism could have resulted from the effects of a circulating TSH receptor blocking antibody.
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ranking = 1
keywords = ophthalmopathy
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9/9. Early onset pretibial myxedema in the absence of ophthalmopathy: a morphologic evolution.

    Pretibial myxedema (PTM) is an uncommon, late manifestation of Graves' disease. It is nearly always preceded by significant ophthalmopathy and classically presents as nonpitting (brawny) edema of the lower extremities. We report a case of PTM that is unusual because of its morphologic evolution, that it occurred prior to the diagnosis of Graves' disease, and in the absence of ophthalmopathy.
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ranking = 6
keywords = ophthalmopathy
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