Pretibial myxoedema: stimulation of mucopolysaccharide production of fibroblasts by serum

We have shown that sera from normal individuals and from patients with pretibial myxoedema contain a factor which simulates mucopolysaccharide biosynthesis in normal human skin fibroblasts cultured in vitro. This factor was present in larger amounts in sera of patients with pretibial myxoedema. The role of growth stimulating factors in serum is reviewed and a hypothesis is put forward that the fibroblast stimulating factor is somatomedin and that its presence in increased amounts in thyroid disease may lead to pretibial myxoedema.     

Skin fibroblast activity in pretibial myxoedema and the effect of octreotide (Sandostatin®) in vitro

The accumulation of glycosaminoglycans in the skin in pretibial myxoedema appears to be a response by local fibroblasts to a stimulating factor in the patient's serum, but the identity of the factor, its ability to stimulate skin fibroblasts as opposed to cultured thyroid cells, and the specificity of its effect to pretibial skin fibroblasts, are all controversial. We have studied fibroblasts cultured from the lesional skin of two women with pretibial myxoedema, and compared their proliferation and secretion of glycosaminoglycans with those of fibroblasts from the patients' forearms and from the forearm skin of two normal subjects. We found that in the presence of the patients' sera all six lines of fibroblasts secreted more glycosaminoglycans [205±21% (SD)] than with normal human sera (147±19%), or fetal calf serum (100%). Fibroblast proliferation showed the same pattern of differences: patients' sera 142±22%; normal human sera 116±9%, and fetal calf serum 100%. These experiments confirm the presence of a serum factor in pretibial myxoedema which is capable of stimulating the activity of skin fibroblasts in vitro, and show that its effects are not restricted to fibroblasts from pretibial skin or to those grown from the skin of the patients. Proliferation of normal fibroblasts cultured in medium supplemented with fetal calf serum was reduced by Sandostatin® (octreotide), but it failed to inhibit their secretion of glycosaminoglycans. In contrast, secretion of glycosaminoglycans by a patient's pretibial skin fibroblasts was almost completely inhibited by 1 mM minoxidil. In the presence of patients' sera Sandostatin® (0.1–10 μg/ml) reduced secretion of glycosaminoglycans by about 50%. Our data support the use of Sandostatin® in pretibial myxoedema, and suggest that it may suppress fibroblast glycosaminogly- can secretion within the skin via depletion of insulin-like growth factor or the blocking of its effect.     

Pretibial myxoedema associated with Hashimoto''s thyroiditis

Pretibial myxoedema is a cutaneous mucinosis typically associated with Graves' disease, although it may also develop in subjects with non-thyrotoxic thyroid pathologies. This report presents a rare case of pretibial myxoedema occurring in a 58-year-old woman with biopsy-proven Hashimoto's thyroiditis. The hypothetical pathogenetic link between the two disorders is discussed with particular attention to the role of thyroid stimulating hormone receptor antibodies.     

胫前粘液性水肿1例

报道1例胫前粘液性水肿.患者女,52岁,双下肢胫前皮肤出现包块1年.临床表现:左侧胫前可见一5 cm×7 cm大小结节,质韧,表面皮肤菲薄紧张;右侧胫前可见大小不等暗红色斑块,皮肤表面凹凸不平.皮损组织病理学检查:表皮轻度角化,真皮内胶原纤维间见大量黏蛋白沉积.阿辛蓝染色阳性.诊断:①胫前粘液性水肿;②甲状腺功能减退....     

Successful surgical treatment of severe pretibial myxoedema

We report a 46-year-old man with severe and long-standing pretibial myxoedema, who responded well to local surgical treatment. This improvement has been maintained over a 12-month period, perhaps because of concomitant treatment with octreotide.     

Obesity-associated lymphoedematous mucinosis

Background: Mucin deposition on the shins is considered as an indicator of pretibial myxoedema, which is typically seen in patients with Graves' disease.
Objective: The purpose of this study was to report the clinical and histopathological features of a group of patients with pretibial mucinosis in the absence of thyroid disease.
Methods: Five patients are included in this series and studied both clinically and histologically and compared with similar cases in the literature.
Results: All patients were middle aged or elderly. Four patients were women. They were characterized clinically by morbid obesity and bilateral lower extremity pitting oedema sparing the feet. Semitranslucent papules and/or nodules and sometimes vesicles were found on the shins. Characteristic histological features include (i) hyperorthokeratosis with epidermal atrophy and effacement of the rete ridge pattern, (ii) oedema in the papillary and upper part of the reticular dermis with mucin deposition stained positively with alcian blue and colloidal iron, (iii) angioplasia in the upper part of dermis with upward-running, increased and thickened capillary vessels and (iv) variable fibrosis in the reticular dermis with separation of collagen bundles and increased stellate or linear fibroblasts. A hypocaloric diet was given in two cases, and an important weight loss was observed, which was accompanied by a marked improvement of the pretibial mucinosis.
Conclusions: Pretibial mucinosis is a histological feature associated with morbid obesity and lymphoedematous features of the legs that should be distinguished from true pretibial myxoedema. The term of 'obesity-associated lymphoedematous mucinosis' seems to be appropriate for this condition.     

Chronic obesity lymphoedematous mucinosis: three cases of pretibial mucinosis in obese patients with pitting oedema

Pretibial mucin deposition on the shins is known as pretibial myxoedema. We report three patients with pretibial mucinosis without thyroid disease. The patients were characterized clinically by morbid obesity and bilateral lower extremity pitting oedema with gradual and painless onset, and that did not involve the feet and ankles. Vesicles, semitranslucent papules or a woody plaque were found on the shins. Histologically, patients showed characteristic features of epidermal atrophy with effacement of the rete ridge pattern, separation of collagen bundles associated with oedema with stellate to linear fibroblasts, upward-running increased capillary and small vessels with haemosiderin deposition, and mucin deposition at the superficial papillary dermis and around the vessels. We propose that the present cases of 'chronic obesity lymphoedematous mucinosis' belong to the clinical entity of pretibial mucinosis.     

Treatment-resistant elephantiasic thyroid dermopathy responding to rituximab and plasmapheresis

A 44-year-old woman was diagnosed with Graves' disease in 1995 and over the following 12 months developed thyroid dermopathy (pretibial myxoedema). Despite being trialled on multiple recognized therapies over the course of 11 years, the patient's dermopathy progressively worsened. She developed ocular proptosis, elephantiasic thyroid dermopathy and acropachy in both hands. In mid 2006, the patient was started on rituximab and plasmapheresis, with rapid response. The patient's condition stabilized and in October 2009 at the age of 58 years she was able to cease therapy.     

Graves' disease presenting as localized myxoedematous infiltration in a smallpox vaccination scar

We describe a 54-year-old woman with diffuse myxoedematous infiltration at the site of a smallpox vaccination scar as the presenting symptom of Graves' disease. Associated features included acute ocular symptoms (vascular congestion of the sclera, epiphora and blurred vision) and transient erythema on both shins. However, there were no signs of pretibial myxoedema. A number of neoplastic, inflammatory and systemic diseases may localize to scar tissue in skin, including at smallpox vaccination sites, but this case demonstrates the unusual occurrence of myxoedematous infiltration at such a site and illustrates a most atypical cutaneous presentation of Graves'disease.     

Intravenous immunoglobulin treatment: Where do dermatologists stand?

Intravenous immunoglobulins (IVIG) are therapeutic products, comprising polyclonal IgGs, which are obtained from human plasma pool of healthy blood donors. Despite the lack of Food and Drug Administration (FDA) approval, the experience of using IVIG in various dermatological diseases increases day by day and exciting results are reported. However, experience with the use of IVIG in dermatological indications are mostly case reports whereas randomized, controlled, double‐blind, multicentric studies have not been performed. Dermatological diseases treated with IVIG are autoimmune bullous skin diseases, Stevens‐Johnson syndrome and toxic epidermal necrolysis, connective tissue diseases, pyoderma gangrenosum, severe atopic dermatitis, chronic urticaria, Kawasaki disease, pretibial myxoedema, scleredema, and graft‐versus‐host disease.     

Refractory pretibial myxoedema with response to intralesional insulin-like growth factor 1 antagonist (octreotide): downregulation of hyaluronic acid production by the lesional fibroblasts

We report a case of refractory pretibial myxoedema (PTM) with Graves' disease in which there was a good clinical response to intralesional injection of the insulin-like growth factor 1 (IGF-1) antagonist octreotide. Intralesional octreotide (200 microg once daily) dramatically improved the tumorous lesions of PTM after 4 weeks, and the lesions remained stable even after reducing the dose to 200 microg once weekly. The amount of hyaluronic acid (HA) in the lesional skin decreased to 5.8 microg mg-1 dry weight from 16.3 microg mg-1 dry weight after 4 weeks of octreotide treatment. IGF-1 showed a dose-dependent stimulatory effect on HA secretion by both normal and patient's fibroblasts at higher concentrations in vitro. Octreotide significantly suppressed IGF-1 induced-HA secretion by the patient's fibroblasts, but not by normal fibroblasts, which suggests that expression of IGF-1 receptor on fibroblasts, or its affinity for IGF-1, are upregulated in PTM, resulting in the oversecretion of HA. These results might suggest that octreotide improves PTM through downregulation of HA production by lesional fibroblasts.     

Pretibial mucinosis in a patient without Graves disease

Although an uncommon location, cutaneous mucinoses may present in the pretibial area in distinct clinical circumstances. The terms pretibial myxedema and pretibial mucinosis often are used interchangeably, but pretibial myxedema should be regarded as a type of pretibial mucinosis. We present a case of cutaneous mucinosis localized to the pretibial area of a patient without Graves disease.     

Antibasement Membrane Zone Antibodies In Localized Pretibial Pemphigoid

To clarify the nosologic position of localized pretibial pemphigoid, Western immunoblotting analysis was carried out using the sodium dodecyl sulfate extracts of normal human epidermis. Sera from patients with localized pretibial pemphigoid and generalized bullous pemphigoid reacted with 220- to 240-kd polypeptide, which is a critical point for a definite diagnosis of bullous pemphigoid. This result suggests that localized pretibial pemphigoid belongs to the same nosologic position as bullous pemphigoid.     

Universal ichthyosiform trichophyton violaceum in myxoedema

In a man aged 29 following thyroidectomy complicated by myxoedema an onychomycotic infection of long duration spread suddenly and fast onto the skin. A serious traffic accident coincided with the insidious onset of myxoedema. The patient was very irregular in taking medicines and continuously on sick pay. Myxoedema worsened and the ringworm progressed into a generalized ichthyosiform--universal mycotic--condition.     

Pretibial epidermolysis bullosa. Successful therapy with a skin graft

A patient with pretibial epidermolysis bullosa was successfully treated with a skin graft. Ultrastructural examination revealed a decreased number of and rudimentary anchoring fibrils (AFs) in the pretibial area in contrast to normal AFs in the grafted skin obtained from a nonpredilection site. Our results indicate the importance of AFs in the pathogenesis of pretibial epidermolysis bullosa.     

Keratoderma of myxoedema

Skin changes are nearly always found in myxoedema. ¹ Scalp hair may be coarse, dry and sparse, the face, and hands puffy with a pasty-yellow complexion. Commonly the skin of the limbs is dry to the touch and may crack and redden over the shins (eczema craquele). ² The nails may be brittle. Palmoplantar keratoderma is a poorly recognized presentation of myxoedema. ^3,4 Two male patients are described.     

Pretibial mucinosis in an euthyroid patient

A case of exuberant pretibial mucinosis in a patient with normal thyroid function is reported. A review of literature on possible etiologies other than thyroid disease for the accumulation of mucin in the pretibial area is presented. In the patient described, it is possible that vascular insufficiency is involved. However, this is not the only factor responsible for the accumulation of mucin, since there are still unidentified causes and many patients with vascular diseases do not develop similar injuries.     

Successful therapeutic approach in a patient with elephantiasic pretibial myxedema

Localized pretibial myxedema is a dermopathy whose treatment is a challenge in dermatology, occurring in 0.5–4% of patients with Graves’ disease. This autoimmune thyroid condition stimulates the production of hyaluronic acid and glycosaminoglycans that are deposited particularly in the pretibial region. Clinically, it presents as a localized, circumscribed, and non-depressible infiltrate in plaques. Several treatment modalities have been proposed, and their results vary, with worse response observed in severe cases. This report presents the case of a patient with elephantiasic pretibial myxedema who was subjected to intralesional corticosteroid applications, resulting in an excellent and encouraging therapeutic response that was maintained.     

Pretibial epidermolysis bullosa and hypothyroidism

BACKGROUND: We report a case of primary non-autoimmune hypothyroidism causing pretibial epidermolysis bullosa. CASE REPORT: A 70-year-old man with primary non-autoimmune hypothyroidism developed blisters of different ages on the lateral aspect of both legs. Pathology reported blisters with subepidermal cleavage. Direct immunofluorescence was negative. Electron microscope examination showed a variable cleavage level and diffuse infiltration of a granulous and amorphous microfibrillar substance. After hormone replacement therapy, euthyroidism was associated with a reduction in the number of bullae and finally complete remission. After 12 months follow-up, the patient has not experienced recurrence. DISCUSSION: Recurrence-free clinical improvement after hormone replacement therapy suggests the diagnosis of hypothyroidism pretibial epidermolysis bullosae. Mochizuki et al. described a similar case which rapidly regressed after hormone therapy but where the electron microscope showed a different cleavage level. These bullae appear to result from a mechanical mechanism due to their localization in areas exposed to friction and also to the presence of bullae of different ages. This hypothesis is confirmed by the presence of a variable level of cleavage and a substance dense to electrons at electron microscopy as well as by the skin weakness. Our case confirms the reality of hypothyroidism pretibial epidermolysis bullosa. Thyroid hormones should be assayed in patients presenting pretibial bullae.