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Successful combined pentoxifylline and intralesional triamcinolone acetonide treatment of severe pretibial myxedema

  • Author(s): Engin, Burhan
  • Gümüşel, Munise
  • Özdemir, Mustafa
  • Çakir, Mehtap
  • et al.
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Successful combined pentoxifylline and intralesional triamcinolone acetonide treatment of severe pretibial myxedema
Burhan Engin1, Munise Gümüşel1, Mustafa Özdemir1, Mehtap Çakir2
Dermatology Online Journal 13 (2): 16

1. Selçuk University, Meram Medical Faculty, Department of Dermatology. burhanengin2000@yahoo.com2. Selçuk University, Meram Medical Faculty, Department of Internal Medicine

Pretibial myxedema (PTM) is an infrequent manifestation of autoimmune thyroiditis, especially can be present in Graves' disease [1]. Massive intradermal deposition of mucin (acid mucopolysaccharide) produces the nodules or plaques on the lower legs [2]. Various treatment modalities have been used for pretibial myxedema. We herein demonstrated a patient who has been used pentoxifylline, intralesional corticosteroid injection with a good clinical response.


Clinical synopsis


Figure 1Figure 2
Figures 1 and 2: Thickened plaques extending around left lower leg

In 2002 a 32-year-old man presented with a 7-month history of non-tender, erythematous, non-pruritic nodules symmetrically localized on his shins. He had a diagnosis of Graves' disease. He was treated surgically with a subtotal thyroidectomy. Thyroxine therapy was commenced for subsequent hypothyroidism. The lesions grew slowly in size and new lesions developed near the original nodules approximately in 1.5 years. On admission, the patient demonstrated erythematous, indurated nodules and plaques with no ulcers on the lateral and anterior aspects of the shin (Figs. 1 and 2). The lesions were neither warm nor tender to the touch. Bilateral exophthalmous was noted. He had bilateral clubbing and melanonychia striate at right and left hand fingernails. Blood cell counts, biochemistry, chest radiography, and thyroid function tests were normal.


Figure 3
Figure 3: Lesions had receded and only a few slight indurated plaques remained

Clobetasol propionate occlusions for 2-3 hours a day and elastic bandage at nights were applied regularly. Pentoxifylline 400 mg three times a day was started. A total dose of 10 ml of intralesional triamcinolone acetonide (5 mg/ml) was injected monthly. After 3 months his lesions receded, and only a few slight indurated plaques remained (Fig. 2).


Discussion

Pretibial myxedema can be present in either Graves' disease or hypothyroidism. Our patient whose lesions started on his shins and went on his pretibial area has Graves' disease [3]. Pretibial myxedema is an infiltrative dermopathy that most frequently appears symmetrically on the anterior tibia and dorsum of the feet. The usual presentation is that of bilateral, asymmetric, raised, firm plaque or nodules of a pink to purple-brown hue. Hyperhidrosis and hypertrichosis may overlie the affected areas in rare cases. Rarely the lesions may be painful or pruritic. Our patient had erythematous, not itching, firm plaques and nodules. There was no maceration and hypertrichosis but the appearance of his legs were as peau d'orange and there was no pitting edema. Ophthalmopathy always accompanies cutaneous findings, usually appears first and dermopathy much later. Thyroid acropachy is a triad consisting of digital clubbing, soft tissue swelling of hands and feet and periosteal new bone formation [3, 4]. Our patient's ophthalmic changes occurred before dermopathy and he had clubbing of his fingernails.

The mechanism that causes myxedema is unclear although animal model studies suggest that thyroid hormones affect the synthesis and catabolism of mucopolysaccharides and collagen by dermal fibroblasts. The fibroblast in the orbital area and pretibial dermis share antigenic sites that underlie the autoimmune process that causes Graves' disease. Thereby cross reaction contributes to the development of myxedema occurring long after euthyroid status is achieved through treatment [3]. Whatever the cause of the increased glycosaminoglycan (GAG) production, accumulation of GAG leads to the characteristic skin lesions associated with thyroid dermopathy. The hyaluronic acid expands the dermal tissue and causes fluid to accumulate. It may also cause compression or occlusion of small local lymphatic and thereby increase the dermal edema [1].

Treatment starts with avoiding the risk factors as avoiding tobacco and reducing weight then normalization of thyroid functions [4]. High potency topical corticosteroids with occlusion or not, or intralesional corticosteroids are the best approach but the cure rate is low. In a prospective study nine patients with pretibial myxedema were treated with intralesional injections of triamcinolone acetonide. Complete resolution was obtained in seven of the nine patients. For most patients the monthly injection of 8 ml or less of a solution containing 5 mg\ml of triamcinolone proved to be the most effective dosage schedule [5]. We used 10 ml (5 mg/ml) of triamcinolone acetonide monthly. Clobetasol propionate occlusion over the legs for 2-3 hours a day was applied and detected no side effects. Because of fluid accumulation the use of compressive bandages provides additional benefit as in our patient used elastic bandage at night [4].

Pentoxifylline, an analogue of the methylxanthine theobromine, inhibits the proliferation of fibroblasts derived from normal human skin and from skin of patients with some fibrotic disorders. In subconfluent fibroblast cultures, pentoxifylline treatment caused a dose-dependent inhibition of serum-driven fibroblast proliferation and glycosaminoglycan synthesis [6]. Its usage widely accepted in pretibial myxedema however the efficacy of the drug and the results of the follow-up were not stated clearly in the literature. After 3 months of combined pentoxifylline and intralesional triamcinolone acetonide our patient's lesions have receded and another 3 months follow-up period they have not recurred.

Treatment of PTM is often difficult. We suggest that the easiest and effective treatment of PTM may be achieved by combined pentoxifylline and intralesional triamcinolone acetonide.

References

1. Schwartz KM, Fatourechi V, Ahmed DDF, Pond GR. Dermopathy of Graves' disease (Pretibial Myxedema): Long term outcome. J Clin Endocrinol Metab. 2002 Feb;87(2):438-46. PubMed.

2. Truhan AP. Pretibial myxedema. Am Fam Physician. 1985 May;31(5):135-8. PubMed.

3. Chung-Leddon J. Pretibial Myxedema. Dermatol Online J. 2001 Feb;7(1):18. PubMed.

4. Fatourechi V. Pretibial myxedema: pathophysiology and treatment options. Am J Clin Dermatol. 2005;6(5):295-309. Review. PubMed.

5. Lang PG, Sisson JC, Lynch PJ. Intralesional triamsinolone therapy for pretibial myxedema. Arch Dermatol. 1975 Feb;111(2):197-202. PubMed.

6. Chang CC, Chang TC, Kao SC, Kuo YF, Chien LF. Pentoxyfilline inhibits the proliferation and glycosaminoglycan synthesis of cultured fibroblasts derived from patients with Graves' ophthalmopaty and pretibial myxedema. Acta Endocrinol (Copenh). 1993 Oct;129(4):322-7. PubMed.

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