DOI: /EP AACE

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1 ENDOCRINE PRACTICE Rapid Electronic Article in Press Rapid Electronic Articles in Press are preprinted manuscripts that have been reviewed and accepted for publication, but have yet to be edited, typeset and finalized. This version of the manuscript will be replaced with the final, published version after it has been published in the print edition of the journal. The final, published version may differ from this proof. Visual Vignette PRETIBIAL MYXOEDEMATOUS ULCER IN GRAVES DISEASE Ismadi, Z MB, BS; Caswell, AJ, MB, BS, FRCPA; Tran, HA, MB, BS (Hons), FRCPA, FRACP, FACE, Doct Medicine EP- From: Department of Clinical Chemistry; Nsw Health Pathology Corresponding author: A/Professor Huy A Tran Department of Clinical Chemistry John Hunter Hospital Newcastle, NSW 2310 NSW HEALTH PATHOLOGY huy.tran@hnehealth.nsw.gov.au Conflict of Interest: NONE Word count: 390 Case Presentation:

2 A 58 year old woman presented with a 6 month history of a chronic discoid ulcer on the right shin following a minor trauma. It has not healed despite conservative treatment with regular dressings, oral antibiotic and strong advice against smoking which was ignored. Her past history is significant for osteoarthritis, obesity, and heavy smoking and Graves disease. The latter has been in remission for several years. On further questioning, she complained of recent weight loss of ~8kg, upper limbs tremor, excessive sweating and palpitation. Examination revealed an obese lady with Body Mass Index (BMI) of 36kg/m 2, normotensive with blood pressure of 120/70, tachycardia at 104 beats per minute and peripheral stigmata of thyrotoxicosis and nicotine stained fingers. There was exophthalmos with lid retraction and lid lag, a diffuse goitre, but no acropachy. A pretibial ulcer measuring 2.5cm in diameter and ~2mm deep with associated erythematous plaque and non-pitting oedema was observed, Figure 1. What is the diagnosis?

3 Figure 1: Right tibial ulcer associated with surrounding oedema and erythematous plaque.

4 Answer: Graves Pretibial Myxoedematous Ulcer on a background of chronic venous insufficiency. The latter was common in obesity and accounted for the skin discoloration in the lower leg. The clinical history was consistent with a relapse of Graves disease. This was consistent with biochemical findings of suppressed thyroid stimulating hormone <0.03mIU/L, (N, ), elevated free tetra-iodothyronine of 35.8pmol/L (N, 9 19), and free tri-iodothyronine 12.7pmol/L (N, ). Thyrotropin receptor antibody level was also elevated 32IU/L (N, <1.8). A diagnosis of bilateral pretibial myxoedema ulcer secondary to a relapse of Graves disease was made. Treatment with anti-thyroid drug was promptly initiated following which the patient was rendered euthyroid after 6 weeks. The pretibial ulcer also rapidly healed after 4 weeks, Figure 2.

5 Figure 2: Resolution of ulcer after treatment with anti-thyroid medication.

6 Pretibial myxoedema is a rare manifestation of Grave s disease. It is due to the accumulation of glycosaminoglycan (GAG), in particular hyaluronic acid in the dermis which is secreted by fibroblast under cytokines stimulation. Its clinical features of bilateral asymmetric non-pitting oedema with skin induration and violaceous plaque or well demarcated papules may be confused with other more common conditions such as venous or lymphatic insufficiency and chronic dermatitis. It is postulated that the relatively rapid ulcer healing is due to the reduction of dermal fibroblast proliferation and its diminished glycosaminoglycan production in direct response to anti-thyroid therapy and improved thyroid status. Pretibial area is the most commonly affected area but lesions on the upper limbs and face have been reported and virtually all patients had coexisting ophthalmopathy. It rarely becomes ulcerated and can be easily mistaken for other aetiologies such as traumatic or venous insufficiency ulcers. Graves disease should be considered in the differential diagnosis in the right clinical context so that the correct management plan can be implemented with a successful outcome as illustrated in this vignette.

7 REFERENCES: 1. Doshi DN, Blyumin ML, Kimball AB. Cutaneous manifestations of thyroid disease. Clin Dermatol 2008; 26: Herskovitz I, Hughes O, MacQuhae F, Kirsner RS. Pretibial myxedema masquerading as venous leg ulcer. Wounds, 2017;29: Ai J, Leonhardt JM, Heymann WR. Autoimmune thyroid diseases: etiology, pathogenesis, and dermatologic manifestations. J Am Acad Dermatol, 2003; 48: 641.