SG02 Transdermal testosterone improves lower-extremity ulceration in a young man with newly diagnosed Klinefelter syndrome (47 XXY)

Abstract A 25-year-old man was referred to dermatology with a 6-month history of a nonhealing right-lower-leg ulcerated lesion. His background was significant for previous varicose vein surgery at age 21 years on the contralateral leg. His family medical history was insignificant for vascular disease. He was of normal body habitus, and occasionally vaped (he did not smoke). The lesion was treated by his general practitioner as likely pyoderma gangrenosum with oral and potent topical corticosteroids, but with minimal improvement. A punch biopsy to the site demonstrated stasis dermatitis changes with no dysplasia or neoplasia. We initiated oral doxycycline and advised cessation of vaping, with minimal improvement. He was referred to vascular surgery, who advised compression stockings and wound dressings three times weekly. Concurrently, the patient was referred to endocrinology by his general practitioner secondary to minimal facial hair. On further questioning our patient reported delayed onset of puberty. Investigations demonstrated a testosterone deficiency at 7 ng dL−1 (normal range 350–890) and elevated follicle-stimulating hormone and luteinizing hormone levels. Karyotyping by G-banding technique revealed a 47 XXY karyotype, confirming Klinefelter syndrome. The patient commenced transdermal testosterone therapy given his deficiency. The patient noted improved ulcer healing at 1.5 months after commencement of transdermal testosterone gel applied to nonlesional skin daily. This improvement continued until his review at our clinic 3 months after commencement of topical testosterone, where the diameter and depth of the ulcer had improved considerably. Leg ulceration in patients with Klinefelter syndrome has traditionally been reported as a result of reduced testosterone levels, chronic venous insufficiency and obesity. While leg ulceration is a recognized complication of Klinefelter syndrome the aetiology remains incompletely understood. Literature discusses the impact of elevated plasminogen activator inhibitor (PAI)-1 levels in this condition, which may result in decreased fibrinolysis, but arterial dysplasia, chronic venous insufficiency and traditionally obesity may all play a role. PAI-1 is produced by the endothelium and adipose tissue and inhibits tissue plasminogen activator and urokinase plasminogen activator, inhibiting fibrinolysis and promoting thrombosis. Low testosterone levels are associated with higher levels of PAI-1. We illustrate the importance of considering Klinefelter syndrome in a young man with vascular disease. We also suggest a role for transdermal topical testosterone in wound healing in patients with confirmed Klinefelter syndrome who are testosterone deficient. Our case illustrates the importance of dermatologists being cognizant of a patient’s medical background, including genetic conditions such as Klinefelter syndrome, when addressing skin concerns.