Outline
Report of a Case. A 37-year-old man was hospitalized three times for the treatment of leg ulcers that were present for 1 year on the left medial malleolus and the lateral side of the lower aspect of the right leg. He had a 6-year history of bilateral varicose veins but no history of deep vein thrombosis or pulmonary embolus.
Previous treatments included pinch grafting, split-thickness grafts, benzoyl peroxide, Debrisan, Duoderm, Burow's compresses, Unna's boot, and Bactigras.
His medical history included asthma and seasonal allergies. He first noted small genitalia at age 16, when he began to put on weight, especially at the breasts and around the hips and thighs.
The patient was a single nonsmoker who worked at a disco. He drank moderate amounts of whiskey. Family history revealed that his father had varicose veins.
On examination, he was 193 cm tall and weighed 100 kg. He had a boyish facial appearance, female scalp line, diminished beard growth, increased fat distribution about the hips and thighs, and bilateral gynecomastia. His penis was 5 cm in length and he had soft testes of 2 cm3. Pubic hair was graded at Tanner stage 3.
A 1.5-cm ulcer was present on the medial aspect of his left ankle with sharp edges and a clean base of granulation tissue. There was surrounding erythema. Multiple varicosities of both lower legs were noted. There was gross pitting edema of both legs, and pedal pulses were poorly palpable. Capillary filling of the toes was mildly delayed. The rest of the physical examination was normal.
Laboratory test results demonstrated a decreased testosterone level (7.7 mmol/L; normal, 12 to 31 mmol/L) and increased luteinizing hormone (45 U/L; normal, 6 to 30 U/L) and follicle-stimulating hormone (37 U/L; normal, 5 to 25 U/L) levels. A complete blood cell count, electrolytes, urinalysis, serum urea nitrogen, creatinine, total protein, albumin, and liver function test results were all normal. Venous reflux plethysmography without tourniquet showed bilateral deep venous insufficiency. By impedance plethysmography, there was no evidence of deep vein thrombosis above the level of the knees.
Chromosome karyotype demonstrated a mosaic Klinefelter's syndrome of 46, XY/46,XX/47,XXY (2/2/46).
A biopsy specimen of the ulcer showed granulation tissue, acute inflammatory cells, and occasional hemosiderin-laden macrophages, consistent with a stasis ulcer.
Comment. There is a growing body of evidence showing an increased risk of leg ulcers in patients with Klinefelter's syndrome. Campbell and coworkers [1,2] reported incidences of hypostatic ulceration of 6% and 13% in such patients. Campbell and coworkers also reported increased rates of varicose veins, deep vein thrombosis, and pulmonary embolism compared with the normal population. Other reports have been made of patients with genotypes XXY, XXXXY, XXYY, and various mosaics presenting with leg ulcerations [3].
The cause and pathogenesis of leg ulcers in Klinefelter's syndrome is unknown. Two cases in the literature demonstrated thrombophlebitis associated with the ulcers [4]. Other reports found varicose veins in patients with ulcers [3]. Obesity may also contribute to venous insufficiency [3]. Higgins et al [5] and others found evidence of platelet hyperaggregability in such patients.
The underlying problem may be associated with androgen deficiency. Stasis ulcers are more common in women and occur in men with supernumerary X chromosomal abnormalities. Men with venous stasis were shown to be less fertile, significantly taller, and more obese than age-matched control subjects. Furthermore, two cases have been reported where the administration of testosterone has resulted in ulcer healing in patients with Klinefelter's syndrome.
Another etiologic factor in ulcer formation may be vascular abnormalities. An increased incidence of multiple cutaneous angiomas in patients with the XXYY genotype and a case of an XXY male with multiple capillary hemangiomas and telangiectasias have been reported. Subarachnoid hemorrhages have also been found in patients with Klinefelter's syndrome.
Our patient, in conjunction with past reports and studies, is an example of the association between Klinefelter's syndrome and leg ulcers. He presented with leg ulceration and this prompted an endocrinologic investigation. It is important to consider Klinefelter's syndrome in young males who develop chronic leg ulcers.
Sunnybrook Health Science Centre
Toronto, Ontario, Canada M4N 3M5
Dr Shear is a career scientist of the Ontario Ministry of Health.
REFERENCES^
1. Campbell WA, Newton MS, Price WH. Hypostatic leg ulceration and Klinefelter's syndrome. J Ment Defic Res. 1980;24:115-117. [Medline Link] [Context Link]
2. Campbell WA, Price WH. Venous thromboembolic disease in Klinefelter's syndrome. Clin Genet. 1981;19:275-280. [Medline Link] [Context Link]
3. Verp MS, Simpson JL, Martin AO. Hypostatic ulcers in 47, XXY Klinefelter's syndrome. J Med Genet. 1983;20:100-101. [Medline Link] [Context Link]
4. Downham TF, Mitek FV. Chronic leg ulcers and Klinefelter's syndrome. Cutis. 1986;38:110-111. [Medline Link] [Context Link]
5. Higgins EJ, Tidman MJ, Savidge GF, et al. Platelet hyperaggregability in two patients with Klinefelter's syndrome complicated by leg ulcers. Br J Dermatol. 1989;120:322. [Medline Link] [Context Link]
Hemangioma; Klinefelter's Syndrome; Leg Ulcer; Varicose Ulcer; Varicose Veins; Androgens