Chronic leg ulcers associated with hereditary protein S deficiency

A 17-year-old Thai man developed erythematous papules on the dorsal surfaces of both feet 7 years previously. The papules progressed to superficial ulcers which slowly increased in size and, although treated by several modalities, never completely healed. Physical examination revealed two irregular-shaped superficial ulcers, 4 × 1 and 5 × 1 cm in size, on the dorsal surface of his right and his left foot, respectively (Fig. 1). The ulcers had granulation tissue at the bases with well-defined borders surrounded by brownish patches. During admission, the superficial vein of the patient's right arm showed painful, warm, cord-like induration. A biopsy specimen from the edge of the ulcer of the left leg showed ulcerated epidermis with pseudoepitheliomatous hyperplasia. Diffuse mixed cellular infiltration composed of lymphocytes, histiocytes, and neutrophils was seen in the dermis with fibrosis and some capillary proliferation. The results of skin biopsy cultures for fungus, bacteria, and mycobacteria were negative. The biopsy specimen from the superficial vein of the right arm showed obliteration of the vessel lumen and mixed cellular infiltration composed of lymphocytes, histiocytes, and neutrophils within the wall compatible with thrombophlebitis. Laboratory studies revealed a normal complete blood cell count, SMA 18, prothrombin time, and partial thromboplastin time. The erythrocyte sedimentation rate was 29 and lupus anticoagulant was not present. Anticardiolipin IgG, IgM, ANA, cryoglobulin, and anti-HIV antibody were all negative. Levels of C3, C4, and CH50 were normal. Bilateral venogram showed deep vein thrombosis of the left leg. The free protein S level was 41% (normal 60%-140%) (Microlatex particle-mediated immunoassay), the protein C level was 90% (normal 75%-150%), and the antithrombin III level was normal. Heparin treatment (Nadroparine 20,000 units subcutaneous Injection twice a day for 10 days) was followed by coumadin 3 mg/day, 2 days per week (days 1 and 4), and 2 mg/day, 5 days per week (days 2, 3, 5, 6 and 7), to keep the prothrombin time between 1.5 and 2 times normal control. The ulcers completely healed 3 months after treatment. The studies of the patient's family members were consistent with hereditary protein S deficiency as in the pedigree shown in Fig. 2. The patient's brother (III-2), mother (11–2), and aunts (11–1, 11–5) all had low levels of protein S (35%, 63%, 51%, and 69% respectively). His uncle (11–3) died with pulmonary embolism in a private hospital. Unfortunately an autopsy was not permitted. We could not obtain blood samples from the patient's father and grandfather.