Extensive attempts to initiate wound healing before discontinuation of treatment included the use of topical and systemic antibiotic therapy, pentoxifylline, hyperbaric oxygen, warfarin, prednisone, Unna vascular boots, and topical wound dressings. None offered significant clinical benefit. Hydroxyurea-induced cutaneous ulcers often occur over the malleoli. One explanation for this localization may be mechanical injury and trauma. In addition, the latency to onset, indolent behavior, and eventual healing after therapy is discontinued all suggest that the mechanism for cutaneous toxicity involves chronic and progressive but reversible cytologic damage.
Histologic examination shows nondiagnostic changes.
A typical histologic photomicrograph of a hydroxyurea-induced ulcer is shown in the bottom panel of the Figure . At the ulcer border, pseudoepitheliomatous hyperplasia and epidermal spongiosis are seen. In the dermis, endothelial cell swelling, edema, and thickening of blood vessel walls are prominent. Perivascular lymphocytic inflammation without vasculitis is common. In chronic lesions, focal hyalinization of blood vessel walls and intraluminal deposition of fibrinoid material directly beneath the ulceration are seen.