Hydroxyurea Associated Leg Ulcer Succesfully Treated with Hyperbaric Oxygen in a Diabetic Patient

Abstract

Oxygen tension in healing tissues is heterogeneous. Increased oxygen mostly stimulates repair mechanisms and enhances tissue healing. Hyperbaric oxygen therapy increases blood and tissue oxygen content and may help maintain cellular integrity and function. Hydroxyurea (HU) is a cytotoxic agent, which leads to inactivation of ribonucleotide reductase, inhibition of cellular DNA synthesis, and cell death in the S phase. HU induced leg ulcers occur after use of this agent for a long time and at higher cumulative doses. Here we describe a diabetic patient with foot ulcer associated with HU treatment for polycythemia vera, who was treated successfully with hyperbaric oxygen and general wound care after discontinuation of HU. Faster improvement of leg ulcer in our patient compared to literature regarding HU withdrawal as single therapy suggests that hyperbaric oxygen may be helpful in the management of HU associated leg ulcers, especially in diabetic subjects.

Key words

diabetes - leg ulcer - hydroxyurea

References

• 1 Sirieix ME, Debure C, Baudot N. et al . Leg ulcers and hydroxyurea: forty-one cases.  Arch Dermatol. 1999;  135 ((7)) 818-820
• 2 Best PJ, Daoud MS, Pittelkow MR, Petitt RM. Hydroxyurea-induced leg ulceration in 14 patients.  Ann Intern Med. 1998;  128 ((1)) 29-32
• 3 Kido M, Tago O, Fujiwara H, Ito M, Niwano H. Leg ulcer associated with hydroxyurea treatment in a patient with chronic myelogenous leukaemia: successful treatment with prostagladin E1 and pentoxifylline.  Br J Dermatol. 1998;  139 ((6)) 1124-1126
• 4 Aragane Y, Okamoto T, Yajima A, Isogai R, Kawada A, Tezuka T. Hydroxyurea-induced foot ulcer successfully treated with a topical basic fibroblast growth factor product.  Br J Dermatol. 2003;  148 ((3)) 599-600
• 5 Stagno F, Guglielmo P, Consoli U, Fiumara P, Russo M, Giustolisi R. Successful healing of hydroxyurea-related leg ulcers with topical granulocyte-macrophage colony-stimulating factor.  Blood. 1999;  94 ((4)) 1479-1480
• 6 Humpert PM, Bartsch U, Konrade I. et al . Locally applied mononuclear bone marrow cells restore angiogenesis and promote wound healing in a type 2 diabetic patient.  Exp Clin Endocrinol Diabetes. 2005;  113 ((9)) 538-540
• 7 Niinikoski JH. Clinical hyperbaric oxygen therapy, wound perfusion, and transcutaneous oximetry.  World J Surg. 2004;  28 ((3)) 307-311
• 8 Roeckl-Wiedmann I, Bennett M, Kranke P. Systematic review of hyperbaric oxygen in the management of chronic wounds.  Br J Surg. 2005;  92 ((1)) 24-32
• 9 Weinlich G, Schuler G, Greil R, Kofler H, Fritsch P. Leg ulcers associated with long-term hydroxyurea therapy.  J Am Acad Dermatol. 1998;  39 ((2 Pt 2)) 372-374
• 10 Velez A, Garcia-Aranda JM, Moreno JC. Hydroxyurea-induced leg ulcers: is macroerythrocytosis a pathogenic factor?.  J Eur Acad Dermatol Venereol. 1999;  12 ((3)) 243-244
• 11 Engstrom KG, Lofvenberg E. Treatment of myeloproliferative disorders with hydroxyurea: effects on red blood cell geometry and deformability.  Blood. 1998;  91 ((10)) 3986-3991
• 12 Faglia E, Favales F, Aldeghi A. et al . Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer. A randomized study.  Diabetes Care. 1996;  19 ((12)) 1338-1343
• 13 Baroni G, Porro T, Faglia E. et al . Hyperbaric oxygen in diabetic gangrene treatment.  Diabetes Care. 1987;  10 ((1)) 81-86
• 14 Kessler L, Bilbault P, Ortega F. et al . Hyperbaric oxygenation accelerates the healing rate of nonischemic chronic diabetic foot ulcers: a prospective randomized study.  Diabetes Care. 2003;  26 ((3)) 2378-2382
• 15 Kalani M, Jorneskog G, Naderi N, Lind F, Brismar K. Hyperbaric oxygen (HBO) therapy in treatment of diabetic foot ulcers. Long-term follow-up.  J Diabetes Complications. 2002;  16 ((2)) 153-158
• 16 Zimny S, Pfohl M. Healing times and prediction of wound healing in neuropathic diabetic foot ulcers: a prospective study.  Exp Clin Endocrinol Diabetes. 2005;  113 ((2)) 90-93
• 17 Montefusco E, Alimena G, Gastaldi R, Carlesimo OA, Valesini G, Mandelli F. Unusual dermatologic toxicity of long-term therapy with hydroxyurea in chronic myelogenous leukemia.  Tumori. 1986;  72 ((3)) 317-321

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