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Leg ulcers in elderly on hydroxyurea: a single center experience in Ph− myeloproliferative disorders and review of literature

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Abstract

Hydroxyurea (HU) is effective in controlling thrombocytosis while reducing the risk of thrombosis in essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF). However, HU may carry more or less severe side-effects. Rare cases of patients with painful leg ulcers have been published. We report our experience on such a side-effect in a large cohort of patients with ET and PV treated with HU and review the literature on the topic. Five (4%) out of our 124 patients (69 ET, 51 PV, 4 MF; 49 males, 75 females; mean age at diagnosis 59.1±11.8 years) treated with HU developed painful leg ulcers. Sixty-one other patients affected with Ph− myeloproliferative disorders (Ph− MPD) developing HU-related painful leg ulcers are described in the English literature. All our five patients were women and developed leg ulcers over the age of 75. Sixty-five percent of all described cases are women; 59% were over 65 years of age and 45% over 70. Most cases received over 1 gr HU per day for at least 1 year. The pathogenesis of HU-induced skin ulcers remains elusive. Treatment is difficult and requires prompt cessation of HU therapy.

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References

  1. Yarbro JW. Mechanism of action of hydroxyurea. Semin Oncol 1992; 19 (Suppl 9): 1–10.

    PubMed  CAS  Google Scholar 

  2. Murphy S. Therapeutic dilemmas: balancing the risk of bleeding, thrombosis and leukemic transformation in myeloproliferative disorders (MPD). Thromb Haemost 1997; 78: 622–6.

    PubMed  CAS  Google Scholar 

  3. Cortelazzo S, Finazzi G, Ruggeri M, et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 1995; 332: 1132–6.

    Article  PubMed  CAS  Google Scholar 

  4. Randi ML, Ruzzon E, Luzzatto G, Tezza F, Girolami A, Fabris F. Safety profile of hydroxyurea in the treatment of patients with Philadelphia-negative chronic myeloproliferative disorders. Haema- tologica 2005; 90: 261–2.

    CAS  Google Scholar 

  5. Kennedy BJ, Smith LR, Goltz RW. Skin changes secondary to hydroxyurea therapy. Arch Dermatol 1975; 111: 183–7.

    Article  PubMed  CAS  Google Scholar 

  6. Berlin NI. Diagnosis and classification of the polycythemias. Semin Hematol 1975; 12: 339–51.

    PubMed  CAS  Google Scholar 

  7. Murphy S, Iland H, Rosenthal D, Laszlo J. Essential thrombo- cythemia: an interim report from the Polycythemia Vera Study Group. Semin Hematol 1986; 23: 177–82.

    PubMed  CAS  Google Scholar 

  8. Vassallo C, Passamonti F, Merante S, et al. Muco-cutaneous changes during long-term therapy with hydroxyurea in chronic myeloid leukaemia. Clin Exp Dermatol 2001; 26: 141–8.

    Article  PubMed  CAS  Google Scholar 

  9. Hirri HM, Green PJ. Skin lesion caused by hydroxyurea. Eur J Haematol 2001; 67: 328–9.

    Article  PubMed  CAS  Google Scholar 

  10. Chaine B, Neonato MG, Girot R, Aractingi S. Cutaneous adverse reactions to hydroxyurea in patients with sickle cell disease. Arch Dermatol 2001; 137: 467–70.

    PubMed  CAS  Google Scholar 

  11. Sirieix ME, Debure C, Baudot N, et al. Leg ulcers and hydrox- yurea: forty-one cases. Arch Dermatol 1999; 135: 818–20.

    Article  PubMed  CAS  Google Scholar 

  12. Poros A, Nadasdy K. Leg ulcer in hydroxyurea-treated patients. Haematologia (Budap) 2000; 30: 313–8.

    Article  CAS  Google Scholar 

  13. Olesen LH, Pedersen BB. Hydroxyurea-induced leg ulcers in patients with chronic myeloproliferative disorders. Ugeskr Laeger 2001; 163: 6908–11.

    PubMed  CAS  Google Scholar 

  14. Nguyen TV, Margolis DJ. Hydroxyurea and lower leg ulcers. Cutis 1993; 52: 217–9.

    PubMed  CAS  Google Scholar 

  15. Best PJ, Daoud MS, Pittelkow MR, Petitt RM. Hydroxyurea-in- duced leg ulceration in 14 patients. Ann Intern Med 1998; 128: 29–32.

    Article  PubMed  CAS  Google Scholar 

  16. Disla E, D’Eamour L, Cioriou M. Hydroxyurea-associated leg ul- ceration. Ann Intern Med 1998; 129: 252–3.

    Article  PubMed  CAS  Google Scholar 

  17. Weinlich G, Schuler G, Greil R, Kofler H, Fritsch P. Leg ulcers associated with long-term hydroxyurea therapy. J Am Acad Dermatol 1998; 39: 372–4.

    Article  PubMed  CAS  Google Scholar 

  18. Ravandi-Kashani F, Cortes J, Cohen P, et al. Cutaneous ulcers associated with hydroxyurea therapy in myeloproferative disorders. Leuk Lymphoma 1999; 35: 109–18.

    Article  PubMed  CAS  Google Scholar 

  19. Vélez A, García-Aranda JM, Moreno JC. Hydroxyurea-induced leg ulcers: is macroerythrocytosis a pathogenic factor? J Eur Acad Dermatol Venereol 1999; 12: 243–4.

    Article  PubMed  Google Scholar 

  20. Bader U, Banyai M, Boni R, Burg G, Hafner J. Leg ulcers in patients with myeloproliferative disorders: disease or treatment- related? Dermatology 2000; 200: 45–8.

    Article  PubMed  CAS  Google Scholar 

  21. Yeh H, Lichtman SM. Hydroxyurea-induced cutaneous ulceration in older patients. J Am Geriatr Soc 2000; 48: 232.

    PubMed  CAS  Google Scholar 

  22. Natarajan S, Williamson D, Grey J, Harding KG, Cooper RA. Healing of an MRSA-colonized, hydroxyurea-induced leg ulcer with honey. J Dermatol Treat 2001; 12: 33–6.

    Article  CAS  Google Scholar 

  23. Young HS, Kirby B, Steward JC. Aggressive, extensive, vasculitic leg ulceration associated with hydroxyurea therapy and a fatal outcome. Clin Exp Dermatol 2001; 26: 664–7.

    Article  PubMed  CAS  Google Scholar 

  24. Demircay Z, Comert A, Adiguzel C. Leg ulcers and hydrox- yurea: report of three cases with essential thrombocythemia. Int J Dermatol 2002; 41: 872–4.

    Article  PubMed  Google Scholar 

  25. Sastre JL, Bravo A, Tembrás S, Gomez R, Ulibarrena C. Leg ulcers associated with hydroxyurea therapy. Haematologica 2003; 88 EIM01.

  26. 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: 317–21.

    PubMed  CAS  Google Scholar 

  27. 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 prostaglandin E1 and pentoxifylline. Br J Dermatol 1998; 139: 1124–6.

    Article  PubMed  CAS  Google Scholar 

  28. 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: 1479–80.

    PubMed  CAS  Google Scholar 

  29. Barbui T, Barosi G, Grossi A, et al. Practice guidelines for the therapy of essential thrombocythemia. A statement from the Italian Society of Haematology, the Italian Society of Experimental Haematology and the Italian Group for bone marrow transplantation. Haematologica 2004; 89: 215–32.

    CAS  Google Scholar 

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Authors and Affiliations

  1. Internal Medicine, Department of Medical and Surgical Sciences, University of Padova, Padova, Italy

    Elisabetta Ruzzon, Maria Luigia Randi MD, Fabiana Tezza, Guido Luzzatto, Raffaella Scandellari & Fabrizio Fabris

Authors
  1. Elisabetta Ruzzon
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  2. Maria Luigia Randi MD
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  3. Fabiana Tezza
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  4. Guido Luzzatto
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  5. Raffaella Scandellari
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  6. Fabrizio Fabris
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Correspondence to Maria Luigia Randi MD.

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Ruzzon, E., Randi, M.L., Tezza, F. et al. Leg ulcers in elderly on hydroxyurea: a single center experience in Ph− myeloproliferative disorders and review of literature. Aging Clin Exp Res 18, 187–190 (2006). https://doi.org/10.1007/BF03324647

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  • DOI: https://doi.org/10.1007/BF03324647

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