(CS-127) Hydroxyurea induced dry gangrene in a patient with history of chronic myelogenous leukemia, a unique case report

Patrick McEneaney, DPM – Northern Illinois Foot and Ankle Specialists

Introduction: Hydroxyurea is a commonly employed medication used for the treatment of sickle cell anemia, Chronic myelogenous leukemia,essential thrombocytopenia and cervical cancer.With recent studies demonstrating its potency and efficacy in the treatment of CML, there has been a prevalence in the use of the medication.Hydroxyurea is known to inhibit DNA synthesis, advantageous to eliminating oncological cells.It causes severe myelosuppression with side effects such a leukopenia and thrombocytopenia well documented.To our knowledge, there have only been two previous case reports which demonstrated ischemic changes after taking hydroxyurea.We demonstrate a rare case of an individual developing ischemic changes after being on hydroxyurea therapy for the treatment of chronic myelogenous leukemia

Methods:

66 y/o female presenting with ischemic changes noted to digits 1 and 2 of the right foot.Her medical history was negative for any metabolic disorders.She was prescribed hydroxyurea for the treatment of chronic myelogenous leukemia.Patient presented a few weeks after onset of dry gangrene to her extremity. At initial visit, she had gangrenous hallux and ischemic second digit. She also underwent CT Angiography which demonstrated three vessel runoff to the foot. Coagulation studies were negative. When the medication was discontinued, there was no further progression of the gangrene.  After demarcation was achieved, she had gangrenous changes to digits 1, 2 and 3 with signs of osteomyelitis on imaging.

Results: Patient underwent transmetatarsal amputation and skin grafts after demarcation of local gangrenous changes.

Discussion: Hydroxyurea decreases the production of deoxyribonucleotides which in turn, synthesizes deoxyribonucleotides and inadvertently DNA. By inhibiting this step, it decreases the production of granulocytes in the bone marrow, thereby acting as an immunosuppressant. While many side effects have been reported, a thorough search through the NCBI database only reveals one such case described as above. Authors hypothesized cessation of hydroxyurea as the only therapeutic option. As hydroxyurea prevents vaso occlusive crisis in sickle cell anemia patients, our hypothesis is that our patient had local ischemic changes which had led to gangrene of pedal digits. As not much is known about medication induced ischemia, one must allow for the tissue to fully necrose and determine level of amputation.
Currently, cessation of hydroxyurea therapy appears to be the only treatment option available, thereby preventing further progression of ischemic changes to the extremity. As the use of hydroxurea continues to rise, foot and ankle specialists should be aware of potential vaso occlusive pedal changes that they may encounter if their patients with myeloproliferative disorders.

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