Ramandeep K. Bambrah, MD, Fauzia Rana, MD, and Dat C. Pham, MD
Department of Medicine, University of Florida College of Medicine, Jacksonville, FL
Sickle cell disease consists of hemolytic anemia and episodes of vaso-occlusion, which are caused by sickling of red blood cells (RBCs) precipitated by deoxygenation. The change in shape of the RBCs is what causes vascular occlusion, leading to acute sickle crisis.
Hydroxyurea has been approved by the US Food and Drug Administration for the treatment of adult patients with clinically severe disease. Hydroxyurea blocks DNA synthesis via enzymatic inhibition of ribonucleotide reductase.1 Administration of hydroxyurea is associated with an increase in HbF (fetal hemoglobin) levels,2 thereby reducing the severity of vaso-occlusive crises, acute pain, acute chest syndrome, transfusion requirements, and hospitalizations. 3 As a cytotoxic, cell cycle–specific agent, hydroxyurea is associated with several adverse reactions, namely bone marrow suppression.4 Other side effects associated with hydroxyurea use include gastrointestinal upset, mild dermatologic reactions, alopecia, and leg ulcers.
The case study presented here focuses on an adult with sickle cell disease who complained of painful discoloration and edema of his hands and feet with blisters about 1 week after starting hydroxyurea therapy.
Case presentation
A 50-year-old black man with a history of atrial fibrillation, avascular necrosis of the shoulder, and sickle cell disease had frequent hospitalizations for acute crises requiring multiple packed RBC transfusions. He had no known history of leukemia/ lymphoma or exposure to other cytotoxic drugs. The patient was placed on hydroxyurea to reduce the frequency of sickle cell crises. Once hydroxyurea was begun, the patient noticed a decrease in acute pain and improvement in his general well-being.
Approximately 1 week after initiation of hydroxyurea therapy, the patient started noticing darkening of his hands. Two weeks later, hyperpigmentation of the palmar creases was noted. Three weeks after hydroxyurea was started, the patient had edema and blisters of his hands and feet with associated desquamation. Symptoms were severe and painful and interfered with activities of daily living (Figure 1). The patient’s fingers were so swollen that he was unable to make a fist. His feet were so edematous that it was difficult to walk. After these signs of hand-foot syndrome developed, his hematologist discontinued hydroxyurea, and the edema and pain gradually improved. Three months after hydroxyurea discontinuation, the edema and erythema had resolved, but the patient still had some hyperpigmentation.
Discussion
Palmar-plantar erythrodysesthesia, also known as hand-foot syndrome or acral erythema, is a known adverse reaction of several antineoplastic medications, although few published articles mention hand-foot syndrome as a common adverse effect of hydroxyurea therapy.3–5 The incidence of hand-foot syndrome in patients being treated with 5-fluorouracil, capecitabine (Xeloda), or liposomal doxorubicin (Doxil) ranges from 7% to 63%.6 It is a known adverse event of hydroxyurea therapy, although its exact frequency has not been established.
In a study examining mucocutaneous changes in 158 patients with chronic myeloid leukemia (CML) and long-term hydroxyurea therapy, 21 had severe changes and acral erythema.7 In these CML patients acral persistent erythema involved palmar, plantar, and facial areas, with less frequent involvement of the scrotum. 7 Symptoms were described as a burning sensation associated with redness, scaling, and fissuring.7 Acral erythema was noted to disappear gradually after discontinuation of hydroxyurea.7 Handfoot syndrome is known to occur in patients with CML being treated with hydroxyurea, but our case report describes a patient with hand-foot syndrome associated with hydroxyurea therapy and sickle cell disease.
Most cases of hand-foot syndrome improve, if not completely resolve, after cessation of the offending agent. Our patient did not require treatment specifically for hand-foot syndrome, as termination of hydroxyurea resulted in resolution of edema and pain.
Among the most common therapeutic agents for hand-foot syndrome is pyridoxine (vitamin B6). Pyridoxine has not been known to prevent the development of hand-foot syndrome, but observations suggest better symptom control with this vitamin, although randomized controlled studies are needed to further support this use.6 Another agent to consider for hand-foot syndrome is topical 99% dimethyl sulfoxide (DMSO). Case descriptions have reported improvement with DMSO in soft-tissue damage and edema in patients being treated with liposomal doxorubicin.8
In conclusion, hand-foot syndrome is a potentially reversible condition that is a common complication of certain chemotherapeutic drugs. However, it is not frequently reported with the use of hydroxyurea in adult patients with sickle cell disease.
Disclosures
The authors have nothing to disclose.
References
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