Doxorubicin-induced cardiomyopathy and hyperpigmentation: a common pathogenesis?

Learning objectives were (1) Recognize potential adverse effects of doxorubicin. (2) Discuss the pathophysiology of doxorubicin toxicity. A 70-year-old African-American male with a history of chemotherapy-treated (CHOP, cumulative doxorubicin dose of 400 mg/[m.sup.2]) immunoblastic T-cell lymphoma presented with 2 weeks of severe shortness of breath and clinical signs of heart failure. The remainder of the physical examination was within normal limits except for mucosal and nailfold hyperpigmentation that was not present prior to starting chemotherapy. A chest x-ray demonstrated fluid overload and an echocardiogram revealed the patient's ejection fraction had dropped from >50% (previous year) to less than 20%. Work-up for other potential etiologies of CHF was negative and the patient was diagnosed with doxorubicin-induced heart failure. Doxorubicin-induced cardiomyopathy and congestive heart failure is a well documented toxicity that appears to be dose-dependent with frequent occurrences as the cumulative dose exceeds 550 mg/[m.sup.2]. Transient mucocutaneous hyperpigmentation has also been associated with doxorubicin use, especially in dark-skinned individuals. Although the mechanism for cardiotoxicity is unknown, there is evidence that doxorubicin induces free radical production resulting in cardiac damage. In addition, doxorubicin has a direct effect on melanin production without affecting the hypothalamic-pituitary-adrenal axis. Furthermore, several in vivo and in vitro studies have demonstrated a correlation between free radical production and increased melanogenesis. Therefore free radical production maybe a unifying mechanism for both doxorubicin-induced cardiomyopathy and hyperpigmentation.

Benjamin B. Hayes, MD, PhD. University of Tennessee College of Medicine--Chattanooga Unit, Chattanooga, TN.