Bleomycin-Induced Lung Injury After Intravenous Iron Administration

Bleomycin is an antibiotic that is often used as a chemotherapeutic agent due to its antitumor activities against a variety of malignancies. A feared and often fatal side effect of this drug is a pulmonary injury causing inflammation that can progress to pulmonary fibrosis. Bleomycin damages lung endothelial cells by the production of free radicals that can only occur when it is bound to certain metals in the body. It forms a complex with iron and once activated by iron reduction, it destroys deoxyribonucleic acid (DNA). Therefore, it is suggested that the availability of iron in the body may play a role in the pathogenesis of bleomycin toxicity although no related cases have been documented. This is a case of a 75-year-old female with no prior history of pulmonary disease who was diagnosed with Hodgkin's lymphoma and received 12 doses of bleomycin over the course of six cycles of chemotherapy. She then presented to the hospital with respiratory failure five months after her completion of treatment. Interestingly, one month prior to presentation, she was given two intravenous iron infusions of ferumoxytol five days apart for the treatment of iron deficiency anemia. Within a week of receiving the iron, she developed dyspnea with a nonproductive cough. About a month after she developed these symptoms, she presented to the hospital and was found to be hypoxic with any activity and was subsequently placed on oxygen via nasal cannula. Her lung imaging showed new reticulonodular and patchy infiltrates bilaterally concerning for pneumonitis and her physical examination was significant for black discoloration of her fingertips and toes along with expiratory rhonchi heard throughout her lungs. During the hospitalization, her oxygen requirements increased, and the patient ended up in the intensive care unit on bilevel positive airway pressure. Her lung imaging, rapid progression, and skin findings made the clinical diagnosis of bleomycin toxicity. Out of concern that the intravenous iron may have played a role in the toxicity, iron chelation was attempted. The patient was given two doses of deferoxamine over two consecutive days and her symptoms of dyspnea along with her oxygen requirements improved. Unfortunately, these positive effects only lasted a few days and the patient continued to decline and ultimately passed away. This case raises many questions regarding iron's role in bleomycin toxicity, including if intravenous iron infusions may increase the risk of pulmonary injury from bleomycin. There are currently no guidelines or recommendations that suggest withholding iron supplementation in patients undergoing chemotherapy with bleomycin. There is also insufficient evidence to support the routine use of iron chelation in a patient that presents with bleomycin-induced lung injury. However, some studies suggest that iron chelation may play a role in preventing pulmonary toxicity. It may also lessen the severity of the toxicity or improve some of the related symptoms, thus warranting further research.