Cytarabine ears – A side effect of cytarabine therapy

Divya Doval , Sanjeev Kumar Sharma, Meet Kumar, Vipin Khandelwal and Dharma Choudhary

Divya Doval, Department of Hematooncology and BMT, BLK Superspeciality Hospital, New Delhi 110005, India.

Email: divyadoval@yahoo.co.uk

Abstract Cytarabine, a pyramidine analog, is used for treating various hematological malignancies such as acute leukemias and lymphomas. Side effects of cytarabine are dose dependent and include bone marrow suppression, fever, cerebellar toxicity, cardiomyopathy, hepato-renal insufficiency, necrotizing enterocolitis, pancreatitis, acute respiratory distress, corneal toxicity and dermatological side effects. The dermatological side effects can be immediate or due to delayed hypersensitivity reactions. They have been attributed largely to release of cytokines. We present three such cases of delayed hypersensitivity to cytarabine affecting the ears bilaterally.

Case report

Case 1 A 41-year-old female, a case of acute myeloid leukemia (intermediate risk), was treated with 7+ 3 induction chemotherapy (cytarabine 100 mg/m2 for seven days by continuous infusion along with daunorubicin 60 mg/m2 for three days). On day 6 of chemotherapy, she developed erythema over one ear not associated with pain or itching (Figure 1), which subsequently spread to both ears, sparing of all other areas of face and body. She did not have any associated fever. 

Case 2 A 60-year-old lady was diagnosed to have acute myeloid leukemia (low risk). She was treated with 7+ 3 induction chemotherapy (cytarabine 100 mg/m2 for seven days twice daily along with daunorubicin 60 mg/m2 for three days). On day 8 of chemotherapy (few hours after the last dose), she developed erythema over both ears with associated itching and mild burning pain (Figure 2). There was no associated fever.

Case 3 A 42-year-old lady with acute myeloid leukemia received 7+3 induction (cytarabine 100 mg/m2 for seven days by continuous infusion along with daunorubicin 60 mg/m2 for three days). On day 7, she developed an erythematous rash on bilateral ear lobes associated with pain and itching.

Management and outcome 

Case 1 The patient subsequently developed neutropenic fever and was treated with broad spectrum antibiotics. Her repeat blood and urine cultures were sterile. The rash started reducing 48 h after cessation of chemotherapy and completely resolved within five days. 

Case 2 The rash and itching were treated with oral fexofenadine and resolved completely over next 72 h. This patient was re-challenged with high-dose cytarabine in the consolidation phase of her chemotherapy without recurrence of any dermatologic manifestations. 

Case 3 This patient was treated with topical hydrocortisone 1% ointment and oral analgesics. The rash turned to bluish purple by day 12 and then subsequently resolved by day 15. This study was approved by the hospital ethics committee and informed consent from patients was taken.

Discussion 

Cytarabine can cause various types of skin reactions. The typical cytarabine-induced skin rash develops 6– 12 h after the drug is started and resolves with cessation of therapy. Incidence of the cytarabine-induced systemic rash varies between 3 and 72% and is more commonly seen in patients receiving high doses of cytarabine.1 The generalized rash has also been reported with low doses and in both adults and children.1,2 It may manifest as maculopapular or morbilliform rash or as hand–foot syndrome, which presents as erythema of palms and soles, associated with pain, tingling and paresthesia, or it may involve trunk and extremities. Isolated involvement of ears has rarely been reported, with only nine cases reported.

J Oncol Pharm Practice 2020, Vol. 26(2) 471–473