Acute promyelocytic leukemia (APML) is a rare entity constituting 1% of all acute leukemias in the pediatric age group. All-trans-retinoic acid (ATRA) is a standard therapy used for its remission. We report a rare adverse event of severe myositis associated with tretinoin (an ATRA preparation) in a child with acute promyelocytic leukemia.

A 5-year-old girl presented with fever, skin and mucosal bleeds, and pallor. Her hemoglobin was 3.6 g/dL, total white cell count 4.5×103/µL and platelet count 13×103/µL. Peripheral smear revealed 30% blasts, confirmed as APML on bone marrow examination. Cytogenetic analysis showed the typical translocation of t(15:17) with 77% of interphase cells expressing PML:RARA gene fusion. Child was started on combination chemotherapy with etoposide (VP16), 6-thioguanine (6TG) and prednisolone. ATRA was added in the dose of 45 mg/m2/day on day 3. On day 10 of treatment, child had severe calf muscle pain restricting her physical activity. There was no fever, joint pain, joint swelling or bleeding. However, there was a mild swelling of the limb in the region of pain. X-ray limbs and sonography of the calf muscles were inconclusive. Magnetic resonance imaging (MRI) of limbs done 2 days later showed edema in muscles of posterior compartment and fluid in the intermuscular planes suggestive of myositis. A diagnosis of ATRA-induced myositis was made. ATRA was discontinued and intravenous dexamethasone was given. Child improved dramatically and ATRA was restarted after 2 days in a lower dose.

The common side effects of ATRA include ATRA syndrome (in 25% of patients), hyperleucocytic syndrome (acute respiratory distress syndrome), isolated fever, weight gain, headache, pseudotumor cerebri, raised aminotransferases, hypertriglyceri-demia, myalgia, hypercalcemia, erythema nodosum, fournier gangrene, Sweet syndrome and necrotizing vasculitis. Isolated muscle involvement due to ATRA therapy in APML has been rarely described(1-4). Most of the reported cases are in adults(4). Till date, to the best of our knowledge, only 2 pediatric cases of ATRA-induced myositis have been reported(4). Our patient developed muscular symptoms on day 7 of ATRA, whereas reported cases in adults had a median time of onset around 18 days (range 9-23), except in one pediatric case where the onset was within 5 days of starting ATRA(1,4). A high index of clinical suspicion coupled with modern imaging methods are required to diagnose this condition. Timely treatment is important to prevent further life threatening complications(5).

Dr Sandhya Kamath, Dean, LTMG Hospital, Sion, Mumbai for granting us permission to publish this case report. Dr Shripad Banavali, Professor & Head, Medical Oncology, Tata Memorial Hospital, Mumbai for guiding us through the management. Dr Ratna Sharma, lecturer, for her contribution to the diagnosis and management.