Pseudotumor Cerebri Associated with All-Trans Retinoic Acid Treatment During Induction Therapy for Acute Promyelocytic Leukemia: A Case Report and Literature Review

Abstract 4264

Pseudotumor cerebri (PC) is a rare disorder characterized by elevated intracranial pressure with normal cerebrospinal fluid composition, normal cranial imaging findings, and symptoms and signs of increased intracranial pressure. A number of medications have been linked to PC including vitamin A and its derivative all-trans-retinoic acid (ATRA). Herein, we describe the case of a 38-year-old woman who was diagnosed with PC during standard induction treatment for acute promyelocytic leukemia (APL). Her neurologic complaints of severe headache and diplopia improved slightly after ATRA was discontinued and she was treated with acetazolamide, but symptoms did not abate until fluconazole was held five days later. Through a literature review, we identified 41 case reports of APL patients with ATRA-associated PC, 23 of which provided details of clinical presentation and follow-up. The median age at diagnosis of PC was 27 for females and 16 for males; the female-to-male ratio was 1.3:1. All 23 patients complained of headache; papilledema was present in all 21 instances (100%) where a retinal exam was described. ATRA was held due to PC in 20 cases (87%), and neurologic symptoms resolved without further intervention in 7 of 20 (35%). The remaining 13 patients were treated with diuretics (11 of 13 cases, 85%), high-volume lumbar punctures (5, 38%), corticosteroids (4, 31%), and/or analgesics (3, 23%). Including our index patient, eight patients were rechallenged with ATRA after neurologic improvement, and 5 (63%) required further interventions to resolve recrudescent symptoms. We identified one other patient whose neurologic complaints persisted despite dose reductions in ATRA. This patient improved only after fluconazole was discontinued. Because both ATRA and fluconazole are metabolized by the cytochrome P-450 system, we suggest that if taken concurrently, they may exacerbate the risk of PC. Physicians should be aware of this interaction between ATRA and fluconazole and consider discontinuing both fluconazole and ATRA in APL patients who develop PC.