Diagnostic Pitfalls in Pediatric Acute Promyelocytic Leukemia: All-trans Retinoic Acid–Associated Hypercalcemia Mimicking Fungal Meningitis and the Risks of Azole Coadministration

Objective: To alert clinicians to the risk of severe hypercalcemia arising from the ATRA-azole interaction and to highlight a rare diagnostic pitfall involving a false-positive cerebrospinal fluid (CSF) (1,3)-β-D-glucan (BDG) result. Background: Concurrent use of all-trans retinoic acid (ATRA) and azole antifungals poses a risk of severe hypercalcemia in pediatric acute promyelocytic leukemia (APL). Methods: We performed a retrospective clinical and laboratory review of two 10-year-old patients with APL who developed drug-induced toxicity during induction therapy. Results: Both patients developed severe hypercalcemia induced by ATRA combined with fluconazole or voriconazole, presenting with intractable vomiting and headache. Notably, one case was confounded by an elevated CSF (1,3)-β-D-glucan level (a false-positive laboratory artifact), which mimicked fungal meningitis and delayed the correct diagnosis. Conclusions: Clinicians must remain vigilant for ATRA-associated hypercalcemia during azole co-administration. Recognizing diagnostic mimics and implementing routine calcium monitoring are crucial to prevent misdiagnosis and severe toxicity.