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.