Mortality Risk Factors in Pediatric Invasive Fungal Rhinosinusitis: The CARE-PIFRS Multicenter Study

Introduction: Pediatric invasive fungal rhinosinusitis (IFRS) is rare but highly lethal in immunocompromised children. Mortality predictors in this population remain poorly defined.

Methods: Multicenter retrospective cohort of patients < 21 years with IFRS from eight tertiary pediatric centers. Demographics, immune status, disease extent, microbiology, timing of diagnosis/treatment, surgical interventions, and outcomes were analyzed. Survivors and non-survivors were compared using univariate analysis; variables with clinical relevance were assessed in logistic regression.

Results: Seventy-one patients were included (median age 10 years; 43.7% female). Most had hematologic malignancy (71.8%) and profound neutropenia (median ANC 0.03 K/µL). Orbital involvement occurred in 18.3% and intracranial extension in 12.7%. Median number of surgeries was 3. Overall mortality was 42.6% (26/61). Hematologic malignancy was more common among survivors (77.1% vs 50.0%, p=0.03). Disease extent, including orbital (23.1% vs 8.6%, p=0.11) and intracranial involvement (15.4% vs 5.7%, p=0.21), trended toward higher mortality but did not reach significance. ANC at presentation was not associated with mortality. Management factors differed between groups. Survivors more frequently underwent endoscopic sinus surgery (68.6% vs 42.3%, p=0.04) and therapeutic drug monitoring (48.6% vs 30.8%, p=0.09), with dose adjustments based on monitoring observed only in survivors (34.3% vs 0%, p< 0.01). Combination antifungal therapy and postoperative complications were not associated with outcome.

Conclusions: Pediatric IFRS carries substantial mortality despite aggressive care. Traditional markers such as neutropenia and disease extent did not independently predict survival, while management factors, including surgical intervention and antifungal dose optimization, were associated with improved outcomes. These findings suggest that treatment strategies may play a critical role in survival and warrant further prospective evaluation.