Intranasal Corticosteroid Use and Risk of Invasive Fungal Sinusitis in Acute Myeloid Leukemia, Myelodysplastic Syndrome and Post Transplant Patients

Background: Invasive fungal sinusitis (IFS) is a severe and often fatal infection with a mortality rate ranging from 50% to 80%, and primarily affects immunocompromised individuals. Previous research has identified several risk factors for IFS, including myeloid malignancies, allogeneic hematopoietic stem cell transplants (HSCTs), graft-vs-host disease (GVHD), delayed white blood cell (WBC) engraftment, and lymphopenia. Additionally, systemic steroid use has been associated with an increased risk of IFS. However, the impact of intranasal steroids (INS)—used locally rather than systemically—on the risk of developing IFS in immunocompromised patients remains unclear.

Methods: We conducted a retrospective study of patients diagnosed with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or who have received autologous or allogeneic hematopoietic stem cell transplants at the University of Arkansas for Medical Sciences (UAMS) between January 1, 2019, and December 31, 2023. Data collected included patient demographics, history of diabetes mellitus, HIV status, smoking history, and systemic steroid use. Additionally, we confirmed whether the use of intranasal corticosteroids (INS) was before or after the diagnosis of invasive fungal sinusitis (IFS). Descriptive statistics are presented as mean (standard deviation). The association between INS usage and risk of developing IFS was evaluated using logistic regression. Firth’s adjustment to logistic regression was done to account for the rare outcome data. The model was adjusted for the effect of age and prior comorbidities. A two-sided p-value of 0.05 was used to determine statistics significance.

Results: There were a total of 1610 patients who met the study inclusion/exclusion criteria. INS usage was observed in 34% (510) patients. 1.5% (24) patients had IFS. Compared to no INS usage, patients with INS usage were younger (mean age of 61 years vs 62 years); less likely to have Myelodysplatic syndrome (42% vs 48%); more likely to have - History Auto and allogenic transplant (49% vs 30%), history of diabetes (32% vs 21%), history of HIV (2.4% vs 0.9%), history of smoking (52% vs 42%), systemic steroid usage (27% vs 11%). Patients with INS usage were more likely to develop IFS (Odds ratio: 4.69, 95% CI: 2.05-11.81, P-value < 0.001). The age and comorbidity adjusted probabilities (95% Cl) of observing IFS among INS users and non-users are 3.01%( 1.68%,5.35%) and 0.69%( 0.33%,1.44%) respectively.

Conclusion: Our study shows that the use of Intranasal corticosteroids is associated with an increased risk of Invasive fungal sinusitis. Thus, INS use should be limited, and clinicians should carefully consider the risk vs benefit of INS use in immunocompromised patients. However, this study has several limitations, including its retrospective nature, the single-center design, and the rarity of IFS cases which limits the sample size. Additionally, this study did not account for the dose and duration of INS use, which could impact the likelihood of developing IFS. To validate these findings and strengthen the evidence, larger multicenter studies with greater sample sizes are warranted.