We retrospectively reviewed 27 patients presenting nasal symptoms possibly related to rhinosinusitis who were admitted in the Hematology Unit. Seven patients were excluded due to the lack of radiological images. Six of the 20 eligible patients were assigned to the study group resulting to be affected by IFS and the remaining 14 patients were assigned to the control group.
The study group consisted of one woman (16.7%) and five men (83.3%) having a mean age of 49.3 years (range, 28–69 years) as is shown in . The etiologic agents were Zygomycetes in three (50%) patients, Aspergillus spp. in two patients (35%) and Fusarium solanii in one patient (15%). IFS began as acute IFS in five patients and one case started as the granulomatous invasive form.
General predisposing factors in all patients of the IFS group were severe neutropenia (five patients underwent allogenic BMT and one had recurrent acute myelogenous leukemia unresponsive to treatment) and high-risk corticosteroid therapy that ranged from 9 to 34 days (mean duration of 16 days) before the IFS development. None of the patients had diabetes. Five patients had a concomitant invasive fungal pulmonary infection. Of these, four cases had developed a pulmonary infection before IFS and, in one case, it had developed after IFS. Previous pulmonary infections had been successfully treated in three cases before IFS occurrence.
The main symptoms of IFS were characterized by nasal obstruction (four cases), headache (three cases), and retro-orbital pain (two cases), and the diagnosis was generally achieved with a mean delay of 5.2 days (range, 2–12 days). Preoperative diagnosis was performed in all patients by a transnasal endoscopy and radiological assessment with a CT scan ( and ). Microbiological assessment was performed in all cases using a nasal swab but only case 5 () had a positive result (Fusarium spp.).
Figure 1. (A) Endoscopic view of the left middle turbinate with invasive fungal infection (Fusarium spp) involving the head of the turbinate (patient 5). (B) Endoscopic view of invasive fungal infection (Rhizomucor) involving the left middle turbinate, having a (more ...)
Figure 2. (A) Computed tomography (CT) scan of a patient affected by right invasive fungal infection with notable anterior septum deviation (arrow) causing nasal obstruction. (B) CT scan of a control group patient (not affected by IFS), complaining of symptoms (more ...)
All but case 4 developed the infection over the summer. The average daily mean temperature and humidity of the 15 days preceding the infection are reported in . All patients of the IFS group were exposed to outdoor environmental conditions during the 15 days before the symptoms occurrence.
Sinonasal and environmental risk factors
Anatomic nasal alterations were found in all patients affected by IFS (). Anterior nasal septum deviation causing nasal or sinus obstruction was found in all but one case. The possible initial location of the disease could be identified in three cases at the level of the head of the middle turbinate (
A). In these three cases, a positive association between the side in which the disease started and the side of the anatomic nasal alteration was observed.
All patients were treated surgically and by antifungal therapy. The surgical treatment was characterized by a transnasal endoscopic approach, which permitted resection of the anatomic structures presenting necrosis until healthy tissue was reached. Case 6 underwent a combined transnasal endoscopic–external approach (orbital exenteration) to remove diseased tissue located at the level of either the lateral wall or the orbit.
Disease-free survival was 50% (three patients died due to progression of IFS). However, the overall survival rate was 16.7% (1/6). Patients who were diagnosed before the 4th day after the occurrence of symptoms had a good disease-related outcome. All patients who were diagnosed on the 4th day or later died due to progression of IFS.
The control group included seven men (50%) and seven women (50%) with a mean age of 41.4 years (range, 22–57 years). General predisposing factors for invasive fungal infection were severe neutropenia in all patients and long-term corticosteroid therapy in 12 cases (85.4%). Three of 14 cases (21%) had a possible or probable pulmonary fungal invasive infection, successfully treated with specific antifungal therapy in all patients.
The nasal symptoms reported in this group were nasal obstruction in 14 cases (100%), rhinorrhea in 4 cases (28.6%), and headache in 4 cases (28.6%). In all cases, a trans-nasal endoscopy and CT were performed but no evidence of disease was found. Symptoms occurred in nine cases (64.3%) during the winter, in two cases (14.3%) during the spring, in two cases (14.3%) during the autumn, and only one case (7.1%) during the summer. All of the 14 patients of the control group were exposed to outdoor environmental conditions during the 15 days before the symptom occurrence. The average temperature and humidity of the 15 days preceding the nasal symptoms and the anatomic nasal alterations noted are reported in .
Comparison between the groups showed a significant association of anterior septum deviation causing nasal obstruction and IFS (p = 0.018; OR, 18.3; CI, 17.3–19.4), and other nasal anatomic alterations and previous sinus disease did not reach statistical significance. Age and previous pulmonary fungal invasive infection were not significantly associated with IFS (p = 0.17 and p = 0.12, respectively). Summer was significantly associated with IFS (p = 0.002; OR, 65.0; CI, 63.1–66.9). There was a significant difference between average daily mean temperatures (p = 0.002), average maximum temperatures (p = 0.002), and average minimum temperatures (p = 0.003) of the 15 days preceding the infection in the two groups. The average mean humidity did not show a significant difference between the two groups (p = 0.15).