AIFRS consists as a rare, aggresive and fatal form of fungal sinusitis that commonly affects immunocompromised patients. Most common presenting comorbidities are diabetes mellitus and hematologic malignancies as reported by several authors [5, 8]. This observation is conformed by the present study as 12 out of 14 patients had these two commorbidities.
In the past decade (2011–2020), data of patients from fourteen series with ten or more AIFRS patients have been published [1–2, 8–19]. From a total of 391 patients within these published series overall survival was 43% (Table 3). Turner et al in a meta-analysis of 52 studies comprising 807 patients recorded an overall survival rate of 49.7% [5]. This observation is confirmed by a review conducted by Craig that reports AIFRS as a complex and devastating disease with around a 50% mortality rate [20]. Our series findings are similar as overall survival was 35.7%.
Table 3
Published series with ten or more patients within the past decade (2011–2020) with reported survival.
| Author | AIFS cases | Overall Survival |
| Monroe et al [1] | 29 | 18% |
| Ergun et al. [2] | 19 | 38,8% |
| Bakhshaee et al [8] | 18 | 83,3% |
| Foshee et al [9] | 27 | 42,3% |
| Gode et al [10] | 37 | 35,1% |
| Pagella et al [11] | 10 | 20,0% |
| Papagiannopoulos et al [12] | 18 | 55.5% |
| Payne et al [13] | 41 | 36,6% |
| Roxbury et al [14] | 54 | 69.2% |
| Fernandez et al.[15] | 19 | 31.6% |
| Vengerovich et al [16] | 34 | 38,20% |
| Lagos et al [17] | 32 | 28,10% |
| Huang Yu-Fang [18] | 21 | 42,00% |
| Valera et al [19] | 32 | 50,00% |
| Total | 391 | 43,00% |
Several authors report that poor prognosis is related to the extensiveness of AIFRS and to the underlying disease [19, 21]. AIFRS or the underlying cause leads to death? Although, there is a lack of information in many published series in regards to long term overall survival of AIFRS patients as well as the differentiation between actual overall survival and disease-specific survival, our series confirms that the main cause of death in AIFRS patients is the underlying condition and not AIFRS. In a meta-analysis of 979 patients, Burton et al report that inpatient mortality rate was 15,8% and highlight that the underlying immune dysfunction is an important predictor of early mortality [22].
In a study conducted by Valera et al patients with aplastic anemia and diabetes had the worst outcomes [19]. Our data confirm the findings of the aforementioned study as patients with hematologic malignancies have a worse overall prognosis and younger patients had a better outcome.
In our series, three out of five patients that survived remained alive and well even without any surgical intervention. These results should be interpreted with caution, but they are an indication that the long-term prognosis is primarily affected by the underlying disease. Since no statistically significant conclusions may be derived from our group authors do not advocate a non-surgical approach but this information should be taken into consideration in decision-making, especially when an aggressive surgical procedure such as orbital exenteration is planned. This is why management of these patients should involve a multidisciplinary team consisting of the surgeon, an infectious diseases specialist, the oncologist or hematologist as well as a diabetes specialist, a psychologist etc., in order to address both the medical and the ethical issues that arise during treatment. Even though surgery is still the mainstay of treatment apart from systemic antifungal therapy, it is frequently aggressive and may lead to early or late complications or facial disfigurement, a possible cause of further psychological distress for these severely ill individuals.
Authors emphasize that early recognition and diagnosis of the disease limits the need of extensive surgery [21–23]. Thus, early endoscopic examination of the patients, CT scans and biopsy plus culture of suspected lesions should be ordered in this group of patients.
Most common AIFRS causative organisms include Aspergillus, Mucor, Rhizopus and atypical organisms. Several studies have identified Aspergillus or Mucor as the most commonly isolated fungal species in AIFRS [20, 22]. In our study Mucor/Rhizopus was isolated in 9 out of 10 positive tissue cultures while Aspergillus in only one. Although the isolated fungi are not particulary diverse, our data indicate that the prognosis of AIFRS is unrelated to the fungus isolated [19].
Current undisputable practice in AIFRS management is surgical treatment and patients who do not receive surgery as part of their therapy, have a poor prognosis [5]. Endoscopic sinus surgery (ESS) with debridement to bleeding margins is generally considered a safe procedure. Multiple operations are sometimes required, with a number of interventions ranging between 2 to 14 per patient, increasing the possibilities of complications, especially since these procedures are destructive rather than functional in nature [24]. ESS may be sometimes quite aggressive. In our series extension of surgery did not exceed standard anterior – posterior ethmoidectomy with sphenoidotomy plus removal of the lateral nasal wall. Furthermore, no endoscopic procedure was extended to the orbit Zuniga et al report that the indications for orbital exenteration remain unclear, but recent studies suggest that this procedure may not change outcome in most patients [25].
All our patients that were operated underwent a single surgical procedure, followed by daily endoscopic debridement. The procedures were performed with an intention to achieve healthy bleeding margins after the resection of the involved bony structures. However, this is not always possible and contamination of the remaining areas is still evident in the immediate postoperative period [10]. Nevertheless, we decided not to amputate any patient considering not only the underlying disease but also their own preferences and consent. Although early surgical debridement and antifungal therapy remain the cornerstones of AIFRS management, surgery is a complementary treatment to antifungal therapy. The surgical rationale is based on the reduction of the infectious load with the debridement of the necrotic tissue, where systemic antifungal therapy would be ineffective [15, 23].