Discussion
AFRS develops in immunocompetent patients, with occurrence influenced by climate, geography, and several identified host factors.AFRS mostly occurs in men aged 21-33 years, which is significantly younger than that of CRSsNP and non-fungal CRSwNP 13, 14. It can also occur in women and children, and AFRS in children is more invasive and prone to serious complications 15. However, there is a lack of multicenter research on the epidemiology of AFRS in our country. In this study, the average age of group A was 33.5 years and group B was 35.4 years, which were significantly lower than 53.9 years in group C(p <0.001).
The confirmed cases of AFRS in our center account for 1% of CRS, which is lower than the reported 5%-10% prevalence rate 4, 16, 17. Based on extensive reports, the prevalence of AFRS is greatly influenced by geographical location and climatic conditions. In the South American States, the prevalence of AFRS can account for 10% -23% of CRS 18. In Japan, the prevalence of AFRS accounts for 1.4%-3.9% of CRS, and the northern region is significantly lower than the southern 19. In Serbia, where the average temperature is lower, the prevalence of AFRS accounts for 1.3% of CRS20. Anhui Province is divided into a north-south climate by the Huaihe River. The north of the Huaihe River belongs to a warm temperate semi-humid monsoon climate, and the south belongs to a subtropical humid monsoon climate, and the average temperature is higher than that in Japan. Is it possible that this climatic condition may cause the prevalence of AFRS to be higher than 1%? In our study, suspected AFRS accounted for 3.41% of CRS. We hypothesized whether the low detection rate of fungi in suspected cases led to the missed diagnosis of AFRS. This conjecture is worthy of our multicenter system research.
AFRS is mostly unilateral paranasal sinuses, and 30.8% of cases are found to be delayed on the contralateral side 21. However, patients with AFRS are often diagnosed late, at an advanced disease stage, resulting in the progress of the disease. Salamah reported that AFRS involved all four sinuses in 69.6% of patients and was bilateral in >53.5% of infected sinuses, of which maxillary sinus and ethmoid sinus were most involved. CT radiological imaging showed sinus expansion (35.3%-51.2%), remodeling (20.6%-37.2%), and wall thinning (41.2%-58.1%) 22. This is similar to our A group cases. In our study, the prevalence of bilateral sinuses accounted for 58.6% of all cases in group A, and the involvement of two or more sinuses was as high as 89.7%, of which the patients with maxillary sinus were the most, accounting for 96.6%, followed by ethmoid sinus 72.4%, frontal sinus 51.7.0% and sphenoid sinus 48.3%. Group B and group C also showed the most involvement of maxillary sinus. However, ethmoid, frontal and sphenoid sinus showed more involvement in group A and group B (Table 1). Statistical analysis showed that there was no significant difference in the number of invaded sinuses and CT Lund-Mackay score between group A and group B (p > 0.1). Besides, we also found bone erosion in the cases, which were 27.6% in group A and 24.6% in group B, but rarely in group C. Bone erosion in AFRS is a mostly reversible process. Complete bone regeneration occurred in more than two-thirds of patients within a short period of time. In addition, the rate of bone regeneration was not affected by the patients’ sex or age, there was no difference in the rate of bone regeneration between pediatric and adult patients23. AFRS is a non-invasive fungal sinusitis, and the process of bone erosion is usually attributed to pressure atrophy and inflammatory mediators induced by the accumulated fungal debris. However, paranasal sinus mucosa and periosteum are usually intact. This may suggest that bone erosion can regenerate after the compression of allergic mucin and inflammatory stimulation are relieved. Therefore, for AFRS patients with orbital and skull base bone resorption, we should pay attention to the mucoperiosteal protection of bone defect during nasal endoscopic sinus surgery.
AFRS is a type 2 immune response, characterized by antifungal IgE sensitivity, eosinophil-rich mucus (ie, allergic mucin), and characteristic CT and magnetic resonance imaging findings in paranasal sinuses 24. Generally, AFRS has a high relapse rate, often requiring repeated or multiple operations, and is still difficult to achieve satisfactorily. Younis and Ahmed retrospectively analyzed 117 patients identified over a 5-year period with the diagnosis of AFRS or EMCRS. Twenty-six of 117 (22%) of the study patients underwent revision surgery. Within the 2-year follow-up period, an additional 5 of 26 (19%) required another revision surgery. Another study included 651 patients with CRSwNP and 45 patients with AFRS, A total of 396 (57%) patients with CRSwNPs/AFRS reported having undergone previous endoscopic nasal polypectomy, of which 182 of the 396 (46%) reported having received more than one operation. Among that, the multiple revision rate of AFRS patients was as high as 58%. The mean number of previous surgeries per patient in the revision group was 3.3 (range 2-30)6.  In our study, the proportion of two or more surgical revisions was 34.5% in group A and 42.0% in group B, which was much higher than 6.4% in group C. This high recurrence rate often indicates that the disease has not been well controlled. Such patients often have uncontrollable symptoms of allergic rhinitis or asthma and may have decreased or even lost sense of smell. We found that 51.7% of patients in group A had decreased sense of smell, 55.2% had allergic rhinitis, and 13.8% had obvious asthma symptoms, which was significantly higher than that in group C (p <0.001). Hence, in the treatment of AFRS, we still need to pay attention to the control of complications.
Statistics showed that there were significant differences between AFRS and FBS in the age, eosinophils and basophils in peripheral blood, positive rate of galactomannan test, total serum IgE, the number of relapses, proportion of allergic rhinitis, asthma, or olfactory decline in our study (p < 0.01). The significant differences were observed in the above indexes between group B and group C (p < 0.01). Another research also pointed out that eosinophils and basophils in peripheral blood were significantly increased in AFRS, and statistical analysis found significantly higher blood eosinophils and basophils levels in AFRS patients who relapsed than in those who did not25. In addition, no significant difference was observed between group A and group B (p > 0.05), which may suggest that there are some similarities between them. Unfortunately, according to Bent-Kuhn’s diagnostic criteria, 69 cases could not be diagnosed as AFRS because of no fungal etiological evidence.
The definition and diagnostic criteria of AFRS are still under debate, and minor progress has been made in the last two decades to achieve a consensus. The most widely used is the Bent-Kuhn criteria. According to each author’s clinical experience and the available literature, different lists of criteria are proposed. These criteria included the characteristic eosinophilic mucin containing hyphae, along with a positive fungal strain or culture, in the absence of tissue invasion by fungi, in addition to other suggestive clinical and biological evidence of an allergy such as positive atopic history, nasal polyposis, absence of immunodeficiency, and elevation of total or specific IgE or a positive skin test to fungal antigens3, 22. However, these diagnostic criteria were not constantly reported in the literature. The strict application of the aforementioned criteria may lead to several AFRS cases going missing diagnosis. In this single-center, the low prevalence of AFRS leads us to think about two questions: 1. Is it because of the unqualified pathological specimens or the limitation of fungal detection methods that affect our diagnosis of AFRS? 2. Whether the prevalence of AFRS in our center is lower than the real prevalence in this area due to the low detection rate of fungi. Hence, we need multi-center research for further discussion.