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.