Fungal Rhinosinusitis Research Articles

Clearing the Air: Acute Invasive Fungal Rhinosinusitis in Hematologic Cancer Patients.

Air quality has been shown to impact the rates of fungal infection of the airway, causing diseases such as acute invasive fungal rhinosinusitis (AIFRS), particularly in immunocompromised patients. We theorize that patients with hematologic malignancies in units with aging air handling units (AHUs) have a higher attack rate of AIFRS. Retrospective chart review identified patients with hematologic malignancy and AIFRS in two distinct and equal time periods between 2013 and 2022, representing the presence of aging AHUs and new AHUs, respectively. Cubic feet per minute (CFM) air flows, AIFRS attack rates, and clinical data were compared between the two groups and statistical analyses performed. The older AHUs produce air flow of 27,610 CFM and the newer AHUs produce air flow of 80,000 CFM. There were 18 patients with air supplied by older AHUs and 7 patients with air supplied by new AHUs who developed AIFRS. There was a significantly higher AIFRS attack rate for patients supplied by the older AHUs compared with patients supplied by newer AHUs (p = 0.033). The patients supplied by the older AHUs tended to be younger. The white blood cell counts, absolute neutrophil counts, and the mean time to diagnosis did not differ between the two groups. To our knowledge, this is the first study to examine AIFRS in immunocompromised patients' inpatient environment. Further research should explore whether higher CFM AHUs can decrease this disease among our most vulnerable patients. 3 Laryngoscope, 134:4466-4470, 2024.

Radiographic Variants Associated With Allergic Fungal Rhinosinusitis: Key Differences for Pre-Operative Planning.

Allergic fungal rhinosinusitis (AFRS) often results in expansion of disease beyond the paranasal sinuses, which may put important structures, such as the anterior ethmoid artery (AEA) or lateral lamella of the cribiform, at risk of injury during endoscopic sinus surgery (ESS). This study aims to compare the AEA to skull base (AEA-SB) length in patients with AFRS versus chronic rhinosinusitis with nasal polyps (CRSwNP), as well as additional anatomic variants. A single institutional retrospective chart review of patients undergoing ESS for AFRS and CRSwNP was performed. AEA-SB length were compared between the 2 groups. Other anatomic variants, including Keros measurement and presence of supraorbital ethmoid air cells (SOEC), concha bullosa (CB), sphenoethmoidal, and infraorbital ethmoid cells were measured and compared between the 2 groups. Twenty-one patients were included in each cohort. The AFRS group was younger in age (P = .015) and had a significantly longer AEA-SB length (P = .014) compared to the CRSwNP group. No significant differences were observed between the 2 groups regarding Keros measurement, presence of concha bullosa, infraorbital ethmoid, sphenoethmoidal, or SOEC. No association was seen between AEA-SB length and Keros class in either group. AFRS harbors anatomical differences when compared to CRSwNP, with the former associated with a longer AEA-SB length. This key difference should be considered in preoperative planning to prevent injury to the AEA in patients undergoing ESS for AFRS.

Evaluation of metagenomic next-generation sequencing (mNGS) combined with quantitative PCR: cutting-edge methods for rapid diagnosis of non-invasive fungal rhinosinusitis.

Fungal rhinosinusitis is a significant and growing health concern in arid regions, with an increasing incidence over recent decades. Without timely and appropriate management, it can lead to severe complications, including potential intracranial spread. This study aims to establish efficient and rapid diagnostics for non-invasive fungal rhinosinusitis (FRS), addressing the challenge of its difficult-to-culture diagnosis. Twenty-eight patients suspected of FRS were studied using endoscopic sinus surgery to obtain tissue samples for histopathology, direct microscopy, fungal culture, quantitative PCR (qPCR) and metagenomic next-generation sequencing (mNGS) detection. A patented qPCR targeting prevalent Aspergillus species was evaluated. The patient cohort had a male-to-female ratio of 9:14, with disease duration up to 50 years. Histopathologically, 23 out of 28 cases were positive. Fungal culture exhibited a sensitivity of 21.74%, with one false positive. qPCR and mNGS showed 100% sensitivity and specificity, with a 100% consistency rate for identification at the species level (23/23), and potential detection of cases with co-infections. The most common pathogen was A. flavus, followed by A. fumigatus and A. niger. Two cases involved mixed infections of A. fumigatus and A. flavus. qPCR and mNGS proved effective in rapidly identifying fungi from fresh sinus tissue that are challenging to culture, surpassing conventional methods. However, further evaluation and optimization with a larger cohort of patients are necessary. Histopathology is still recommended to confirm the clinical significance of the detected fungal species.

Invasive Fungal Rhinosinusitis: The First Histopathological Study in Vietnam.

Invasive fungal rhinosinusitis (IRFS) is a rare but highly fatal disease. The two primary groups of pathogens, Mucorales and Aspergillus, require different treatments and have distinct prognoses. This study aimed to analyze the histopathological features of IFRS. We conducted a retrospective study involving 57 IFRS cases. Demographic and comorbid characteristics were obtained from clinical records. Two pathologists independently examined the histopathological features using H&E, PAS, and GMS-stained slides. Fungal groups were identified with PCR under the guidance of histopathology. The mean age of IFRS was 58.9 ± 13.4. The male-to-female ratio was 1.4:1. 100% of cases had diabetes comorbidity. Mucorales, Aspergillus, and other fungi were found in 61.4%, 33.3%, and 5.3% of cases, respectively. No Aspergillus and Mucorales co-infections were detected. Histopathology and PCR results were strongly concordant in classifying pathogens (Cohen's kappa = 84.2%, 95% CI 60.1% - 100%, p < 0.001). Mucormycosis exhibited higher rates of extensive necrosis and vascular invasion, and lower rates of pigment and spore presence than the non-Mucormycosis group (p < 0.001, p = 0.01, p = 0.02, p = 0.03, respectively). Extensive necrosis and vascular invasion were statistically significantly correlative (OR = 13.03, 95% CI 2.62-64.75, p = 0.002). IFRS predominantly affects older adults and males. Histopathology is a reliable method for differentiating between Mucorales and Aspergillus. When extensive necrosis is detected, it is critical to investigate for vascular invasion carefully. The vascular invasion, degree of necrosis, pigments, and spores are valuable factors for distinguishing fungal agents of IFRS.

High M2/M1 Macrophage Ratio Observed in Nasal Polyps Formed in Allergic Fungal Rhinosinusitis.

Allergic fungal rhinosinusitis (AFRS) shares similarities with eosinophilic chronic rhinosinusitis (ECRS), both characterized by intractable nasal polyps. The key distinction lies in the presence of fungal infection within the nasal cavity. While ECRS nasal polyps are known for significant infiltration of M2 macrophages and eosinophils, as well as an increase in high endothelial venule (HEV)-like vessels, these features are less commonly reported in AFRS. This study compared clinicopathological findings between AFRS (n=10), ECRS (n=12), and non-ECRS (n=10) patients' nasal polyps using immunohistochemical analysis for CD163 and CD68 to assess the M2/M1 macrophage ratio, and peripheral lymph node addressin (PNAd) and CD34 to evaluate the proportion of HEV-like vessels. AFRS showed a significantly higher number of CD163-positive M2 macrophages and an increased M2/M1 ratio compared with ECRS. However, the percentage of HEV-like vessels and the number of eosinophils infiltrating the nasal polyps were similar in both AFRS and ECRS. The observed increase in M2 macrophages in AFRS nasal polyps is presumed to be induced by fungal infection in the nasal cavity, in comparison with ECRS. These results highlight the distinctive immunological profiles of AFRS and ECRS, emphasizing the role of macrophage polarization in their pathogenesis.

How Common is Allergic Fungal Rhinosinusitis in Chronic Rhinosinusitis Patient - A Retrospective Institutional Study

How Common is Allergic Fungal Rhinosinusitis in Chronic Rhinosinusitis Patient - A Retrospective Institutional Study

Chronic Invasive Fungal Sinusitis Mimicking Malignancy Post-Radiotherapy: A Case Report.

Invasive fungal sinusitis is a life-threatening form of fungal rhinosinusitis. Due to the aggressive clinical presentation and radiological appearance, there is diagnostic difficulty in differentiating invasive fungal sinusitis from a malignant process. This is even more challenging in oncological patients who have undergone previous head and neck radiotherapy, due to possibility of a recurrence of primary malignancy and radiation-induced neoplasms. We report a rare case of invasive fungal sinusitis mimicking a malignancy in a post-radiotherapy patient.Our patient was a 68-year-old male, 25-years post-radiotherapy for nasopharyngeal carcinoma. He presented with a 3-month history of purulent sputum and right facial paraesthesia. Magnetic resonance imaging showed an irregular destructive enhancing mass of the greater wing of right sphenoid and pterygoid bone with extensive extension into nearby structures. In view of extensive local and bony invasion, and a history of radiotherapy, initial suspicions were that of primary malignancy, specifically radiation-induced sarcoma, and recurrence of nasopharyngeal carcinoma. He underwent transpterygoid biopsy of the lesion, and histopathology demonstrated Aspergillus species, with no malignancy identified.Our report highlights the diagnostic difficulties in the post-radiotherapy cancer patient presenting with symptoms suggestive of aggressive sino-nasal disease. Invasive fungal sinusitis closely mimics the clinical and radiological findings of several neoplastic processes. We discuss the clinical and radiological characteristics of pathologies that may mimic invasive fungal sinusitis. Histological examination remains the gold standard for diagnosis, and early fungal staining is crucial. Furthermore, one should not presume the initial histopathological diagnosis to be confirmatory of isolated fungal disease. Repeat radiological investigations for disease resolution and histopathologic re-evaluation if required should be performed, keeping in mind possibility of coexisting malignancy.

Surgical Intervention Outcome for Patients With Acute Vision Loss Due to Allergic Fungal Rhinosinusitis: A Systematic Review and Meta-Analysis.

Allergic fungal rhinosinusitis (AFRS) is a severe type of chronic rhinosinusitis (CRS) characterized by a high risk of acute vision loss resulting from the affection of optic nerves. This vision loss results from direct pressure upon the optic nerve by the sinus tissues and bone degradation. This is why early involvement of a professional is significant so as not to result in a permanent disability. This systematic review and meta-analysis will analyze the efficacy of surgical operations in enhancing visual outcomes in patients with acute vision loss due to AFRS. A systematic search was carried out based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using PubMed, Embase, Cochrane Library, and Scopus with the keywords "acute vision loss," "allergic fungal rhinosinusitis," and "surgical intervention." The studies included patients who developed AFRS-related acute vision loss, those assessing the outcomes of the surgical interventions, and those published in English. Two separate researchers extracted data and conducted quality assessments. The data synthesis process employed the R studio software (Posit, Boston, MA). The identified studies for the review constituted 12 and involved 320 patients. The mean pooled event rate regarding acute vision loss of AFRS patients was 33.1%. Ear, nose, and throat surgeries, including functional endoscopic sinus surgery (FESS) and optic nerve decompression, had a mean pooled success in vision recovery of 68%. Early treatment and utilization of other types of corticosteroids were utilized to enhance the results. Hence, early and proper surgery like FESS, optic nerve decompression, and corticosteroid treatment have better visual prognosis in AFRS patients. Standard early diagnosis and management guarantee the prevention of irreversible blindness, which stresses the need for an interdisciplinary approach and further studies.

A mini-update on chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is an inflammatory disorder of the paranasal sinuses and the nasal cavity lasting longer than 12 weeks. This disease is a common clinical syndrome with significant monetary burden due to the high costs of medical visits, diagnostic tests, medications, and surgical therapies. CRS without nasal polyposis (CRSsNP) is the most common subtype of CRS, accounting for about 70% of all patients. Other subtypes include CRS with nasal polyposis (CRSwNP) and allergic fungal rhinosinusitis (AFRS). CRSwNP has the worldwide prevalence of 2% to 4% and is often accompanied by type 2 inflammation and asthma as a comorbid condition. Pediatric chronic sinusitis is distinct from adult chronic sinusitis and is currently considered an infectious process, characterized by persistent inflammation representing an exaggerated immune response to an external stimulus. The medical and surgical management of CRS has been remarkably modified in the past two decades. The aim of this study was to present an update on CRS based on the recent years’ literature.

Impact of Biologics on Surgery in Chronic Rhinosinusitis with Polyps and Allergic Fungal Sinusitis.

To compare the efficacy of th2-targeted biologic medications (dupilumab, omalizumab, and mepolizumab) on absolute risk reduction (ARR) of functional endoscopic sinus surgery (FESS) in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) and allergic fungal rhinosinusitis (AFRS). The TriNetX Research Network database was queried for each mAb's market lifespan through March 2024. Adults with CRSwNP were propensity score matched against non-mAb controls based on age, sex, race, and asthma diagnosis. The primary outcome was rate of FESS, with secondary outcomes including inpatient admission, emergency department (ED) visit, and incidence of acute sinusitis. Subgroup analysis was performed for patients with AFRS. All mAbs decreased FESS risk (dupilumab, ARR 11.48%, 95% CI 9.82%-13.15%, p < 0.001; omalizumab, ARR 12.02%, 95% CI 4.36%-19.68%, p = 0.002; mepolizumab, ARR 10.32%, 95% CI 5.24%-15.40%, p < 0.001) in CRSwNP patients. Only dupilumab also reduced risk of inpatient admission (ARR 8.59%, 95% CI 7.04%-10.15%, p < 0.001), ED visit (ARR 5.94%, 95% CI 4.28%-7.61%, p < 0.001), and acute sinusitis (ARR 2.60%, 95% CI 1.09%-4.12%, p = 0.001). In AFRS patients, only dupilumab reduced the risk of all outcomes: FESS (ARR 6.97%, 95 CI 2.86%-11.09%, p = 0.001), inpatient admission (ARR 16.93%, 95% CI 11.30%-22.57%, p < 0.001), ED visit (ARR 13.15%, 95% CI 7.15%-19.14%, p < 0.001), and acute sinusitis (ARR 7.17%, 95% CI 2.18%-12.17%, p = 0.005). Although all mAbs reduced FESS risk in CRSwNP, only dupilumab reduced secondary outcomes as well. Similarly, only dupilumab improved all outcomes in AFRS patients. These data demonstrate the potential of mAbs in reducing disease burden and enhancing patient outcomes in CRSwNP and AFRS. NA Laryngoscope, 2024.

The accuracy of deep learning models for diagnosing maxillary fungal ball rhinosinusitis.

To assess the accuracy of deep learning models for the diagnosis of maxillary fungal ball rhinosinusitis (MFB) and to compare the accuracy, sensitivity, specificity, precision, and F1-score with a rhinologist. Data from 1539 adult chronic rhinosinusitis (CRS) patients who underwent paranasal sinus computed tomography (CT) were collected. The overall dataset consisted of 254 MFB cases and 1285 non-MFB cases. The CT images were constructed and labeled to form the deep learning models. Seventy percent of the images were used for training the deep-learning models, and 30% were used for testing. Whole image analysis and instance segmentation analysis were performed using three different architectures: MobileNetv3, ResNet50, and ResNet101 for whole image analysis, and YOLOv5X-SEG, YOLOv8X-SEG, and YOLOv9-C-SEG for instance segmentation analysis. The ROC curve was assessed. Accuracy, sensitivity (recall), specificity, precision, and F1-score were compared between the models and a rhinologist. Kappa agreement was evaluated. Whole image analysis showed lower precision, recall, and F1-score compared to instance segmentation. The models exhibited an area under the ROC curve of 0.86 for whole image analysis and 0.88 for instance segmentation. In the testing dataset for whole images, the MobileNet V3 model showed 81.00% accuracy, 47.40% sensitivity, 87.90% specificity, 66.80% precision, and a 67.20% F1 score. Instance segmentation yielded the best evaluation with YOLOv8X-SEG showing 94.10% accuracy, 85.90% sensitivity, 95.80% specificity, 88.90% precision, and an 89.80% F1-score. The rhinologist achieved 93.5% accuracy, 84.6% sensitivity, 95.3% specificity, 78.6% precision, and an 81.5% F1-score. Utilizing paranasal sinus CT imaging with enhanced localization and constructive instance segmentation in deep learning models can be the practical promising deep learning system in assisting physicians for diagnosing maxillary fungal ball.

Outcomes in Hematologic Malignancy Patients with Acute Invasive Fungal Rhinosinusitis

Outcomes in Hematologic Malignancy Patients with Acute Invasive Fungal Rhinosinusitis

Characterising the allergic fungal rhinosinusitis microenvironment using full-length 16S rRNA gene amplicon sequencing and fungal ITS sequencing.

Allergic fungal rhinosinusitis (AFRS) is a severe phenotype of chronic rhinosinusitis with nasal polyposis (CRSwNP), characterised by localised and exaggerated type 2 inflammation. While fungal antigenic stimulation of unregulated Th2-mediated inflammation is the core pathophysiological mechanism, the direct and synergistic role of bacteria in disease modification is a pervasive hypothesis. We set out to define the microenvironment of AFRS to elucidate virulent organisms that may be implicated in the pathophysiology of AFRS. We undertook a cross-sectional study of AFRS patients and non-fungal CRSwNP patients. Demographics, disease severity, culture and microbiome sequences were analysed. Multimodality microbiome sequencing included short-read next-generation sequencing (NGS) on the Illumina Miseq (16S rRNA and ITS) and full-length 16S rRNA sequencing on the Oxford Nanopore Technologies GridION (ONT). Thirty-two AFRS and 29 non-fungal CRSwNP patients (NF) were included in this study. Staphylococcus aureus was the dominant organism cultured and sequenced in both AFRS and NF groups (AFRS 27.54%; NF 18.04%; p = .07). Streptococcus pneumoniae (AFRS 12.31%; NF 0.98%; p = .03) and Haemophilus influenzae (AFRS 15.03%; NF 0.24%; p = .005) were significantly more abundant in AFRS. Bacterial diversity (Shannon's index) was considerably lower in AFRS relative to NF (AFRS 0.6; NF 1.0, p = .008). Aspergillus was the most cultured fungus in AFRS (10/32, 31.3%). The AFRS sequenced mycobiome was predominantly represented by Malassezia (43.6%), Curvularia (18.5%) and Aspergillus (16.8%), while the NF mycobiome was nearly exclusively Malassezia (84.2%) with an absence of Aspergillus or dematiaceous fungi. A low diversity, dysbiotic microenvironment dominated by Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae characterised the bacterial microbiome of AFRS, with a mycobiome abundant in Malassezia, Aspergillus and Curvularia. While Staphylococcus aureus has been previously implicated in AFRS through enterotoxin superantigen potential, Streptococcus pneumoniae and Haemophilus influenzae are novel findings that may represent alternate cross-kingdom pathophysiological mechanisms.

Chronic invasive fungal rhinosinusitis with septal perforation: a case report

Background: Chronic Invasive Fungal Rhinosinusitis (CIFRS) is a sub-entity of fungal rhinosinusitis, with the most common causes being Aspergillus and Mucor. Non-specific symptoms such as nasal obstruction, headaches, face pain, rhinorrhea, and epistaxis are frequently observed in patients with CIFRS. Extension to the nasal septal is a scarce case. This case report aims to present a rare case report of a 50-year-old female considered immunocompetent with chronic invasive fungal rhinosinusitis with septal perforation at our hospital who underwent Functional Endoscopic Sinus Surgery (FESS). Case Presentation: Fifty-year-old female was referred to the Otorhinolaryngology Department, Mangusada Regional Hospital, with a blocked nose, especially on the right side, with frequently purulent nasal discharge, headache, and she had a foul smell in the nose for about 5 years, then in the last few months, the symptoms became worse, and she frequently had bloody discharge and anosmia. The patient came to our hospital due to failure of previous medical therapy. She denied any history of underlying systemic disease, relevant trauma, and nasal surgery. A large polypoid mass with an obstructed right middle meatus was detected on nasal endoscopy. A dark-brown substance resembling clay was found in the right posterior nasal cavity, close to the posterior nasal septum. The same material was seen in the left posterior nasal cavity, close to the posterior nasal septum. Computed Tomography (CT)-scan demonstrated a soft tissue density in the right maxillary sinus. The density extended into the left nasal cavity through a septal defect. The patient was done surgically with FESS to restore the drainage of the nasal cavity and paranasal sinuses. It is crucial to remove all the debris and infected tissue altogether. After the surgery, the patient was given nasal irrigation therapy with physiological saline solution 2 times a day and the condition improved. Conclusion: Diagnosing invasive fungal rhinosinusitis can be challenging due to its non-specific clinical presentation. Awareness, early diagnosis, and intervention help prevent permanent complications.

Invasive fungal rhinosinusitis: current evidence and research opportunities.

To summarize the evidence surrounding diagnosis, treatment, prognosis, and surveillance of patients with acute invasive fungal sinusitis (AIFS) and discuss future research needs. New risk factors for AIFS such as COVID have been identified, and a new prognostic staging system has been developed. Most patients who develop AIFS are immunocompromised, with the majority having a history of diabetes or a hematologic malignancy. Unfortunately, there are not any highly sensitive and specific diagnostic tools. Therefore, a combination of signs and symptoms, imaging, endoscopy, biopsy, and labs should be used to diagnosis AIFS. Although surgery and systemic antifungals are known to improve outcomes, there is limited data on time to intervention, duration of antifungals, and surveillance patterns. There is also limited information on factors that can predict outcomes in AIFS patients. However, sensory/perceptual changes, prolonged neutropenia duration, and comorbidity burden may be associated with a poor prognosis.

Number of sinus procedures reduces inpatient mortality for invasive fungal rhinosinusitis

ObjectivesTo evaluate surgical outcomes of invasive fungal rhinosinusitis Materials and methodsThe National Inpatient Sample Database (2000–2015 Q3) was queried for patients with a diagnosis of aspergillosis and/or mucormycosis and a diagnosis of acute sinusitis using the International Classification of Diseases, Ninth Edition. Factors associated with inpatient mortality were then identified with multivariate logistic regression. Results514 adult patients with a median age of 57.0 years were identified, of which 231 (44.9 %) underwent sinus surgery. Surgical patients had a longer length of stay (17.0 vs 9.0 days, p < 0.001) and higher total charges ($139,762.00 vs $57,945.00, p < 0.001). The number of sinus procedures was associated with reduced odds of inpatient mortality (OR 0.69; p < 0.001) in multivariate analysis. Hypertension (OR 0.34, p = 0.002) and chronic kidney disease (OR 0.23, p = 0.034) were associated with reduced odds of inpatient mortality. Total number of procedures (OR 1.24; p = 0.002), mucormycosis (OR 2.75, p = 0.002), age (OR 1.03, p = 0.006) and acid-base disorders (OR 2.85, p = 0.012) were associated with increased odds of inpatient mortality. ConclusionThis represents the first large scale study to evaluate outcomes for invasive fungal rhinosinusitis. These findings suggest the odds of inpatient mortality decrease with greater extent of sinus surgery performed. The potentially protective roles of hypertension and chronic kidney disease should be evaluated in future research.

Burden of Fungal Rhinosinusitis in Rhinology unit of Tribhuvan University Teaching Hospital, Kathmandu

Burden of Fungal Rhinosinusitis in Rhinology unit of Tribhuvan University Teaching Hospital, Kathmandu

Dupilumab as an emerging treatment for refractory allergic fungal rhinosinusitis: a case series and literature review

Background: Allergic Fungal Rhinosinusitis (AFRS) is a chronic, inflammatory, non-invasive fungal disease of the nose, sinuses, and paranasal sinuses. Dupilumab is an emerging biological therapy with promising outcomes in the treatment of patients with refractory AFRS. In this case series, we aimed to assess the effectiveness and safety of dupilumab in the treatment of refractory AFRS. Case description: Our case series included seven patients, all of whom met the inclusion criteria. Of these, four were male (57.1%) and three were female (42.9%). The ages of the patients ranged from 20 to 44 years, with a mean of 30.4. For post-treatment Sinonasal Outcome Test-22 (SNOT-22) scores, six patients (85.7%) reported improvement by one category (two from severe to moderate and four from moderate to mild). Only one patient (14.2%) reported an improvement by two categories (severe to mild). Post-treatment IgE levels ranged from 39 to 590 IU/mL, with a mean of 301.8 IU/mL. There was a significant decrease in the mean IgE level by 93% after dupilumab administration. The average number of surgeries in the included patients ranged from 2 to 4, with a mean of 2.7 surgeries. Post-treatment, none of the patients required revision surgery or steroids after three months of dupilumab therapy. Conclusions: Dupilumab is an emerging biological therapy with promising benefits in the treatment of refractory AFRS. It can be used if functional endoscopic sinus surgery and steroid treatment do not improve symptoms.

Allergic fungal rhinosinusitis linked to other hyper-IgE syndromes through defective TH17 responses

BackgroundIn a gene expression analysis comparing sinus mucosa from allergic fungal rhinosinusitis (AFRS) to that from non-AFRS chronic rhinosinusitis with nasal polyp (CRSwNP) subjects, the antimicrobial peptide (AMP), histatin 1 (HTN1), was found to be the most differentially down-regulated gene in AFRS. ObjectiveTo identify the molecular etiology of the down regulated expression of HTN1 MethodsWe used RT-PCR to compare the expression of AMPs and utilized a fungistasis assay to evaluate the anti-fungal activity of sinus secretions. Using flow cytometry, we characterized the presence of Th17/22 cells and STAT signaling from AFRS, non-AFRS CRSwNP patients, and healthy controls. ResultsWe confirm the decreased expression of AMPs in AFRS sinus mucosa with concordant decrease in antifungal activity in sinus secretions. We show that IL-22 and IL-22-producing T cells are deficient within sinus mucosa of AFRS subjects. In vitro studies demonstrated a defect in IL-6/STAT3 signaling critical for TH17/TH22 differentiation. Epithelial cells from AFRS patients could express AMPs when stimulated with exogenous IL-22/IL-17 and circulating Th17 cell abundance was normal. ConclusionSimilar to other hyper-IgE syndromes, but distinct from CRSwNP, AFRS patients express a defect in STAT3 activation limited to IL-6-dependent STAT3 phosphorylation that is critical for Th17/TH22 differentiation. This defect leads to a local deficiency of IL-17/IL-22 cytokines and deficient AMP expression within diseased sinus mucosa of AFRS patients. Our findings support evaluation of therapeutic approaches that enhance airway AMP production in AFRS.

Primary Radical Extended Sinus Surgery for Management of Extensive Allergic Fungal Rhinosinusitis

Introduction: Allergic fungal rhinosinusitis (AFRS), a subset of sinusitis secondary to hypersensitivity, is clinically similar to chronic rhinosinusitis with nasal polyp but histologically different with rich eosinophils and Charcot Leyden crystals. Since the primary pathology in AFRS is immune mediated, the recurrence rates are high. In this study, we describe the application of radical extended sinus surgery (RESS) as the surgical technique with the usage of postoperative high-volume steroidal nasal irrigation and short-term oral steroid therapy – a threefold strategy – for the prevention of recurrence of this disease. Materials and Methods: A retrospective surgical chart audit of patients diagnosed with AFRS and treated between January 2012 and December 2019 was done. The clinical findings and postoperative outcomes performed by a single senior surgeon in a tertiary referral institution were extracted and analyzed. Results: Of the 17 patients, 88% of patients were immunocompetent and Lund Mackay (LM) of 24, 16 patients had Grade 3 nasal polyps, except one with Grade 1 nasal polyps and an LM score of 8. All patients underwent RESS and received postoperative high-volume topical steroid irrigation with oral steroids in the immediate postoperative period and on follow-up, if recurrence was noted, none required revision surgery. Conclusions: A three-fold strategy is beneficial in the management of AFRS-RESS followed by oral steroids during the immediate postoperative period along with long-term topical high-volume steroid nasal irrigation.