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Objectives: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Philip Chen recieves consulting fees from Medtronic, speaking honoraria from GlaxoSmithKline and Optinose, and research funding from Aerin Medical.

Objective: 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)., Methods: 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., Results: 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)., Conclusion: 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., Level of Evidence: NA Laryngoscope, 135:593-601, 2025., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Chronic rhinosinusitis (inclusive of subtypes with nasal polyps [CRSwNP], without nasal polyps [CRSsNP], and allergic fungal rhinosinusitis [AFRS]) causes inflammation of the nose mucosa and paranasal sinuses. Unfortunately, evidence supporting use of clinical outcome assessments (COAs) in regulated clinical trials to assess key measurement concepts of these conditions is limited., Objective: To identify key disease-related symptoms and impacts, potential outcomes of interest for new treatments, and COAs available to measure those outcomes among adult and adolescent individuals living with CRSwNP, CRSsNP, and AFRS., Methods: Literature, clinical trial, and product label reviews were conducted to identify symptoms, impacts, and COAs used to assess CRSwNP, CRSsNP, and AFRS patient experiences in clinical trials. The disease related concepts identified in the literature were mapped to selected COAs to determine conceptual coverage of each COA., Results: Twenty-five articles, twenty-five clinical trial records, and four product labels were included in the review. Across conditions, nasal obstruction, nasal discharge, and altered smell were the most frequently identified symptoms. The most frequently identified impacts of CRSwNP and CRSsNP were on emotional functioning and sleep, and adopting new behaviors for AFRS. Findings for key symptoms and impacts in adolescents were limited. More than 20 COAs used in these conditions were identified, and 14 COAs (e.g., Sinonasal Outcome Test [SNOT-22]) were evaluated for conceptual coverage of the concepts identified in the literature., Conclusion: Results specify several symptom and impact outcomes, that if improved, would reflect treatment benefit for patients living with CRSwNP, CRSsNP, and/or AFRS. Several COAs demonstrated coverage of key measurement concepts and warrant further evaluation for use in clinical trials., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: BK, MCB, and ALS are employees of Adelphi Values; NI and KC were employees of Adelphi Values at the time of the study. Adelphi Values received payment from Sanofi to conduct the study. VA is an employee of Sanofi and may have stocks or stock options with Sanofi US Services, Inc., (© 2024. The Author(s).)

Background: Allergic fungal sinusitis (AFS) is a form of paranasal mycosis that often involves bone destruction and can extend into the orbit and anterior skull base. Intracranial and intraorbital involvement are published but not both in each included patient of a series. The purpose of the present study was to review cases of extensive AFS with orbital or/and skull base erosion, including the presenting symptoms, patient socioeconomic background, imaging features, surgical technique, and post-operative outcomes., Methods: The records of 30 patients with the histological diagnosis of AFS and both intracranial and intraorbital involvement were reviewed., Results: The average age of the patients was 25.2 years. 83 % of patients were male. 70 % were African American. 66 % of patients had Medicaid or were uninsured. Presenting symptoms were headaches (80 %), nasal obstruction (33 %), proptosis (40 %), vision change (23 %), facial pressure (10 %), and decreased sense of smell (7 %). 100 % of patients had bone erosion observed on computerized tomography scans with disease extending intracranially through the anterior skull base or posterior wall of the frontal sinus along with disease that eroded through the lamina papyracea. All patients had failed medical management. All patients underwent surgery by Otolaryngology, Ophthalmology, and Neurosurgery with transnasal endoscopic approaches and orbitotomy. 80 % also underwent a bifrontal craniotomy for removal of intracranial extradural disease with cranialization. 53 % of patients had orbital implants remaining after surgery; 23 % had nasal stents. There were no postoperative cerebrospinal fluid leaks. Average hospital stay was 4.8 days. Preoperatively, 13 % of patients underwent allergy testing. 94 % saw an Allergist postoperatively. 21 % required follow up surgery., Conclusions: A team approach of Otolaryngologists, Ophthalmologists, and Neurosurgeons is recommended for this slowly growing but locally destructive disease. Most patients with AFS will present with headaches and nasal obstruction. While most cases of AFS can be successfully managed with transnasal endoscopic techniques, orbitotomy and craniotomy represents an effective treatment for severe AFS cases with extensive intracranial and intraorbital involvement. This disease is found most commonly in young African American males and in the underinsured., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: 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., Methodology: 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)., Results: 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., Conclusion: 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., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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.

Background: In a gene expression analysis comparing sinus mucosa samples from allergic fungal rhinosinusitis (AFRS) patients with samples from non-AFRS chronic rhinosinusitis with nasal polyp (CRSwNP) patients, the antimicrobial peptide (AMP) histatin 1 (HTN1) was found to be the most differentially downregulated gene in AFRS., Objective: We sought to identify the molecular etiology of the downregulated expression of HTN1., Methods: We used RT-PCR to compare the expression of AMPs and a fungistasis assay to evaluate the antifungal activity of sinus secretions. Using flow cytometry, we characterized the presence of T H 17/T H 22 cells and signal transducer and activator of transcription (STAT) signaling from AFRS patients, non-AFRS CRSwNP patients, and healthy controls., Results: We confirmed decreased expression of AMPs in AFRS sinus mucosa with concordant decrease in antifungal activity in sinus secretions. IL-22 and IL-22-producing T cells were deficient within sinus mucosa of AFRS patients. In vitro studies demonstrated a defect in IL-6/STAT3 signaling critical for T H 17/T H 22 differentiation. Epithelial cells from AFRS patients could express AMPs when stimulated with exogenous IL-22/IL-17 and circulating T H 17 cell abundance was normal., Conclusions: Similar 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 T H 17/T H 22 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., Competing Interests: Disclosure statement This work was supported by National Institutes of Health grants R01HL117181 (D.B.C.), HL140398 (D.B.C.), R01AI135803 (D.B.C.), and R01AI135803 (D.B.C.) and Department of Veterans AffairsBiomedical Laboratory Research and Development Merit Review Award I01BX004828 (D.B.C.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health or the Veterans Administration Office of Research and Development. This project was further supported by the Cytometry and Cell Sorting Core at Baylor College of Medicine with funding from the CPRIT Core Facility Support Award (CPRIT-RP180672), and the National Institutes of Health (CA125123 and RR024574). Disclosure of potential conflict of interest: A. U. Luong owns stock in Aerin Medical (Mountain View, Calif) and serves as a consultant for GlaxoSmithKline (Brentford, United Kingdom), Lyra Therapeutics (Watertown, Mass), Maxwell Biosciences (Austin, Texas), Medtronic (Dublin, Ireland), NeuroENT (Galway, Ireland), Sanofi (Paris, France), SoundHealth (San Francisco, Calif), and Stryker (Kalamazoo, Mich). D. B. Corry owns stock options in Maxwell Biosciences (Austin, Texas). M. J. Citardi serves as a consultant for 3D Matrix (Newton, Mass), Acclarent (Irvine, Calif), LynxMD (Palo Alto, Calif), MicroGenDx (Lubbock, Texas), and NeuroENT (Galway, Ireland). W. C. Yao is a consultant for Acclarent (Irvine, Calif), Aerin Medical (Mountain View, Calif), and Medtronic (Minneapolis, Minn) and is on the Speaker’s Bureau for Optinose Inc (Yardley, Pa)., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

"Allergic fungal sinusitis (AFS)" is typically diagnosed using radiologic images like computed tomography (CT) scans and magnetic resonance imaging (MRI), with the "Hounsfield unit (HU)" in CT scans and T2-weighted images (T2WI) in MRI serving as reliable objective parameters. However, diagnosing AFS might be difficult because of possible signal changes and densities caused by variations in the secretion concentration in the sinus. Few studies have compared the diagnostic performance of MRI and CT scans. This study aimed to investigate the value of MRI signal intensity in evaluating AFS compared with CT HUs. This retrospective study included 111 patients with pathologically confirmed AFS who underwent CT imaging followed by MRI evaluation at King Saud Medical City, Riyadh, Saudi Arabia, from January 2012 to December 2022. Radiographic densities of sinus opacities on CT scan, including the mean HU values, and MRI findings, including signal voids on T1-weighted images and T2WI, were gathered and analyzed. To determine the efficacy of these radiographic characteristics in predicting the disease and the best cutoff value, we employed receiver operator characteristic curves. The mean age was 31.9 ± 15.6 years, and most patients were 74 females (66.7%). The main symptom was nasal obstruction in 73 patients (65.8%). In comparison, between HU and signal void on T2WI, there was moderate predictive performance [area under the curve: 0.856, P = .001]. An ideal HU cutoff value of 69.50 HU was obtained with a sensitivity of 100% and a specificity of 44.7%. However, the receiver operator characteristic for T1-weighted images could not be plotted, as no signal was avoided to predict AFS and it was not statistically significant (area under the curve: 0.566; P = .287). The study found a CT HU of 69.5 can predict MRI T2WI signal values with a void signal, aiding in diagnostic workup and evaluation for AFS., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Allergic fungal rhinosinusitis (AFRS) is a subtype of chronic rhinosinusitis (CRS) that has previously been associated with younger age and Black patients. However, the role of demographic and socioeconomic factors in AFRS severity remains to be fully elucidated., Objective: The objective of this study was to determine whether demographic and socioeconomic factors are associated with incidence of AFRS, as well as with disease severity in Northern California., Methods: A retrospective cohort study was conducted of adult patients with AFRS and CRS from 2010 to 2019. AFRS was determined by the Bent and Kuhn criteria, and severity was assessed by radiographic evidence of cranioorbital invasion and other clinical parameters. Chi-square and t-test were used to assess demographic and socioeconomic differences between AFRS and CRS cohorts, and multivariable logistic regression was used to assess risk factors for severe AFRS., Results: Black patients represented 26.2% (55/210 patients) of the AFRS group and 4.9% (842/17,300 patients) of the CRS group, with pairwise comparison of race/ethnicity categories showing that the AFRS group had significantly higher proportions of Black race/ethnicity compared with other race/ethnicities (p < 0.01). AFRS and CRS groups differed significantly by age, with mean ages of 48.7 and 51.0 years, respectively (p = 0.04). There were no significant differences in gender, Medicaid status, comorbidities, and socioeconomic status measures. Multivariate logistic regression showed that Black patients had higher odds of having severe AFRS (adjusted odds ratio = 2.29; 95% confidence interval: 1.18-4.45)., Conclusion: AFRS has a unique predilection for Black patients, and severe disease is also more likely in this population., Competing Interests: Conflicts of Interest This manuscript was presented at the American Rhinologic Society conference in September 2022 in Philadelphia, PA.

Allergic fungal rhinosinusitis (AFRS) is a subtype of chronic rhinosinusitis, characterized by excessive immune responses to environmental molds or fungi. The diagnosis and classification of AFRS into systemic and local types remain clinically challenging due to overlapping characteristics. This study investigated the prevalence of AFRS, its manifestation and associated factors in systemic and local AFRS. A total of 200 patients diagnosed with fungal rhinosinusitis underwent both skin provocation tests (SPT) and nasal provocation tests (NPT) to confirm AFRS and classify systemic and local types. Patients were considered to have AFRS if either the SPT or NPT was positive. Among these, patients with systemic AFRS were those who had a SPT positive. Local AFRS was when patients had a negative SPT and a positive NPT. Medical history, serum total IgE level, nasal endoscopy examinations, and CT scans were also recorded. Most patients were female (65.8%), with a mean age of 55.6 years (SD = 14.4). Based on the SPT and NPT results, 31% of patients (n = 62) were diagnosed with AFRS. Among these, 54.8% (n = 34) had systemic AFRS, while 45.2% (n = 28) had local AFRS. Patients with AFRS exhibited significantly higher levels of total IgE, eosinophils, and more pronounced signs and symptoms compared to those without AFRS. However, no statistically significant differences were observed between patients with systemic AFRS and those with local AFRS. AFRS was prevalent in our study. Among patients with AFRS, both systemic AFRS and local AFRS were also prevalent. While allergic indicators and clinical presentations can aid in AFRS diagnosis, minimal distinctions were observed between systemic and local AFRS. A comprehensive assessment incorporating both local and systemic allergic responses through provocation tests, such as a combination of skin and nasal tests, is imperative for optimizing AFRS diagnosis and management., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The purpose of this study was to analyze barriers to medical care and follow-up in patients with allergic fungal rhinosinusitis (AFRS)., Study Design: Cross-sectional questionnaire-based study with retrospective chart review., Setting: Tertiary Medical Center., Methods: Subjects with AFRS and chronic rhinosinusitis with nasal polyps (CRSwNP) were prospectively recruited for completion of the Barriers to Care Questionnaire (BCQ) and formal chart review., Results: Fifty-nine AFRS and 51 CRSwNP patients participated. AFRS patients were more likely to be lost to follow-up within 6 months of surgery (35.6% vs 17.7%, P = 0.04) and no-show at least 1 appointment (20.3% vs 5.9%, P = 0.03) compared to CRSwNP patients. Men with AFRS were more likely to have only a single follow-up visit (37.0% vs 3.1%, P < 0.001) and be lost to follow-up (66.7% vs 9.4%, P < 0.001) than women. There were no significant differences in the BCQ between groups; however, rate of questionnaire completion was lower in the AFRS group than the CRS group (62.7% vs 80.4%, P = 0.042). AFRS patients who did not complete the BCQ were more likely to be male (63.6% vs 35.1%, P = 0.034), lost to follow-up (77.3% vs 10.8%, P < 0.0001), and have a single follow-up visit (40.9% vs 5.4%, P < 0.0001). Younger age was associated with increased likelihood of having a single follow-up visit (odds ratio 1.143, 95% CI 1.022-1.276)., Conclusion: Young, male AFRS patients are more frequently lost to follow-up after surgery and less likely to complete questionnaires assessing barriers to care. Further investigation is needed to assess barriers to follow-up in these at-risk groups., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

To document a case of `preliminary` identification of Alternaria sp (a phaeohyphomycotic agent) based on morphology in tissue section in a patient with allergic fungal rhinosinusitis. A 25-year-old male, a known asthmatic in a post Covid -19 state, presented with headache, facial swelling and nasal block with discharge of brownish mucoid material. Debrided material from the right maxillary antrum and middle turbinate showed brownish mucoid material admixed with firm to hard degenerated bony spicules sent in formalin and subjected for histopathological examination. Histopathology showed fragments of tissue, mucoid material, degenerated bony spicules, and blood clots. Amidst ulcerated epithelium and mucoid debris were seen scattered pigmented fungi in a state of `vegetative sporulation` with characteristic brownish multicellular `macroconidia` diagnostic of Alternaria sp. A diagnosis of `Phaeohyphomycosis` possibly due to Alternaria sp was offered. The patient was treated with Amphotericin B. The patient was lost to follow up. Clinical materials such as tissue sections or smears from nasal mucus secretions in cases of allergic fungal rhinosinusitis provide a very good source for `preliminary` identification of species and early institution of therapy while waiting for the fungal culture report.

Background: Central compartment atopic disease (CCAD) is an emerging phenotype of chronic rhinosinusitis with nasal polyposis (CRSwNP) characterized by prominent central nasal inflammatory changes. This study compares the inflammatory characteristics of CCAD relative to other phenotypes of CRSwNP., Methods: A cross-sectional analysis of data from a prospective clinical study was performed on patients with CRSwNP who were undergoing endoscopic sinus surgery (ESS). Patients with CCAD, aspirin-exacerbated respiratory disease (AERD), allergic fungal rhinosinusitis (AFRS), and non-typed CRSwNP (CRSwNP NOS) were included and mucus cytokine levels and demographic data were analyzed for each group. Chi-squared/Mann-Whitney U tests and partial least squares discriminant analysis (PLS-DA) were performed for comparison and classification., Results: A total of 253 patients were analyzed (CRSwNP, n = 137; AFRS, n = 50; AERD, n = 42; CCAD, n = 24). Patients with CCAD were the least likely to have comorbid asthma (p = 0.0004). The incidence of allergic rhinitis in CCAD patients did not vary significantly compared to patients with AFRS and AERD, but was higher compared to patients with CRSwNP NOS (p = 0.04). On univariate analysis, CCAD was characterized by less inflammatory burden, with reduced levels of interleukin 6 (IL-6), IL-8, interferon gamma (IFN-γ), and eotaxin relative to other groups and significantly lower type 2 cytokines (IL-5, IL-13) relative to both AERD and AFRS. These findings were supported by multivariate PLS-DA, which clustered CCAD patients into a relatively homogenous low-inflammatory cytokine profile., Conclusions: CCAD has unique endotypic features compared to other patients with CRSwNP. The lower inflammatory burden may be reflective of a less severe variant of CRSwNP., (© 2023 ARS-AAOA, LLC.)

Objective: Some previous studies have shown an increased prevalence of allergic fungal rhinosinusitis (AFRS) among young, black patients with poor access to health care; however, results have been mixed. The purpose of this study was to investigate the relationship between social determinants of health and AFRS., Data Sources: PubMed, Scopus, CINAHL., Review Methods: A systematic review was performed searching for articles published from date of inception to September 29, 2022. English language articles describing the relationship   between social determinants of health (i.e., race, insurance status) and AFRS as compared to chronic rhinosinusitis (CRS) were selected for inclusion. A Meta-analysis of proportions with comparison (Δ) of weighted proportions was conducted., Results: A total of 21 articles with 1605 patients were selected for inclusion. The proportion of   black patients among AFRS, chronic rhinosinusitis with nasal polyps (CRSwNP), and chronic rhinosinusitis without nasal polyps (CRSsNP) groups was 58.0% [45.3%-70.1%], 23.8% [14.1%-35.2%], and 13.0% [5.1%-24.0%], respectively. This was significantly higher among the AFRS population compared to both the CRSwNP population (Δ34.2% [28.4%-39.6%], p < .0001) and the CRSsNP population (Δ44.9% [38.4%-50.6%], p < .0001). The proportion of patients who were either uninsured or covered by Medicaid among the AFRS, CRSwNP, and CRSsNP populations was 31.5% [25.4%-38.1%], 8.6% [0.7%-23.8%], and 5.0% [0.3%-14.8%], respectively. This was significantly higher among the AFRS group than the CRSwNP group (Δ22.9% [15.3%-31.1%], p < .0001) and the CRSsNP group (Δ26.5% [19.1%-33.4%], p < .0001)., Conclusion: This study confirms that AFRS patients are more likely to be Black and either uninsured or on subsidized insurance than their CRS counterparts., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Objectives: Allergic fungal rhinosinusitis (AFRS) and eosinophilic mucin chronic rhinosinusitis (EMRS) are two forms of chronic sinusitis distinguished by the presence (AFRS) or absence (EMRS) of fungal elements in sinus mucin. Detection of the fungal elements, however, is complex and it is difficult to say whether EMRS is in fact an entity distinct from AFRS. The aim of the present study, based on a retrospective series of AFRS and EMRS, was to identify the specific clinical and radiological elements distinguishing between the two., Materials and Methods: A 2-center retrospective observational study following STROBE guidelines included patients managed for AFRS or EMRS between 2009 and 2022. Clinical, mycological, pathologic and radiological data were collected. Type of treatment and disease progression were also analyzed. Intergroup comparison used Student's test for mean values of quantitative variables, with calculation of P-values, and Pearson's Chi 2 test or Fisher's exact test for categoric variables, with calculation of relative risk and 95% confidence intervals., Results: The AFRS group comprised 41 patients and the EMRS group 34. Demographic data were comparable between groups. EMRS showed a higher rate of asthma (79.4 vs. 31.4%; P<0.001), more severe nasal symptomatology (rhinorrhea, P=0.01; nasal obstruction, P=0.001), and more frequent bilateral involvement (85.3 vs. 58.5%; P=0.021). AFRS showed more frequent complications (19 vs. 0%; P=0.006). Radiologically, mucin accumulation was greater in AFRS, filling the sinus in 84.2% of cases, versus 26.3% (P<0.001), with more frequent sinus wall erosion (19 vs. 5.8%; P=0.073). The recurrence rate was higher in EMRS: 38.2 vs.21.9% (P=0.087)., Conclusion: The present retrospective study found a difference in clinical and radiological presentation between AFRS and EMRS, with EMRS more resembling the presentation of severe nasal polyposis., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Allergic fungal rhinosinusitis (AFRS) is a unique clinical entity that falls under the broader umbrella of chronic rhinosinusitis with nasal polyps with type 2 inflammation. It is characterized by nasal polyposis, production of characteristic thick eosinophilic mucin, and expansile change of involved sinus cavities. The diagnosis is classically made using the Bent and Kuhn criteria. However, recent studies have indicated the lack of specificity of some major criteria. The need to fulfill all 5 criteria before diagnosing AFRS partially mitigates this but renders the criteria cumbersome to use, and highlights the need to develop more specific criteria. Our understanding of AFRS pathophysiology has advanced significantly and has helped elucidate the lack of histatins contributing to the inability to clear fungal spores, consequently leading to fungi-induced disruption of the epithelial barrier and stimulation of sinonasal epithelial cells. These trigger a cascade of type 2 inflammatory cytokines driven by both the adaptive and innate immune system. Although more research is needed, these findings could hypothetically point to a limited type 3 immune response at the sinus mucosa, resulting in a compensatory overstimulation of type 2 inflammatory processes. Treatment for AFRS remains centered on surgery and topical corticosteroids. Short courses of systemic corticosteroids may be used with caution, and fungal-specific immunotherapy and systemic antifungals are options in recalcitrant disease. Biologics show early promise, as we await data from randomized controlled trials under way. Finally, new insights into AFRS pathology provide opportunities for novel therapeutic strategies., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Allergic fungal rhinosinusitis (AFRS) forms a significant group of patients presenting with the commonest health problem encountered in rhinology. Patients commonly present with typical symptoms of sinusitis, and the diagnosis is often made after imaging and/or intraoperatively. Infections caused by Chrysosporium species are very rare and are very rarely been reported to cause sinusitis in humans. Usually, human chrysosporial infections are mild and unmarked by symptoms. We report a rare case of allergic fungal sinusitis (AFS) caused by Chrysosporium species in a 41-year-old male with the history of diabetes mellitus., Competing Interests: None

Objectives: The objective of this study was to compare the efficacy of itraconazole and systemic steroids as an adjuvant to topical steroids in post-operative patients with allergic fungal rhinosinusitis (AFRS) using both subjective and objective outcome measurements., Design: A prospective comparative study., Setting: A tertiary care centre., Participants: Sixty patients diagnosed with AFRS were included. Patients with chronic systemic illness and those undergoing revision surgery were excluded. Post-operative patients were divided into two groups of 30 each which received itraconazole 400 mg OD or methylprednisolone in tapering doses over 6 weeks., Main Outcome Measures: The outcomes were measured at the end of 6 weeks-Kupferberg endoscopic staging, absolute eosinophilic count (AEC), serum immunoglobulin (IgE), and Sino Nasal Outcome Test-20 scores., Results: Our study showed no statistical significance in outcomes between the two groups treated with itraconazole and methylprednisolone regarding recurrence, AEC, IgE and quality of life assessment (p < 0.01)., Conclusion: Itraconazole was comparable to methylprednisolone in preventing disease recurrence in the post-operative management of AFRS. It may be a viable alternative to replacing systemic steroids where the latter may be contraindicated. Itraconazole given at a dose of 400 mg once daily for 6 weeks was a safe dose., (© 2022 John Wiley & Sons Ltd.)

Purpose of Review: The aim of this article is to review the current literature regarding development of new or recurrent inflammation of uninvolved contralateral sinuses in unilateral allergic fungal rhinosinusitis (AFRS) and discuss management strategies., Recent Findings: AFRS is a subtype of chronic rhinosinusitis with nasal polyposis (CRSwNP) that can manifest as either unilateral or bilateral disease. Particular to AFRS compared with other CRSwNP subtypes is the high propensity for recurrence. Multiple recent studies have evaluated the recurrence rate of uninvolved contralateral sinuses in unilateral AFRS and demonstrated eventual involvement of the nondiseased side. Additionally, postoperative medical therapy of the nondiseased side reduced recurrence rates overall., Summary: Recurrence of AFRS is high in both the ipsilateral and contralateral sinuses. Upfront bilateral medical and/or surgical treatment of patients presenting with unilateral AFRS may be considered to improve long-term inflammatory control., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To investigate the different clinical manifestations in Egyptian patients with orbital complications of rhinosinusitis (RS) according to the pathology within the paranasal sinuses., Methods: The medical records of patients presented with chronic RS between August 2018 and December 2020 were retrospectively reviewed., Results: This study included 64 patients: 28 patients with subperiosteal abscess (SPA), 10 with allergic fungal RS, 6 with isolated fungal RS, 6 with invasive fungal RS, and 14 with mucocele. The most common manifestation was proptosis, limitation of ocular motility, periorbital swelling, and pain. A relative afferent pupillary defect was present in all cases of invasive fungal sinusitis. Surgical interventions were performed in 63 out of 64 cases. All the ophthalmological manifestations were reversible except for patients with invasive fungal rhinosinusitis., Conclusion: Orbital complications of RS may require early surgical intervention with multidisciplinary counseling between ophthalmologists, otorhinolaryngologists, radiologists, and neurologists.

Allergic fungal rhinosinusitis (AFRS) is primary, Th2-mediated, chronic rhinosinusitis, which is diagnosed when the criteria defined by Bent and Khun are met. The disease is most common in countries located in the subtropical and tropical regions characterized by high temperatures and high levels of humidity, which favour the wider occurrence of fungi in the environment. The presence of specific IgE antibodies directed against fungal allergens, which is one of the diagnostic criteria, proves the systemic nature of the disease and allows one to distinguish AFRS from eosinophilic fungal rhinosinusitis. There is no unified treatment method for AFRS described in the literature, and relapses are common. Sinus surgery remains the treatment of choice. Oral and topical steroid therapy plays an important role in the treatment process. The effectiveness of antifungal treatment and immunotherapy is unclear. Biological treatment, the results of which are promising, has raised great hopes. The aim of this study was to reveal how often AFRS occurs in European countries, what environmental factors influence its development, and how important it is to specify its diagnostic criteria and treatment methods. We present an overview of the available literature. In addition, we share our own experience and describe two cases of AFRS diagnosed and treated at our centre., (© 2023 S. Karger AG, Basel.)

Allergic fungal rhinosinusitis (AFRS) is a noninvasive subtype of chronic rhinosinusitis with nasal polyps (CRSwNP) that usually develops in immunocompetent atopic individuals and is more common in geographic regions characterized by warm temperatures and high humidity, conducive to higher environmental fungal presence. Allergic fungal rhinosinusitis usually presents with unique computed tomography findings and significant polyp burden, yet patients often report minimal sinus symptoms. Patients with AFRS often have extremely elevated serum total and fungal-specific IgE levels. Treatment almost always requires surgery, in which adjuvant medical therapy is critical to success. However, until recently the choice of adjuvant therapy has consisted primarily of either oral and/or topical steroids. Although oral corticosteroids decrease recurrence after surgery, data for the effectiveness of other adjunctive pharmacologic agents, including topical and oral antifungal agents and immunotherapy, have remained unclear and hence are not recommended in recent guidelines including the International Consensus of Allergy and Rhinology. Three biologics, omalizumab, dupilumab, and mepolizumab, have recently been approved for treating CRSwNP in general, but clinical trials to date with these biologics did not involve AFRS patients. Recently published case reports and smaller prospective studies have shown good efficacy of these biologics on the AFRS subgroup of patients. This article provides an overview of the understanding of the pathophysiology of AFRS, implications of this understanding on the possible role of biologics, and clinical reports on the use of biologics in treating AFRS. Because biologics are indicated for treating CRSwNP, follow up real-world evidence studies are needed for AFRS., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The prevalence of allergic fungal rhinosinusitis (AFRS) and its associated risk factors have been an issue of debate. Some epidemiological factors have been correlated to the disease prevalence., Objectives: To observe the prevalence pattern of AFRS worldwide and to investigate the effect of specific epidemiological factors on the disease prevalence., Methods: A systematic review was derived from 1983 to December 2018. Data on the prevalence of AFRS were collected from the selected studies. Relevant factors assessing each city's climate, socioeconomics and geography were used to study the association with AFRS prevalence., Results: 35 cities across 5 continents were investigated. The worldwide average rate of AFRS in CRS cases is 7.8% (0.2%-26.7%) in which more than half of the investigated cities (57%) had low AFRS prevalence, while the remaining cities had intermediate (11%) and high (32%) prevalence. Cities with higher temperatures were associated with a higher prevalence of AFRS ( p -value 0.002), whereas cities with humid continental climate were significantly associated with a low prevalence of AFRS ( p -value 0.032). Humidity and wind speed were lower in the cities with higher AFRS prevalence ( p -value 0.018 and 0.008, respectively). There were no significant correlations between AFRS prevalence and economic levels, presence of water bodies, rainfall amounts, altitude, and presence of forests., Conclusion: AFRS has a worldwide distribution pattern with varying prevalence. In this ecological study, we observed a correlation between AFRS prevalence and climatic factors (climate classification, humidity, temperature, and wind speed). Socioeconomic factors should be analyzed on an individual basis for better assessment of the relationship with disease prevalence., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Neoscytalidium dimidiatum is a rare dematiaceous fungus that was first described in 1916 as Dothiorella mangiferae. From the standpoint of epidemiology and therapy, early detection of fungal rhinosinusitis (FRS), the causative agents, and their associated risk factors can improve the therapeutic outcome and decrease the mortality rates among patients. In this study, we report a 34-year-old Iranian female patient with allergic bronchopulmonary aspergillosis (ABPA), who presented to our facility with an 8-year history of chronic fungal sinusitis, drug-resistant asthma, pneumonia, bronchitis, post-nasal discharge, nasal obstruction, nasal polyposis, and anemia. The patient was subjected to diagnostic nasal endoscopy and computed tomography (CT) scan of paranasal sinuses, as well as routine, complementary mycological, and molecular methods, which confirmed the diagnosis of allergic fungal rhinosinusitis in patients with ABPA. Neoscytalidium dimidiatum was isolated from the sinus of the patient. Results of in vitro susceptibility tests indicated that the case isolate was susceptible to amphotericin B and itraconazole at concentrations which are commonly achieved in patients receiving recommended dosages for invasive mycoses (0.25 to 0.75 mg/kg of body weight daily for amphotericin B and 100 to 400 mg daily for itraconazole) and resistant in vitro to caspofungin, voriconazole, and posaconazole. The patient was successfully treated with amphotericin B / itraconazole + postoperative oral corticosteroids (OCS). Neoscytalidium dimidiatum infection should be considered as a possible additional factor in the etiology of AFRS, especially in immunocompromised patients., Competing Interests: Conflicts of interest The authors declare no potential conflicts of interest with respect to research, authorship, and/or publication of this article. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2021 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

In the last two decades, the development of culture-independent genomic techniques has facilitated an increased appreciation of the microbiota-immunity interactions and their role in a multitude of chronic inflammatory diseases such as chronic rhinosinusitis (CRS), asthma, inflammatory bowel disease and dermatitis. While the pathologic role of bacteria in chronic inflammatory diseases is generally accepted, the understanding of the role of fungi remains controversial. Chronic rhinosinusitis, specifically the phenotype linked to nasal polyps, represents a spectrum of chronic inflammatory diseases typically characterized by a type 2 immune response. Studies on the microbiota within sinus cavities from healthy and diseased patients have focused on the bacterial community, mainly highlighting the loss of diversity associated with sinus inflammation. Within the various CRS with nasal polyps (CRSwNP) phenotypes, allergic fungal rhinosinusitis presents an opportunity to investigate the role of fungi in chronic type 2 immune responses as well as the antifungal immune pathways designed to prevent invasive fungal diseases. In this review, we examine the spectrum of fungi-associated sinus diseases highlighting the interaction between fungal species and host immune status on disease presentation. With a focus on fungi and type 2 immune response, we highlight the current knowledge and its limitations of the sinus mycobiota along with cellular interactions and activated molecular pathways linked to fungi., (© 2021 ARS-AAOA, LLC.)

Background: Central compartment atopic disease (CCAD) is a variant of chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) characterized by polypoid changes of the superior nasal septum, middle (MT), and/or superior turbinates (ST). This study evaluates surgical outcomes in patients with CCAD compared with other CRSwNP subtypes., Methods: Retrospective analysis was performed at Emory University from May 2012 to November 2019. Patients undergoing primary endoscopic sinus surgery (ESS) for CCAD, aspirin-exacerbated respiratory disease (AERD), allergic fungal rhinosinusitis (AFRS), and CRSwNP not otherwise specified (CRSwNP NOS) were included consecutively, beginning with the earliest date of CCAD patient. Outcome measures included polyp recurrence, revision ESS, oral steroid use, and oral antibiotic use. Pearson chi-square and univariate analysis of variance (ANOVA) were performed for group comparisons., Results: Data was collected for 132 patients (CCAD = 38, AERD = 20, AFRS = 37, CRSwNP NOS = 37; 58 females, mean age 42.9 years [range, 13-85 years]). CCAD patients demonstrated polyp recurrence less frequently than expected, whereas AFRS patients had polyp recurrence more frequently than expected (p = 0.003; phi 0.32). CCAD patients underwent revision ESS less frequently than expected; AFRS and CRSwNP NOS underwent revision ESS more frequently than expected (p = 0.03; phi 0.26). CRSwNP NOS patients received more total antibiotic courses than those with CCAD (p = 0.01; eta-squared 0.09) and more courses of antibiotics per month than those with AFRS (p = 0.03; eta-squared 0.07). There was no significant difference in follow-up measures across groups (number of visits, total months, or visits per month)., Conclusion: Rates of polyp recurrence and revision ESS were significantly lower in CCAD patients compared with patients with other CRSwNP subtypes, suggesting durable benefit of ESS and postoperative medical therapy in CCAD patients., (© 2021 ARS-AAOA, LLC.)

Introduction: Fungal rhinosinusitis (FRS) remains a rare disease. The noninvasive forms are hard to diagnose. The management protocols remain controversial. We aim to describe the clinical, radiological and pathological features of noninvasive FRS and present our management protocol and follow-up results., Patients and Methods: This descriptive study was conducted in the ear-nose-throat department of the university hospital, Taher Sfar in Mahdia, Tunisia. All patients who responded to the definition of noninvasive FRS (fungal balls and allergic fungal sinusitis) were included. The study was conducted over a three year period (May 2017 - April 2021)., Results: Eleven patients were included in this study: four cases of fungal balls and seven cases of allergic fungal sinusitis. Patients presented with symptoms of chronic recurrent rhinosinusitis with no response to conventional treatments. Computed tomodensitometry scan showed opacification of the paranasal sinuses in all patients. Other signs were heterogeneous opacities, local calcifications and thinning of the bony walls of the sinuses. Histopathological findings were inflammatory polyps in all cases of allergic FRS with the presence of fungal hyphae in 42.8% of the cases. All patients underwent surgery after a median delay of 12 [6-24] months of the symptom's onset. The used procedures were endoscopic middle meatal antrostomy for all patients, ethmoidectomy (81.8%) and sphenoidotomy (36.4%). None received systemic antifungals or corticosteroids with a favorable outcome in all cases., Conclusion: Symptoms of noninvasive FRS are nonspecific. The scan images contribute to the diagnosis, but the perioperative findings and the histopathological results remain crucial.  The management is mainly surgical., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Masmoudi M et al.)

Objectives: We report a case of acutely worsening allergic fungal sinusitis in a patient receiving immunotherapy with pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor., Methods: A 53-year-old man with a history of metastatic melanoma and recent initiation of pembrolizumab therapy presented with acutely worsening headaches, left abducens nerve palsy, and neuroimaging demonstrating an erosive skull base lesion with bilateral cavernous sinus involvement., Results: Intraoperative findings were consistent with non-invasive allergic fungal sinus disease. Microbiology and histopathologic data ruled out malignancy and demonstrated Aspergillus fumigatus without concern for angioinvasion. After treatment with antifungal therapy, the patient's symptoms and abducens nerve palsy resolved. Symptoms were well-controlled 7 months after his initial presentation., Conclusions: Inflammatory sinusitis in patients receiving anti-PD-1 therapy may be secondary to T-cell infiltration, a similar pathophysiology as immune-related adverse events, and warrants appreciation by otolaryngologists given our increasing exposure to immunotherapy and its head and neck manifestations.

Allergic fungal sinusitis (AFS) arises from a host hypersensitivity reaction to fungi residing within the sino-nasal tract. Computed tomography imaging may show heterogenous sinus opacification with bony erosion and expansion into the orbits. With advanced orbital involvement there is a risk of optic neuropathy and irreversible vision loss. We present a patient with AFS who presented with bilateral proptosis and early optic neuropathy. Radiologically, there was evidence of bony erosion and orbital wall compression. Following oral corticosteroids and full-house endoscopic sinus surgery, these changes reversed considerably. This case shows that bony and anatomical orbital changes from AFS are reversible with adequate surgical treatment.

A review of the treatment of allergic and invasive fungal sinusitis, as well as a presentation of the first recorded case of a conversion from allergic fungal sinusitis (AFS) to chronic granulomatous invasive sinusitis and the fourth case of invasive fungal sinusitis associated with Curvularia. This immunocompetent patient suffering from chronic AFS converted after repeated high-dose steroid tapers and noncompliance. AFS may present atypically and should be suspected even in immunocompetent patients with sinus disease who report new onset pain and neurologic symptoms. Clinicians should consider the potential complications associated with repeated systemic steroid administration. Laryngoscope, 129:2447-2450, 2019., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Allergic fungal rhinosinusitis (AFRS) is characterized by higher revision endoscopic sinus surgery (ESS) rates and unique radiographic features when compared to chronic rhinosinusitis with nasal polyposis (CRSwNP) or chronic rhinosinusitis without nasal polyposis (CRSsNP)., Objective: We hypothesized that an increased frequency of concha bullosa in AFRS or other radiographic nuances might allow for accumulation of allergic mucin and contribute to increased ESS revision rates., Methods: A retrospective cohort study was performed. Patient diagnosis (AFRS, CRSwNP, and CRSsNP), basic demographics, and prior ESS rates were collected., Results: A total of 210 consecutive patients were included (AFRS = 70, CRSwNP = 70, and CRSsNP = 70). Pediatric AFRS patients had more unilateral disease (38.1% vs 4.4%; P = .007) and anterior ethmoid skull base erosion (23.8% vs 6.7%; P = .047) than adult AFRS patients. AFRS patients were more likely to be younger (24.9 ± 10.1 years vs 45.6 ± 14.4 years vs 48.7 ± 18.2 years; P < .001), African American (70% vs 14.3% vs 11.4%; P < .001), and have undergone prior ESS (54.3% vs 45.7% vs 31.4%; P = .02) than CRSwNP or CRSsNP patients. Concha bullosa were more prevalent in AFRS patients than CRSwNP or CRSsNP patients across the population (42.9%, 18.6%, and 14.3%; P < .001) and in the setting of no previous surgery (53.1%, 31.6%, and 16.7%; P < .001)., Conclusion: In this cohort, pediatric AFRS patients had more unilateral disease and anterior ethmoid skull base erosion. Concha bullosa prevalence was significantly higher in AFRS as compared to those with CRSwNP or CRSsNP, despite prior ESS. Surgeons should consider concha bullosa as a potential anatomical subsite to harbor recurrent or residual disease.

Objectives: We reviewed the phenotyping and endotyping of chronic rhinosinusitis (CRS) and treatment options., Methods: We searched PubMed, Google, Google Scholar, and the Proquest Central Database of the Kırıkkale University Library., Results: Phenotypes are observable properties of an organism produced by the environment acting upon the genotype, that is, patients with a particular disorder are subgrouped according to common characteristics. Currently, CRS is usually phenotyped as being with (CRSwNP) or without (CRSsNP) nasal polyps. However, this is not immutable as some individuals progress from nonpolyp to polypoid CRS over time. Phenotypes of CRS are also based on inflammatory patterns, generally CRSwNP is eosinophilic, CRSsNP neutrophilic; but there is a spectrum, rather than a clear-cut division into 2 types. An endotype is a subtype of a condition defined by a distinct functional or pathobiological mechanism. Endotypes of CRS can be (1) nontype Th2, (2) moderate type Th2, and (3) severe type Th2 immune reactions, based on cytokines and mediators such as IL4, 5, 13. CRS endotyping can also include a (1) type 2 cytokine-based approach, (2) eosinophil-mediated approach, (3) immunoglobulin E-based approach, and (4) cysteinyl leukotriene-based approach. Subdivisions of CRSwNP can be made into nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, allergic fungal sinusitis, and eosinophil pauci-granulomatous arteritis by testing. General treatment for all CRS is nasal douching. The place of surgery needs careful reconsideration. Endotype-directed therapies include glucocorticosteroids, antibiotics, aspirin, antifungals, anticytokines, and immunoglobulin replacement. The recognition of united airways and the co-occurrence of CRSwNPs and severe asthma should lead to common endotyping of both upper and lower airways in order to better direct therapy., Conclusion: Endotyping can allow for the identification of groups of patients with CRS with a high likelihood of successful treatment, such as patients with a moderate type 2 immune reaction or those with acquired immune deficiency.

Background: Revision surgery rates following endoscopic sinus surgery (ESS) range between 7% and 50% and are influenced by many factors. This study investigates ESS outcomes for chronic rhinosinusitis (CRS) subtypes., Methods: Retrospective review of adult CRS patients undergoing ESS with a single surgeon (2010-2015) was conducted. Outcomes were analyzed by CRS subtypes., Results: ESS was performed in 424 CRS patients (CRS with nasal polyps [CRSwNP], n = 170; CRS without polyps [CRSsNP], n = 254). Most patients (309; 72.9%) could not be specifically subtyped; 115 (27.1%) were subtyped as follows: aspirin-exacerbated respiratory disease (AERD), n = 47 (11.1%); allergic fungal sinusitis (AFS), n = 39 (9.2%); immunodeficiency, n = 21 (5.0%); granulomatosis with polyangiitis (GPA), n = 5 (1.2%); and eosinophilic granulomatosis with polyangiitis (EGPA), n = 3 (0.7%). All subgroups experienced clinically meaningful reduction in postoperative 22-item Sino-Nasal Outcome Test (SNOT-22) scores. At median follow-up of 28 months (interquartile range [IQR], 10-47 months), 19 patients (4%) underwent revision ESS (CRSwNP, n = 6; CRSsNP, n = 13). Revision ESS rates were 3.5% and 5.1% for CRSwNP and CRSsNP, respectively. Revision ESS rate for subtypes were: AERD 2%; AFS 2%; immunodeficiency 14%; GPA 40%; EGPA 0%; and "all other CRS" 4% at median follow-up duration of 36, 28, 41, 37, 44, and 26 months, respectively., Conclusion: All CRS subtypes demonstrated clinically meaningful improvement in postoperative SNOT-22 scores following ESS. Our overall revision ESS rate was 4% (3.5% in CRSwNP). AFS, AERD, and EGPA groups demonstrated low revision rates, while immunodeficiency and GPA patients required more revision surgery. A contemporary understanding of CRSwNP subtypes facilitated surgical and medical strategies in improving outcomes for AERD, AFS, and EGPA patients. CRSsNP subtypes with immunodeficiency and GPA merit further investigation to optimize outcomes., (© 2018 ARS-AAOA, LLC.)

Objective Allergic fungal rhinosinusitis (AFRS) is a clinical subtype of chronic rhinosinusitis with nasal polyps (CRSwNP), characterized by eosinophilic mucin, evidence of fungal elements within the mucin, fungal-specific type I hypersensitivity, and characteristic computed tomography findings. It remains controversial whether AFRS represents a disease with a unique pathophysiology from chronic rhinosinusitis or is merely a severe form of CRSwNP. The goal of this study was to identify molecular features unique to AFRS. Study Design Cross-sectional case-control. Setting Single academic tertiary referral institution. Subjects and Methods Subjects included 86 patients undergoing endoscopic sinus surgery: CRSwNP (n = 34), AFRS (n = 37), and healthy controls (n = 15). Pathway and correlation analyses were performed with whole-genome microarray data for study patients undergoing surgery for recalcitrant chronic rhinosinusitis. Our findings were confirmed with quantitative polymerase chain reaction and immunohistochemical studies. Results AFRS was uniquely characterized by a pronounced association with adaptive T helper 2-associated immune gene expression. AFRS exhibited altered expression of proteins associated with secretory salivary peptides-namely, histatin, a peptide with known antifungal activity in the oral cavity. Furthermore, the expression of histatins correlated negatively with that of type 2 inflammatory mediators. We confirm the decreased expression of histatins in AFRS when compared with CRSwNP by quantitative polymerase chain reaction and localized its expression to a submucosal cell population. Conclusion There exist clear molecular profiles that distinguish AFRS from CRSwNP. This divergence translates into an altered ability to control fungal growth and may in part explain some of the phenotypical differences between CRSwNP and AFRS.

Introduction: Fungal paranasal sinusitis can be either invasive or non-invasive. Saprophytic infections, fungus balls (FB) and allergic fungal rhinosinusitis are non-invasive (AFR)., Materials and Methods: The present study examined 521 patients who underwent endoscopic sinus surgery between January 2016 and April 2017 due to chronic paranasal sinusitis at the Department of Laryngology and Laryngological Oncology of the Upper Silesian Medical Centre in Katowice. The aim of the study was to analyse the histopathological and microbiological material collected intraoperatively and to determine the incidence and type of fungal infections among patients treated for chronic sinusitis., Results: Chronic fungal sinusitis was confirmed in 10 of 521 operated patients. The study group consisted of 9 females and 1 male. Histopathological examination revealed dead mycelium in 5 patients and colonies of Aspergillus spp. in 4, while microbiological examination revealed Candida albicans infection in 1 case. Allergy to inhalant allergens of fungal spores of Alternaria and Penicillinum was confirmed in a 73-year-old patient, which, based on the whole clinical presentation, enabled to diagnose chronic allergic fungal sinusitis. The most common location of mycelium was the maxillary sinus, followed by the sphenoid sinus., Discussion: The most common form of non-invasive fungal sinusitis is the so-called fungus ball, which was also confirmed in our report (95% of the test subjects). AFRS is more likely to occur in warm, moist climates that favour the growth of fungi.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents a subset of chronic sinusitis with various causes. Some forms of the disease are driven by allergy, often in association with asthma. Refractory CRSwNP can be associated with cystic fibrosis and other clinical syndromes. More recent literature is presented regarding roles of innate immunity and superantigens. Effective treatment of CRSwNP requires careful endoscopic sinus surgery followed by an individualized treatment plan that often includes oral and topical steroids. Recidivism of polyps is common, and patients require long-term follow-up., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Retromaxillary pneumatization of posterior ethmoid (PE) air cells is an area that is yet to have appropriate description in rhinologic literature., Study Design: Case series with chart review., Setting: Tertiary care hospital., Subjects and Methods: First, 524 sides in 262 paranasal sinus computed tomography scans were analyzed: 350 normal sides were examined for PE pneumatization lateral to the sagittal plane of the medial wall of maxillary sinus posteriorly, and 174 diseased sides were similarly reviewed to check how pathology may affect identification and measurements. Following that, 153 operated sides in 84 cases prepared for revision endoscopic sinus surgery (ESS) were studied for residual diseased cells at different anatomic locations., Results: Overall, retromaxillary PE pneumatization was identifiable in 416 of the 524 sides (79.4%). Lateral retromaxillary extension varied from 0.5 to 12.3 mm (mean ± SD, 4.8 ± 2.3 mm). This area of pneumatization is bounded anteroinferiorly by the junction between the posterior and superior walls of the maxillary sinus. Three cell types were described depending on the degree of lateral extension (type I, <3 mm; type II, 3-6 mm; type III, >6 mm). This cell, which we refer to as the Herzallah cell, was distinguishable from the anterior ethmoid Haller cell and was found to have residual disease in 50.3% of cases prepared for revision ESS., Conclusion: Retromaxillary extension of PE air cells varies considerably and requires attention during ESS. Residual undissected retromaxillary cell is a common finding in revision ESS and can contribute to inadequate disease clearance., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.)

Background: The presence of allergic mucin in allergic fungal sinusitis (AFS) is a manifestation that identifies it as a hypersensitivity process. AFS has a phenomenon of cross-reactivity to IgE-bound proteins having at least two shared epitopes., Clinical Report: A 13-year-old male with nasal obstructive symptoms of three years of evolution. An obstructive mass was identified in the sinuses through physical examination and CT. In endoscopic surgery, the left nostril polyp was identified with the macroscopic appearance of allergic mucin; the polyp was resected. Final histopathological examination using periodic acid-Schiff and Grocott's methenamine silver staining indicated Aspergillus. Two weeks after surgery, percutaneous tests showed sensitization to Alternaria, Helminthosporium sativum, and Deramatophagoides farianae with negativity to Aspergillus fumigatus., Conclusions: The absence of significant titers of specific IgE antibodies to Aspergillus fumigatus was the evidence that the hypersensitivity response was triggered by a pathogen other than that isolated in histopathological study, which coupled with positive tests for other fungi may be explained by the cross-reactivity phenomenon in a phenomenon of likely hypersensitivity.

Background: Chronic rhinosinusitis (CRS) and asthma describe inflammation of the upper and lower airway, respectively. Not surprisingly, the prevalence of CRS and asthma has been linked, with up to 50% asthma prevalence in CRS with nasal polyposis (CRSwNP) patients. However, these prevalence rates do not address subtypes of CRSwNP including allergic fungal rhinosinusitis (AFRS). This study sets out to objectively determine asthma prevalence in CRS subtypes prospectively., Methods: A prospective prevalence study of adult CRS patients was conducted over a 1-year period at a tertiary care center. Patients were grouped into CRSwNP, CRS without nasal polyposis (CRSsNP), or AFRS. Patients were administered the Asthma Screening Questionnaire (ASQ) and asthma was confirmed by pulmonary function testing (PFT) if positive on the ASQ. Chi square analysis was performed to compare the asthma prevalence among the CRS subtypes., Results: A total of 410 patients (age 48.1 ± 16.4; 53.5% male) were included. Of these, 178 (43.4%) had CRSwNP, 166 (40.5%) had CRSsNP, and 66 (16.1%) met criteria for AFRS. Analysis revealed that 48.3% of CRSwNP patients, 16.5% of CRSsNP patients, and 23.6% of AFRS patients had asthma confirmed by PFTs. Chi square analysis showed a significant difference in asthma prevalence between CRSwNP and AFRS (p = 0.0016) and CRSwNP and CRSsNP (p = 0.0000), but no significant difference between CRSsNP and AFRS (p = 0.2380)., Conclusion: There is a significant difference in the prevalence of asthma between CRSwNP and AFRS, suggesting a fundamental distinction in their etiologies despite similar immunologic profiles. Further efforts to delineate these biological disparities are underway., (© 2015 ARS-AAOA, LLC.)

Background: Vitamin D3 (VD3 ) levels have been recently found to be responsible for a number of immunological, anti-inflammatory and anti-infectious roles. Some studies reported that some forms of allergic fungal rhinosinusitis (AFRS), occurs more commonly in patients who are more susceptible to VD3 deficiency. The aim of this work was to measure VD3 levels in patients with AFRS and chronic rhinosinusitis (CRS)., Methods: We report a prospective case control study conducted at Ain Shams University. It included 74 participants divided into 4 groups: group A, 25 patients with AFRS; group B, 15 patients with CRS with nasal polyps (CRSwNP); group C: 15 patients with CRS without nasal polyps (CRSsNP); and group D, 19 controls., Results: There was a statistically significant (p < 0.001) difference of VD3 between groups A and B compared with groups C and D. There were no statistically significant differences between the 4 groups regard calcium levels. Finally, there was a statistically significant difference in phosphate levels when we compared groups A and B with groups C and D (p = 0.001)., Conclusion: Serum level of VD3 in patient with CRSwNP and AFRS is significantly lower than that of patients with CRSsNP and control subjects. Although these results do not imply a specific etiological or therapeutic relationship, VD3 levels may constitute an inexpensive prophylactic and cost-effective option in the therapeutic armamentarium in the control of AFRS and CRSwNP, either by itself or as a synergistic agent with traditional agents., (© 2015 ARS-AAOA, LLC.)

Fungal sinusitis is characterized into invasive and noninvasive forms. The invasive variety is further classified into acute, chronic and granulomatous forms; and the noninvasive variety into fungus ball and allergic fungal sinusitis. Each of these different forms has a unique radiologic appearance. The clinicopathologic and corresponding radiologic spectrum and differences in treatment strategies of fungal sinusitis make it an important diagnosis for clinicians and radiologists to always consider. This is particularly true of invasive fungal sinusitis, which typically affects immuno compromised patients and is associated with significant morbidity and mortality. Early diagnosis allows initiation of appropriate treatment strategies resulting in favorable outcome., (Published by Elsevier Inc.)

Objectives: Allergic fungal rhinosinusitis (AFRS) may present with significant bone erosion of the orbital walls or cranial base. Although proptosis is fairly common, cranial neuropathies are rarely reported. The objectives of this study are to describe strategies for AFRS-induced neuropathies and evaluate ophthalmologic outcomes following endoscopic sinus surgery., Study Design: Case series with chart review., Setting: Tertiary referral center., Subject and Methods: A retrospective review identified 9 patients treated from 2008 to 2014 with AFRS-induced cranial neuropathies. Data regarding patient demographics, preoperative imaging, ophthalmologic symptoms, surgical intervention, histopathologic findings, and postoperative sinonasal and ophthalmologic outcomes were recorded., Results: Patients with AFRS (average age, 38 years) presented with optic neuropathy or abducens nerve palsy. Clinical presentation included unilateral visual loss secondary to optic nerve compression (n=5), diplopia from unilateral (n=2) or bilateral (n=1) abducens nerve palsy, and bitemporal hemianopsia secondary to optic chiasm compression (n=1). On average, the duration of ocular symptoms was 17 days. All patients underwent endoscopic surgical decompression of the sinuses and oral steroid therapy. Two individuals had an additional optic nerve decompression at the time of surgery. Seven patients had complete return of nerve function, whereas 2 had partial recovery at an average of 5 weeks following surgery., Conclusion: Bone erosion of the sphenoid sinus walls by AFRS can lead to compression of surrounding neural structures producing cranial neuropathies. Identification of these symptoms and prompt surgical decompression and removal of disease, along with aggressive medical therapy, provided excellent outcomes in the current series of patients., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.)

Background: Allergic fungal rhinosinusitis (AFRS) is a disease demonstrating substantial eosinophilic inflammation and characteristic radiographic bony erosion/expansion. Periostin is an extracellular matrix protein associated with eosinophil accumulation in eosinophilic esophagitis, allergic asthma mucus production, and chronic rhinosinusitis (CRS) polyp formation. Receptor activator of nuclear factor κ-B ligand (RANKL) is an osteoclast activator present in osteoporosis and periodontal disease. We sought to evaluate periostin and RANKL expression in AFRS and correlate these levels with radiographic scales of disease severity., Methods: Thirty sinus tissue specimens were intraoperatively collected from 3 patient groups: AFRS; CRS without nasal polyps (CRSsNP); and controls (n = 10 per group). Specimens were analyzed by semiquantitative reverse-transcription polymerase chain reaction (sq-RT-PCR) and immunofluorescence (IF) labeling/confocal microscopy for the presence of both periostin and RANKL. Immunofluorescence staining intensity was quantified by pixel density analysis. Preoperative computed tomography (CT) scans from each patient were scored using both the Lund-Mackay and CT bone erosion scoring systems., Results: Periostin was significantly elevated in AFRS sinus tissue compared to CRSsNP and controls, as demonstrated by IF (p < 0.001) and PCR (p = 0.011). RANKL was not detected in sinus tissue by IF or PCR. Periostin levels positively correlated with radiographic indices of disease severity for both soft tissue and bone, using Lund-Mackay (r = 0.926 [PCR] and r = 0.581 [IF]) and CT bone erosion (r = 0.672 [PCR] and r = 0.616 [IF]) scoring systems, respectively., Conclusion: Periostin is increased in AFRS tissue compared to CRSsNP and controls. Periostin levels positively correlate with radiologic disease severity scores. The increased levels of periostin in AFRS are possibly tied to its intense eosinophilic inflammatory etiology., (© 2014 ARS-AAOA, LLC.)

Unlabelled: BACKGROUNd: We report a case of allergic fungal sinusitis (AFS) involving the lacrimal sac and review the current English literature. A literature search for AFS involving the lacrimal sac revealed two reports with only one of the two cases demonstrating histological evidence of fungal elements. This is just the third such case and only the second reported case with histopathologic confirmation of fungal elements by Gomori methenamine silver (GMS) stain., Materials and Methods: A PubMed database search was performed using combinations of the following key words: allergic fungal sinusitis, lacrimal sac, nasolacrimal duct, ophthalmology, epiphora, orbit. A 70-year-old white man with a history of chronic conjunctivitis and nasal polyps presenting with chronic epiphora was found to have dacryostenosis on the left side. A CT scan of the orbits revealed mucoperiosteal thickening completely obliterating the frontal, ethmoid and sphenoid sinuses., Results: A left external dacryocystorhinostomy (DCR) was performed and the lacrimal sac contents were studied histopathologically. Microscopic examination of the lacrimal sac contents disclosed allergic mucin with laminated aggregates of eosinophils in various stages of degeneration, Charcot-Leyden crystals and rare noninvasive fungal hyphae confirming the diagnosis of AFS. Fungal elements stained positively with Gomori methenamine silver stain., Conclusion: Although rarely reported, AFS can affect the lacrimal sac. AFS should be suspected in patients with a history of recurrent refractory sinusitis, recurrent dacryocystitis and nasal polyposis. Early diagnosis is important for adequate treatment and prevention of recurrence.

Background and Purpose: This case involves a common disease, allergic fungal sinusitis (AFS), with the uncommon complication of intracranial abscess. Although AFS is known to result in bone erosion, invasive complications are rare., Methods: The clinical and pathologic information were reviewed. A literature review was performed to clarify the clinical, radiologic, and pathologic features of AFS., Results: The clinical and radiographic presentations were typical for AFS, including the relatively common complication of sinus wall erosion. Follow-up imaging demonstrated spread of fungal disease into the adjacent masticator space and intracranial spread by foramen ovale., Conclusion: This case illustrates the importance of identifying AFS and describing findings such as sinus erosion that may alter management. In this example, knowledge of the altered anatomy and potential for mucosal injury may facilitate surgical planning and decrease the likelihood of future complications., (Copyright © 2011 by the American Society of Neuroimaging.)

Background: Mold pathogens are a leading cause of chronic rhinosinusitis. Successful isolation of mold on culture is helpful in establishing a diagnosis and guiding therapy. Though mucolytic agents are commonly used in European countries, they are not part of everyday use in North America. In this case-control prospective study, we investigated the yield of fungal culture before and after treatment of sinus aspirates with the mucolytic agent dithiothreitol in a United States hospital., Methods: Over a 5-month period during 2011-2012, 359 sinus aspirates from 294 patients with symptoms suspicious for chronic sinusitis or allergic fungal sinusitis were collected. Aspirates were cultured on fungal medium before and after treatment with dithiothreitol., Results: Of the 359 pairs of cultures, 62 (17.3%) demonstrated mold growth on at least 1 of the plates, 9 (14.5%) of which grew more than 1 species of mold. A total of 75 molds were identified, 41 (54.7%) of which were successfully cultured only when the mucus was pretreated with dithiothreitol (p < 0.0001). Quantitatively, more colonies grew from dithiothreitol-treated mucus than from direct-inoculation (p < 0.0001)., Conclusion: This study confirms improved recovery of mold from sinus cultures after pretreatment of samples with dithiothreitol. Further studies are needed to correlate these findings with clinical outcome., (© 2013 ARS-AAOA, LLC.)