Allergic Fungal Sinusitis Patients Research Articles

A Case-Control Analysis of Risk Factors Associated With Allergic Fungal Sinusitis Patients

A Case-Control Analysis of Risk Factors Associated With Allergic Fungal Sinusitis Patients

Role of interleukin-5 in allergic fungal sinusitis: deeper insight

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is an allergic response characterized by type 2 inflammatory reactions mediated by T helper 2 cells (Th2). Th2 is characterized by elevated type 2 cytokines related to the humoral response, including Interleukin-4 (IL-4), IL-5, IL-6, IL-9, IL-10, IL-13, IL-25 and IL-33. Allergic fungal sinusitis (AFS) is a distinguishable form of CRSwNP and is characterized by primary localized disease with non-invasive fungal hyphae, which causes immunoglobulin E (IgE)-mediated mucosal hypersensitivity resulting in the formation of eosinophilic mucin. Interleukin-5 (IL-5) is a pro-inflammatory factor that plays a very important role in eosinophil biology.ObjectiveTo explore the relation between IL-5 tissue protein expression and AFS.MethodsA prospective study performed on 70 patients divided into 2 groups (50 cases of AFS and 20 control who underwent septoplasty and partial inferior turbinectomy) to assess the role of IL5 in AFS compared to control.ResultsIL-5 was overexpressed in polyps of AFS patients compared to the control group denoting AFS as an eosinophilic mediated type 2 inflammation and highlighting a positive correlation with Lund MacKay radiological score and Sino-nasal Outcome Test (SNOT-22) score for severity of chronic rhinosinusitis (CRS) symptoms.ConclusionIL-5 plays a pivotal role in the pathogenesis and severity of AFS. Thus, our results provide encouraging evidence supporting targeting IL5 as an eligible therapy of promising benefits in AFS.

Prevalence of allergic fungal sinusitis among patients with nasal polyposis.

To determine the frequency of allergic fungal sinusitis among patients with nasal polyps, and to compare Lund-Mackay scores of patients with and without allergic fungal sinusitis. The cross-sectional longitudinal study was conducted at a tertiary healthcare centre in Karachi, Pakistan, from December 2016 to November 2018, and comprised patients with sinonasal polyposis undergoing surgery. The patients were categorised as having allergic fungal sinusitis when histopathology showed allergic mucin with fungal hyphae and culture was positive for fungal growth. Lund-Mackay scoring of each patient was noted and mean scores of allergic fungal sinusitis and non-allergic fungal sinusitis patients were compared. Data was analysed using SPSS 25. Of the 114 patients, 61(53.5%) were males. The overall mean age was 37.3±15.3 years. Of the total, 27(23.7%) patients had allergic fungal sinusitis. There was a significant relationship between asthma and allergic fungal sinusitis (p=0.03). The mean Lund-Mackay score was significantly higher for allergic fungal sinusitis patients (p<0.01). Recurrence was seen in 11(9.6%) cases. About one-fourth of patients with nasal polyps had allergic fungal sinusitis, and such patients showed significantly high mean Lund-Mackay score.

Chronic rhinosinusitis in unified airway disease: surfactant proteins as mediators of respiratory immunity.

The aim of this review is to describe the co-occurrence of chronic rhinosinusitis (CRS) with other inflammatory illnesses of the lower respiratory system characterised by airway obstruction and hyperresponsiveness, such as asthma, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD) in the context of the unified airway disease (UAD). We also sought to discuss the novel role of surfactant proteins as mediators of innate immunity in the sinonasal epithelium and their potential as therapeutic interventions. Different epidemiological and physiological studies in CRS and asthma have outlined that there are common clustering patterns in the phenotypes/endotypes of both diseases, reinforcing the notion of the UAD. Also, surfactant proteins A (SP-A) and SP-D have now emerged as novel innate immunity molecules in bacterial sinusitis and allergic fungal sinusitis patients, respectively. CRS and asthma coexist and are interconnected. Therefore, management of CRS and asthma must be jointly carried out as one functional entity. SP-A and SP-D bridge the innate and adaptive immunity mechanisms of the sinonasal epithelium to bring together a well-orchestrated mechanism that effectively fights pathogens. The use of SP-A to ameliorate the innate immune responses in CRS is a new concept and is likely to lead to new horizons in CRS therapeutic regimens. &nbsp.

Revision endoscopic sinus surgery rates by chronic rhinosinusitis subtype.

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. Retrospective review of adult CRS patients undergoing ESS with a single surgeon (2010-2015) was conducted. Outcomes were analyzed by CRS subtypes. 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. 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.

Allergic fungal sinusitis and eosinophilic mucin rhinosinusitis: diagnostic criteria

Chronic sinusitis is one of the most common otolaryngological diagnoses. Allergic fungal sinusitis and eosinophilic mucin rhinosinusitis can easily be misdiagnosed and treated as chronic sinusitis, causing continuing harm. To better identify and characterise these two subgroups of patients, who may suffer from a systemic disease requiring multidisciplinary treatment and prolonged follow up. A retrospective, longitudinal study of all patients diagnosed with allergic fungal sinusitis or eosinophilic mucin rhinosinusitis within one otolaryngology department over a 15-year period. Thirty-four patients were identified, 26 with eosinophilic mucin rhinosinusitis and 8 with allergic fungal sinusitis. Orbital involvement at diagnosis was commoner in allergic fungal sinusitis patients (50 per cent) than eosinophilic mucin rhinosinusitis patients (7.7 per cent; p < 0.05). Asthma was diagnosed in 73 per cent of eosinophilic mucin rhinosinusitis patients and 37 per cent of allergic fungal sinusitis patients. Allergic fungal sinusitis and eosinophilic mucin rhinosinusitis have the same clinical presentation but different clinical courses. The role of fungus and the ability to confirm its presence are still problematic issues, and additional studies are required.

The prevalence of allergic fungal rhinosinusitis in sinonasal polyposis

Allergic fungal sinusitis (AFS) is a noninvasive form of fungal rhinosinusitis with a prevalence of 6-9 % among all rhinosinusitis cases requiring surgery. The fungi causing AFRS have a great diversity and regional variation in the incidence of AFS has been reported worldwide. The aim of this study was to evaluate the prevalence of AFS among rhinosinusitis patients in the north east of Iran. In a prospective cross-sectional study 127 patients with sinonasal polyposis who were candidates for surgery were recruited. All cases were evaluated by sinonasal CT scan, Prick test for common regional allergens, total serum immunoglobulin E (IgE) level, and allergic mucin culture for fungi in suspected cases. Data analyses were done using SPSS version 13.0. Their mean age was 37.4 ± 11.6 years, the male-to-female ratio was 69/58. Eleven patients (9.45 %) met the AFS criteria. Nine cases had a positive culture for Aspergillus specimen and three for Alternaria. Prick test was positive for at least one allergen in 28 cases (22.05 %). The most common allergen was weed. The total IgE level was significantly higher in AFS patients. This study showed the prevalence of AFS among patients with nasal polyposis to be 9.45 %.

Prognostic Factors Associated with Revision Surgery in Allergic Fungal Sinusitis

Objective: 1) Examine the efficacy of FESS combined with aggressive postoperative medical management in the treatment of allergic fungal sinusitis (AFS). 2) Determine prognostic factors associated with disease recurrence and the need for subsequent revision surgery in a population of AFS patients. Method: A retrospective case control study examined demographic and disease-related characteristics and adjuvant therapies in patients undergoing combined surgical and medical treatment of AFS in a single tertiary academic center. Exclusion criteria included follow-up of less than 6 months. The dependent variable was revision surgery. Average follow-up was 29.4 months. Results: Eighty consecutive AFS patients from 2002 to 2009 were identified and 62 patients did not require revision surgery (78%). Conclusion: AFS can be effectively controlled with multimodality therapy. Compliance with postoperative medical therapy and topical steroid use are prognostic factors associated with treatment success, decreasing the rate of revision surgery to 13%. African-American race and prior surgeries are prognostic factors associated with revision surgery, suggesting more aggressive disease.

Imaging of granulomatous and chronic invasive fungal sinusitis: Comparison with allergic fungal sinusitis

Objective To study the radiological features of chronic/granulomatous invasive fungal sinusitis (IFS) and identify differentiating characteristics, if any, from allergic fungal sinusitis (AFS). Study design Prospective radiological study. Setting Tertiary hospital in northern India. Subjects and methods Subjects were nonacute fungal sinusitis patients with orbital involvement presenting between January 1999 and December 2003. Seventeen IFS and 12 AFS patients with mean age 27 years (range 7-59 years) underwent computed tomographic scan (CT) and magnetic resonance imaging (MRI) of paranasal sinuses with contrast. These were operated within one month of doing the scans and had histologically confirmed fungal sinusitis. Outcome measures were characteristics of opacity produced by the diseased tissue on CT and MRI, side and number of sinuses involved, expansion of sinuses, areas of bone erosion, and extra-sinus extension. Results IFS showed homogenous opacity (isodense or hyperdense to muscle tissue) on CT and isointense and hypointense signal on T1- and T2-weighted MR images respectively. IFS showed involvement of one or two sinuses only, homogenous contrast enhancement, lack of expansion of sinuses, and bone erosion localized to the area of extra-sinus extension, and the extra-sinus component of the disease was more than the intra-sinus component. AFS showed heterogenous opacities with hyperattenuation areas on CT, isointense/hypointense to signal void on T1- and T2-weighted MR images. Expansion of sinuses, extensive bone erosion, lack of contrast enhancement, multiple sinus involvement, and major bulk of disease being intra-sinus rather than extra-sinus were other characteristics of AFS. Conclusion Radiological features of IFS are described that are different from AFS.

Nasal Polyp Cell Populations and Fungal-Specific Peripheral Blood Lymphocyte Proliferation in Allergic Fungal Sinusitis

Background Allergic fungal sinusitis (AFS) is considered a different disease from other polypoid chronic rhinosinusitis diseases (CRS) with eosinophilic mucus (EM) termed eosinophilic mucus chronic rhinosinusitis (EMCRS). To substantiate this, studies on cellular responses to fungi and sinus mucosal inflammatory cell populations in AFS and other EMCRS diseases are. required. This study was designed to examine polyp inflammatory cell populations and peripheral blood fungal-specific T-cell responses in AFS, other EMCRS subgroups (defined later), and polypoid CRS without EM. Methods A prospective study was performed. Clinical characteristics, including CRS symptoms, sinus computed tomography (CT) scans, allergy status, intraoperative endoscopy, presence of EM, and fungal culture results were used to define patient groups. Polyps and peripheral blood were examined for populations of eosinophils, lymphocytes (CD4+, CD8+ T cells, natural killer cells, and B cells), and neutrophils using immunohistochemistry, cytospin preparations and flow cytometry. Fungal-specific peripheral blood lymphocyte proliferation was examined in AFS patients, other EMCRS patients, CRS patients, and controls. Results There was no significant difference in the percentage of cell populations and fungal-specific lymphocyte proliferation between AFS and other EMCRS diseases. However, AFS and other EMCRS polyps had a higher percentage of eosinophils and CD8+ T cells whereas CRS polyps had higher CD44 T cells. Fungal-specific lymphocyte proliferation was significantly greater in AFS and other EMCRS patients regardless of fungal allergy, whereas in CRS and controls, higher proliferation was observed in fungal-allergic individuals. Conclusion These findings question the basis for differentiating AFS from, other EMCRS diseases based on fungal allergy and fungi in EM. Fungal-specific cellular response was present in AFS and other EMCRS diseases, different from, that associated with fungal allergy, suggesting a nonallergic fungal immune response. Increased CD8+ T cells in EMCRS polyps signify a different type of inflammation to CRS that may be driven by CD8+ T cells.

Nasal polyp cell populations and fungal-specific peripheral blood lymphocyte proliferation in allergic fungal sinusitis.

Allergic fungal sinusitis (AFS) is considered a different disease from other polypoid chronic rhinosinusitis diseases (CRS) with eosinophilic mucus (EM) termed eosinophilic mucus chronic rhinosinusitis (EMCRS). To substantiate this, studies on cellular responses to fungi and sinus mucosal inflammatory cell populations in AFS and other EMCRS diseases are required. This study was designed to examine polyp inflammatory cell populations and peripheral blood fungal-specific T-cell responses in AFS, other EMCRS subgroups (defined later), and polypoid CRS without EM. A prospective study was performed. Clinical characteristics, including CRS symptoms, sinus computed tomography (CT) scans, allergy status, intraoperative endoscopy, presence of EM, and fungal culture results were used to define patient groups. Polyps and peripheral blood were examined for populations of eosinophils, lymphocytes (CD4+, CD8+ T cells, natural killer cells, and B cells), and neutrophils using immunohistochemistry, cytospin preparations and flow cytometry. Fungal-specific peripheral blood lymphocyte proliferation was examined in AFS patients, other EMCRS patients, CRS patients, and controls. There was no significant difference in the percentage of cell populations and fungal-specific lymphocyte proliferation between AFS and other EMCRS diseases. However, AFS and other EMCRS polyps had a higher percentage of eosinophils and CD8+ T cells whereas CRS polyps had higher CD4+ T cells. Fungal-specific lymphocyte proliferation was significantly greater in AFS and other EMCRS patients regardless of fungal allergy, whereas in CRS and controls, higher proliferation was observed in fungal-allergic individuals. These findings question the basis for differentiating AFS from other EMCRS diseases based on fungal allergy and fungi in EM. Fungal-specific cellular response was present in AFS and other EMCRS diseases, different from that associated with fungal allergy, suggesting a nonallergic fungal immune response. Increased CD8+ T cells in EMCRS polyps signify a different type of inflammation to CRS that may be driven by CD8+ T cells.

Allergic fungal sinusitis: pathophysiology, diagnosis and management

Allergic fungal sinusitis (AFS) is a noninvasive form of fungal rhinosinusitis with an incidence of between 6 and 9% of all rhinosinusitis requiring surgery. Regional variation in incidence has been reported, with the southern and southwestern US particularly endemic. Patients with AFS commonly present with chronic rhinosinusitis with nasal polyps, inhalant atopy, elevated total serum immunoglobulin E (IgE), and sinus-obstructing inspissates of a characteristic extramucosal 'peanut buttery' visco-elastic eosinophil-rich material called 'allergic mucin' that contains sparse numbers of fungal hyphae. Sinus CT is always abnormal, showing findings of chronic rhinosinusitis that often include central areas of increased contrast ('hyperattenuation') within abnormal paranasal sinuses that represent the presence of fungal-containing allergic mucin. AFS has been found to be analogous in several ways to allergic bronchopulmonary aspergillosis (ABPA). Both are chronic inflammatory respiratory tract disorders that are driven by hypersensitivity responses to the presence of small numbers of extramucosal fungi found growing within airway-impacting allergic mucin. AFS allergic mucin typically cultures positive for either dematiaceous fungi such as Bipolaris spicifera or Curvularia lunata, or Aspergillus species such as A. fumigatus, A. flavus or A. niger. As with ABPA, patients have type I immediate hypersensitivity to the etiologic mold in AFS. Further, both AFS and ABPA have been found to have association with specific class II major histocompatibility alleles. Proper diagnosis of AFS and differentiation from the other forms of both noninvasive and invasive fungal rhinosinusitis requires strict adherence to published diagnostic criteria. Medical treatment of AFS has been modeled to an extent after treatment approaches for ABPA that includes the use of postoperative oral corticosteroids and aggressive antiallergic inflammation therapy. The use of follow-up measurements of total serum IgE during treatment of both AFS and ABPA patients can help to monitor disease activity. Future AFS research will lead to further insights into pathogenesis, improved treatments, and ultimately decreases in surgical recurrence rates for this highly recurrent hypertrophic rhinosinusitis disorder.

Microarray analysis of allergic fungal sinusitis and eosinophilic mucin rhinosinusitis

Our goal was to determine and compare the differential gene expression in allergic fungal sinusitis (AFS) and eosinophilic mucin rhinosinusitis (EMRS). We conducted a complementary DNA microarray analysis of prospectively gathered tissue from a tertiary rhinology practice. Compared to normal subjects, 38 genes or potential genes were differentially expressed in AFS patients, while 10 genes were differentially expressed in EMRS patients. Four genes differentially expressed in EMRS were not differentially expressed in AFS: cathepsin B, sialyltransferase 1, GM2 ganglioside activator protein, and S100 calcium binding protein. These genes mediate lysosomal activity and are known to have differential expression in inflammatory and neoplastic states. EMRS and AFS show some similarities in gene expression profiles using microarray analysis. Significant differences in gene expression in both EMRS and AFS patients compared with normal subjects provide early clues to the pathophysiology of EMRS and AFS. This study demonstrates that complementary DNA microarray analysis is a feasible tool for studying different disease subclassifications and is the first to study these subclasses in chronic rhinosinusitis.

Orbital Volumetric Analysis of Allergic Fungal Sinusitis Patients with Proptosis before and after Endoscopic Sinus Surgery

The aim of this study was to examine the changes of orbital volumes in allergic fungal sinusitis (AFS) patients with proptosis who undergo endoscopic sinus surgery. A retrospective study of operative patients with proptosis due to AFS was performed. Normative data were obtained using patients with chronic sinusitis without orbital involvement. Orbital volume measurements were obtained using digitized images and computer software to calculate volumes (cm3) of outlined regions on 1.3-mm axial computed tomography images. Orbital volumes were measured as total volumes and volumes within the bony orbit. Bony orbits were defined using two techniques: (1) the region posterior to a line from ipsilateral zygoma to contralateral zygoma and (2) the region posterior to a line from zygoma to ipsilateral lacrimal bone. Four affected orbits in three AFS patients with proptosis were evaluated. Twenty-eight unaffected orbits in 14 patients were used as normal comparisons. Orbital involvement by AFS resulting in proptosis decreased orbital volumes within the bony orbit to a mean of 70% of normal. After successful endoscopic sinus surgery, bony orbital volumes normalize or approach normal ranges to a mean 90% of normal with resolution of clinically apparent proptosis. Total volumes remained stable before and after surgery. Massive AFS may affect the orbit resulting in proptosis. Spontaneous orbital remodeling with clinical resolution of proptosis and normalization of bony orbital volumes can be seen in AFS patients several months after sinus surgery and aggressive medical treatment. Surgical orbital reconstruction typically is not needed once the sinus disease is adequately addressed.

IgE immunoblot reactivity in allergic fungal sinusitis

P. S. Hutcheson1, M. S. Schubert2, R. G. Slavin1; 1Internal Medicine/Allergy & Immunology, Saint Louis University School of Medicine, St. Louis, MO, 2Allergy Asthma Clinic, Ltd., Phoenix, AZ. RATIONALE: Although patients with allergic fungal sinusitis (AFS) have IgE skin reactivity to the etiologic fungus, the role of IgE in the disease has been questioned. Since the identification of the etiologic fungus is sometimes difficult and serial cultures from some AFS patients may grow several different fungi, we attempted to identify possible crossreacting fungal antigens. METHODS: Ten patients with Bipolaris spicifera AFS were enrolled and IRB-approved consent obtained. IgE immunoblots utilized 25ug protein from 7 fungal extracts: Alternaria alternata, Aspergillus fumigatus, Bipolaris sorokiniana, Bipolaris/Curvularia spicifera, Epicoccum purpurascens, Fusarium moniliforme, and Phoma betae. Nitrocellulose membranes were incubated with patient serum, goat anti-human IgE, bovine alkaline phosphatase conjugated anti-goat IgG, and BCIP/NBT chromogen. RESULTS: Nine out of ten Bipolaris spicifera AFS patients exhibited IgE to all 7 fungi tested. One patient lacked IgE to Aspergillus and Phoma. Positive IgE bands were seen from ~10 kD-160 kD, with Bipolaris/Curvularia producing the most positive bands. No single molecular weight band appeared among the 7 fungi, and not all patients reacted to the same molecular weight antigens. CONCLUSION: All of our Bipolaris spicifera AFS patients showed some degree of IgE cross reactivity to 6 other fungi, although no single molecular weight antigen across all species was seen. The most intense bands were produced from the AFS-causative mold Bipolaris/Curvularia spicifera. A relationship between overall degree of fungal IgE immunogenicity and clinical disease is suggested. Funding: Saint Louis University School of Medicine 214 Study on Dermatophagoides pteronyssinus Allergens Fingerprinting by Two-Dimensional Immunoblotting J. Sun1, H. Zhang1, W. Ying2, X. Qian2; 1Dept. of Allergy, Peking Union Medical College Hospital, Beijing, CHINA, 2Center of Proteiomics, Beijing Radiation Institute, Beijing, CHINA. RATIONALE: To explore Dermatophagoides pteronyssinus (D. pteronyssinus) Allergens finger printing with two-dimensional (2D) electrophoresis and 2D immunoblotting. METHODS: D. pteronyssinus purified mite bodies (PMB) extracts were prepared with Trizol reagent. In protein concentration assay, BCA reagents were used. Mixed sera pool consisted of twelve D. pteronyssinus allergic patients. 2D electrophoresis and 2D immunoblotting were done with D. pteronyssinus. extract and mixed sera pool. RESULTS: Identification of IgE-binding components of D. pteronyssinus (Der p)PMB with MS pool were as follows: Der p 1(pI 5.4, Mr=25.6Kd);Der p 2(pI 7.6-9.0, Mr=15.2Kd);Der p 3(pI 8.1-8.5, Mr=28.5-28.6Kd);Der p 4(pI 6.5-7.0, Mr=61.0-62.0Kd);Der p 5(pI 7.0-7.3, Mr=14.8Kd);Der p 6(pI 5.86.1, Mr=25.5-25.8Kd);Der p 7(pI 6.9-7.1, Mr=26.5Kd);Der p 8(pI 6.8-7.0, Mr=24.9Kd);Der p 9(pI 8.8, Mr=28.1Kd);Der p 10(pI 6.5-6.8, Mr=36.4Kd). Some allergens similar to Le Mao described: C(pI 8.4-8.9, Mr=20Kd);D(pI 7.4-8.5, Mr=37.6-38.6Kd),E(pI 7.0-7.6, Mr=40.5-41.5Kd); F(pI 5.3, Mr=43.8Kd).Der p 14 (pI 6.5-6.9,175-180Kd) was initially showed in 2D immunoblotting in this study. Der p 11 (pI 6.9-7.3, Mr=90-93Kd). Der p 16 (pI 6.98-7.38, Mr=57.0-56.0Kd);Der p 18(pI 7.1-7.5, Mr=69.7-70.7Kd);isoform of Der p 5(9.0, Mr=14.8Kd). CONCLUSIONS: D. pteronyssinus allergens in 2D finger printing could be seen their pI and Mr at the same map. In addition, Der p 14 and other new components immunoblotted showed that more components immunoblotted in D. pteronyssinus could be found if we extract it with Trizol reagent.

Sensitization to recombinant Aspergillus fumigatus allergens in allergic fungal sinusitis

Allergic bronchopulmonary mycosis is primarily caused by Aspergillus fumigatus. Despite similarities, allergic fungal sinusitis (AFS) is thought to be caused by various fungi. Identify fungal elements in AFS allergic mucin and determine the prevalence of specific immunoglobulin (Ig)E to recombinant A. fumigatus allergens (rAsp) in AFS patients. Allergic mucin from 17 definitive and 10 probable AFS patients were histologically examined for fungal elements. Sera from 18 definitive AFS patients, 10 probable AFS patients, 6 chronic sinusitis patients, and 5 A. fumigatus-allergic patients were tested for specific IgE to A. fumigatus and five rAsps. Ten of the 17 definitive cases had hyphae morphologically resembling Aspergillus or Fusarium spp. One probable AFS patient had similar findings. Of definitive patients, 94% (17 of 18) showed A. fumigatus-specific IgE (> or = 0.35 kUa/L), and 67% were positive to one or more rAsp. Four of 10 probable patients demonstrated A. fumigatus-specific IgE, and 2 had IgE to one or more rAsp. The definitive group had greater mean A. fumigatus IgE (P < 0.05) versus the probable and chronic sinusitis groups. The definitive group's rate of IgE to the rAsps was statistically greater. All definitive patients with Aspergillus or Fusarium spp. in situ had A. fumigatus-specific IgE, and 7 of 10 had IgE to at least one rAsp. Most definitive AFS patients have A. fumigatus-specific IgE and many have specific IgE to rAsps. Many also demonstrate Aspergillus spp. or Fusarium spp. in situ. Findings suggests that A. fumigatus is an important causative agent in AFS in the southeast United States.

Allergic fungal sinusitis

Allergic fungal sinusitis (AFS) is considered an allergic inflammation against fungus, and has been reported to be refractory, with very high recurrence. In Europe and the United States, AFS incidence is reported from 4% to 7% in patients with chronic sinusitis undergoing endoscopic sinus surgery (ESS). In Japan, however, only 5 patients, including ours have been reported, making AFS very rare in Japan. We prospectively studied the incidence, pathogenesis and diagnosis of AFS in Japan among 102 patients with chronic sinusitis who underwent ESS. Four cases (3.9%) were diagnosed with AFS based on the criteria of Bent and Kuhn. This incidence is slightly lower than that reported in Europe and the United States. We report the diagnosis, treatment, and course in 4 AFS patients. Of these, an allergen provocation test against detected fungus was conducted in 2 from whom informed consent was obtained. In the immediate phase, positive reactions were observed. Immunoglobulin E (IgE) antibody-mediated type I allergy may be involved in the pathogenesis of AFS.

A pilot study of aspirin treatment of patients with rhinosinusitis-asthma following negative aspirin challenge

VOLUME 109, NUMBER 1 BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) and allergic fungal sinusitis (AFS) share similar characteristics including atopy, elevated serum IgE, positive skin test to the offending fungus, and allergic mucin containing fungal elements, eosinophils, and Charcot-Leyden crystals. We have previously identified risk factor HLA-DR markers in patients with ABPA (-DR 2 and 5, and 7 to a lesser extent) and found those same HLA types in 3 out of 4 aspergillus AFS (A-AFS) patients. However, HLA-DQ2, a protective marker in aspergillus sensitive nonABPA patients, was also present in 3 out of 4 A-AFS patients indicating that -DQ2 plays a different role in A-AFS than ABPA. OBJECTIVE: The purpose of this study was to extend our previous observations on the role of HLA-D in the pathogenesis of AFS. Because AAFS is relatively rare, patients with bipolaris AFS (B-AFS), a much more common condition, were recruited. Thirty patients who met strict criteria for B-AFS were enrolled in this IRB approved study. Three chronic hypertrophic sinusitis (CHS) patients were also enrolled as controls. The mucin from these nasal polyposis patients lacked evidence of fungal involvement (absence of fungi on both culture and histopathology). HLA-DR and -DQ frequencies were determined by low resolution DNA typing. RESULTS: Fifteen out of 30 patients (50%) were -DR4 + and 9 out of 30 were DR5 +. These are both more than twice the general population frequency of 24.2% and 14%, respectively. HLA-DQ3, commonly associated with -DR4 and -DR5, was present in 67% of these patients; its frequency in the general population is 21.7%. HLA-DR2 was present in 16.7% and -DQ2 in 43.3%. Two out of the three CHS patients were -DR4 +; the other was -DR2 and -DR5 +. Only two were -DQ typed and they were both -DQ3. CONCLUSION: It thus appears that in B-AFS and CHS, there is a three times greater frequency of HLA-DQ3 than in the general population which strongly suggests an important role for selective HLA class II haplotypes in the development of hypertrophic sinus disease. It is also accompanied by an increase in -DR4 and -DR5 frequencies over that seen in the general population. HLA-DQ3 was not seen in any A-AFS patient, nor was -DR4. Differences in HLA class lI phenotypes between A-AFS and B-AFS/CHS patients may represent differing aspects of HLA class II molecule biology

Eosinophilic Mucin Rhinosinusitis: A Distinct Clinicopathological Entity

Allergic fungal sinusitis (AFS) was recognized in 1981. Since 1983, a form of sinusitis histologically similar to AFS except for the absence of fungal hyphae has also been noted. The designation "eosinophilic mucin rhinosinusitis (EMRS)" is proposed. Its relationship to AFS is controversial and problematic. To determine whether distinctive clinical and immunological differences exist to differentiate the histological entity of EMRS from AFS. Literature review and comparison of cases of AFS (n = 418) to EMRS (n = 40) from the literature, as well as cases of AFS (n = 13) and EMRS (n = 29) accrued in the present study. A total of 431 AFS patients were compared with 69 EMRS patients. The mean age of patients with AFS was significantly younger than patients with EMRS (30.7 y compared with 48.0 y, respectively; P < .001). Male-to-female ratios were 1.03:1 and 1.26:1 for AFS and EMRS, respectively, and were not significantly different. Forty-one percent of patients with AFS were asthmatic compared with 93% of patients with EMRS (P < .0001). Thirteen percent of patients with AFS were aspirin sensitive compared with 54% of patients with EMRS (P < .0001). Polyp occurrence was almost 100% in both groups. Eighty-four percent of patients with AFS had allergic rhinitis (AR), while only 63% of patients with EMRS had AR (P = .004). Fifty-five percent of AFS patients had bilateral disease, in contrast to the 100% of EMRS patients with bilateral disease (P < .0001). Although average total immunoglobulin E (IgE) was elevated in both groups, it was significantly more elevated in AFS patients (range, 12-13,084 mg/ dL; mean, 1,941 mg/dL) compared with EMRS patients (range, 14-1,162 mg/dL; mean, 267 mg/dL; P < .001). Total immunoglobulin G (IgG) and IgG subclasses were seldom reported in the cases available from the literature of either AFS or EMRS. However, in the present series of EMRS, IgG1 deficiency occurred in 50% of evaluated patients (mean, 475 +/- 175 mg/dL; range, 250-869 mg/dL; normal, 422 to 1,200 mg/dL) but in no cases of AFS reported in the literature. Significant clinical and immunological differences exist to distinguish AFS from EMRS. It is postulated that AFS is an allergic response to fungi in predisposed individuals, while EMRS occurs because of a systemic dysregulation of immunological controls. Because EMRS is a systemic disease, unilateral disease is not seen. In contrast, AFS, an allergic response to fungi, may occur unilaterally or bilaterally depending on the antigenic stimulation. EMRS also has a significantly higher association with asthma, an increased incidence of aspirin sensitivity, and an increased incidence of IgG1 deficiency. Therapy with a systemic steroid, a potent and indiscriminant anti-inflammatory agent, is a useful adjunct in both disorders. Fungal immunotherapy following surgical extirpation of AFS is useful in preventing AFS recurrence. It is predicted that fungal immunotherapy and antifungal agents will be ineffective in patients with EMRS. It is important to differentiate these two similar histopathological entities in future trials assessing therapeutic efficacy. Inclusion of both entities in a study could obscure recognition of the true effectiveness of intervention, because of the possible variable response differences between the two entities. This study shows that significant clinical and immunological differences exist between EMRS and AFS. The future awaits an exploration of the pathophysiological basis of these differences.

The Diagnosis and Incidence of Allergic Fungal Sinusitis

To reevaluate the current criteria for diagnosing allergic fungal sinusitis (AFS) and determine the incidence of AFS in patients with chronic rhinosinusitis (CRS). This prospective study evaluated the incidence of AFS in 210 consecutive patients with CRS with or without polyposis, of whom 101 were treated surgically. Collecting and culturing fungi from nasal mucus require special handling, and novel methods are described. Surgical specimen handling emphasizes histologic examination to visualize fungi and eosinophils in the mucin. The value of allergy testing in the diagnosis of AFS is examined. Fungal cultures of nasal secretions were positive in 202 (96%) of 210 consecutive CRS patients. Allergic mucin was found in 97 (96%) of 101 consecutive surgical cases of CRS. Allergic fungal sinusitis was diagnosed in 94 (93%) of 101 consecutive surgical cases with CRS, based on histopathologic findings and culture results. Immunoglobulin E-mediated hypersensitivity to fungal allergens was not evident in the majority of AFS patients. The data presented indicate that the diagnostic criteria for AFS are present in the majority of patients with CRS with or without polyposis. Since the presence of eosinophils in the allergic mucin, and not a type I hypersensitivity, is likely the common denominator in the pathophysiology of AFS, we propose a change in terminology from AFS to eosinophilic fungal rhinosinusitis.