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This case report describes patient in their 40s with a medical history of sleep apnea and diabetes and no history of immunosuppression who presented with left-sided nasal obstruction for 1 year and was found to have an Epstein-Barr virus­positive plasmacytoma.

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Biologic agents, monoclonal antibodies that target highly-specific molecular pathways of inflammation, are becoming integrated into care pathways for multiple disorders that are relevant in otolaryngology and allergy. These conditions share common inflammatory mechanisms of so-called Type 2 inflammation with dysregulation of immunoglobulin E production and eosinophil and mast cell degranulation leading to tissue damage. Biologic agents are now available for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, eosinophilic granulomatosis with polyangiitis (EGPA), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU). This paper summarizes the diagnosis and management of these conditions and critically reviews the clinical trial data that has led to regulatory approval of biologic agents for these conditions.

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BACKGROUND: Multimodal perioperative analgesia including acetaminophen is recommended by current guidelines. The comparative efficacy of intravenous vs oral acetaminophen in sinus surgery is unknown. We aimed to determine whether intravenous or oral acetaminophen results in superior postoperative analgesia following sinus surgery. METHODS: This was a prospective randomized trial with blinded endpoint assessments conducted at a single large academic medical center. Subjects undergoing functional endoscopic sinus surgery were randomized to intravenous vs oral acetaminophen in addition to standard anesthetic and surgical care. The primary outcome was visual analogue scale pain score at 1 hour postoperatively. RESULTS: One hundred and ten adult patients were randomized; 9 were excluded from the data analysis. Fifty patients were assigned to intravenous acetaminophen and 51 to oral acetaminophen. Postoperative pain scores at 1 hour (primary endpoint) were not significantly different between the intravenous and oral acetaminophen groups. Similarly, there was no significant difference in pain scores at 24 hours postoperatively. Finally, there was no significant difference in postoperative opioid usage in the postanesthesia care unit or over the first 24 hours postoperatively. CONCLUSIONS: This is the first comparative efficacy trial of oral vs intravenous acetaminophen in sinus surgery. There was no significant difference in pain scores at 1 or 24 hours postoperatively, and no difference in postoperative opioid use. Intravenous acetaminophen offers no apparent advantage over oral acetaminophen in patients undergoing sinus surgery. LEVEL OF EVIDENCE: 1b.

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Objective Epistaxis is a primary complaint in 90% to 96% of patients with hereditary hemorrhagic telangiectasia (HHT). Numerous surgical and medical treatments aim to decrease the frequency and severity of epistaxis in this patient population. Bevacizumab is a recombinant, humanized monoclonal antibody to vascular endothelial growth factor, an angiogenic factor elevated in HHT. It has been used in several forms to treat epistaxis in HHT but thus far, evidence-based recommendations are limited. Study Design Systematic review with evidence-based recommendations. Methods A systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed using Embase, MEDLINE, MEDLINE In-Process/Epub, and Cochrane databases. English language abstracts were reviewed for relevance. Results Eleven manuscripts met inclusion criteria and were analyzed. Submucosal injection, submucosal injection plus laser coagulation, intravenous (IV), and topical formulations of bevacizumab were evaluated for their therapeutic impact on epistaxis in patients with HHT. Three randomized controlled trials failed to show topical bevacizumab to be more effective in controlling epistaxis than saline or other moisturizers. Conclusions The use of submucosal and IV bevacizumab shows promise, but further study is necessary to determine the true efficacy in the treatment of epistaxis as only grade C level exists currently. Based on the available literature, the use of topical bevacizumab is not recommended (grade B).

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BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant hereditary disorder resulting in vascular dysplasia and formation of arteriovenous malformations. Recurrent epistaxis is a hallmark of the disease. An array of medical therapies are used in this patient population, but robust evidence-based recommendations regarding the medical treatment of epistaxis are lacking. This systematic review was performed to look at the current literature and make meaningful evidence-based recommendations. METHODS: A search of the Ovid MEDLINE, Embase, and Cochrane databases was conducted by a research librarian. Abstracts in the English language and published in a peer-review journal were reviewed for relevance and inclusion. PRISMA guidelines were followed. RESULTS: Eighteen studies met the inclusion criteria. In a few small studies, thalidomide was shown to consistently improve severity and frequency of epistaxis and improve hemoglobin concentrations while decreasing the need for transfusion. Tranexamic acid appeared to only impact the epistaxis severity score and not other clinical outcomes. Selective estrogen modulators (SERMs), propranolol, rose geranium oil, and N-acetylcysteine, have demonstrated promising efficacy in small trials. CONCLUSION: Appropriate medical therapies for epistaxis outcomes in HHT remain undefined, and there is no "gold standard." Many of the studies are small and the data reported are heterogeneous, and therefore the ability to make strong evidence-based recommendations is limited. However, many different medications appear to be promising options.

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BACKGROUND: The relationship between allergic sensitization and radiographic sinus inflammation remains unclear. OBJECTIVES: To determine whether specific allergen sensitization is correlated with sinonasal radiographic opacification. METHODS: Patients with chronic sinonasal symptoms were selected and included if they had allergy testing and a computed tomography (CT) of the paranasal sinuses. Data regarding demographic characteristics, in vitro allergy test results, and comorbidities were collected. CTs were reviewed, and an overall Lund-Mackay score (LMS) was calculated for each patient. A two-sample t-test was used to compare mean LMS between patients who were sensitized and patients who were not sensitized. A multiple linear regression model was used to determine whether a relationship existed among LMS and allergy results, asthma, nasal polyps, immunoglobulin E (IgE) level, medication usage, in-season versus out-of-season CTs, age, and sex. Significance was determined at an alpha level of 0.05. RESULTS: There were 437 patients included, of whom, 251 had positive specific allergen test results and 186 had negative test results. A total of 282 patients had allergic rhinitis symptoms without a documented diagnosis of sinusitis, and 155 carried a diagnosis of chronic rhinosinusitis. The mean LMS did not differ between patients who were sensitized and patients who were not sensitized (5.56 versus 5.28; p = 0.61). Linear regression demonstrated an increase in LMS in patients with asthma (p = 0.02), male sex (p < 0.01), elevated IgE (p < 0.01), a history of anaphylaxis (p = 0.03), and nasal polyps (p < 0.01). There was a statistically significant decrease in LMS in patients with an in-season CT (p = 0.02). CONCLUSIONS: Patients with a positive specific in vitro allergen test result did not have higher overall rates of radiographic sinus inflammation. Asthma, male sex, polyps, elevated IgE, and a history of anaphylaxis were associated with higher LMS.

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BACKGROUND: The purpose of this study was to determine if total serum immunoglobulin E (IgE) could predict monosensitization compared to polysensitization in patients with allergic rhinitis (AR). METHODS: This was a retrospective study of a cohort of 1073 patients who underwent allergy testing. Differences in total IgE level between unsensitized, monosensitized, and polysensitized subjects were calculated. Pearson correlation coefficient was calculated to determine whether there was a relationship between total IgE level and the number of positive allergen sensitizations. In addition, allergen sensitization class was calculated for each allergen sensitization and totaled for each patient. Pearson correlation coefficient was calculated to determine the relationship between total IgE level and weighted allergen sensitization by class. RESULTS: There were 159 patients who were monosensitized compared to 492 patients who were polysensitized. Of the monosensitized patients, almost 50% (74) were sensitized to one or both dust mites. Total IgE was higher in polysensitized patients compared to monosensitized compared to controls (p < 0.001). Pearson correlation coefficient between total IgE and number of positive allergen sensitizations was 0.465 (p ≤ 0.001). Pearson correlation coefficient between total IgE and allergen class-weighted sensitizations was 0.529 (p ≤ 0.001). CONCLUSION: IgE level can be used to predict monosensitization vs polysensitization. There is a moderate correlation between total IgE sensitization and the number of positive allergen sensitizations, as well as allergen class-weighted sensitizations.

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OBJECTIVE: To examine the effect of final exam stress on the concentrations of leukotriene B4 (LTB4) and vascular endothelial growth factor (VEGF) in the upper airways among healthy and asthmatic individuals. METHOD: Nasal samples were collected from 12 individuals with asthma and 23 healthy controls early and late in a final exam period, and during a low-stress period in the semester. We determined LTB4 and VEGF concentrations using Enzyme-Linked Immunoassays. RESULTS: Mixed effects analysis of variance models showed that asthmatic participants with allergies in contrast to healthy individuals experienced a decrease in nasal LTB4 during the final exam period as compared to mid-semester (low stress period). There were no significant changes in nasal VEGF across the observation period. Changes in nasal LTB4 and VEGF were not associated with salivary cortisol, exhaled nitric oxide, or spirometric lung function. CONCLUSIONS: Our results suggest that nasal LTB4 concentrations change in periods of psychological stress for asthmatic individuals with allergies.

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Allergic fungal sinusitis (AFS) or rhinosinusitis (AFRS) is a form of polypoid chronic rhinosinusitis that is believed to be due to hypersensitivity to fungal antigens. The disease is characterized by type 1 hypersensitivity to fungal allergens, dramatically elevated total serum IgE, accumulation of thick eosinophil-laden mucin with non-invasive fungal hyphae within the paranasal sinuses, nasal polyposis, and sinus bony remodeling. Because of many clinicopathologic similarities to allergic bronchopulmonary aspergillosis (ABPA), these conditions can be considered analogous examples of disease in the unified airway. However, these conditions rarely occur together and their treatment differs. The treatment of AFRS relies upon surgical removal of fungal hyphae in eosinophilic mucin, while antifungal therapy is used to clear fungi from the airways in ABPA. Several uncontrolled studies suggest there may be some benefit to antifungal agents in AFRS, but randomized trials of topical and systemic antifungal therapies have not shown beneficial results in chronic rhinosinusitis (CRS). Antifungal treatment within the sinonasal cavities does not appear to be an effective approach for most chronic sinusitis, and antifungal therapy for AFRS is unproven.

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BACKGROUND: Primary immunodeficiency is rare but should be considered in patients who present to the otolaryngologist with recurrent, severe, or treatment refractory infections. METHODS: Recent literature and consensus statements on immunodeficiency were reviewed for clinically important information of relevance to otolaryngologists. RESULTS: The most common and most relevant immunodeficiencies are humoral deficiencies with inadequate antibody production or an impairment in the production of specific antibody after antigen exposure. For otolaryngologists the most important immunodeficiencies include immunoglobulin A (IgA) deficiency, common variable immunodeficiency (CVID), and specific antibody deficiency. Simple screening tests can be used by the otolaryngologist to exclude the most common immunodeficiencies. The general treatment approach to patients with these immunodeficiencies includes airway hygiene, early and aggressive treatment of infections, immunization, and antibody replacement therapy. CONCLUSION: By virtue of their scope of practice, otolaryngologists are in a position to recognize and initiate the diagnostic workup of patients with immunodeficiency. Patients with a diagnosed primary immunodeficiency are best managed in a multidisciplinary manner with close cooperation among the otolaryngologist, immunologist, and other specialists that are involved in treating these multisystem diseases.

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BACKGROUND: Clinical practices for the diagnosis and treatment of allergic disease evolve over time in response to a variety of forces. The techniques used by various physician specialties are not clearly defined and may vary from published descriptions or recommendations in the literature. METHODS: This work is a Web-based survey enrolling 250 U.S. physicians in the following specialties: otolaryngology (ENT), allergy-immunology (A/I), and primary care (PCP). RESULTS: Respondents reported that skin-prick testing is the most common diagnostic testing method, followed by in vitro specific immunoglobulin E (IgE) testing. ENTs were more likely to use intradermal testing compared to other specialties (p = 0.0003 vs A/I; p < 0.0001 vs PCP). Respondents reported a wide distribution in number of allergens tested, regardless of testing method (range, 11 to >60). Significant use of home immunotherapy injections (defined as >10% of immunotherapy patients) ranged from 27% to 36% of physicians, with no statistically significant difference noted based upon specialty. PCPs reported greater use of sublingual immunotherapy (PCP, 68%; A/I, 45%; otolaryngology, 35%; A/I vs PCP, p = 0.005; ENT vs PCP p < 0.001)). CONCLUSION: A variety of allergy testing and treatment methods are employed by U.S. physicians, with some differences noted based upon specialty. Home immunotherapy continues to be employed in allergy practices, and sublingual immunotherapy is a common form of delivery, especially in primary care practices.

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Asthma is a heterogeneous syndrome of cough, wheeze, dyspnea, and chest tightness. However, in a subset of patients, these symptoms may indicate a different underlying disease process with variable responsiveness to classic asthma therapies. Disease may progress while practitioners attempt conventional asthma therapy. Additionally, some types of asthma may require alternative approaches to relieve symptoms successfully. This article describes the differential diagnosis of asthma and discusses some of the more common asthma variants and asthma mimickers.

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BACKGROUND: Sarcoidosis is a chronic disease process characterized by non-caseating granulomatous inflammation, usually involving the lower respiratory tract. Given the rarity of rhinologic involvement, the objectives of the present study were (1) to describe clinical features, and (2) to review outcomes of rhinologic surgery for sinonasal sarcoidosis. METHODS: Retrospective analysis was performed of patients evaluated at a tertiary care referral center between January 2006 and July 2011. RESULTS: The mean age of the 38 patients with sinonasal sarcoidosis was 52 years, with a female:male ratio of 2.8:1. The most common presenting symptoms included nasal obstruction (65.8%), crusting (29.9%), and epistaxis (18.4%). Most frequent endoscopic findings included crusting (55.3%), mucosal thickening (44.7%), and subcutaneous nodules (21%). Computed tomography (CT) imaging demonstrated turbinate or septal nodularity (21%), osteoneogenesis (15.8%), and bone erosion (10.5%). Medical management was typically comprised of saline irrigations (73.3%), topical nasal steroids (68.4%), and oral steroids (63.2%). Refractory sinus symptoms required sinonasal surgery in 4 cases. Overall subjective symptom improvement was noted in 39.5% at mean follow-up of 16.2 months. CONCLUSION: Sinonasal involvement was noted in approximately 30% of patients with known sarcoidosis evaluated in the otolaryngology clinic. Patients typically present with nasal obstruction and endoscopic evidence of crusting and mucosal thickening. Medical therapy with irrigations and topical/oral steroids suffices in majority of patients, with surgery for refractory symptoms being required in a small subset of cases.

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BACKGROUND: The purpose of this work was to perform a systematic review regarding ossifying fibroma and its multiple variants of the paranasal sinuses, and to identify any clinical differences between the multiple variants. METHODS: A search of the U.S. National Library of Medicine (PubMed) database was performed for the non­Medical Subject Heading (MeSH) search term "ossifying fibroma." The bibliographies of the retrieved manuscripts were searched to identify additional potentially relevant articles. Finally, textbooks of head and neck pathology were searched to identify peer-reviewed literature that addresses the histopathology of ossifying fibroma and its variants. Abstracts were screened by 2 of the authors to identify reports of ossifying fibroma lesions (and its variants) that involved the paranasal sinuses. Extracted data from case reports or case series included the clinical presentation, age, gender, site of involvement, surgical approach, treatment outcome, follow-up period, and recurrence rate. Information derived from cases is summarized in tables, and simple descriptive statistics were applied to the data. RESULTS: A total of 137 distinct patients were identified in 103 reports. Extracted data did not show any appreciable difference in clinical presentation or outcomes. Data on recurrence of these lesions was often limited by a lack of follow-up. CONCLUSION: Although differentiation between the subtypes of ossifying fibroma can be made histologically, and a diverse nomenclature exists, there does not appear to be any overriding clinical significance to the histopathologic differentiation of OF variants.

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BACKGROUND: The purpose of this work was to describe a clinical and radiographic pattern of findings that helps localize the site of spontaneous cerebrospinal fluid (CSF) leaks. METHODS: This study was a retrospective review of CSF leaks treated at the University of Texas Southwestern Medical Center from 2000 to 2009. Data collected included demographics, nature of presentation, imaging findings, intraoperative location of skull-base defect, and clinical follow-up. RESULTS: Forty-six patients' charts were reviewed. Among these patients, 15 did not show a bony skull-base defect on high-resolution computed tomography (CT) scan. They did, however, each show a small area of opacification in the olfactory cleft. In each case, this area of opacification correlated with the site of the CSF leak. Intrathecal fluorescein was not used, except in 2 instances. Successful repair was noted in all patients on follow-up, without evidence of recurrence at the repair site. CONCLUSION: In the absence of a clearly identifiable bony skull-base defect, opacification of the olfactory cleft is a localizing sign in some cases of spontaneous CSF rhinorrhea. Such a finding should direct endoscopic repair, and may serve as the only marker for the specific leak site.

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The "Cochrane Corner" is a quarterly section in the Journal that highlights systematic reviews relevant to otolaryngology-head and neck surgery, with invited commentary to aid clinical decision making. This installment features a Cochrane Review, titled "Topical Steroid for Chronic Rhinosinusitis without Polyps," that finds good evidence to support therapeutic benefits with no increase in adverse events compared with placebo controls.

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BACKGROUND: The objective of this study was to prospectively evaluate the clinical impact of intraoperative computed tomography (CT) imaging on endoscopic sinonasal and skull base procedures. METHODS: A total of 49 patients were enrolled after informed consent from December 2009 to May 2010. Patients underwent intraoperative volume CT imaging (xCAT, Xoran Technologies, Ann Arbor, MI) at the conclusion of their proposed surgery. RESULTS: The mean age was 48.6 years with male:female ratio of 1.3:1. Surgical procedures included revision or primary endoscopic sinonasal surgery (ESS) (36), endoscopic benign or malignant tumor resection (10), endoscopic mucocele drainage (2), and endoscopic tumor biopsy (1). The mean Lund-Mackay (L-M) score was 10.6 (range 1-21). The indications for intraoperative imaging included extent of paranasal sinus dissection in 38 (77.6%), extent of tumor resection in 11 (22.4%), adequacy of mucocele drainage in 3 (6.1%), and frontal stent position in 2 (4.1%) cases. Average acquisition time was 5.3 minutes. The CT acquisition quality was deemed excellent in 24 (49.0%), good in 15 (30.6%), fair in 5 (10.2%), and unattainable in 5 (10.2%) cases. Additional interventions were performed in 8 of 44 cases (18%) based on the intraoperative CT dataset. Analysis of predictive factors for additional intervention, including presence of polyps, presence of tumor, previous surgery, use of image guidance, and CT quality did not reach statistical significance. CONCLUSION: Intraoperative CT scanning may hold important utility in selected endoscopic sinonasal and skull base procedures with additional interventions being performed in 18% of cases. The present study was unable to identify specific factors that would preoperatively predict the need for intraoperative imaging. Future clinical trials should include a multi-institutional design to better delineate these important variables.

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Allergic fungal rhinosinusitis is a phenotype of chronic rhinosinusitis with nasal polyposis, characterized by type 1 hypersensitivity to fungi, eosinophilic mucin with fungal hyphae in sinus secretions, and propensity for mucocele formation and bone erosion. Although its differentiation from other forms of chronic polypoid rhinosinusitis with eosinophilic mucin is sometimes problematic, type 1 hypersensitivity is a component of the disease process. Medical and surgical management can be augmented by immunotherapy directed toward the patient's specific allergen sensitivities. The primary rationale for immunotherapy is to control the allergic diathesis that may be contributing to the patient's chronic sinus inflammation.

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