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1.  Gene expression profiles in chronic idiopathic (spontaneous) urticaria 
Allergy & Rhinology  2015;6(2):e101-e110.
The pathophysiology of chronic idiopathic (spontaneous) urticaria (CIU) is poorly understood.
We hypothesized that a study of gene expression in active lesions from patients with CIU would uncover unexpected associations.
We enrolled eight patients with CIU and six healthy controls, and obtained 4 mm punch biopsy specimens of active lesions and unaffected skin of patients with CIU and of skin from normal controls. Routine histologic evaluation was performed, RNA was isolated, and gene expression data were assessed. Due to technical reasons, the final evaluation included six samples of lesional skin, six samples of nonlesional skin, and five samples of normal skin.
As expected, lesional skin had more inflammatory cells per high-powered field (mean ± SE, 96 ± 6) than did samples from nonlesional skin of the subjects with CIU (17 ± 2) (p < 0.01). Lesions of CIU showed significant upregulation of 506 genes and reduced expression of 51 genes. Those most upregulated were predominantly involved in cell adhesion (e.g., selectin E [SELE]), cell activation (e.g., CD69), and chemotaxis (e.g., CCL2). Twelve independent canonical pathways with p ≤ 0.001 were identified (including intracellular kinase pathways (RAs-related nuclear protein [RAN] and Janus activated kinase/interferon), cytokine signaling pathways (IL-9, IL10, and IFN), a strong inflammatory response (interferon, IL-9, IL-10, inducible nitric oxide synthase and glucocorticoid pathways) and increased cell proliferation (RAN signaling, cell cycle control, and tRNA charging).
This preliminary study describes a method to study gene activation in urticarial lesions and demonstrated a strong inflammatory response with a large variety of activated genes that are distinct from those reported with other dermatologic conditions.
PMCID: PMC4541630  PMID: 26302730
Chronic urticaria; gene expression; kinase; interferon
2.  Association of IL13R alpha 1 +1398A/G polymorphism in a North Indian population with asthma: A case-control study 
Allergy & Rhinology  2015;6(2):e111-e117.
Interleukin 13 (IL13) is directly involved in the secretion of total serum immunoglobulin E (IgE), which plays a major role in the asthma pathogenesis.
One of the polymorphic receptor of IL13 is IL13Rα1, which after binding to IL13, initiates signal transduction that results in mucin secretion, airway hyperreactivity, fibrosis, and chitinase up-regulation, which increases asthma risk.
In the present study, the role of IL13Rα1 +1398A/G gene polymorphisms in asthma was detected with a total of 964 individuals, including 483 healthy controls and 481 asthma patients from a North Indian population using polymerase chain reaction-restriction fragment length polymorphism method.
Statistical analysis revealed that the mutant allele (G) is predominant in asthma patients (42.7%) than the controls (38.2%), which shows an increased risk toward asthma with odds ratio = 1.21, 95% confidence interval (1.00–1.45), χ2 = 4.10 and p = 0.043. Furthermore, the phenotypic characteristics also reveal a significant association with the disease (p < 0.05).
This is the first study conducted in India and +1398A/G polymorphism in noncoding region of IL13Rα1 confer risk toward asthma in the studied population.
PMCID: PMC4541631  PMID: 26302731
Asthma; interleukin 13Rα1; North India; polymorphism; total immunoglobulin E
3.  Bioabsorbable steroid-releasing sinus implants in the frontal and maxillary sinuses: 2-year follow-up 
Allergy & Rhinology  2015;6(2):e118-e121.
Mometasone furoate-releasing implants have been approved for use in the ethmoid sinuses following endoscopic sinus surgery (ESS) to reduce the need for medical and surgical intervention postoperatively. Outcomes have not yet been studied when these implants are utilized in other paranasal sinuses after ESS.
To present a case in which bioabsorbable steroid-eluting implants were used to maintain patency and to decrease inflammation in the frontal and maxillary sinuses after revision ESS.
52-year-old male with lifelong allergic rhinitis, chronic allergic fungal rhinosinusitis, and inflammatory bowel disease had previously undergone four endoscopic sinus surgeries, subcutaneous injection immunotherapy, and topical therapy with budesonide and amphotericin sinus irrigations. In July, 2012, during revision left frontal sinusotomy and right maxillary antrostomy (the fifth ESS), two bioabsorbable steroid-releasing implants were placed in the left frontal recess and the right maxillary sinus respectively and followed clinically, endoscopically, and radiographically for two years.
Two year followup demonstrated near complete clinical, endoscopic, and radiographic resolution of the patient's signs and symptoms of chronic rhinosinusitis.
The steroid-releasing implants during the critical phase of wound-healing appear to have allowed the patient, now over two years postoperatively, to achieve a healthier state and to allow more successful management than the preceding 15–20 years.
PMCID: PMC4541632  PMID: 26302732
Chronic rhinosinusitis; steroid-releasing implant; nasal polyposis
4.  Nasal septal perforation associated with pyoderma gangrenosum 
Allergy & Rhinology  2015;6(2):e122-e124.
Pyoderma gangrenosum (PG) is a skin condition characterized by necrotic ulcers and most commonly occurs on the legs in association with inflammatory bowel disease and rheumatoid arthritis; however, PG rarely involves the head and neck, and very rarely causes nasal septal perforation.
Here, we describe a case report of PG causing nasal septal perforation in a 71-year-old male with truncal lesions in the absence of either inflammatory bowel disease or autoimmune arthritis.
Case report with histologic description.
Histology from nasal mucosal biopsies showed chronic inflammation and reactive change without evidence of malignancy. Together with serologic and nonserologic testing, as well as clinical evaluation, we were able to rule out other causes of septal perforation including Wegener's granulomatosis, lymphoma, and vasculitis, and concluded that the cause of nasal septal perforation was most likely PG.
Septal perforation etiology should include a complete history and physical to evaluate for systemic etiologies, including rare ones such as PG.
PMCID: PMC4541633  PMID: 26302733
Chronic inflammation; chronic rhinitis; diagnosis of exclusion; leukocytic infiltration; pyoderma gangrenosum; septal perforation; skin ulceration
5.  Successful endoscopic endonasal repair of nasal meningoencephalocele in a 21-day-old neonate 
Allergy & Rhinology  2015;6(2):e125-e128.
Indications of surgical intervention in congenital nasal meningoencephaloceles includes presence of cerebro spinal fluid rhinorrhea having a risk of causing meningitis, episodes of prior meningitis and bilateral nasal obstruction causing respiratory difficulty in these obligate nasal breathers. Many authors would like to wait till the patient attains the age of 2 to 3 years for repair of the defect due to surgical feasibility. However, early intervention prevents further episodes of meningitis in the future. We present the youngest patient of nasal meningoencephalocele successfully repaired via endoscopic approach.
Case Report:
A 21 days old neonate was referred to us with a nasal meningoencephalocele with active cerebrospinal fluid rhinorrhoea. Radiological investigation showed a cribriform plate defect on the right side. Repair was done by endoscopic route by multi-layered closure of the defect which was augmented with a mucoperichondrial flap from the septum. Patient was asymptomatic in the post-operative follow up period and did not have any episode of meningitis till date.
Early repair by transnasal endoscopic route is a feasible surgical option for congenital anterior skull base defects with meningoencephaloceles to prevent further episodes of meningitis. This is feasible even in the neonatal period due to improved technique and instrumentation now available for endoscopic nasal surgeries.
PMCID: PMC4541634  PMID: 26302734
Neonatal meningoencephalocele; endoscopic repair; single-layered repair; CSF leak
6.  Ethmoid pneumocele presenting with exophthalmos 15 years after endoscopic sinus surgery 
Allergy & Rhinology  2015;6(2):e129-e132.
A pneumocele is an abnormal dilation of an air-containing sinus beyond the normal margins of bone, with associated bony thinning. A delayed ethmoid pneumocele after sinus surgery has not previously been reported.
A case report of a patient with a delayed ethmoid pneumocele after sinus surgery. The diagnostic workup, operative approach, and postoperative results were evaluated.
A 57-year-old female with a history of endoscopic sinus surgery 15 years prior presented with right eye proptosis and severe orbital and facial pressure. A maxillofacial computed tomography showed a markedly expanded air-filled right anterior ethmoid space with a dehiscent lamina papyracea, consistent with a pneumocele. Marsupialization of the pneumocele as well as a revision ethmoidectomy were performed, with a visible return of the orbital contents to a more natural position. The patient experienced worsened diplopia immediately postoperatively that resolved within two weeks.
This case demonstrates that a pneumocele can present even years after endoscopic sinus surgery, and acute but temporary development or worsening of diplopia can result from surgical decompression of the pneumocele as the eye returns to its natural position.
PMCID: PMC4541635  PMID: 26302735
Exophthalmos; pneumocele; sinus surgery
7.  Nasal epithelial myoepithelial carcinoma: An unusual cause of epiphora, a case report and review of the literature 
Allergy & Rhinology  2015;6(2):e133-e137.
Epithelial myoepithelial carcinoma (EMC) of the nasal cavity is a rare tumor, and here we describe the first case of EMC of the nasal cavity presenting with epiphora. A case presentation and review of the literature is provided.
A case report is described of a 63-year-old man who presented with unilateral epiphora and was found via a thorough history and physical examination to have a nasal tumor. The physical examination consisted of an ocular examination, including probing and irrigation, and a detailed nasal examination (anterior rhinoscopy, nasal endoscopy). The nasal examination was prompted by the patient's report of concurrent nasal symptoms during history taking. Immunohistochemistry subsequently identified the nasal tumor as EMC. A literature search was performed to gain insights into similar malignancies of the nasal cavity.
Eight cases of EMC of the nasal cavity were identified in the literature, none of the patients presented with epiphora. The case presented here resulted in resolution of the patient's symptoms and no evidence of disease after surgical excision.
Epithelial myoepithelial is a rare salivary gland malignancy that can arise in the nasal cavity. Unilateral epiphora with concurrent nasal symptoms should prompt nasal cavity examination for the possibility of an obstructive tumor.
PMCID: PMC4541636  PMID: 26302736
Anterior skull base; epithelial cell; skull base; endoscopic minimally invasive skull-base; endoscopic skull base surgery
8.  Bilateral meningoencephaloceles with cerebrospinal fluid rhinorrhea after facial advancement in the Crouzon syndrome 
Allergy & Rhinology  2015;6(2):e138-e142.
Cerebrospinal fluid (CSF) rhinorrhea and encephaloceles are rare complications of craniofacial advancement procedures performed in patients with craniofacial dysostoses (CD) to address the ramifications of their midface hypoplasia including obstructed nasal airway, exorbitism, and impaired mastication. Surgical repair of this CSF rhinorrhea is complicated by occult elevations in intracranial pressure (ICP), potentially necessitating open, transcranial repair. We report the first case in otolaryngology literature of a patient with Crouzon syndrome with late CSF rhinorrhea and encephalocele formation after previous LeFort III facial advancement surgery.
Describe the case of a patient with Crouzon syndrome who presented with CSF rhinorrhea and encephaloceles as complications of Le Fort III facial advancement surgery. Review the literature pertaining to the incidence and management of post-operative CSF rhinorrhea and encephaloceles. Analyze issues related to repair of these complications, including occult elevations in ICP, the utility of perioperative CSF shunts, and the importance of considering alternative repair schemes to the traditional endonasal, endoscopic approach.
Review of the literature describing CSF rhinorrhea and encephalocele formation following facial advancement in CD, focusing on management strategies.
CSF rhinorrhea and encephalocele formation are rare complications of craniofacial advancement procedures. Occult elevations in ICP complicate the prospect of permanent surgical repair, potentially necessitating transcranial repair and the use of CSF shunts. Though no consensus exists regarding the utility of perioperative CSF drains, strong associations exist between elevated ICP and failed surgical repair. Additionally, the anatomic changes in the frontal and ethmoid sinuses after facial advancement present a challenge to endoscopic repair.
Otolaryngologists should be aware of the possibility of occult elevations in ICP and sinonasal anatomic abnormalities when repairing CSF rhinorrhea in patients with CD. Clinicians should consider CSF shunt placement and carefully weigh the advantages of the transcranial approach versus endonasal, endoscopic techniques.
PMCID: PMC4541637  PMID: 26302737
Anterior skull base repair; complications of facial advancement surgery; craniofacial dysostosis; Crouzon syndrome; CSF leak recurrence; CSF leaks; encephaloceles; endoscopic repair of encephaloceles; transcranial repair of encephaloceles
9.  Steroid sparing effect of omalizumab in seropositive allergic bronchopulmonary aspergillosis 
Allergy & Rhinology  2015;6(2):e143-e145.
Allergic bronchopulmonary aspergillosis (ABPA) is a common serious hypersensitivity reaction to airway colonization with Aspergillus in patients with asthma or cystic fibrosis. While steroids are effective in controlling the respiratory symptoms of ABPA, they have many side effects that make them undesirable for long term use. Antifungals have been used to reduce dependency on systemic steroids but long term use can be limited by side effects and there is the possibility of developing resistance to azoles. Some clinicians have successfully used anti-immunoglobulin E (anti-IgE) therapy in various populations, though it is frequently added to antifungals.
Further describe the utility of anti-IgE therapy for ABPA for patients unable to tolerate antifungals.
We describe the case of a patient with serologic ABPA who did not tolerate therapy with antifungals but was able to significantly reduce her average daily steroid use while receiving anti-IgE therapy with omalizumab added to her other respiratory medications.
After therapy with omalizumab, our patient was able to reduce her need for daily corticosteroids by nearly 80%.
Omalizumab may reduce corticosteroid dependence in patients with allergic bronchopulmonary aspergillosis for patients unable to tolerate antifungals, though use may be limited by cost. Additional studies are needed. identifier NCT00787917.
PMCID: PMC4541638  PMID: 26302738
ABPA; allergic bronchopulmonary aspergillosis; anti-IgE; asthma; omalizumab; steroid-sparing; Xolair
10.  Commentary on gender differences in prevalence, treatment, and quality of life of patients with chronic rhinosinusitis 
Allergy & Rhinology  2015;6(2):e82-e88.
To examine the existing evidence on gender differences in the prevalence, treatment, and quality of life of patients with chronic rhinosinusitis (CRS).
Review of the literature and expert opinion.
From a sociologic standpoint, women have historically been considered more likely to report symptoms, seek medical care, and give poorer self-evaluation of health, which may bias data toward increased prevalence and a greater effect of CRS on quality of life in women. However, the influence of gender seems to be restricted primarily to the evaluation of general quality of life, whereas the disease-specific health-related quality of life is not different between genders. Furthermore, migraine headaches, which are more common among women, may be misdiagnosed as CRS, which contributes to gender differences in the prevalence of CRS. The degree to which reported differences in prevalence and health utilization represent biologic or physiologic differences between genders is not known; however, differences in anatomic size, tobacco susceptibility, and hormonal factors have been speculated to increase the overall susceptibility to CRS in women compared with men.
Focused research that examines the effect of gender on the development, treatment, and outcomes of CRS is warranted.
PMCID: PMC4541639  PMID: 26302727
chronic rhinosinusitis; quality of life; gender; surgical outcomes; burden of disease; migraine headaches; State Ambulatory Surgery Database
11.  Assessment of allergen-induced respiratory hyperresponsiveness before the prescription of a specific immunotherapy 
Allergy & Rhinology  2015;6(2):e89-e93.
Asymptomatic sensitization is a frequent condition that must be considered before the indication of allergic-specific immunotherapy.
The aim of this study was to appreciate and correlate the local and spirometric changes elicited by the allergen-specific nasal provocation test (NPT) to define practical and feasible guidelines for the allergist/immunologist to demonstrate specific respiratory hyperresponsiveness before the indication of allergic-specific immunotherapy.
A total of 172 subjects (children and adults) with a diagnosis of allergic rhinitis were submitted to flow-volume spirometry immediately before and after the NPT performed with Dermatophagoides antigens. The differences between the pre- and postspirometric estimated values of peak expiratory flow rate (PEFdif%), forced expiratory volume in 1 second (FEV1dif%), and forced vital capacity (FVCdif%) were correlated with the results of the nasal provocation test symptom score (NPT-SS).
There were 119 subjects (69%) with NPT-SS > 2. Among these patients who were reactive, the mean NPT-SS was 6.3. The Spearman's correlation between PEFdif% and NPT-SS was r = −0.44 (p = 0.01); the Spearman's correlation between FEV1dif% and NPT-SS was r = −0.22 (p = 0.01), and the Spearman's correlation between FVCdif% and NPT-SS was r = −0.21 (p = 0.04).
The combined utilization of the allergen-specific NPT-SS with the spirometry (or PEF meter) is a safe methodology to evaluate allergen-specific nasal and bronchial hyperresponsiveness (which sometimes acts as a bronchial provocation test) in patients with allergic rhinitis and asthma due to hypersensitivity who are candidates for allergen-specific immunotherapy.
PMCID: PMC4541640  PMID: 26302728
Nasal provocation tests; diagnosis; Dermatophagoides antigens; rhinitis; asthma; spirometry; bronchial provocation tests; child; peak expiratory flow rate; hypersensitivity
12.  Nasal histamine responses in nonallergic rhinitis with eosinophilic syndrome 
Allergy & Rhinology  2015;6(2):e94-e100.
Nonallergic rhinitis with eosinophilic syndrome (NARES) is persistent, without atopy, but with ≥25% nasal eosinophilia. Hypereosinophilia seems to contribute to nasal mucosa dysfunction.
This analytical case-control study aimed at assessing the presence and severity of nonspecific nasal hyperactivity and at finding out whether eosinophilia may be correlated with the respiratory and mucociliary clearance functions.
The symptom score was assessed in 38 patients and 15 controls whose nasal smear was also tested for eosinophils and mucociliary transport (MCT). Nonspecific nasal provocation tests (NSNPT) with histamine were also carried out, and total nasal resistance (TNR) was determined.
The symptom score of NARES after NSNPT were not significantly different from the control group, and there was poor or no correlation among the single symptoms and the differences studied for every nasal reactivity class. This correlation improved when using the composite symptom score. The most severe eosinophilia was observed in high reactivity groups, and it was correlated with an increase in TNR. MCT worsened as eosinophilia and nasal reactivity increased. Unlike controls, a significant correlation was observed between the increase in MCT and TNR.
In NARES, nonspecific nasal hyperreactivity is the result of epithelial damage produced by eosinophilic inflammation, which causes MCT slow down, an increase in TNR, and nasal reactivity classes, with possible impact on classification, prognosis, and treatment control.
PMCID: PMC4541641  PMID: 26302729
Nonspecific nasal provocation test with histamine; symptom score; mucociliary clearance; eosinophils; total nasal resistance; nonspecific nasal hyperactivity; NARES.
13.  Practical recommendations for mixing allergy immunotherapy extracts 
Allergy & Rhinology  2015;6(1):e1-e7.
Critical aspects of formulating allergy immunotherapy vaccines include the selection, total number, and proportions of each allergen component in therapeutic mixtures. The immunotherapy prescription, determined by a medical provider, details the dosing and schedule for treatment as well as the specific composition of the treatment vials. Allergen extracts are composed of many components such as proteins, glycoproteins, and proteases. Some components in allergen extracts are cross-reactive, meaning that treatment with an extract from one species may confer partial protection against a triggering allergen from another species. Conversely, some allergen extracts are incompatible with other extracts when combined in a mixture for treatment, resulting in lowered therapeutic potential for the patient. Therefore, knowledge of allergen extract cross-reactivities and incompatibilities guides the preparation of subcutaneous immunotherapy prescriptions. In a clinical setting, an understanding of what can and can not be mixed is one critical element in improving treatment outcomes.
PMCID: PMC4388870  PMID: 25860164
Allergen; allergy; compatibility SCIT; cross-reactivity; disease modifying; extract; immunotherapy; Joint Task Force guideline; USP 797
14.  Endoscopic dacryocystorhinostomy as treatment for lower lacrimal pathway obstructions in adults: Review article 
Allergy & Rhinology  2015;6(1):e12-e19.
Obstruction of the lacrimal pathway is manifested by epiphora, infection, and blurred vision as well as ocular and facial pain. Conservative treatments only achieve temporary relief of symptoms, thus surgery is the treatment of choice. Dacryocystorhinostomy (DCR) is recognized as the most suitable treatment for patients with obstructions of the lacrimal system at the level of the sac or in the nasolacrimal duct. The aim of this operation is to create a bypass between the lacrimal sac and the nasal cavity. During the past 2 decades, advances in rigid endoscopic equipment and other instruments have made it possible to obtain more information about the anatomic landmarks of the nasolacrimal system, which led to the development of less-invasive and safer endoscopic techniques. However, many parts of the treatment process related to endoscopic endonasal dacryocystorhinostomy (EN-DCR) still remain controversial. This article reviews the published literature about the technical issues associated with the success of EN-DCR, and clarifies the pros and cons of different pre- and postoperative procedures in adults with lower lacrimal pathway obstructions.
PMCID: PMC4388871  PMID: 25860166
Dacryocystorhinostomy; endonasal; endoscopy; epiphora; lower lacrimal pathway; review
15.  A postal survey of hereditary hemorrhagic telangectasia in the northeast of England 
Allergy & Rhinology  2015;6(1):e20-e27.
The aim of this study is to identify the demographics and epistaxis burden of hereditary hemorrhagic telangiectasia (HHT). A questionnaire was sent to participants with HHT who were recruited from a prospectively maintained respiratory clinic data base in a tertiary hospital. Details on demographics, HHT symptoms, family history, epistaxis severity, and treatment received were recorded. There were 34 of 60 responses (57%). Two responses were from families of the deceased. Of the 32 evaluable patients (men, 14; women 18), the average age was 51 years (range, 23–78 years). The average age of HHT diagnosis was 31 years (range, 3–61 years). The diagnosis of HHT was made by the respiratory team in 13 patients; neurologist (2); ear, nose, and throat (ENT) specialist (4); general practitioner (5); hematologist (4); gastroenterologist (1); and not mentioned in two patients. Twenty-seven of 32 patients (84%) had a positive family history of HHT. Only 13 patients had formal genetic testing (4 endoglin, 1 activin receptor–like kinase, 8 unknown gene). All patients who presented to the respiratory clinic had a background of epistaxis, which was noted on presentation. The average age at initial epistaxis was 14 years (range, 2–50 years). The frequency of epistaxis was daily 63% (n = 20), weekly 9% (3), monthly 16% (5), and a few times a year 10% (3), and unstated in one patient. Nine of 32 patients (28%) required a transfusion. Six patients thought that they were unable to perform daily activities due to epistaxis. Only 15 of 32 patients (47%) were under the care of an ENT specialist. The treatment plan for epistaxis management was deemed good by 7 patients, adequate in 8, poor in 6, and not stated by 11 patients. In conclusion, this survey is the first to quantify the epistaxis burden within the northeast of England. The management of epistaxis needs specific education and treatment to optimize the quality of life among these patients.
PMCID: PMC4388872  PMID: 25860167
Hereditary hemorrhagic telangiectasia; epistaxis
16.  Monitor height ergonomics: A comparison of operating room video display terminals 
Allergy & Rhinology  2015;6(1):e28-e32.
A surgeon's eyes should be positioned 1 meter (m) distant and no more than 15° below the top of an operating monitor (0.27 m). We sought to determine which operating room video display terminal can best accommodate ergonomically optimized gaze during surgery. Floor to eye height was measured for surgeons in seated, perched, and standing positions. These ranges were then compared to vertical displacement ranges for monitors measured from floor to top of the screen. Eye height was measured for standing (1.56–1.80 m), perched (1.40–1.65 m), and seated (1.10–1.32 m) positions. The minimum distance (min) between the floor and the top of the monitor and the vertical mobility range (VR) of the monitor were measured throughout a tertiary medical center including towers with boom arms (TcB) (min: 1.58 m, VR: 0.37 m), towers without booms (TsB) (min: 1.82 m, VR: 0.025 m), ceiling mounted booms (CMB) (min: 1.34 m:, VR: 1.04 m), and portable monitors (PM) (min: 1.73 m, VR: 0.04 m). The tangent of 15° declination was used to calculate a correction factor to determine the minimum optimal ergonomic display height. The correction factor was subtracted from the eye height at each position to determine the lowest target height and the highest target floor to eye distance for each position. Analysis of variance with least significant difference post hoc testing identified all minimum distances and vertical ranges to be statistically different (p < 0.001). Monitor vertical displacement varied between styles of carts. CMB video display terminal systems can accommodate standing, perched and the tallest seated surgeons. TcB, TsB and PM systems cannot adequately accommodate all standing, perched or seated surgeons.
PMCID: PMC4388873  PMID: 25860168
Endoscopic sinus surgery; video display terminals; surgical ergonomics; fatigue; computer terminals; task performance and analysis; operating rooms; occupational health; otolaryngology; human engineering
17.  Changes of micro-RNAs in asymptomatic subjects sensitized to Japanese cedar pollen after prophylactic sublingual immunotherapy 
Allergy & Rhinology  2015;6(1):e33-e38.
Japanese cedar pollinosis is the predominant seasonal allergic rhinitis in Japan, and it has increased in prevalence during the past 10 years. Sublingual immunotherapy (SLIT) is considered a safe and effective treatment for pollinosis. Micro-RNAs (miRNAs) are a class of short single-stranded RNA molecules that posttranscriptionally silence gene expression and may mediate allergic immune responses. The aim of this study was to investigate the miRNA alteration in asymptomatic subjects sensitized to Japanese cedar pollen under prophylactic SLIT under part of a randomized, double-blind, placebo-controlled, multiple-center trial. Analysis was undertaken in 15 asymptomatic subjects sensitized to Japanese cedar pollen–specific IgE (ImmunoCAP class ≥2) who participated in 2013. The SLIT group (n = 6) received standardized Japanese cedar pollen extract and the placebo group (n = 9) received an inactive placebo for 5 months covering the cedar pollen season. Changes in serum miRNAs were measured by real-time quantitative polymerase chain reaction to determine whether SLIT had effects on profiles of circulating miRNA. Seven subjects in the placebo group developed pollinosis symptoms, whereas no subjects in the SLIT group did (p = 0.007). Serum hsa-miR-223 was significantly up-regulated in postseason compared with preseason samples. The hsa-let-7b was significantly more down-regulated in postseason than in preseason samples from the placebo group; however, no significant differences were observed in those from the SLIT group. A significant decrease in circulating let-7b was also observed in the subjects who developed symptoms. Prophylactic SLIT was effective in preventing the development of pollinosis. Alterations in miRNA expression occurred in asymptomatic, sensitized subjects during cedar pollen season.
PMCID: PMC4388874  PMID: 25675113
Allergic rhinitis; biomarker; immunotherapy; micro-RNA; placebo; pollinosis; prophylaxis; sensitization; tolerance
18.  A retrospective study of peanut and tree nut allergy: Sensitization and correlations with clinical manifestations 
Allergy & Rhinology  2015;6(1):e39-e43.
Peanut (PN) and tree nut (TN) allergies are among the leading causes of fatal food-induced anaphylaxis and are increasing in prevalence, especially in children. Their cosensitization and concurrent clinical allergy have been understudied. This retrospective study investigated the correlation between PN and TN allergy, both in terms of in vitro sensitization (IVS) and clinical allergic manifestations. We conducted a retrospective medical record review at the Allergy Clinic at University Hospital of Brooklyn. Fourteen hundred six charts were reviewed, of which 76 (5.4%) had documented relevant clinical allergy: PN allergy but not TN allergy (n = 29) or TN allergy but not PN allergy (n = 11) or both (n = 30). Six patients with PN allergy but no TN exposure history were not included in the analysis. The majority of patients (67/76, 88.1%) had a concurrent history of asthma, rhinoconjunctivitis, or AD. Sensitivity of TN IVS predicting PN IVS was 38/39 (97%). Similarly, sensitivity of PN IVS predicting TN IVS was 38/42 (91%). Sensitivity of TN clinical allergy predicting PN allergy was 30/59 (51%). Sensitivity of PN clinical allergy predicting TN allergy was 30/41 (73%). The total number of organ systems involved in reported clinical reactions correlated with IVS to TN (p = 0.004) but not IVS to PN (p = 0.983). In summary, we found PN sensitization predicts TN sensitization in vitro, with lower predictability for clinical reactions.
PMCID: PMC4388875  PMID: 25860169
Allergy; clinical reaction; cosensitization; cross-reactivity; peanut; sensitization; tree nut
19.  Chronic vulvovaginal Candida hypersensitivity: An underrecognized and undertreated disorder by allergists 
Allergy & Rhinology  2015;6(1):e44-e49.
Vulvovaginal candidiasis infections are estimated to occur at least once during the lifetime of 75% of the female population. It has been proposed that some women with recurrent vulvovaginal candidiasis (RVVC) develop sensitization to Candida albicans and clinically improve in response to Candida immunotherapy. Here, we report a case series of 12 women diagnosed with chronic vulvovaginal Candida hypersensitivity subsequently treated with Candida immunotherapy and review potential systemic and localized host immune defense mechanisms involved in C. albicans overgrowth and sensitization. A retrospective review of vulvovaginal Candida hypersensitivity in women who were treated with C. albicans immunotherapy over the past eight years was conducted. Twelve women who qualified for a diagnosis of vulvovaginal Candida hypersensitivity were treated with Candida immunotherapy. Eleven of the 12 (92%) women reported clinical improvement after immunotherapy. The majority of these women were not sensitized to seasonal or perennial aeroallergens and clinically responded to lower concentrations of C. albicans allergen than what has been previously reported. In general, Candida immunotherapy was well tolerated. Chronic vulvovaginal Candida hypersensitivity is an underrecognized disorder by primary care physicians and therefore an undertreated disorder by allergists. A double-blinded, placebo-controlled randomized trial is necessary to firmly establish the efficacy of treatment with Candida immunotherapy. This investigation should be designed to include mechanistic studies that would help to better understand the etiology of this disorder.
PMCID: PMC4388876  PMID: 25860170
Candida albicans; hypersensitivity; immunotherapy; recurrent vulvovaginal candidiasis; cell-mediated immunity; humoral immunity; Treg cells
20.  Perioperative management for patients with hereditary angioedema 
Allergy & Rhinology  2015;6(1):e50-e55.
Hereditary angioedema (HAE) is a rare autosomal dominant disease that results from mutations in the C1-esterase inhibitor (C1-INH) gene. HAE is characterized by recurrent episodes of angioedema of the skin (face, extremities, genitalia, trunk), the gastrointestinal tract, and respiratory tract. Symptoms experienced can be debilitating, may impact quality of life, and can be life threatening. Preventing attacks particularly for patients undergoing procedures is critical. Patients with HAE may now treat acute attacks or prevent attacks with medications that have recently become available in the United States; however, these same medications can be used for perioperative management for patients undergoing medical, surgical, and dental procedures. Periprocedural planning is important for patients to reduce the incidence of acute attacks. Education is critical and increasing awareness of short-term prophylaxis options will allow providers to develop an appropriate action plan for their patients. The goal of this review is to increase awareness for HAE treating physicians, surgeons, anesthesia, and emergency room physicians by examining the available treatment options, researching the literature, and summarizing available data for periprocedural management. The availability of treatment options has increased over the past few years, expanding options for physicians and patients living with HAE and improve safety during the perioperative period and at the time of other procedures.
PMCID: PMC4388877  PMID: 25860171
Anesthesia; C1-esterase inhibitor; danazol; dental; ecallantide; fresh frozen plasma; hereditary angioedema; icatibant; surgery
21.  Nickel sensitization and dietary nickel are a substantial cause of symptoms provocation in patients with chronic allergic-like dermatitis syndromes 
Allergy & Rhinology  2015;6(1):e56-e63.
Data in literature seem to show that, in patients with contact allergic dermatitis, dietary nickel might be a cause of systemic dermatitis, but little information exists in literature about the role of nickel sensitization and dietary nickel in patients with allergic-like chronic dermatitis syndromes. The prevalence of nickel sensitization in patients with chronic allergic-like, non-IgE-mediated skin diseases, and the possible impact of dietary nickel on symptom provocation and persistence has been assessed in the present retrospective study on a case series of 1726 patients referred to our allergy unit for chronic allergic-like skin diseases. IgE-mediated pathogenesis and other differential diagnoses excluded, patients were patch tested. Nickel-positive patients underwent an elimination diet and double-blind placebo-controlled nickel challenge (DBPCNC) test. A total of 339 (20%) tested nickel-positive. Fifty-two patients (15%) recovered by avoiding sources of nickel contact and 29 (10%) dropped out. Out of the remaining nickel-sensitized patients, 277 (80%) achieved complete or near complete recovery with low-nickel content diet, and 185 of them (89%) were positive to DBPCNC. We conclude that nickel sensitization and dietary nickel seem to be the chief trigger for provocation and persistence of symptoms in an important part (∼11%) of patients with chronic allergic-like dermatitis syndromes.
PMCID: PMC4388878  PMID: 25747857
Nickel allergy; nickel sensitization; allergic-like chronic dermatitis; chronic urticarial; adult atopic eczema; chronic pruritus; systemic contact dermatitis; dietary nickel; nickel diet; nickel challenge test
22.  Successful desensitization of a patient with aplastic anemia to antithymocyte globulin 
Allergy & Rhinology  2015;6(1):e64-e67.
Antithymocyte globulin (ATG) is a polyclonal gamma immunoglobulin derived from either rabbit or equine serum that serves as therapy for aplastic anemia; however, ATG causes serum sickness in up to 70% and anaphylaxis in up to 5% of recipients. Intradermal (ID) skin testing has been the primary technique used to evaluate for a preexisting Gell and Coombs type I hypersensitivity reaction to ATG. There are no data reporting the predictive value of delayed reactions to ID testing on the risk of serum sickness. This study was designed to establish the importance of epicutaneous and ID skin testing before the administration of ATG through a case report and literature discussion. We report a patient with severe aplastic anemia that was successfully desensitized to ATG after a negative epicutaneous skin test and positive ID skin test. The patient had neither systemic nor localized reactions during the desensitization. Desensitization to ATG in patients with positive epicutaneous skin testing has been shown to be associated with serious and potentially life-threatening complications and should only be considered when the benefits outweigh the risks. Epicutaneous skin testing should be considered in conjunction with ID skin testing when screening for potential sensitivity to ATG. Because of the serious risk of anaphylaxis, desensitization should be performed in an intensive care unit setting in conjunction with a physician familiar with drug desensitization and the management of anaphylaxis.
PMCID: PMC4388879  PMID: 25730287
Anaphylaxis; antithymocyte globulin; ATG; drug allergy
23.  In-office use of a steroid-eluting implant for maintenance of frontal ostial patency after revision sinus surgery 
Allergy & Rhinology  2015;6(1):e68-e75.
Achieving long-term, successful outcomes with endoscopic sinus surgery (ESS) can be challenging in patients with recalcitrant chronic rhinosinusitis (CRS). Local complications, including scar formation and ostial stenosis, can lead to recurrent blockage and subsequent relapse. The frontal sinus is particularly vulnerable to surgical failure given its narrow outflow and inaccessibility to topical therapies. The advent of steroid-eluting sinus implants has enhanced ESS outcomes, with significant reductions in synechiae, inflammation, and secondary postoperative interventions when placed in the ethmoid cavity. However, use of this technology in the frontal sinus has yet to be described. The purpose of this report is to present two cases, in which in-office frontal placement of a mometasone furoate (MF)-eluting implant facilitated maintenance of ostial patency after revision ESS. The clinical presentation, in-office intervention, and treatment outcomes were examined. Two patients (male, 63 and 68 years of age) with a history of multiple ESS presented with recurrent unilateral frontal headache refractory to medical therapy. Nasal endoscopy/imaging revealed frontal sinus outflow obstruction. Both declined revision ESS under general anesthesia and underwent endoscopic frontal sinustomy/ostial dilation in the clinic. A MF-eluting implant was placed in the frontal sinus at the end of the procedure, with preservation of ostial patency upon last follow-up at 3 and 11 months, respectively. In-office placement of a MF-eluting implant successfully maintained frontal ostial patency in patients with a history of multiple ESS. Additional randomized trials are necessary to determine statistical significance, cost-effectiveness analysis, and long-term efficacy of frontal sinus implantation.
PMCID: PMC4388880  PMID: 25668577
Chronic; endoscopic; frontal; implant; in-office; patency; rhinosinusitis; sinus; steroid eluting
24.  Maxillary sinus manifestations of methamphetamine abuse 
Allergy & Rhinology  2015;6(1):e76-e79.
Methamphetamines are the second most commonly used illicit drug worldwide and cost the United States health-care system ∼$23.4 billion annually. Use of this drug affects multiple organ systems and causes a variety of clinical manifestations. Although there are commonly known sequelae of methamphetamine abuse such as “meth mouth,” there is limited evidence regarding maxillary sinus manifestations. The following cases highlight the initial evaluation and management of two methamphetamine abusers with loculated purulent collections within the maxillary sinus as a result of methamphetamine abuse. Our aim was to delineate the otolaryngologic symptoms associated with the patients' methamphetamine abuse. Computed tomography and magnetic resonance imaging studies revealed loculated purulent collections within the maxillary sinus of probable odontogenic origin in both patients. Methamphetamine abuse leading to rampant caries and poor oral hygiene may predispose individuals for craniofacial infections and fluid collections. These cases illustrate the development of maxillary sinusitis and maxilla mucoceles that have been associated with methamphetamine use.
PMCID: PMC4388881  PMID: 25675268
Abscess; abuse; cyst; intranasal; maxillary; methamphetamine; odontogenic; route; sinus
25.  Sinus penetration of saline solution irrigation and atomizer in a cadaveric polyp and allergic fungal sinusitis model 
Allergy & Rhinology  2015;6(1):e8-e11.
Allergic fungal sinusitis (AFS) is a stubborn disease requiring surgical and medical management. Delivery of topical medication is paramount in these patients, but the most difficult to accomplish. We investigated heavy irrigation (nasal douche) and atomized medication delivery potential in a cadaveric sinus model of polypoid AFS disease. Three disease models were created: a control that involved unoperated sinuses and no simulated disease; an unoperated AFS with type II polyposis mode; and an operated model with recurrent allergic fungal sinusitis with type II polyposis. The maxillary sinus showed the best irrigation and overall the heavy irrigator was more efficient than the atomizer.
PMCID: PMC4388882  PMID: 25860165
Rhinology; sinus surgery; allergic fungal sinusitis; nasal polyp; cadaver model; topical sinus penetration; nasal irrigation

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