Allergic rhinitis (AR) is among the most prevalent allergic diseases in the world and has a large impact on quality of life, school performance, and work productivity. The aim of this exploratory study was to identify the genetic variants that might be associated with AR in the Malaysian population through whole-exome sequencing. A total of 13 AR patients and 10 healthy controls were recruited from the ENT Clinic at the Pusat Kanser Tun Abdullah Ahmad Badawi and Universiti Sains Malaysia Specialist Hospital. Whole-exome sequencing of genomic DNA was performed. To prioritize the variants, bioinformatic analysis was performed according to the American College of Medical Genetics (ACMG) guidelines, and potentially pathogenic variants were looked for. The 5 HLA-DRB1 variants identified (rs1059582, rs17882084, rs17879995, rs11554463, and rs188617679) were classified as potentially pathogenic or likely pathogenic, using ACMG criteria. Of these, rs1059582 had a statistically significant association with AR (P = .0457), which implies that it may be involved in susceptibility to AR. The present preliminary exploratory study revealed that a number of HLA-DRB1 variants, especially HLA-DRB1 rs1059582, are candidate genetic risk factors for AR in the Malaysian population. These results are preliminary and suggest that HLA-DRB1 may be a potential biomarker, but needs to be further validated in larger cohorts.
Background Endoscopic endonasal approach (EEA) has gained widespread acceptance as a surgical approach for treating sinonasal malignancies in the last decade. Objectives This study examined the validity of the EEA as a standard modality for the surgical treatment of sinonasal malignancies. Design A retrospective multicenter cohort study Methods This study included patients with nasoethmoidal malignancies who underwent initial surgical treatment between 2014 and 2016 at 10 tertiary referral hospitals in Japan. The EEA, craniofacial approach (CA), and EEA combined with CA (EEAwCA) were used as the surgical methods. Results The total number of participants was 110, with a median posttreatment observation period of 69 months. The olfactory cleft (26%) was the most frequent lesion site. Squamous cell carcinoma (29%) and olfactory neuroblastoma (24%) were the most frequently observed pathological classifications. EEA was performed in early-stage cases, and EEAwCA, which is frequently used for tumors that extend into the orbit and/or intracranial regions, was performed in advanced-stage cases. Negative-margin resection was achieved in 85%, 78%, and 64% of EEA, EEAwCA, and CA cases, respectively; postoperative radiotherapy was performed in 50%, 56%, and 36% of patients with EEA, EEAwCA, and CA, respectively; and the 5-year local control rates were 90%, 78%, and 82% for EEA, EEAwCA, and CA, respectively. En bloc resection for EEA, and postoperative irradiation for EEA and EEAwCA were associated with fewer local recurrences. Validation of the operation time, hospitalization period, intraoperative blood loss, and postoperative complications demonstrated the low invasiveness of the EEA. Conclusion The EEA is a minimally invasive surgical modality with preferable oncological outcomes for the treatment of nasoethmoidal malignancies when adequately planned. Plain Language Summary A look back at nose cancer surgery using a less invasive method through the nose Purpose This study looked at a newer, less invasive surgery called the endoscopic endonasal approach (EEA), which goes through the nose to remove tumors in the nose and nearby areas. The goal was to see if this method could be used as a standard treatment. How the Study Was Done Researchers looked back at 110 patients in Japan who had surgery for cancer in the nose and surrounding areas between 2014 and 2016. They had surgery using one of three methods: EEA (through the nose) CA (a more traditional open surgery) EEA combined with CA (used for more serious cases) What They Found 1) Most patients had tumors in a part of the nose related to the sense of smell. 2) The most common types of cancer were squamous cell carcinoma and a rare nerve-related tumor. 3) The EEA was mostly used for early-stage cancers, and the combined method was used for more advanced cases. 4) The cancer was completely removed in about 85% of EEA cases, 78% of combined cases, and 64% of traditional cases. 5) People who had EEA had fewer side effects, lost less blood, and stayed in the hospital for a shorter time. 6) After 5 years, the cancer had not come back in 90% of EEA cases, 78% of combined cases, and 82% of traditional cases. 7) Patients who had radiation after surgery or had tumors removed in one piece had better results. Conclusion The EEA is a safe and effective option for treating certain nose cancers, especially when it's carefully planned. It causes less harm to the body and works well for early-stage cancers.
Allergic fungal rhinosinusitis (AFRS) is defined as a benign, extramucosal, non-invasive fungal condition of the paranasal sinuses, resulting from a type 1 IgE-mediated hypersensitivity reaction. AFRS is most commonly seen in young adults, although it also occurs in the pediatric population. Currently, biological therapy has been proposed as an effective treatment for adult patients with AFRS. However, the use of biologics in the pediatric population has not yet been introduced in the literature. Hence, this study reports a unique case involving the use of Dupilumab to treat a pediatric patient with refractory AFRS and bronchial asthma. A 13-year-old girl with a long-standing history of bronchial asthma who was diagnosed with AFRS, started Dupilumab with a loading dose of 600 mg, followed by 300 mg biweekly. The patient showed improvement in her condition after the initiation of Dupilumab, in terms of clinical, endoscopic, and radiological outcomes. Additionally, Dupilumab was shown to be a helpful treatment in controlling the patient's bronchial asthma. In conclusion, Dupilumab appears to be a promising treatment for pediatric patients with refractory AFRS to improve their clinical, endoscopic, and radiological outcomes. However, further studies are needed in the future to validate these findings.
Background:Type 2 inflammation plays a pivotal role in various allergic and inflammatory diseases, including chronic rhinosinusitis, asthma, atopic dermatitis, and eosinophilic esophagitis. Dupilumab is one of the emerging therapeutic targets that modulate the key mediators and cellular players involved in type 2 inflammation, aiming to improve the immune response and the quality of life of the patient. Objective:Here, we describe the experience made on 792 patients enrolled by several specialists of a multidisciplinary team working on inflammatory type 2 diseases. Design:Retrospective study. Methods:Patients were treated with dupilumab according to the prescribed indications and were evaluated by several exams, tests, and questionnaires at baseline (T0) and after 12 (T1), 18 (T2), and 24 (T3) months. Results:Overall, dupilumab exerts beneficial effects as demonstrated both by patients-reported outcomes and by objective assessments. Compared to baseline, all examined efficacy indicators showed an improvement after 12 months, with positive effects sustained through the 2 years of observation. Our results align with several previous trials. Conclusion:Understanding the interconnection between different type 2 inflammatory diseases provides insight into potential avenues for precision medicine approaches and targeted therapies.
Background:Endoscopic sinus surgery (ESS) has become the gold standard for treating patients with chronic rhinosinusitis (CRS) refractory to medical therapy. It is considered a relatively safe and effective procedure in all age groups, with overall success rates ranging from 76% to 97.5%. However, failure of primary endoscopic sinus surgery (PESS) occurs at a rate ranging from 2% to 24%. Patients who are still symptomatic after PESS and optimal medical therapy are candidates for revision endoscopic sinus surgery (RESS). Objectives:to study the outcomes of ESS and assess the risk factors of recurrence of nasal polyps, as well as to compare the outcomes of PESS and RESS at a tertiary care teaching hospital. Design:A retrospective cross-sectional study. Methods:This study is conducted on patients with CRS with nasal polyps (CRSwNP) who underwent ESS at King Saud University Medical City (KSUMC) between May 2015 and December 2021. During this period, ESS was performed 470 times for CRSwNP. The Sinonasal Outcome Test 22 (SNOT-22) questionnaire, the Lund-Kennedy (LK) score, the Lund-MacKay (LM) score, and the polyp grading system were used to evaluate subjective and objective outcomes. They were scored preoperatively and from 6 to 12 months postoperatively. Results:Out of the 470 endoscopic sinus surgeries, 321 (68.3%) were PESS and 149 (31.7%) were RESS. Asthma, aspirin sensitivity, and Samter's triad were observed more in the RESS group. The LK and LM scores were significantly different between primary and revision sinus surgeries, revealing that PESS patients had better postoperative LK and LM scores. The RESS patients had significantly worse postoperative SNOT-22 scores compared to PESS patients. Conclusion:Lund-MacKay, Lund-Kennedy, and SNOT-22 scores improved after ESS for both primary and revision ESS patients, with better outcomes observed after PESS compared to RESS. The presence of asthma, aspirin sensitivity, Samter's Triad, high-grade nasal polyps, and older age were identified as risk factors for CRSwNP recurrence, which may require RESS.
Background Selective anti-polysaccharide antibody deficiency (SPAD) with CD5 B-cell predominance and autoimmune phenomena was identified in a male cohort first reported by Antall et al in 1999. The phenotypically likewise and genotypically identical X-linked immunodeficiency with magnesium defect, Epstein–Barr Virus infection, and neoplasia (XMEN) disease was defined as a novel primary immunodeficiency (PID) in 2011. Recent studies of the magnesium transporter 1 (MAGT1) gene mutation reveal glycosylation defects contributing to more phenotypic variance than the “XMEN” title pathologies. The updated title, “X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect,” was proposed in 2020. Objectives To reflect the patient population more accurately, a prospective classification update may consider MAGT1 glycobiological errors contributing to phenotypic variance but also pre-genetic testing era reports with CD5 B-cell predominance. Methods Patient 1 from Antall et al presented at 28 years of age for further immunological evaluation of his CD5/CD19 B-cell predominance diagnosed at 5 years old. Design Immune re-evaluation done through flow cytometry and next-generation sequencing. Results Flow cytometry B-cell phenotyping revealed persistent CD5+CD19+ (93%). Flow cytometric histogram quantified reduced activator CD16+CD56+ natural killer and CD8+ T-cell receptor, Group 2, Member D (NKG2D) glycoprotein expression. A c.923-1_934 deletion loss of function mutation was identified in the MAGT1 gene. Conclusion We suggest the novel PID XMEN, based on its CD5 B-cell predominance, had been discovered and reported over a decade earlier as CD5+ PID based on the MAGT1 mutation found in the same. We encourage consideration of combining these labels and recent findings to offer the most accurate classification of this disease. Keywords X-linked immunodeficiency with magnesium defect , Epstein–Barr Virus infection , and neoplasia , XMEN , primary immunodeficiency , CD5 , selective anti-polysaccharide antibody deficiency , SPAD , magnesium transporter 1 , MAGT1 , glycosylation defect , flow cytometry
Vaccinations for pathogenic organisms have been utilized for decades in both the protection and diagnosis of immunodeficiency patients. Some of these immunodeficient patients may not create an adequate response to vaccination, although some who have significant aberrancies in their immune system may surprisingly create antibodies to immunizations. We present a patient with a large Ig heavy chain deletion (severe deficiency of serum IgG1, IgG2, IgG4, and IgA1) that showed a considerable response (presumably through IgG3) after the Pfizer BioNTech COVID-19 vaccination. This finding in this unique immunodeficient patient warrants further research into alternate antibody response pathways against COVID-19.
Background:Since the coronavirus pandemic in 2020, there is not much reported about the disease course of COVID-19 in patients with allergic diseases.Objectives:The aim of this study was to investigate the cumulative incidence and severity of COVID-19 among patients from the allergy department compared with the general Dutch population and people from their household.Design:We conducted a comparative longitudinal cohort study.Methods:In this study patients of the allergy department were included with their household members as a control group. Data from the beginning of the pandemic were systematically obtained through questionnaires by telephonic interviews and retrieved from electronic patient files between October 15, 2020 and January 29, 2021. Main outcomes were confirmed SARS-CoV-2 infection, disease duration, hospitalization, intensive care admission, and mortality. Questions regarding applied social distancing measures were inventoried as well.Results:Three hundred and eighty nine patients (median age 39.1 (18.7-84.7) years, 69.9% female) and 441 household members (median age 42.0 (18.0-91.5), 44.1% female) were included. The cumulative COVID-19 incidence in patients was higher compared with the general population (10.5% vs 5.6%, P < .001). In total, 41 (10.5%) patients attending the allergy clinic compared to 38 (8.6%) household members were infected with SARS-CoV-2 (P = .407). Median disease duration was 11.0 (0.0-61.0) days in patients compared to 10.5(1.0-232.0) days in household members (P = .996).Conclusion:The cumulative COVID-19 incidence in patients from the allergy cohort was higher compared with the general Dutch population, but similar compared with household members. There was no difference in symptoms, disease duration, or hospitalization rate between the allergy cohort and their household members.
Background:Central compartment atopic disease (CCAD) is a recent, novel phenotype of chronic rhinosinusitis. Only a few studies have assessed olfactory function in patients with CCAD.Objectives:We aimed to investigate olfactory function changes after functional endoscopic sinus surgery (FESS) in patients with CCAD and proposed some surgical techniques to enhance the postoperative olfactory outcomes in such patients.Design:A retrospective cohort study.Methods:We collected data from 23 patients (8 men and 15 women) with CCAD who underwent FESS performed by a surgeon in Taiwan, between June 2018 and December 2021. The demographic data, olfactory function, and serum and tissue eosinophil percentages of the included patients were analyzed. The Top International Biotech Smell Identification Test (TIBSIT; Top International Biotech, Taipei, Taiwan) was used to assess olfactory function.Results:Of the 23 patients, most (95%) showed a positive reaction to aeroallergens, and 2 patients (8.7%) had asthma. Ten patients (43.5%) had peripheral eosinophilia, and 9 (39%) had eosinophilic nasal polyps. Moreover, the patients presented with variable olfactory dysfunction; the mean preoperative TIBSIT (pr-TIBSIT) score was 12.8 ± 2.3 (range: 0-43), whereas the mean postoperative TIBSIT (po-TIBSIT) score was 29.2 ± 1.9 (range: 16-44). The po-TIBSIT score was significantly better than the pre-TIBSIT score (paired t test, P < .0001). The improvement in olfactory function was not significantly correlated with the patients' age, serum eosinophil percentages, and nasal polyp eosinophil counts.Conclusion:Our findings indicate that CCAD is significantly associated with olfactory dysfunction and that FESS can effectively improve olfactory function. To optimize postoperative olfactory outcomes, precise removal of polyps from the olfactory cleft without damaging the neuroepithelium is recommended. Our study provides valuable insights into the management of CCAD patients undergoing FESS and can guide surgical decision-making to achieve optimal olfactory function outcomes.
Allergic fungal rhinosinusitis (AFRS) is a subtype of chronic noninvasive sinusitis accounting for 7.8% (0.2%-26.7%) of all chronic rhinosinusitis cases. A definitive diagnosis is usually made after sinus surgery. Successful treatment requires a combination of surgical and medical management. Although orbital involvement is relatively common, reports on optic neuropathy and acute vision loss are limited. Herein, we present a series of 3 patients with AFRS who presented with acute visual loss as the chief complaint. All 3 patients were otherwise healthy adults in their early 20s with extensive nasal polyps on endoscopic nasal examination and bone erosion in the bilateral orbits and lateral wall of the sphenoid sinus on the affected side on imaging. One of the 3 patients had bilateral cranial nerve IV defects in addition to cranial nerve III defects. All patients underwent endoscopic sinus surgery with orbital decompression and were followed up postoperatively by both otolaryngology and ophthalmology services with endoscopic and radiologic evaluation. Unfortunately, no meaningful improvement in vision was observed in any patient despite successful nerve decompression. Prompt diagnosis and early medical and surgical intervention are warranted to prevent complications in patients with AFRS with orbital extension.
Background: Despite epinephrine's historical use for over a century and Food and Drug Administration (FDA) approval for EpiPen's use in 1987 to treat anaphylaxis, little information exists regarding selection of the 0.3 mg adult dose. A review of literature was conducted to provide a historical retrospective regarding the evolution of the dosage selected for today's EpiPen. The first adrenal gland extract, isolation of the epinephrine active ingredient, observation of physiological effect, selection of the intramuscular route for administration, the dosage range recommended by independent physicians based on their clinical observations and selection of the ultimate standardized dosage are profiled. Conclusion: This retrospective review illustrates the drug development process prior to the rigors required for today's clinical trials and provides clinical evidence supporting the dose in EpiPen and other similar life-saving epinephrine products.
BackgroundNasal cavity length (NCL) is important for determining analyzed nasal segment (ANS) of acoustic rhinometry (AR). AR is a technique for nasal airway assessment which nasal cross-sectional areas and nasal volume (NV) are obtained. NCL or ANS is the important parameter to determine NV measured by AR. The ANS used to calculate NV in previous literatures vary from 4 to 8 cm. However, there has not been any study regarding NCL of Asians which is probably different from that of Western countries. ObjectivesTo measure NCL in Thai adults using nasal telescope and compared NCL between left and right sides as well as male and female as well as among age groups. DesignProspective study MethodsThis study was performed on patients, aged 18-95 years, who underwent nasal telescopy under local anesthesia at the Department of Otorhinolaryngology, Siriraj Hospital. Baseline characteristics (sex and age) of patients were collected. NCL (from anterior nasal spine to posterior edge of nasal septum) of both nasal cavities was measured using rigid nasal telescope of 0 degree. Mean NCL length of both nasal cavities was calculated. ResultsThere were 1277 patients, with 498 (39%) male and 779 (61%) female. The mean +/- standard deviation (SD) of NCL of male was 6 +/- 0.6 cm whereas that of female was 5.7 +/- 0.5 cm. There were no significant differences in NCL between left and right sides as well as among age groups in each gender (p > 0.05 all). However, male had significantly longer NCL compared with that of female (p < 0.001). The mean +/- SD of NCL of total population was 5.9 +/- 0.6 cm. ConclusionThe NCL of Thais was approximately 6 cm. These data are useful to determine ANS used to calculate NV when AR is performed. Plain Language Summaries The length of nasal cavity (LNC) is important variable for acoustic rhinometry (AR) which is the instrument to measure nasal volume (NV). We use AR in clinical researches to diagnose and monitor the results of treatment of nose and sinus diseases The LNC used to calculate NV in previous studies vary from 4 to 8 cm. However, there has not been any study of LNC of Asians which is probably different from that of Western countries We measured LNC in 1277 Thai adults, aged 18-95 years, with 498 (39%) male and 779 (61%) female using nasal rigid endoscope and compared LNC between male and female. The average of LNC was 5.9 cm. Male had longer LNC compared with that female. The LNC of Thais was approximately 6 cm. These data are useful for AR to calculate NV.
Background:Selective anti-polysaccharide antibody deficiency (SPAD) with CD5 B-cell predominance and autoimmune phenomena was identified in a male cohort first reported by Antall et al in 1999. The phenotypically likewise and genotypically identical X-linked immunodeficiency with magnesium defect, Epstein-Barr Virus infection, and neoplasia (XMEN) disease was defined as a novel primary immunodeficiency (PID) in 2011. Recent studies of the magnesium transporter 1 (MAGT1) gene mutation reveal glycosylation defects contributing to more phenotypic variance than the "XMEN" title pathologies. The updated title, "X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect," was proposed in 2020. Objectives:To reflect the patient population more accurately, a prospective classification update may consider MAGT1 glycobiological errors contributing to phenotypic variance but also pre-genetic testing era reports with CD5 B-cell predominance. Methods:Patient 1 from Antall et al presented at 28 years of age for further immunological evaluation of his CD5/CD19 B-cell predominance diagnosed at 5 years old. Design:Immune re-evaluation done through flow cytometry and next-generation sequencing. Results:Flow cytometry B-cell phenotyping revealed persistent CD5+CD19+ (93%). Flow cytometric histogram quantified reduced activator CD16+CD56+ natural killer and CD8+ T-cell receptor, Group 2, Member D (NKG2D) glycoprotein expression. A c.923-1_934 deletion loss of function mutation was identified in the MAGT1 gene. Conclusion:We suggest the novel PID XMEN, based on its CD5 B-cell predominance, had been discovered and reported over a decade earlier as CD5+ PID based on the MAGT1 mutation found in the same. We encourage consideration of combining these labels and recent findings to offer the most accurate classification of this disease.
Visual loss is a rare manifestation of allergic fungal rhinosinusitis (AFRS). We report a case of an adult male who was diagnosed with AFRS and who presented during the COVID-19 pandemic lockdown with sudden-onset complete vision loss and a lack of recovery after surgical and medical management. We reviewed the literature on reported cases of AFRS complicated by visual loss to identify factors associated with visual outcomes. We found 50 patients who were diagnosed with acute visual loss due to AFRS, with an average age of 28 ± 14 years. Complete and partial recovery after surgical intervention were reported in 17 and 10 cases, respectively. However, the absence of vision improvement was reported in 14 of the cases. Early diagnosis and prompt intervention can return vision back to normal. However, delayed presentation, complete loss of vision, and acute onset of visual loss are associated with worse outcomes.
Background Allergic rhinitis (AR) is the most common inflammatory disorder of the upper airway caused by aberrant immune responses to allergens in genetically predisposed individuals. Recently, the long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) has been identified as a novel genetic factor associated with increased AR risk. Objectives This study aimed to evaluate the potential correlation of ANRIL gene single nucleotide polymorphisms (SNPs) with AR risk in the Kurdish population of Kermanshah, Iran. Methods In this case–control study, 130 AR patients and 130 healthy controls were recruited to genotype for two SNPs of the ANRIL gene (rs1333048 and rs10757278) using the Tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) method. Results Our results showed no significant difference for the alleles and genotypes frequency distribution of lncRNA ANRIL SNPs (rs1333048 and rs10757278) between AR patients and healthy controls (p > 0.05). Additionally, the dominant, additive and recessive genetic models of both SNPs were not associated with altered susceptibility to AR risk (p > 0.05). Conclusion The results demonstrated that the ANRIL gene rs1333048 and rs10757278 polymorphisms might not be associated with susceptibility to AR in the Kurdish population of Kermanshah, Iran
IgM deficiency is characterized by remarkably low serum levels of IgM with normal IgG and IgA levels. These patients clinically present with recurrent infections, autoimmune disorders, and malignancies. While unknown, the proposed mechanisms explain the pathophysiology as an issue due to impaired IgG antibody response. The connexin genes encode for gap junctional proteins where mutations can cause hearing deficits and immune dysregulation. We present a unique case of an 18-year-old patient with recurrent sinusitis, diagnosed connexin-26 mutation and an IgM deficiency. An 18-year-old male with chronic sinusitis, Marfanoid joint hypermobility syndrome, and sensorineural hearing loss due to connexin-26 deficiency with bilateral cochlear implants. This patient's mutation is a GJB2 deletion located on chromosome 13 which encodes for the connexin-26 protein. The patient experienced recurrent infections, and serum immunoglobulins showed a normal IgA (84 mg/dL; normal: 70-400 mg/dL), IgG (922 mg/dL; normal: 700–1600 mg/dL) and reduced IgM (26 mg/dL; normal: 40–230 mg/dL) levels. The patient was responsive to Mumps, Measles, Rubella, and Diphtheria vaccinations among others, consistent with SIGMD diagnoses. Antibody responses to polysaccharide antigens were absent. The leukocyte counts were within normal limits. His parents are connexin-26 deficient carriers, and his older brother was diagnosed with SIGMD. Connexin-26 has been identified with multiple immunological mechanisms. Although mutations of this gene have no direct tie to antibody formation in relation to IgM, the presence of these 2 pathologies in 1 patient is intriguing and may suggest a pathophysiologic connection. We describe the first case of connexin mutation with an IgM deficiency in an 18-year-old male.
