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Immediate drug hypersensitivity reactions (DHRs) are historically thought to be because of immunoglobulin E (IgE) cross-linking, causing mast cell degranulation and release of mediators like tryptase and histamine. With the increasing use of monoclonal antibodies, it has become apparent that some patients present atypical features during immediate DHRs, including occurrence in initial exposure, a lack of urticaria and angioedema, and the presence of fever, chills, rigors and musculoskeletal pain as the predominant symptoms. This observation led to the recognition of a novel phenotype of immediate DHRs called cytokine release syndrome (CRS). Other types of immediate DHRs include infusion-related reactions (which present similarly to CRS), and mixed reactions (which share overlapping features of both type 1 reactions and CRS). Desensitization to culprit drugs can be a lifesaving option in patients who develop immediate DHRs to first-line treatment. Whereas robust data are supporting the safety and efficacy of drug desensitization, breakthrough reactions can still occur and CRS seems to be a more common cause than type 1 reactions. Tryptase has been the only available biomarker for immediate DHRs and is associated with type 1 reactions. Emerging evidence consistently found the association between increased serum interleukin 6 level and DHR-related CRS, suggesting that interleukin 6 can be a novel biomarker, in addition to tryptase, to distinguish various types of DHRs. In the era of precision medicine, phenotyping and endotyping hypersensitivity reactions to chemotherapy and monoclonal antibodies using validated biomarkers should be part of routine drug allergy care., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Data on beta-lactam hypersensitivity (BLH) are mainly focused on immediate or mild nonimmediate reactions in the ambulatory setting, but limited in patients with concurrent illness and moderate-to-severe nonimmediate reactions in the hospitalized setting., Objective: To investigate the entire spectrum of BLH in Thai tertiary hospital., Methods: Clinical characteristics of 357 patients with suspected BLH were evaluated in a 7-year period. Culprit drug identification was performed in 335 patients by combined skin testing, in vitro testing, or drug provocation tests., Results: The predominant BLH presentations were non-immunoglobulin (Ig)E-mediated reactions with severe cutaneous adverse reactions of 18.9%, and BLH status was definitively confirmed in 18.1%. The most common verified culprits were cephalosporins (34.8%), particularly in hypersensitivity type IV reactions. Natural penicillins were the main implicated drugs in 48.5% of ambulatory patients. In contrast, cephalosporins and carbapenems were the main implicated drugs in hospitalized patients. Non-IgE-mediated anaphylaxis and serum sickness-like reaction remained diagnostically challenged. New generations of beta-lactams, hospitalized patients, recent allergic history, and underlying malignancies or autoimmune diseases were associated with increased BLH risk., Conclusion: At present, cephalosporins are the leading causes of BLH, particularly in non-IgE-mediated reactions. More research on the verification of non-IgE hypersensitivity reactions from new generations of beta-lactams should be better emphasized., Clinical Trial Registration: The registry was approved by the Ethics and Research Committee of the Faculty of Medicine, Chulalongkorn University, and listed on ClinicalTrials.gov (Identifier: NCT01667055; https://www., Clinicaltrials: gov/ct2/show/NCT01667055)., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: It has been known that a high serum total immunoglobulin E (IgE) level is a predisposing factor of allergic asthma; however, there are considerable limitations to apply it in clinical practice., Objective: To determine the clinical significance of the serum-free IgE level in patients with adult asthma., Methods: We measured free IgE levels using our homemade enzyme-linked immunosorbent assay by applying a novel IgE TRAP protein (GI innovation, Seoul, Republic of Korea) in sera of adults with asthma (n = 116) compared with healthy controls (n = 32); enzyme-linked immunosorbent assay inhibition test was performed to validate its binding specificity. Associations between asthma-related clinical and laboratory parameters were analyzed. The diagnostic value and cutoff point for detecting atopy and type 2 asthma were determined using receiver operating characteristic curve analysis., Results: The serum-free IgE levels were significantly higher in adults with asthma than in healthy controls and were significantly associated with atopic status and type 2 asthma (all P < .001). In the receiver operating characteristic analysis, serum-free IgE had a significantly greater area under the curve (AUC) than serum total IgE for assessing asthma, especially type 2 asthma (AUC, 0.810 vs 0.743; P = .006 and AUC, 0.729 vs 0.572; P < .001). The optimal cutoff points for predicting atopy and type 2 asthma were 82.8 and 120.8 ng/mL, respectively., Conclusion: It is suggested that a higher serum-free IgE level may be a useful biomarker of atopy and type 2 asthma in adults with asthma., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To review novel concepts in drug hypersensitivity and the management of immediate hypersensitivity reactions., Data Sources: English language literature on MEDLINE and Embase surrounding drug hypersensitivity and desensitization., Study Selections: References were selected based on relevance, date of publication, and originality., Results: There are numerous citations looking at categorizing drug reactions, pathogenesis, biomarkers, and desensitization. Current understanding supports the use of a phenotype-endotype-biomarker model for categorizing immediate hypersensitivity reactions. Drug desensitization is a powerful therapeutic strategy that enables temporary induction of tolerance to medications that triggered immediate reactions., Conclusion: Immediate hypersensitivity reactions are diverse in presentation and pathogenesis. Drug desensitization is an effective intervention with sufficient evidence to support its more widespread availability., (Copyright © 2020. Published by Elsevier Inc.)

Background: Diagnosis of Periplaneta americana (American cockroach, ACR) allergy is commonly performed based on clinical history and skin prick test (SPT) or specific serum IgE (sIgE) measurement. The concordance of the findings with the SPT and sIgE results has never been investigated., Objective: To compare the results of SPT with commercial ACR-extract (C-ACE) and sIgE measurement, using commercial kit and in-house enzyme-linked immunosorbent assay (ELISA) to the locally produced ACR extract (L-ACE) and native Per a 1, Per a 5, Per a 7, and Per a 9., Methods: Sera from 66 individuals clinically diagnosed with chronic allergic rhinitis were included; 46 were positive SPT to C-ACE, and 20 were negative. Specific serum IgE levels were established by using a commercial test kit (ImmunoCap) and an in-house IgE-ELISA RESULTS: The percentage the C-ACE SPT-positive cases that were positive by the ImmunoCap-sIgE was 32.6%, indicating low concordance of the 2 assays. With the in-house ELISA, Per a 9 gave the highest sensitivity (98.00%), positive predictive value (PPV; 95.74%), and negative predictive value (NPV; 94.74%) of the sIgE quantification. The correlation coefficients (R) of the L-ACE-SPT and sIgE to L-ACE, Per a 1, Per a 5, Per a 7, and Per a 9 and ImmunoCap sIgE were 0.133, 0.278, 0.419, 0.280, and 0.432, and 0.256, respectively., Conclusion: Skin prick test and sIgE measurement using commercial reagents have low concordance. Data of this study showed that sIgE to the native Per a 9 should be considered as an adjunct to the clinical history in diagnosis of ACR sensitization/allergy, particularly when the SPT and the nasal challenge, which is the gold standard method, cannot be performed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Immediate hypersensitivity reactions (IHRs) to iodinated contrast media (ICMs) remain a common clinical concern. Positive skin test and basophil activation test results suggest a specific IgE-mediated mechanism in some cases. Skin test and controlled challenge test (CCT) are useful to manage these patients., Objective: To study clinical and allergologic features of IHRs to ICMs in a Spanish tertiary hospital during a 7-year period., Methods: Demographic and clinical data concerning the reaction were recorded. Patients treated at the Allergy Department of Hospital General Universitario Gregorio Marañón, Madrid, Spain, underwent skin tests. In those with positive results, CCTs with an alternative skin-test-negative ICM was performed. Global reaction rate was calculated and compared for each ICM., Results: A total of 342 reactions occurred in 329 patients. Cutaneous symptoms were the most common (87.7%). A total of 196 patients underwent an allergy workup, 15 (7.6%) of whom had positive skin test results. Reactions were more severe in patients with positive vs negative skin test results (grade 1, 46.7% vs 73.6%; grade 2, 33.3% vs 20.9%; grade 3, 20% vs 5.46%; P < .05). Three patients had cross-reactivity to 3 ICMs, all including ioversol and iomeprol. Six patients allergic to iopamidol tolerated ioversol and 1 tolerated iomeprol. Four patients allergic to ioversol and 1 allergic to iomeprol tolerated iopamidol. The global reaction rate was 0.2%, differing for each ICM (iopamidol, 0.14%; ioversol, 0.2%; and iomeprol, 0.4%; P < .001). Positive skin test results were found in a low percentage of patients in whom skin test-based CCT identified an alternative non-cross-reactive ICM. Low-grade cross-reactivity was found, especially between iopamidol and ioversol. Reactions were more severe in patients with positive skin test results. The reaction rate was greater for iomeprol compared with iopamidol (reaction rate, 2.8%) and ioversol (reaction rate, 2%)., Conclusion: This study identified a possible underlying specific IgE-mediated mechanism by positive skin test result in a low percentage of patients with IHRs to ICMs. In these patients, the CCT based on skin test results was useful for identifying an alternative non-cross-reactive ICM. More studies are needed to investigate the underlying mechanism in patients with IHRs and negative skin test results., (Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Atopic diseases have increased since the second half of the previous century. Atopic workers are at higher risk to be sensitized to latex, and the first years of exposure are supposed to be especially risky., Objective: To assess atopic status and rate of latex sensitization in health care students starting their exposure to latex gloves., Methods: We analyzed medical surveillance data from 1,628 health care students from 2010 to 2016. Students completed a questionnaire focused on their previous and current latex exposure and personal and family histories of allergic diseases; underwent skin prick testing with common allergens and latex extract (and/or total and latex-specific immunoglobulin E in serum); and underwent a medical examination., Results: Skin prick test results for common inhalant allergens showed that 807 of 1,628 students (49.6%) had atopy. Atopy by skin prick testing was associated with male sex (odds ratio 1.49, 95% confidence interval 1.18-1.86), a personal history of oculorhinitis or asthma (odds ratio 10.22, 95% confidence interval 7.4-14.13), and atopic eczema (odds ratio 1.87, 95% confidence interval 1.05-3.36) at multivariate regression analysis. Eleven students (0.7% of total population) were found to be sensitized to latex and all had atopy., Conclusion: Despite the high prevalence of atopy in health care students of Trieste, the latex sensitization rate is very low and comparable to general population. This is reasonably due to the low exposure to latex gloves at the time of the evaluation and to low latex release from the gloves currently used in our hospital., (Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Although previous studies have investigated the association between atopy phenotypes and allergic diseases, atopy characterizations in association with the development of allergic diseases remain poorly understood., Objective: To identify atopy phenotypes in school-age children and to evaluate the association between atopy phenotypes and allergic diseases., Methods: We enrolled 616 children with atopy defined as 1 or more positive allergen responses on skin prick tests and 665 children without atopy from the Children's Health and Environmental Research (CHEER) study. All children were followed up for 4 years at 2-year intervals. Atopy phenotypes were classified using latent class analysis., Results: Four atopy phenotypes were characterized: later sensitization to indoor allergens (cluster 1); multiple early sensitization (cluster 2); early sensitization to outdoor allergens, especially Alternaria, and later sensitization to indoor allergens, including Aspergillus (cluster 3); and early sensitization to indoor allergens and later sensitization to outdoor allergens (cluster 4). New cases of asthma during follow-up were increased in clusters 2 and 3 (adjusted odds ratio [aOR], 2.76 and 4.25, respectively). The risk of new-onset bronchial hyperresponsiveness was highest in cluster 3 (aOR, 5.03). Clusters 2 and 4 had an increased risk of allergic rhinitis (aOR, 7.21 and 2.37, respectively)., Conclusion: Identification of atopy phenotypes facilitates prediction of the development of asthma and bronchial hyperresponsiveness in school-age children. Our study suggests prevention of additional sensitization is required to modify the progression of allergic diseases., (Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Eosinophilic esophagitis (EoE) has repeatedly been associated with atopic manifestations, which are reported more frequently in these patients than in the general population., Objective: To systematically assess the evidence and strength of the associations between EoE and atopy., Methods: We performed a systematic search of the MEDLINE, EMBASE, and SCOPUS databases for case-control studies comparing the frequency of atopic diatheses among patients with EoE and control subjects representing the general population without EoE. Using random-effects meta-analyses, we calculated summary estimates, including 95% confidence intervals (CIs), for bronchial asthma, atopic rhinitis, and eczema. Publication bias risks were assessed by means of funnel plot analysis and specific statistical tests., Results: Of the 2,954 references identified, data were collected from 21 studies, including a total of 53,542 patients with EoE and 54,759 controls. The criteria for defining a diagnosis of atopy in patients with EoE or controls was not structurally considered in most of the studies. Overall, allergic rhinitis was significantly more common among patients with EoE compared with control subjects (odds ratio [OR], 5.09; 95% CI, 2.91-8.90; I 2  = 86.7%) as were bronchial asthma (OR, 3.01; 95% CI, 1.96-4.62; I 2  = 84.5%) and eczema (OR, 2.85; 95% CI, 1.87-4.34; I 2  = 57.1%). Food allergies and other atopic conditions were also assessed. No significant publication bias was found for studies dealing with allergic rhinitis and eczema in EoE., Conclusion: Despite pointing to a significant association between atopy and EoE, most of the studies provided no normalized diagnostic criteria for atopy. Further research should provide clear and standardized definitions of such conditions., Trial Registration: www.crd.york.ac.uk/PROSPERO Trial Identifier: CRD42016036161., (Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Because of time and cost constraints, objective classification of atopic and nonatopic asthma has been limited in large epidemiologic studies. However, as we try to better understand exposure-outcome associations and ensure appropriate treatment of asthma, it is important to focus on phenotype-defined asthma classification., Objective: To compare atopic and nonatopic asthma in rural children with regard to risk factors and clinical outcomes., Methods: We conducted a cross-sectional study in rural Saskatchewan, Canada, in 2011. Parents of 6- to 14-year-old children completed a health and exposure survey. Skin prick tests were completed in a subsample of 529 children. Asthma was based physician diagnosis. Asthma status was defined as no asthma, nonatopic asthma, and atopic asthma., Results: Asthma prevalence was 14.7% of which 32.1% of cases were atopic. After adjustment, early respiratory illness and a family history of asthma were predictors of childhood asthma, regardless of atopic status (P < .05). Being overweight and having a dog in the home were associated with an increased risk of nonatopic asthma (P < .05). A mother with a history of smoking increased the risk of atopic asthma (P = .01). Compared with those with nonatopic asthma, in the past 12 months, children with atopic asthma were more likely to report a sneezy, runny, or blocked nose or have shortness of breath (odds ratio >2), whereas those with nonatopic asthma were more likely to have parents who missed work (odd ratio >3). Those with nonatopic asthma had significantly lower forced expiratory volume in 1 second compared w2ith those with atopic asthma., Conclusion: Exposures may contribute differentially to atopic and nonatopic asthma and result in differential clinical presentation or burden. The study of these characteristics is important for etiologic understanding and management decisions., (Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The evaluation of antibiotic immediate-type hypersensitivity is intricate because of nonstandardized skin testing and challenge method variability., Objective: To determine the safety outcomes and risk factors for antibiotic challenge reactions in patients reporting a history of antibiotic immediate-type hypersensitivity., Methods: A 5-year retrospective review of patients evaluated for immediate-type antibiotic allergy was conducted. Data analyzed included patient demographics, index reaction details, and outcomes of skin testing and challenges, classified as single-step or multistep., Results: Antibiotic hypersensitivity history was identified in 211 patients: 78% to penicillins, 10% to fluoroquinolones, 7.6% to cephalosporins, and 3.8% to carbapenems. In total, 179 patients completed the challenges (median age 67 years, range 50-76 years, 56% women), and compared with nonchallenged patients, they reported nonanaphylactic (P < .001) and remote index (P = .003) reactions. Sixteen patients (8.9%) experienced challenge reactions (5 of 28 for single-step challenge, 11 of 151 for multistep challenge), and 11 of these patients had negative skin testing results before the challenge. Challenge-reactive patients were significantly younger (P = .007), more often women (P = .036), and had additional reported antibiotic allergies (P = .005). No correlation was detected between the reported index and observed challenge reaction severities (κ = -0.05, 95% confidence interval -0.34 to 0.24). Anaphylactic rates were similar during single-step and multistep challenges (3.6% vs 3.3%)., Conclusion: In the present population, younger women with multiple reported antibiotic allergies were at greatest risk for challenge reactions. Negative skin testing results did not exclude reactions, and index severity was not predictive of challenge outcome. The multistep and full-dose methods demonstrated a comparable reaction risk for anaphylaxis., (Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: To review the literature on immediate hypersensitivity reactions to corticosteroids and classify them according to manifestations, routes of exposure, causative preparations, diagnostic tests, and management., Data Sources: PubMed search for English-language publications from January 1, 2004 through December 31, 2014 using search terms corticosteroid, glucocorticoid, or steroid combined with hypersensitivity, allergy, or anaphylaxis., Study Selection: Only reports of immediate hypersensitivity reactions that occurred sooner than 24 hours after administration of a corticosteroid were included. Excluded were reports on patients with delayed reactions, including contact dermatitis., Results: Forty-eight articles fulfilled the criteria, reporting 120 reactions in 106 patients 2 to 90 years of age (55 male and 51 female). The most commonly reported manifestation was anaphylaxis in 60.8% (73 of 120) followed by urticaria and/or angioedema in 26.7%. Exposure to corticosteroid was through any route, with intravenous being the most common (44.2%, 53 of 120), followed by oral in 25.8% and intra-articular in 11.7%. Methylprednisolone was the most commonly implicated (40.8%) followed by prednisolone (20.0%). Some reacted to more than 1 preparation. Pharmacologically-inactive ingredients were implicated in 28.3%. Diagnosis was based primarily on medical history and in most cases was confirmed by challenge testing. Skin tests were positive in 74.1%. The vast majority of patients tolerated at least 1 alternative preparation, and very rarely desensitization was required., Conclusion: Corticosteroids seem to be rare causes of immediate hypersensitivity reactions but possibly are misdiagnosed or under-reported relative to their worldwide use. Physicians should be cognizant of this entity and identify safe alternative preparations., (Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: In most children with asthma and atopy, onset of disease occurs early in life, indicating a crucial role of in utero and early childhood environment. However, only a small part of this burden of disease established early in life has been explained., Objective: To examine the effects of early environmental exposures on the development of asthma and atopy within the setting of an affluent urban population., Methods: The authors followed 526 German children from birth to 5 years of age. Parental interviews in pregnancy and then yearly assessed the health of the child and environmental characteristics. Endotoxin and allergens in house dust were measured at 3 months. Atopic sensitization was assessed at 1 and 5 years., Results: In atopic mothers, acute atopic symptoms during pregnancy were associated with increased risk of early atopic dermatitis (adjusted odds ratio [aOR] 1.74, 95% confidence interval [CI] 1.00-3.02) and allergic rhinitis at 5 years (aOR 2.11, 95% CI 1.01-4.41). Further, maternal illnesses during pregnancy (ie, repeated common colds) increased the risk of asthma at 5 years (aOR 2.31, 95% CI 1.12-4.78). Endotoxin in the child's mattress was inversely associated with atopic sensitization (aOR 0.79, 95% CI 0.64-0.97) and asthma (aOR 0.71, 95% CI 0.55-0.93). A contrasting effect of early endotoxin and mite exposure was observed for mite sensitization: mite exposure increased the risk of mite sensitization at 5 years (aOR 1.30, 95% CI 1.11-1.53), whereas endotoxin exposure was inversely associated with mite sensitization (aOR 0.73, 95% CI 0.57-0.95)., Conclusion: Factors affecting the in utero environment, such as maternal atopy and infections, and bacterial exposure in pregnancy or early life may act as immunomodulators enhancing or inhibiting the development of asthma and atopy in childhood., (Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Approximately 60% to 80% of children and young adults with asthma are sensitized to at least one allergen. In contrast, previous studies from specific subpopulations of older patients with asthma suggest that allergic sensitization is significantly lower in this age group. The prevalence and patterns of IgE-mediated sensitization have not been compared among a broad population of younger and older patients with asthma., Objective: To determine the prevalence and patterns of IgE-mediated sensitization among a broad population of younger and older patients with asthma., Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 to compare IgE-mediated sensitization rates between younger (20-40 years) and older (≥55 years) patients with current asthma. Atopy was defined as a detectable serum IgE to at least 1 allergen in a panel of 19 allergens. The associations among sensitization, current asthma, and asthma control measures (health care use and symptoms) were examined by logistic regression., Results: In a group of 2,573 patients, either 20 to 40 years of age or 55 years or older, 108 (6.7%) and 43 (4.5%) patients with current asthma were identified, respectively. Allergic sensitization rates among the adults with asthma differed only moderately and not statistically significantly between the age groups; 75.4% of the younger and 65.2% of the older asthmatic patients were sensitized to at least 1 allergen. The association between sensitization and markers of asthma control did not appear to differ among the age groups., Conclusion: Allergic sensitization in older patients with asthma may be more common than previously reported., (Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: A family history of atopy has been considered an independent risk factor for atopic diseases in children., Objective: To relate the risk of an infant developing IgE-mediated cow's milk allergy (IgE-CMA) to the atopic status of parents., Methods: Assessment of the parental atopic status of children with IgE-CMA (n = 66) previously identified in a large-scale prospective study was compared with the parental atopic status of a control group of healthy infants (n = 156). The atopic status was identified both by self-reporting and skin prick tests (SPTs)., Results: Analysis for the risk for infants to develop IgE-CMA depended on the assessment method used. No significant differences were noted in self-reported parental atopic status between the IgE-CMA patients and the control group. However, among the subgroup of infants with persistent IgE-CMA (n = 25), maternal but not paternal self-reporting for atopy was more likely compared with parents of the control group (P = .04). In contrast, when analyzed by SPT, in both this persistent subgroup and the total allergic cohort, no significant differences were noted whether analyzed by single parent or both parents and whether the parent tested singly or multiply positive on the SPT., Conclusion: In families with children with persistent IgE-CMA, self-reporting of atopy by parents may be biased. Furthermore, the demonstration of IgE-mediated responses to allergens in parents is insufficient by itself, in a general population cohort, to predict which infants are at greatest risk of developing IgE-CMA., (Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: No available test diagnoses allergic reactions to radiocontrast media (RCM). The basophil activation test (BAT) has been introduced for the diagnosis of both immunoglobulin (Ig) E and non-IgE-dependent mast cell degranulation, but its value to diagnose immediate RCM reactions is still unknown., Objective: This study aims to evaluate the diagnostic value of BAT in immediate RCM hypersensitivity., Methods: The BATs were performed in 26 patients with immediate RCM reactions and in 43 specimens from healthy volunteers. The sample's whole blood was incubated with the responsible RCM and % activated (CD63+/CCR3+) basophils were analyzed by flow cytometry. Receiver operating characteristics (ROC) curve analysis was performed to calculate the optimal cutoff value of activated basophils to diagnose patients with RCM hypersensitivity., Results: The incubation of blood with RCM yielded significantly higher activated basophil percentages in patients with a history of immediate RCM reactions than in normal controls with both 1:100 and 1:10 dilutions (13.11% vs. 2.71%, P value = .01; and 19.23% vs. 3.73%, P = .001, respectively). Both % activated basophils and stimulation index (SI) had acceptable discrimination powers to diagnose RCM hypersensitivity. The area under the curve was 0.79 (95% CI 0.67-0.91, P = .000) by using SI as the diagnostic criteria with 1:100 dilution of RCM. The specificity of the test ranged from 88.4% to 100%., Conclusion: Our study demonstrated the potential of BAT as a diagnostic tool for an immediate RCM hypersensitivity, particularly as a confirmation test. Further studies are required to confirm the test accuracy and identify a patient's predisposing factors., (Copyright © 2011. Published by Elsevier Inc.)

Objective: To review research regarding locally produced IgE and its impact on patients with chronic rhinitis., Data Sources: PubMed search with the following keywords: entopy, local IgE, nonallergic rhinitis, idiopathic rhinitis, vasomotor rhinitis, and allergic rhinitis., Study Selection: Articles were selected based on their relevance to entopy and locally produced IgE and its clinical effect and relationship to idiopathic rhinitis (IR)., Results: Local IgE has been found in a variety of tissues, including nasal and bronchial mucosa. IgE is produced in these local tissues and not simply the product of migration to the tissue from regional lymphoid tissue or blood. Local IgE has been identified in most of both atopic and nonatopic asthmatic patients and allergic rhinitis patients. Up to 40% of patients with IR and a positive nasal provocation test result have evidence of locally produced IgE, which has been coined entopy. Although patients with allergic rhinitis and IR show similar inflammatory patterns with increased activated mast cells, eosinophils, and T-cell subsets in some studies, other studies on IR patients are conflicting with regard to both inflammation and allergen-specific nasal provocation test results., Conclusion: The concept of local allergy in IR patients is both intriguing and controversial. Studies have reported conflicting results, and currently there is no single best test to evaluate for entopy. It is known that there are a large number of IR patients for whom current treatment regimens are suboptimal. Therefore, further research elucidating the mechanisms of IR and the concept of localized IgE are needed to optimally diagnose this condition and treat this group of patients., (Copyright © 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The workers in an animal laboratory are exposed to laboratory animal allergens (LAAs)., Objectives: To evaluate the difference of sensitization to LAAs and the symptoms according to the exposure levels and to investigate the risk factors for sensitization to LAAs., Methods: The subjects were divided into 3 groups according to the presence or absence of exposure: 74 subjects were in the direct exposure group, 33 subjects were in the indirect exposure group, and 30 subjects were in the control group. Each group answered the questionnaire and underwent skin prick tests that included 10 common allergens and 10 LAAs. The levels of total IgE and specific IgE to mouse and rat urine allergen were measured by enzyme-linked immunosorbent assay in 2 exposure groups. Allergic symptoms, skin sensitization, and serum IgE level were compared between the study groups., Results: Twenty-five (34%) of the 74 subjects in the direct exposure group experienced allergic symptoms since their exposure to laboratory animals. The subjects in the direct and indirect exposure groups had more sensitization to LAAs than did the control subjects. The direct exposure group had more positive results for total IgE than did the indirect exposure group. The subjects in the direct exposure group with atopy had more severe allergic symptoms than the subjects in the indirect exposure group with atopy. Atopy and total IgE level were risk factors for the sensitization to LAAs for the direct exposure group (odds ratios, 7.47 and 7.33, respectively)., Conclusions: Indirect exposure may be as risky for sensitization to LAAs as direct exposure. More careful protection is needed for laboratory animal workers with atopy.

Background: The chance of a nonspecific intradermal skin test response at venom concentrations greater than 1.0 microg/mL limits the diagnostic range and can interfere with the diagnosis of some affected patients., Objective: To compare the diagnostic ranges and clinical detection rates of skin tests using dialyzed yellow jacket venom (DYJV) and undialyzed YJV (UYJV), particularly in patients who have had negative venom skin test results., Methods: Both DYJV and UYJV from the same original lot were diluted from 100 microg/mL to skin test concentrations of 0.01, 0.1, 1.0, 3.0, and 10 microg/mL. Participants included 10 nonallergic controls, 20 patients with a positive history and positive skin test results using UYJV, and 24 patients with a positive history but negative skin test results using UYJV (17 of whom had a positive IgE anti-YJV serology)., Results: Dialyzed venom skin test results were positive at 10 microg/mL or less in 79% of patients with a positive history but negative skin test reactions using UYJV. The dialyzed venom skin test results showed a half-log shift to the left from the undialyzed venom results in linear regression analysis, indicating a greater detection rate with skin tests using DYJV. Results of skin tests with dialyzed venom were positive in 3 of 4 patients who had negative undialyzed venom skin test results and who experienced a systemic reaction to challenge stings., Conclusions: The DYJV improves the ability of skin tests to detect yellow jacket allergy and should be subject to further study.

Background: The response to innate immune stimuli seems to be critical to conditioning adaptive immunity. Early exposure to endotoxin initiates immune responses that have been shown to alter the risk of asthma and allergic diseases. The toll-like receptor 4 (TLR4) gene encodes the principal innate immunity receptor in humans for bacterial endotoxin. Polymorphisms in the TLR4 gene may regulate the effects of endotoxin exposure and could play a role in the development of asthma and atopy-related phenotypes., Objective: To investigate the association between TLR4 polymorphisms and allergic phenotypes in nonsmokers., Methods: The data from 915 nonsmoking students were available for the study. The TLR4 299 and 399 polymorphisms were genotyped using mouthwash samples. The TLR4 299 and 399 polymorphisms were grouped together to define the TLR4 polymorphic group. Skin prick tests were conducted in a subgroup of healthy participants. A brief questionnaire was administered to determine demographic characteristics and chronic health conditions., Results: The prevalence of hay fever was 0% in the TLR4 polymorphic group and 7.5% in the wild-type group (P = .01). After controlling for age group and sex using logistic regression, the odds of having hay fever were reduced by 88% (P = .009) in the TLR4 polymorphic group compared with the wild-type group. In a subgroup analysis, the association between TLR4 polymorphisms and atopy was only observed among females., Conclusions: To our knowledge, this study is the first to report an association between TLR4 polymorphisms and atopy-related phenotypes in a nonsmoking population. Further investigation of the role of TLR4 polymorphisms in asthma and atopy-related phenotypes is warranted.

Background: Asthma is an inflammatory condition of the airways, and there is some evidence to suggest that it is associated with a systemic inflammatory response, as measured by C-reactive protein (CRP) and fibrinogen. Exhaled nitric oxide is a noninvasive measure of asthmatic airway inflammation., Objective: To determine if there is an association between exhaled nitric oxide and these systemic inflammatory markers., Methods: The Dunedin Multidisciplinary Health and Development Study is a birth cohort of approximately 1,000 individuals born between April 1, 1972, and March 31, 1973. At the age of 32 years, study members were assessed for diagnosis of asthma, atopy by skin prick testing, smoking, body mass index, exhaled nitric oxide, high-sensitivity serum CRP, and plasma fibrinogen level., Results: There was no significant association between exhaled nitric oxide and CRP (P = .99). There was a trend to an inverse association between exhaled nitric oxide and fibrinogen (P = .049), but this was not significant after adjusting for smoking and use of corticosteroids or after further adjustment for body mass index and atopy (P = .71)., Conclusion: In this population-based sample of young adults, there was no association between airway inflammation, as measured by exhaled nitric oxide, and systemic inflammation, as measured by either CRP or fibrinogen.

Background: Several risk factors for the development of asthma and atopic disease in children have been described. Furthermore, there is consistent evidence that the prevalence of atopy increases with higher socioeconomic status. The knowledge about risk factors and preventive factors for atopy needs to be improved., Objective: To compare 2 child populations (foster care and reference children) with different risk and protective factors for the development of atopy., Methods: The study group consisted of 415 children, living in all 10 community foster homes in Lodz, a large industrial city in Poland. The study was performed from April 2, 2004, to April 30, 2006. The reference group consisted of 500 children, living with their parents at home, recruited from primary care centers. The primary outcome measures were skin prick test results and specific IgE in serum. Secondary outcomes included symptoms of allergic diseases and family history, including life conditions in early childhood., Results: The full analysis set included 408 study children and 402 reference children. Significant differences were observed in the prevalence of atopy between the study and reference groups (11.3% vs 25.9%). We observed more positive skin prick test results in children from the reference group than in study children. To explain this phenomenon, we selected 16 variables that differ in both groups in early life and relate these to atopy. We found that the more cumulative features characteristic of the foster home population (poor living conditions), the lower the risk of atopy., Conclusion: Extremely unfavorable environmental circumstances, which are characteristic of the foster home population during early childhood, might prevent from atopy.

Background: Differences between children with atopic asthma (AA) and nonatopic asthma (non-AA) have been shown in epidemiologic studies. In developing countries, even when non-AA is more prevalent than AA among schoolchildren, no data are available regarding clinical, functional, and epidemiological differences between these 2 groups., Objective: To evaluate differences between Chilean children with AA and non-AA., Methods: In this cross-sectional study, skin prick tests were performed on all patients (age range, 4-14 years) admitted to our tertiary care hospital with the diagnosis of asthma who were consequently classified as having AA or non-AA. Demographic characteristics, spirometry results, exercise bronchial challenge test results, and eosinophil counts measured in the last 12 months were recorded., Results: Among the 237 asthmatic children, 62.5% had AA. Non-AA children had a significantly earlier onset of asthma and a more frequent history of pneumonia and tobacco consumption at home. Children with AA had higher nasal eosinophilia levels and a higher prevalence of dermatitis and severe exacerbation episodes of asthma in the past year (emergency department consultation and oral corticosteroids courses). Lung function was similar in both groups. After the multivariate analysis, only the number of oral steroid courses was significantly different between the groups and was associated with AA., Conclusions: In this selected population of asthmatic schoolchildren, the prevalence of non-AA (37.6%) is not negligible, and some differences between AA and non-AA children exist.

Background: Physicians who practice alternative medicine often prescribe bee pollen as a food supplement and a treatment for various ailments., Objectives: To determine the qualitative and quantitative composition of bee pollen and to investigate the cutaneous reactivity of atopic patients to bee pollen extracts., Methods: The absolute number of pollen grains per gram of bee pollen was calculated, and morphologic identification of the botanical family was performed. Five extracts of bee pollen were prepared for skin prick testing, according to standard methods. Two hundred two volunteers participated in the study; 145 were atopic patients with respiratory allergy. The remaining 57 were healthy volunteers or nonatopic patients and served as a control group. All participants underwent skin prick testing with a standard battery of 6 aeroallergens (olive, grasses mix, Parietaria, mugwort, Dermatophagoides pteronyssinus, and Dermatophagoides farinae) and with all homemade bee pollen extracts., Results: All samples of bee pollen contained Oleaceae pollen in high concentrations. Small amounts of anemophilous pollen (Compositeae, Chenopodiaceae) were detected in various samples. A strong positive correlation was observed between cutaneous reactivity to bee pollen extracts and olive, grasses, and mugwort., Conclusions: Bee pollen contains a large amount of pollen, which belongs to various allergenic families of plants. Bee pollen retains its allergenic potential as demonstrated by strong cutaneous responses to bee pollen extracts observed in atopic patients in contrast to nonatopic subjects. Regarding pollen allergic individuals, further studies are needed to evaluate the safety of ingesting large amounts of bee pollen.

Background: The allergist usually sees patients with anaphylaxis after the event for the purposes of identifying the cause, establishing a prognosis, and preventing further episodes. Knowledge of the characteristics of such patients is essential to achieve these goals., Objective: To examine the natural history, clinical manifestations, and factors that affect the patients' adherence to suggested treatment and preventive strategies of anaphylaxis., Methods: A retrospective medical record review spanning 25 years (1978-2003) and follow-up questionnaires were used to obtain data on 601 patients who presented with anaphylaxis of unknown origin to a private university-affiliated allergy-immunology practice., Results: Patients ranged in age from 1 to 79 years, with a mean age of 37 years. Females comprised 62% of cases. Causes of anaphylaxis were elucidated in 41% of cases. Known causes included foods in 131 patients (22%), medications in 69 cases (11%), and exercise in 31 cases (5%). Two hundred twenty-three patients (37%) were found to be atopic by history confirmed with skin prick testing. The most common manifestation was urticaria and/or angioedema, reported in 87% of patients. Systemic mastocytosis was found in 3 patients. Episodes tended to decline in frequency with time. Adherence to instructions to carry epinephrine can be improved with more effective teaching., Conclusions: In most cases, the cause of anaphylaxis is undetermined. Women are affected more commonly than men. Systemic mastocytosis should be considered in cases of idiopathic anaphylaxis, and patients with a history of atopy are at an increased risk of developing anaphylaxis. Patients are more reliably carrying epinephrine as a result of changes in physician instructions. Finally, anaphylactic episodes tend to decrease in frequency and severity with time.

Background: Results of epidemiologic studies have shown that childhood atopy is probably a hereditary disorder. In the atopic population, some individuals are sensitized to only 1 class of allergens (monosensitized), whereas others are sensitized to more than 1 class of allergens (polysensitized)., Objective: To investigate whether atopy and its profile (monosensitization/polysensitization) tend to coincide in sibling pairs., Methods: We evaluated sensitization to 5 classes of aeroallergens (house dust mites, animal danders, pollens, molds, and cockroach) using skin prick testing in 564 children with symptoms suggestive of allergic diseases (index children) and their paired siblings., Results: The frequency of sibling atopy was highest (56.8%) for polysensitized index children (n=222), intermediate (45.4%) for monosensitized index children (n=196), and lowest (30.8%) for nonsensitized index children (n=146). The proportion of polysensitization among atopic siblings was significantly higher for polysensitized (47.6%) than for monosensitized (32.6%) index children. Polysensitized index children were found to more frequently have polysensitized siblings (27.0%) than were monosensitized index children (14.8%), with an odds ratio of 2.13 (95% confidence interval, 1.30-3.49), whereas the likelihood of having a monosensitized sibling was similar for monosensitized and polysensitized index children., Conclusion: These data suggest a coincidence of atopy and its profile in terms of monosensitization and polysensitization in sibling pairs, although the relative importance of genetic and environmental influences requires further study.