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Approximately 60% of perioperative anaphylactic reactions are thought to be immunoglobulin IgE mediated, whereas 40% are thought to be non-IgE mediated hypersensitivity reactions (both considered non-dose-related type B adverse drug reactions). In both cases, symptoms are elicited by mast cell degranulation. Also, pharmacological reactions to drugs (type A, dose-related) may sometimes mimic symptoms triggered by mast cell degranulation. In case of hypotension, bronchospasm, or urticarial rash due to mast cell degranulation, identification of the responsible mechanism is complicated. However, determination of the type of the underlying adverse drug reaction is of paramount interest for the decision of whether the culprit drug may be re-administered. Neuromuscular blocking agents (NMBA) are among the most frequent cause of perioperative anaphylaxis. Recently, it has been shown that NMBA may activate mast cells independently from IgE antibodies via the human Mas-related G-protein-coupled receptor member X2 (MRGPRX2). In light of this new insight into the patho-mechanism of pseudo-allergic adverse drug reactions, in which as drug-receptor interaction results in anaphylaxis like symptoms, we critically reviewed the literature on NMBA-induced perioperative anaphylaxis. We challenge the dogma that NMBA mainly cause IgE-mediated anaphylaxis via an IgE-mediated mechanism, which is based on studies that consider positive skin test to be specific for IgE-mediated hypersensitivity. Finally, we discuss the question whether MRGPRX2 mediated pseudo-allergic reactions should be re-classified as type A adverse reactions., Competing Interests: The authors declare no conflict of interest.

Background: The association between early weight gain and later allergic outcomes has not been well studied. We examined the relation between weight gain and the subsequent development of allergic outcomes in the first 36 months of life in a Singapore birth cohort., Methods: In repeated visits in the first 15 months, we measured infant weight and administered questionnaires ascertaining allergic outcomes. At ages 18 and 36 months, we administered skin prick tests (SPTs) to inhalant and food allergens., Results: At 18 months, 13.5% had a positive SPT, 3.5% had wheeze and a positive SPT, 3.9% had rhinitis and a positive SPT, and 6.1% had eczema and a positive SPT. Higher weight gain from 6 to 9 months, 9 to 12 months and 12 to 15 months were independently associated with a reduced risk of developing a positive SPT at 18 months (p-trend ≤0.03). At 36 months, 23.5% had a positive SPT, 11.9% had wheeze and a positive SPT, 12.2% rhinitis and a positive SPT, and 11.5% eczema and a positive SPT. Higher weight gain from 12 to 15 months was associated with a reduced risk of developing a positive SPT at 36 months (p-trend <0.01). No significant associations were observed between weight gain in any period and wheeze, rhinitis or eczema combined with a positive SPT at 18 or 36 months., Conclusion: Higher weight gain in the first 15 months of life was associated with a reduced risk of allergen sensitization, but not with combinations of allergic symptoms., Trial Registration: NCT01174875 Registered 1 July 2010, retrospectively registered.

We conducted a prospective study to evaluate nasal signs and symptoms and to perform allergen-specific immunoglobulin E (IgE) testing to investigate the relationship between migraine and allergic rhinitis. Our study group consisted of 40 patients diagnosed with migraine-22 men and 18 women, aged 21 to 38 years (mean: 25.7). We compared their findings with a control group of 40 healthy adults-15 men and 25 women, aged 19 to 36 years (mean: 25.1). Allergen-specific IgE measurements were obtained with six groups of allergens: fungi, grass pollens, tree pollens, wild herbs, house dust mite 1, and house dust mite 2. We found no significant difference between the migraine patients and the controls in the incidence of nasal signs and symptoms (i.e., discharge, congestion, itching, and sneezing) or inferior turbinate signs (i.e., color and edema). According to the IgE assays, 14 migraine patients (35.0%) were sensitized to one or more allergens, compared with 11 of the controls (27.5%); the difference was not statistically significant. Sensitization was highest for the grass pollens panel in both groups. Even though we did not find an association between migraine and allergic rhinitis, the recent literature supports a correlation between migraine and atopy. The two conditions share common neural pathways and common mediators, and they can be linked statistically in patients and their families. A pathophysiologic association between the two conditions seems more likely than an etiologic association. In this regard, future efforts could be focused on the determination of atopy in migraine patients and the therapeutic implications of this diagnosis.

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: Rapid drug desensitization (RDD) has become a cornerstone in the management of immediate drug hypersensitivity reactions (DHRs) to chemotherapeutic agents. Because of the inherent risk of anaphylaxis during RDD, biomarkers to predict patients at risk of developing such severe reactions are needed. The basophil activation test (BAT) has been used in DHRs as a diagnostic tool., Objective: We evaluated basophil CD63 and CD203c expression (BAT) as a biomarker to assess the safety and effectiveness of RDD in platinum compounds-allergic patients., Methods: Patients allergic to platinum compounds (n = 15) undergoing RDD were assessed through clinical history, skin testing, serum tryptase levels, and BAT. BAT was performed immediately before RDD, assessing CD203c and CD63 expression on basophils. BAT was also performed in 6 patients tolerant to platinum compounds and in 6 healthy volunteers., Results: BAT was positive to CD203c or CD63 in 11 out of 15 patients allergic to platinum compounds (73%), with increased expression of CD203c and CD63 in 11 (73%) and 6 (40%) patients, respectively. Increased CD63 expression tended to be associated with more severe initial reactions. All controls had negative test results. Reactions during RDD were associated with BAT positivity and increased tryptase levels. Only 1 of 4 patients with negative BAT had a mild reaction during RDD. BAT remained positive in multiple sequential RDD., Conclusions: BAT identified patients allergic to platinum compounds with an increased risk of reactions during desensitization and higher CD63 expression was observed in severe reactions. Multiple RDDs to platinum compounds did not induce persistent hyporesponsiveness on basophils. BAT is a potential biomarker for RDD., (Copyright © 2016 American Academy 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: Antivenoms are mammalian immunoglobulins with the ability to neutralize snake venom components and to mitigate the progression of toxic effects. Immediate hypersensitivity to antivenoms often occurs during the first administration of these heterologous antibodies. A comparable clinical situation occurred after introduction of cetuximab, a chimeric mouse-human antibody, for cancer treatment. The carbohydrate epitope galactose-alpha-1,3-galactose, located on the Fab region of cetuximab, was identified as the target responsible for IgE reactivity., Objective: To investigate whether serum IgE antibodies directed to the α-gal epitope are associated with hypersensitivity to equine antivenoms., Methods: Antivenoms were screened for α-gal epitopes via immunoblot and in comparison with cetuximab and pork kidney by IgE reactivity assays. Basophil activation tests were used to investigate reactivity to antivenoms in samples from 20 patients with specific IgE antibodies to α-gal and 10 controls. Additional IgE detection, IgE inhibition, ImmunoCAP inhibition, and skin prick tests were performed using samples from selected patients., Results: Both antivenoms and cetuximab induced positive skin prick test results in patients with sIgE to α-gal. Alpha-gal epitopes were detected by immunoblotting on antivenoms. Measurements of IgE reactivity and ImmunoCAP inhibition indicated that the antivenoms contained lower α-gal contents than cetuximab. Deglycosylation assays and IgE inhibition tests confirmed that IgE-mediated reactivity to antivenom is associated with α-gal. Antivenoms, pork kidney, and cetuximab activated basophils from patients with IgE to α-gal., Conclusion: Alpha-gal is a potential target of IgE-mediated reactivity to equine antivenom and a possible cause of the high incidence of hypersensitivity reactions during the first application of equine antivenom., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.)

The environmental factors which may affect children's respiratory health are complex, and the influence and significance of factors such as traffic, industry and presence of vegetation is still being determined. We undertook a cross-sectional study of 360 school children aged 5-12 years who lived on the outskirts of a heavy industrial area in Western Australia to investigate the effect of a range of environmental factors on respiratory health using the forced oscillation technique (FOT), a non-invasive method that allows for the assessment of the resistive and reactive properties of the respiratory system. Based on home address, proximity calculations were used to estimate children's exposure to air pollution from traffic and industry and to characterise surrounding green space. Indoor factors were determined using a housing questionnaire. Of the outdoor measures, the length of major roads within a 50m buffer was associated with increased airway resistance (Rrs 8 ). There were no associations between distance to industry and FOT measures. For the indoor environment the presence of wood heating and gas heating in the first year of life was associated with better lung function. The significance of both indoor and outdoor sources of air pollution and effect modifiers such as green space and heating require further investigation., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

The definition, classification, pathogenesis, test methods, clinical findings, criteria for diagnosis, and therapies of allergic conjunctival disease are summarized based on the Guidelines for Clinical Management of Allergic Conjunctival Disease (Second Edition) revised in 2010. Allergic conjunctival disease is defined as "a conjunctival inflammatory disease associated with a Type I allergy accompanied by some subjective or objective symptoms." Allergic conjunctival disease is classified into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Representative subjective symptoms include ocular itching, hyperemia, and lacrimation, whereas objective symptoms include conjunctival hyperemia, swelling, folliculosis, and papillae. Patients with vernal keratoconjunctivitis, which is characterized by conjunctival proliferative changes called giant papilla accompanied by varying extents of corneal lesion, such as corneal erosion and shield ulcer, complain of foreign body sensation, ocular pain, and photophobia. In the diagnosis of allergic conjunctival diseases, it is required that type I allergic diathesis is present, along with subjective and objective symptoms accompanying allergic inflammation. The diagnosis is ensured by proving a type I allergic reaction in the conjunctiva. Given that the first-line drug for the treatment of allergic conjunctival disease is an antiallergic eye drop, a steroid eye drop will be selected in accordance with the severity. In the treatment of vernal keratoconjunctivitis, an immunosuppressive eye drop will be concomitantly used with the abovementioned drugs., (Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

To assess the associations of obesity with newly diagnosed and previously known atopic disorders in Chinese adults. 4,629 adults aged 18 years or older were recruited in Harbin, China. Among them, 1,114 were previously diagnosed atopic cases, 1,298 were newly diagnosed cases, and 2,217 non-atopic controls. Obesity and overweight are defined according to the criteria established by the Working Group on Obesity in China. The associations of obesity with known and newly diagnosed atopic disorders were assessed using logistic regressions. Obesity was significantly associated with known atopic disorders (adjusted OR = 2.41 (95% CI: 1.81, 3.22)). The association of obesity with newly diagnosed atopic cases was not as strong as that with known cases, and was not statistically significant (adjusted OR = 1.27 (95% CI: 0.94, 1.72)). The similar pattern was observed in different allergic diseases, gender and age stratifications. The association between overweight and atopic diseases were not significant. Obesity is strongly associated with previously diagnosed atopic cases but not so with newly diagnosed atopic cases in Chinese adults. It is likely that people with atopic disorders have a higher risk of developing obesity. Our findings are important for the management of atopic disorders and chronic disease prevention among atopic disease patients.

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.)

Purpose: To investigate predictors of discordance between symptoms and signs in dry eye disease (DED)., Design: Cross-sectional association study., Participants: A total of 648 patients with dry eye from the Groningen LOngitudinal Sicca StudY (GLOSSY), a tertiary dry eye clinic patient cohort from the Netherlands., Methods: Patient symptoms were assessed using the Ocular Surface Disease Index (OSDI) questionnaire. Dry eye signs were assessed by tear osmolarity, Schirmer test, tear breakup time, corneal and conjunctival staining, and meibomian gland dysfunction, all in both eyes, and a composite dry eye signs severity score was calculated from these 6 tests for each patient. Linear regression analysis was used to test the association of discordance between symptoms and signs with a wide range of independent variables (demographic and environmental variables, systemic diseases, ocular traits, and medications)., Main Outcome Measures: Predictors of discordance between symptoms and signs in DED, defined by the difference between the rank score of the OSDI and the rank score of the dry eye signs severity score., Results: Of the 648 subjects in this cohort, 536 (82.7%) were female and the mean age was 55.8 years (standard deviation, 15.6 years). Significant predictors of greater symptoms than signs were the presence of a chronic pain syndrome, atopic diseases, a known allergy, the use of antihistamines (all P < 0.001), depression (P = 0.003), osteoarthritis (P = 0.008), and the use of antidepressants (P = 0.02). Predictors of lesser symptoms than signs were increased age (P < 0.001) and the presence of Sjögren's disease (P < 0.001) (primary Sjögren's disease, P < 0.001) more than secondary Sjögren's disease (P = 0.08), and graft-versus-host disease (P = 0.04). Furthermore, greater symptoms compared with signs were highly associated with lower self-perceived health (P < 0.001)., Conclusions: This large clinical study has shown that discordance between symptoms and signs in DED is an indicator of self-perceived health. The study found important predictors of greater symptoms to signs but also predictors of lesser symptoms to signs. Awareness of these predictors is helpful in assessing patients with dry eye in clinical practice., (Copyright © 2016 American Academy of Ophthalmology. All rights reserved.)

Background: Bronchial asthma is a chronic inflammatory and remodeling disorder of the airways, in which many cells, cellular elements, and cytokines play important roles. Stem cell factor (SCF) may contribute to the inflammatory changes occurring in asthma. We aimed to show the expression of SCF gene in patients with asthma as a means of diagnosis and its association with severity and atopic state in these patients., Methods: This study was carried out on 80 subjects, 50 asthmatic patients and 30 age and gender matched healthy control persons. They were subjected to full history taking, general and local chest examination, spirometric measurements (pre and post broncodilators) using a spirometer, serum IgE, and real time PCR for assessment of SCF mRNA expression., Results: This study showed significant difference between the studied groups regarding pulmonary function tests (P < 0.001). Asthmatic patients had significant higher SCF expression compared to control (P < 0.001), also atopic patients vs non atopic (P = 0.03) and severe asthmatic patients vs mild ones (P < 0.001). SCF expression at cut off point (0.528) is sufficient to discriminate asthmatic patients from control while at cut off point (1.84) for discrimination of atopic patients from non-atopic patients and at cut off point (1.395) for discrimination of severe asthmatic patients from mild ones. A significant negative correlation between SCF expression and inhaled steroid while significant positive correlation with serum IgE was found., Conclusion: Measuring SCF mRNA expression can be used as an efficient marker for evaluation of atopy and detection of severity of bronchial asthma.

Background and Objective: Eosinophilic esophagitis (EoE) is an increasingly prevalent chronic inflammatory disease of the esophagus with an immunoallergic etiology. Few studies have been published on EoE in children and adolescents. The objective of this study was to analyze the demographic, clinical, serologic, endoscopic-histologic, and atopic characteristics of pediatric patients with EoE and to identify atopic and digestive comorbidities., Methods: We conducted a prospective observational study in children and adolescents (<16 years) assessed in a specialized multidisciplinary EoE unit in a tertiary referral hospital in a central region of Spain between 2011 and 2015., Results: Thirty-five patients were included in the study. Twenty-eight (80%) were male. The mean age was 9.6 years, 83% were atopic, and 28% reported a family history of atopy. The most common symptom was dysphagia (51%). Eosinophilia was detected in the blood of 60% of patients. Eosinophil cationic protein and total IgE were elevated in 88% and 77% of patients, respectively. The most frequent endoscopic finding was linear grooves (57%). Skin tests with aeroallergens were positive in 82% of patients (pollen 62% and food 60%). The main atopic comorbidities were asthma (48%) and rhinoconjunctivitis (37%). Digestive diseases were more often associated with gastritis and Helicobacter pylori infection (17%)., Conclusions: Our results are similar to those previously reported. EoE is more common in boys and in individuals with a history of atopy and sensitization to airborne allergens and food. These results support the consideration of EoE as an atopic disease and underline the important role of allergists in early diagnosis and treatment.

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.)

European Network on Drug Allergy (ENDA) has proposed an algorithm for diagnosing immediate beta-lactam (BL) allergy. We evaluated its performance in real life. During 1994-2014, 1779 patients with suspected immediate reactions to BL were evaluated following ENDA's short diagnostic algorithm. Five hundred and nine patients (28.6%) were diagnosed of BL hypersensitivity. Of them, 457 (25.7%) were at first evaluation [403 by skin tests (ST), 12 by positive IgE and 42 by controlled provocation tests (CPT)]. At second evaluation (SE), 52 additional patients (10.2% of allergic patients) were diagnosed, [50 (2.8%) by ST and 2 (0.1%) by CPT]. Time between reaction and study was significantly longer in patients diagnosed at SE (median 5 vs 42 months; IQR 34 vs 170; P < 0.0001). Anaphylaxis was significantly associated with a diagnosis at SE. European Network on Drug Allergy/EAACI protocol was appropriate and safe when evaluating BL immediate reactions. Re-evaluation should be performed, particularly when anaphylaxis and long interval to diagnosis are present., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Although the low incidence of immediate-type gadolinium-based contrast agent (GBCA) allergic reactions is widely known, preventing these reactions and properly managing them to reduce their adverse sequel can improve the already exceedingly favorable GBCA safety profile. This review article should help those who order, supervise, or administer GBCA contrast agents, including recognizing and handling allergic reaction risks intrinsic to their use. Areas of focus include factors indicating increased allergic reaction risk, patient selection strategies, skin testing, premedication, and treatment of adverse events.

Problem: Maternal atopy is a risk factor for allergy. B cells are poorly studied in reproduction and atopy. We aimed to assess how pregnancy affects B cells in atopic women and whether B cells relate to allergic manifestations in offspring., Method of Study: Women with and without atopic asthma, pregnant and non-pregnant were enrolled for the study, and circulating B cells were evaluated by flow cytometry, using CD19, CD27, CD38, IgD, and IgM., Results: Compared to healthy non-pregnant, atopic asthmatic non-pregnant (ANP) women presented increased B cell counts, enlarged memory subsets, less transitional cells, and plasmablasts. Atopic asthmatic pregnant (AP) and healthy pregnant (HP) women showed similarities: reduced B cell counts and percentages, fewer memory cells, especially switched, and higher plasmablast percentages. Transitional B cell percentages were increased in AP women with allergic manifestations in their progeny., Conclusion: Atopic asthmatic non-pregnant women have a distinctive B cell compartment. B cells change in pregnancy, similarly in AP and HP women. The recognition that AP women with allergy in their progeny have a typical immune profile may help, in the future, the adoption of preventive measures to avoid the manifestation of allergic diseases in their newborns., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objective: Obesity is associated with an increased risk of asthma in children. Atopic sensitization is a major risk factor for asthma including severe asthma in children. It is unclear if obesity is associated with worse asthma control or severity in children and how its effects compare to atopy. We sought to examine relationships of weight status and atopy to asthma control and severity among a population of predominantly low income, minority children and adolescents with persistent asthma., Methods: A cross-sectional analysis of 832 children and adolescents, age range 5-17 years, with persistent asthma was performed. Clinical assessments included asthma questionnaires of symptoms, asthma severity score, health care utilization and medication treatment step, lung function testing, and skin prick testing as well as measures of adiposity. Data were collected between December 2010 and August 2014 from Johns Hopkins Hospital in Baltimore, MD and Children's Hospital of Boston, MA., Results: Obesity was not associated with worse asthma control or severity in this group of predominantly low income, minority children and adolescents with persistent asthma. However, a greater degree of atopy was associated with lower lung function, higher asthma severity score, and higher medication treatment step., Conclusion: Atopy may be a more important risk factor for asthma severity than obesity among low-income minority children and adolescents with persistent asthma living in Northeastern cities in the United States., Competing Interests: Declaration of Interest All of the authors have indicated they have no potential conflicts of interest to disclose. All of the authors have indicated they have no financial relationships relevant to this article to disclose.

IgE-associated allergic diseases belong to the most common inflammatory conditions. Their clinical manifestation ranges from mild symptoms to life-threatening episodes. Often patients experience a reduction in physical and psychologic well-being and suffer from a decreased quality of life due to disease activity. The continuously rising number of people that are affected by an allergic condition indicates an urgent need for better diagnostics and more efficient treatment options. Recent progress in the understanding of pathophysiologic mechanisms underlying IgE-associated allergic disorders has led to the identification of novel therapeutic targets and the development of drug candidates that are currently under evaluation. In this review, we highlight studies and clinical trials, which have helped to gain further insight in the etiology of IgE-associated allergic conditions as well as advances in the development of diagnostic tools and therapeutic approaches recently published in Allergy (European Journal of Allergy and Clinical Immunology)., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Acute nonrenal adverse reactions to gadolinium-based contrast agents are infrequent and occur often unexpectedly. Most reactions are self-limiting and do not require treatment. The remaining adverse reactions are either moderate or severe and they require medical treatment. Prompt and effective treatment is very important and requires knowledge, training, and preparation.

Atopic conditions (atopic dermatitis, rhinitis, and asthma) belong to the most common noncommunicable diseases and are driven by chronic inflammatory reactions. They have a strong impact on the quality of life and represent a substantial and growing socio-economic burden. Interestingly, there is an increasing interest in the development of new therapeutic options with a number of biologics and small molecules targeting potential key mechanisms in atopic conditions. However, besides the safety issue, most of the new active substances are still evaluated according to the traditional efficacy paradigm focusing on the success in treating exacerbations and flares. Instead, the future approaches in drug development and assessment should rather concentrate on the long-term control of these diseases and consider their potential as disease-modifying strategies in the era of precision medicine. To reach this goal, a number of unsolved issues have to be addressed and consensually accepted by the stakeholders in this field. Thus, a successful and rapid development of new treatments requests a paradigm shift and a new way of thinking in the mind of physicians, pharmaceutical industry, regulators, and HTAs. This seems mandatory in order to optimize drug development and to facilitate the accessibility of new therapies to the growing population of patients suffering from atopic conditions on a global level., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The aim of this paper was to review the classification of adverse drug reactions, highlight the known pathophysiology of immediate hypersensitivity reactions, and discuss the utility of diagnostic testing for immunologically mediated immediate reactions to gadolinium-based contrast agents (GBCAs)., Methods: Current literature on immediate reactions to GBCA was reviewed and summarized., Results: Adverse drug reactions to GBCA are rare, and can be attributed to physiologic, immunologic, and nonimmunologic processes. When immunologic reaction is suspected, particularly in the case of severe reactions, skin testing may be useful to confirm allergy and identify alternative agents for subsequent studies., Conclusion: As GBCAs are widely used for the diagnosis and monitoring of disease, the incidence of adverse drug reactions to GBCA warrants ongoing development of approaches to diagnosis and avoidance of these adverse events.

Background: The skin prick test (SPT) is a valid and approved tool that is used to diagnose atopic diseases. The SPT is accurate, safe, simple and inexpensive. However, the histamine concentration used as a positive control in the SPT varies among centers., Objective: To compare SPT results using different concentrations of locally-prepared and imported histamine solutions., Method: This prospective, randomized, double-blind, self-controlled study was performed in healthy adult volunteers. The SPT was performed using 4 concentrations of histamine solutions (imported, 1 mg/mL; locally-prepared, 1, 5 and 10 mg/mL). Locally-prepared histamine positive controls were prepared from histamine biphosphate monohydrate using sterile technique., Results: Seventy-five adult volunteers (mean age, 36 years) were included in the study. Eight volunteers were male and 9 had a history of atopy. Mean wheal diameter (MWD) for imported histamine was 3.49 mm for a concentration of 1 mg/mL, and that of locally-prepared histamine was 2.94 mm, 5.05 mm and 5.52 mm for concentrations of 1, 5 and 10 mg/mL histamine, respectively. Negative SPT results (MWD <3 mm) were found in 11 subjects (14.7%) who received imported histamine and 26 subjects (34.7%) who received the locally-prepared histamine at concentration of 1 mg/mL. All subjects tested with locally-prepared histamine at concentrations of 5 and 10 mg/mL had a MWD > 3 mm., Conclusions: Locally-prepared histamine base at concentrations of 5 and 10 mg/mL yielded better positive results than both imported and locally-prepared histamine at a concentration of 1 mg/mL.

Background: High serum basal tryptase (sBT) levels have been identified as a risk factor for both venom- and food-induced severe allergic reactions. The aim of this study was to compare sBT levels in children with different severity of actual drug hypersensitivity reactions (DHRs) with those of age- and sex-matched controls without any history of DHRs., Method: Patients between 0 and 18 years of age with a history of immediate-type DHRs manifested in 0-6 h after the culprit drug intake were included. Following ENDA (European Network for Drug Allergy) inquiries, patients were evaluated with skin and/or provocation tests to define the actual drug-hypersensitive patients. Serum BT levels were determined for both patients and controls., Results: Of 345 children, 106 patients (30.7%) [(58.5% male), median age (interquartile range) 8.0 years (4.2-12.2)] were diagnosed as drug hypersensitive. Ninety-eight controls were also included. The sBT levels of drug-hypersensitive patients with and without anaphylaxis and the control group were similar [2.6 (2.0-3.6) μg/l vs. 2.8 (1.6-4.3) μg/l vs. 2.6 (1.8-3.6) μg/l, respectively, (p > 0.05)]. The sBT levels of the patients with sole cutaneous symptoms 2.8 (1.6-4.3) μg/l, mild anaphylaxis 3.0 (1.9-4.9) μg/l, and moderate-to-severe anaphylaxis 2.6 (2.0-3.6) μg/l were also comparable (p > 0.05). The onset of DHRs [those occurring in 1 h (n = 87) or in 1-6 h (n = 19) after the drug intake], positive results with skin tests with the culprit drug, or the classification of the patients according to different age groups [(0-2 years), (2-6 years), (6-12 years), (12-18 years)] did not correlate with sBT levels., Conclusion: The sBT levels in children with actual drug hypersensitivity would not be a risk factor for severe systemic reactions on the contrary to children with allergic reactions to food or insect venom., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Several seeds have been increasingly incorporated in various food items, with consequent risk of hypersensitivity reactions that are often severe. Identification of the specific seed as the culprit is often not explored or is difficult to verify. In this article, we reviewed the English literature from January 1930 to March 2016 using PubMed and Google Scholar searching for publications relevant to hypersensitivity to common edible seeds, namely sesame, sunflower seed, poppy seed, pumpkin seed, flaxseed, and mustard seed. Considering the worldwide consumption of those seeds, the number of published articles on the subject was relatively small and was mainly as case reports rather than large series. Allergy to sesame was more reported than to other seeds, with an estimated prevalence of 0.1-0.2%. In this review, we summarize the information relevant to each of the six seeds and their oils regarding the manifestations, routes of exposure, identified major allergens, and cross-reactivity with other seeds or other foods. We also addressed the important role of a thorough history taking in suspecting seed allergy, the limited reliability of routine diagnostic procedures, and the importance of verification by appropriate challenge tests. At present, management is basically dietary avoidance and the use of symptomatic medications that may include epinephrine auto-injectors. We did not encounter any well-designed studies on immunotherapy for seed allergy, but it is hoped that such a gap be filled by the development of safe effective protocols in the near future., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The diagnosis of a perioperative allergic reaction is based on clinical features associated with a suggestive timeline, the exclusion of other diagnoses, elevated concentrations of degranulation markers (histamine, tryptase), and positive allergy assessments (skin tests, specific IgE). After initiating appropriate treatment, the anesthesiologist should take blood samples to measure histamine and tryptase concentrations just after the reaction and repeat them 1-2hours later to validate the diagnosis of immediate hypersensitivity. A delayed measurement of basal tryptase is useful to rule out mastocytosis and to interpret moderate tryptase levels. The anesthesiologist must inform the patient of the reaction to obtain adhesion and consent to subsequent investigations and must record the timing of the reaction and of the blood sampling, the possible causal agents, and the treatment administered. These data must be shared with the laboratory and the allergist. An adverse drug reaction report must be filed. The gold standard for allergy assessment is skin testing. These tests should be done in an appropriate facility, with experienced staff and in compliance with current guidelines. Specific IgE assays and cellular assays can help when clinical features and skin tests are discordant. Provocation tests are sometimes required. After allergy assessment, the safest protocol for subsequent anesthesia is determined in collaboration with the anesthesiologist. The patient must be informed and carry an allergy alert card., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The prevalence of allergic conditions has continuously increased in the last few decades in Westernized countries. A dysbiotic gut microbiome may play an important role in the development of allergic diseases. Genetic, environmental, and dietary factors may alter the commensal microbiota leading to inflammatory dysregulation of homeostasis. Murine and human studies have begun to elucidate the role of the microbiota in the pathogenesis of atopic diseases including asthma, atopic dermatitis, and food allergies. However, the role of the microbiome in most eosinophilic gastrointestinal diseases (EGIDs) is not yet known. This review provides an overview of what is currently known about the development of tolerance from both molecular and clinical standpoints. We also look at the gut-specific microbiome and its role in atopic conditions with the hope of applying this knowledge to the understanding, prevention, and treatment of EGIDs, particularly EoE., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: For many physicians, quantification of serum drug-specific IgE (sIgE) antibodies constitutes the first measure in the diagnostic approach of immediate drug hypersensitivity reactions (IDHR)., Aim: To review the accuracy and limitations of the main drug-sIgE tests, especially those that are commercially available., Methods: A literature search was conducted, using the key-words allergy, diagnosis, drugs, hypersensitivity, specific IgE antibodies; this was complemented by the authors' own experience., Results: The drugs that have mostly been studied appeared to be β-lactam antibiotics, neuromuscular blocking agents (NMBA) and morphine, the latter as a biomarker for sensitisation to substituted ammonium structures that constitute the major epitope of NMBA. For β-lactams sensitivity and specificity varied between 0-85% and 52-100%, respectively. For NMBA, sensitivity and specificity varied between 38.5-92% and 92-100%, respectively. With respect to sIgE to morphine it appears this drug to be a sensitive biomarker for sensitisation to rocuronium and suxamethonium but not for atracurium. However, sIgE morphine should not be applied in isolation to diagnose IDHR to NMBA nor opiates., Conclusions: Although drug-sIgE assay can provide valuable information they should not be performed in isolation to establish correct diagnosis, as their predictive value is not per se absolute. Larger comprehensive studies are urgently required to determine the accuracy of drug-sIgE assays., (Copyright © 2016. Published by Elsevier B.V.)

Polyethylene glycols (PEGs) or macrogols are polyether compounds widely used in medical and household products. Although generally considered biologically inert, cases of mild to life-threatening immediate-type PEG hypersensitivity are reported with increasing frequency. Nevertheless, awareness of PEG's allergenic potential remains low, due to a general lack of suspicion towards excipients and insufficient product labelling. Information on immediate-type reactions to PEG is limited to anecdotal reports, and the potential for PEG sensitization and cross-sensitization to PEGylated drugs and structurally related derivatives is likely underestimated. Most healthcare professionals have no knowledge of PEG and thus do not suspect PEG's as culprit agents in hypersensitivity reactions. In consequence, patients are at risk of misdiagnosis and commonly present with a history of repeated, severe reactions to a range of unrelated products in hospital and at home. Increased awareness of PEG prevalence, PEG hypersensitivity, and improved access to PEG allergy testing, should facilitate earlier diagnosis and reduce the risk of inadvertent re-exposure. This first comprehensive review provides practical information for allergists and other healthcare professionals by describing the clinical picture of 37 reported cases of PEG hypersensitivity since 1977, summarizing instances where PEG hypersensitivity should be considered and proposing an algorithm for diagnostic management., (© 2016 John Wiley & Sons Ltd.)

Background: Although ibuprofen and other arylpropionic acid derivatives (APs) are the most common medicines involved in hypersensitivity drug reactions (HDRs) to NSAIDs, no patient series studies have been performed regarding immediate selective reactions (SRs) to these drugs., Objective: To characterize patients with immediate selective HDRs to ibuprofen and other APs through clinical history and challenge., Methods: Subjects who developed an HDR to APs less than 1 h after drug intake were included. Tolerance to aspirin was assessed and challenge was performed with ibuprofen in all cases, and additionally with the culprit drug (if different) in those patients that tolerated ibuprofen. Serum tryptase levels and tryptase immunohistochemical staining in skin biopsies were also assessed in some patients with a positive DPT to ibuprofen., Results: From a total of 245 patients with a confirmed history of HDRs to APs, 17% were classified as selective immediate hypersensitivity reactors by both clinical history and challenge. A selective response to naproxen and dexketoprofen with tolerance to ibuprofen was found in 16 of 20 cases. Significant differences in serum tryptase levels were observed between 2 and 24 h in the 11 cases that were studied further., Conclusions: Within the group of patients with HDRs to NSAIDs, APs can induce immediate SRs. Within this group, selective responses to a single drug or responders to several APs may exist, suggesting potential immunological cross-reactivity., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The term "breakthrough reactions" designates repeated hypersensitivity reactions to iodinated contrast media (ICM) despite premedication with glucocorticoids and antihistamines. We aimed to retrospectively evaluate the rate of positive skin test (STs) in our cohort of patients with previous breakthrough reactions to different ICMs., Methods: A series of 35 patients, who experienced at least one breakthrough reaction to ICM and who underwent STs within 6 months from the reaction were studied, and results were compared to a control group of patients with a first hypersensitivity reaction occurred without premedication. Skin prick tests (SPT), intradermal tests (IDT) and patch tests (PT) at different dilutions, with a set of three to four ICM were performed., Results: Of the 35 patients with prior breakthrough reactions, 57% had an immediate reaction (IR) and 43% had a non-immediate reaction (NIR). Patients who experienced the first hypersensitivity IR or NIR, later had one or more breakthrough IR or NIR, respectively. Overall, 29% (10/35) of patients with prior breakthrough reactions resulted positive to STs compared to 57% (16/28) of the control group (p < 0.05). No significant difference in allergy history, age, sex, other clinical / demographic features nor chronic use of ACE-inhibitor, beta-blockers or NSAIDs was observed., Conclusion: This preliminary finding suggests that patients with prior breakthrough reactions have significantly lower immunologically proven ICM reactions (positive STs) if compared to non-breakthrough patients. According to that, a considerable number of breakthrough reactions seems to be non-allergic hypersensitivity reactions or reactions which could be mostly prevented by a proper, well-timed skin testing. Larger prospective studies are needed to confirm these results, with a more careful analysis of patients' risk factors, a laboratory assessment that includes an in vitro allergy diagnostics, and hopefully a drug provocation test for selected cases.

Importance: The diagnostic properties of a graded provocation challenge (PC) among children presenting with a rash in the course of amoxicillin treatment are currently unknown., Objective: To assess the accuracy and the negative predictive value of the PC in a cohort of children referred with suspected allergy to amoxicillin., Design, Setting, and Participants: A cohort study was conducted between March 1, 2012, and April 1, 2015, at the allergy clinic of the Montreal Children's Hospital, Montreal, Quebec, Canada. All children referred with suspected allergy to amoxicillin were approached. In addition, 346 eligible children were followed up to assess reactions to subsequent use of amoxicillin at the time of illness in cases with negative PC results. Data were collected on clinical characteristics, suspected antibiotic exposure, personal and first-degree relatives' comorbidities, and history of atopy and management of the reaction. Univariate and multivariate logistic regressions were compared to determine factors associated with immediate and nonimmediate reactions to the PC., Interventions: All children had a graded PC., Main Outcomes and Measures: Reactions to the graded PC, the negative predictive value of the PC for nonimmediate reactions, and factors associated with immediate and nonimmediate reactions to the PC., Results: A total of 818 children were assessed (median age, 1.7 years [interquartile range, 1.0-3.9 years]; 441 [53.9%] male). Among all participants, 770 (94.1%) tolerated the PC, 17 (2.1%) developed mild immediate reactions, and 31 (3.8%) developed nonimmediate reactions. The graded PC had a specificity of 100.0% (95% CI, 90.9%-100.0%), a negative predictive value of 89.1% (95% CI, 77.1%-95.5%), and a positive predictive value of 100.0% (95% CI, 86.3%-100.0%). Among all 346 participants eligible for annual follow-up, 250 (72.3%; 95% CI, 67.2%-76.8%) responded, 55 of whom received subsequent full treatment with amoxicillin; 49 of these 55 participants (89.1%) reported tolerance to subsequent full treatment with amoxicillin, while 6 (10.9%) developed nonimmediate cutaneous reactions. History of a reaction occurring within 5 minutes of exposure was associated with immediate reactions to the PC (adjusted odds ratio = 9.6; 95% CI, 1.5-64.0), while a rash that lasted longer than 7 days (adjusted odds ratio = 4.8; 95% CI, 1.4-16.4) and parental history of drug allergy (adjusted odds ratio = 3.0; 95% CI, 1.3-6.8) were associated with nonimmediate reactions to the PC., Conclusions and Relevance: Graded PCs provide an accurate and safe confirmatory test for skin-related reactions to amoxicillin. Further studies are required to assess factors associated with the PC outcome groups.

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) take first or second place as the cause of drug-induced hypersensitivity reactions. The oral provocation test (OPT) is a gold standard for the diagnosis of NSAID hypersensitivity. We investigated which analgesics patients took after a negative OPT and determined the proportion of patients that experienced a hypersensitivity reaction despite a negative OPT., Methods: We selected 115 patients (67.8% female, age 54.9 ± 16.7 years) with a negative aspirin OPT and a convincing history of immediate hypersensitivity to aspirin or NSAIDs. In a telephone survey, we identified the analgesics taken after the OPT and possible adverse events., Results: The mean follow-up time was 5.1 ± 2.0 years. All subjects needed at least one analgesic drug. Despite the negative outcome of the aspirin OPT, only 33.9% of subjects took aspirin and 0.9% had a hypersensitivity reaction. The negative predictive value (NPV) of the aspirin OPT was 97.4%. Overall, 16 (13.9%) subjects experienced a hypersensitivity reaction, 12 of which occurred after taking a drug not tested with the OPT. The NPV of the OPT for all NSAIDs was 96.4%., Conclusions: Our results support the available data that most subjects do not re-take the tested drug regardless of the high NPV of the OPT.

Although fluoroquinolones (FQs) are generally well-tolerated antibiotics, increasing numbers of hypersensitivity reactions have been reported. These can be evaluated in vitro by basophil activation tests (BATs); however, sensitivity is not optimal. Many factors could influence sensitivity such as basophil activation markers. The objective of this study was to evaluate the influence of 2 different activations markers, CD63 and CD203c, on the sensitivity of BAT to FQ. We studied 17 patients with immediate allergic reactions to FQ. BAT was performed with moxifloxacin and ciprofloxacin using CD193 (CCR3) for basophil selection and CD203c or CD63 as activation markers. Stimulation with ciprofloxacin induced a significantly higher expression of CD63 in ciprofloxacin-allergic patients compared to moxifloxacin-allergic patients (P = 0.002). In patients allergic to moxifloxacin with anaphylactic shock, we have observed an increase in the percentage of cells that upregulate CD203c, whereas patients with anaphylaxis preferentially upregulate CD63. The best sensitivity-specificity was obtained using a cutoff of 3 and the culprit FQ, using CD203c for moxifloxacin-allergic patients (sensitivity = 36.4%; specificity = 94.4%), and CD63 for ciprofloxacin-allergic patients (sensitivity = 83.3%; specificity = 88.9%). A negative correlation was found between the upregulation of CD63 and CD203c and the time interval between the reaction occurrence and the performance of the test (Spearman r = -0.446; P < 0.001 for CD63 and Spearman r = -0.386; P < 0.001 for CD203c). The performance of BAT for FQ allergy must be optimized for each drug, taking into account possible differences in the stimulation mechanism that leads to the upregulation of different activation markers.

Background: Skin prick test (SPT) is a common test for diagnosing immunoglobulin E-mediated allergies. In clinical routine, technicalities, human errors or patient-related biases, occasionally results in suboptimal diagnosis of sensitization., Objective: Although not previously assessed qualitatively, lancet weight is hypothesized to be important when performing SPT to minimize the frequency of false positives, false negatives, and unwanted discomfort., Methods: Accurate weight-controlled SPT was performed on the volar forearms and backs of 20 healthy subjects. Four predetermined lancet weights were applied (25 g, 85 g, 135 g and 265 g) using two positive control histamine solutions (1 mg/mL and 10 mg/mL) and one negative control (saline). A total of 400 SPTs were conducted. The outcome parameters were: wheal size, neurogenic inflammation (measured by superficial blood perfusion), frequency of bleeding, and the lancet provoked pain response., Results: The mean wheal diameter increased significantly as higher weights were applied to the SPT lancet, e.g. from 3.2 ± 0.28 mm at 25 g to 5.4 ± 1.7 mm at 265 g (p<0.01). Similarly, the frequency of bleeding, the provoked pain, and the neurogenic inflammatory response increased significantly. At 265 g saline evoked two wheal responses (/160 pricks) below 3 mm., Conclusion and Clinical Relevance: The applied weight of the lancet during the SPT-procedure is an important factor. Higher lancet weights precipitate significantly larger wheal reactions with potential diagnostic implications. This warrants additional research of the optimal lancet weight in relation to SPT-guidelines to improve the specificity and sensitivity of the procedure.

Background: Immunologists often measure several correlated immunological markers, such as concentrations of different cytokines produced by different immune cells and/or measured under different conditions, to draw insights from complex immunological mechanisms. Although there have been recent methodological efforts to improve the statistical analysis of immunological data, a framework is still needed for the simultaneous analysis of multiple, often correlated, immune markers. This framework would allow the immunologists' hypotheses about the underlying biological mechanisms to be integrated., Results: We present an analytical approach for statistical analysis of correlated immune markers, such as those commonly collected in modern immuno-epidemiological studies. We demonstrate i) how to deal with interdependencies among multiple measurements of the same immune marker, ii) how to analyse association patterns among different markers, iii) how to aggregate different measures and/or markers to immunological summary scores, iv) how to model the inter-relationships among these scores, and v) how to use these scores in epidemiological association analyses. We illustrate the application of our approach to multiple cytokine measurements from 818 children enrolled in a large immuno-epidemiological study (SCAALA Salvador), which aimed to quantify the major immunological mechanisms underlying atopic diseases or asthma. We demonstrate how to aggregate systematically the information captured in multiple cytokine measurements to immunological summary scores aimed at reflecting the presumed underlying immunological mechanisms (Th1/Th2 balance and immune regulatory network). We show how these aggregated immune scores can be used as predictors in regression models with outcomes of immunological studies (e.g. specific IgE) and compare the results to those obtained by a traditional multivariate regression approach., Conclusion: The proposed analytical approach may be especially useful to quantify complex immune responses in immuno-epidemiological studies, where investigators examine the relationship among epidemiological patterns, immune response, and disease outcomes.

Objective: To identify house dust mite (HDM) sensitivity by skin prick test in children with allergic rhinitis, allergic wheezing and eczema., Methods: In this prospective study, children with persistent or recurrent allergic symptoms of rhinitis, wheezing and eczema were enrolled to undergo skin prick testing. Sensitivity was checked for three mites: Dermatophagoide farinae, Dermatophagoide pteronyssinus, and Blomia tropicalis., Results: Total 92 children underwent skin prick test; 49 (53.2 %) showed significant positivity to one or more dust mite. In the HDM sensitized group, a positive family history of allergic disorders was present in 32 children (65.3 %). In the HDM sensitized group, 18 (36.7 %) children had allergic rhinitis. The youngest child in this group was 12-mo-old. Ten (55.55 %) children were less than 24 mo of age. Significant sensitization to mites was detected in 7 (14.28 %) children with eczema. All children were below 24 mo of age. In children with a tendency to wheeze frequently without any evidence of infections or other systemic disease, 24 (48.9 %) had sensitization to HDM. The youngest child was 15 mo of age. Ten (41.6 %) children were below 24 mo of age. Sensitivity to Blomia tropicalis was detected in 6 (12.24 %) children. Significantly more number of children were sensitive to D. pteronyssinus as compared to D. farinae (65.31 % vs. 46.94 %; p = 0.034)., Conclusions: Children in Mumbai show early sensitization to HDM. D. pteronyssinus is the commonest offending allergen in the index study.

The availability of allergen molecules ('components') from several protein families has advanced our understanding of immunoglobulin E (IgE)-mediated responses and enabled 'component-resolved diagnosis' (CRD). The European Academy of Allergy and Clinical Immunology (EAACI) Molecular Allergology User's Guide (MAUG) provides comprehensive information on important allergens and describes the diagnostic options using CRD. Part A of the EAACI MAUG introduces allergen molecules, families, composition of extracts, databases, and diagnostic IgE, skin, and basophil tests. Singleplex and multiplex IgE assays with components improve both sensitivity for low-abundance allergens and analytical specificity; IgE to individual allergens can yield information on clinical risks and distinguish cross-reactivity from true primary sensitization. Part B discusses the clinical and molecular aspects of IgE-mediated allergies to foods (including nuts, seeds, legumes, fruits, vegetables, cereal grains, milk, egg, meat, fish, and shellfish), inhalants (pollen, mold spores, mites, and animal dander), and Hymenoptera venom. Diagnostic algorithms and short case histories provide useful information for the clinical workup of allergic individuals targeted for CRD. Part C covers protein families containing ubiquitous, highly cross-reactive panallergens from plant (lipid transfer proteins, polcalcins, PR-10, profilins) and animal sources (lipocalins, parvalbumins, serum albumins, tropomyosins) and explains their diagnostic and clinical utility. Part D lists 100 important allergen molecules. In conclusion, IgE-mediated reactions and allergic diseases, including allergic rhinoconjunctivitis, asthma, food reactions, and insect sting reactions, are discussed from a novel molecular perspective. The EAACI MAUG documents the rapid progression of molecular allergology from basic research to its integration into clinical practice, a quantum leap in the management of allergic patients., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)