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Background: There is no accepted grading system classifying the severity of immediate reactions to drugs., Objective: The purpose of this article is to present a proposed grading system developed through the consensus of drug allergy experts from the United States Drug Allergy Registry (USDAR) Consortium., Methods: The USDAR investigators sought to develop a consensus severity grading system for immediate drug reactions that is applicable to clinical care and research., Results: The USDAR grading scale scores severity levels on a scale of 0 to 4. A grade of no reaction (NR) is used for patients who undergo challenge without any symptoms or signs, and it would confirm a negative challenge result. A grade 0 reaction is indicative of primarily subjective complaints that are commonly seen with both historical drug reactions and during drug challenges, and it would suggest a low likelihood of a true drug allergic reaction. Grades 1 to 4 meet the criteria for a positive challenge result and may be considered indicative of a drug allergy. Grade 1 reactions are suggestive of a potential immediate drug reaction with mild symptoms. Grade 2 reactions are more likely to be immediate drug reactions of moderate severity. Grade 3 reactions have features suggestive of a severe allergic reaction, whereas grade 4 reactions are life-threatening reactions such as anaphylactic shock and fatal anaphylaxis., Conclusion: This proposed grading schema for immediate drug reactions improves on prior schemata by being developed specifically for immediate drug reactions and being easy to implement in clinical and research practice., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Epigenetic mechanisms integrate both genetic variability and environmental exposures. However, comprehensive epigenome-wide analysis has not been performed across major childhood allergic phenotypes. We examined the association of epigenome-wide DNA methylation in mid-childhood peripheral blood (Illumina HumanMethyl450K) with mid-childhood atopic sensitization, environmental/inhalant and food allergen sensitization in 739 children in two birth cohorts (Project Viva-Boston, and the Generation R Study-Rotterdam). We performed covariate-adjusted epigenome-wide association meta-analysis and employed pathway and regional analyses of results. Seven-hundred and five methylation sites (505 genes) were significantly cross-sectionally associated with mid-childhood atopic sensitization, 1411 (905 genes) for environmental and 45 (36 genes) for food allergen sensitization (FDR<0.05). We observed differential methylation across multiple genes for all three phenotypes, including genes implicated previously in innate immunity (DICER1), eosinophilic esophagitis and sinusitis (SIGLEC8), the atopic march (AP5B1) and asthma (EPX, IL4, IL5RA, PRG2, SIGLEC8, CLU). In addition, most of the associated methylation marks for all three phenotypes occur in putative transcription factor binding motifs. Pathway analysis identified multiple methylation sites associated with atopic sensitization and environmental allergen sensitization located in/near genes involved in asthma, mTOR signaling, and inositol phosphate metabolism. We identified multiple differentially methylated regions associated with atopic sensitization (8 regions) and environmental allergen sensitization (26 regions). A number of nominally significant methylation sites in the cord blood analysis were epigenome-wide significant in the mid-childhood analysis, and we observed significant methylation - time interactions among a subset of sites examined. Our findings provide insights into epigenetic regulatory pathways as markers of childhood allergic sensitization.

Background: Early menarche is linked to higher incidence of adult asthma, suggesting that earlier puberty may influence type 2 immune response characteristics of allergic diseases. We examined the hypothesis that timing of breast and pubic hair development, which precede menarche, is associated with increased childhood atopic conditions., Methods: Girls were enrolled at 6-8 yr of age (2004-2007) in the Breast Cancer and the Environment Research Program Puberty Study and were followed through 2011. Pubertal stages were assessed and atopic conditions were queried annually. Associations of age at pubertal stage 2 for breast or pubic hair development with atopic conditions were assessed using prevalence ratios (PR) or odds ratios (OR) and 95% confidence intervals (CI) from log-binomial regression and generalized estimating equation models, controlling for body mass index and other covariates. A total of 1055 girls with medical and pubertal stage data were included., Results: Asthma (ever vs. never) was associated with younger pubarche (≤10 vs. >10 yr, PR = 1.15, CI: 1.04-1.28 adjusted for race/ethnicity and site; PR = 1.13, CI: 1.01-1.25 further adjusted for BMI), but not thelarche. In longitudinal models, risk of developing allergies increased with younger age at pubarche (adjusted OR = 1.60, CI: 1.10-2.34; ≤10 vs. >10 yr). Risks were highest among black girls with earlier pubarche (n = 248/326); for allergies, their fully adjusted OR was 2.35, CI: 1.06-5.19 for pubarche ≤10 vs. >10 yr., Conclusions: Atopic conditions during childhood are associated with younger age at pubarche, independent of obesity, and these relationships may vary by racial/ethnic groups., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Atopy varies by ethnicity, even within Latino groups. This variation might be due to environmental, sociocultural, or genetic factors., Objective: We sought to examine risk factors for atopy within a nationwide study of US Latino children with and without asthma., Methods: Aeroallergen skin test responses were analyzed in 1830 US Latino subjects. Key determinants of atopy included country/region of origin, generation in the United States, acculturation, genetic ancestry, and site to which subjects migrated. Serial multivariate zero-inflated negative binomial regressions stratified by asthma status examined the association of each key determinant variable with the number of positive skin test responses. In addition, the independent effect of each key variable was determined by including all key variables in the final models., Results: In baseline analyses African ancestry was associated with 3 times (95% CI, 1.62-5.57) as many positive skin test responses in asthmatic participants and 3.26 times (95% CI, 1.02-10.39) as many positive skin test responses in control participants. Generation and recruitment site were also associated with atopy in crude models. In final models adjusted for key variables, asthmatic patients of Puerto Rican (exp[β] [95% CI], 1.31 [1.02-1.69]) and mixed (exp[β] [95% CI], 1.27 [1.03-1.56]) ethnicity had a greater probability of positive skin test responses compared with Mexican asthmatic patients. Ancestry associations were abrogated by recruitment site but not region of origin., Conclusions: Puerto Rican ethnicity and mixed origin were associated with degree of atopy within US Latino children with asthma. African ancestry was not associated with degree of atopy after adjusting for recruitment site. Local environment variation, represented by site, was associated with degree of sensitization., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Proper diagnosis of adverse drug reactions, although often complicated and difficult, is important for the patient and the physician. Often the question of whether it is safe to readminister a medication is an important clinical judgment that needs to be made. Alternative medications may be less effective or have greater toxicities or cost, or both. Areas of ongoing research to improve diagnostic precision for allergic drug reactions include further understanding of the immunochemistry of allergenic medications, improvement of the reproducibility and sensitivity of relevant in vitro assays, and further validation of computer-assisted evaluation of adverse drug events. The positive and negative predictive values for these diagnostic tests need to be better defined whenever possible. At present, the primary diagnostic tool for properly assessing immunologic drug reactions remains a meticulous and detailed history obtained by an astute, knowledgeable, and motivated physician.

Background: This report of the prevalence of latex glove allergy in 3 Department of Veterans Affairs (VA) medical centers was a collaboration of the VA, the Centers for Disease Control and Prevention, and the National Institute for Occupational Safety and Health., Objective: To enroll and evaluate personnel from across the entire hospital workforce for latex hypersensitivity and to determine the type and extent of latex glove use., Methods: A questionnaire was administered that covered demographics, job category, latex glove use, and current latex glove allergic symptoms. Skin testing to aeroallergens was performed to evaluate the presence of atopy. Blood was drawn for analyses of serum antilatex IgE antibody by CAP assay., Results: Of 1,959 subjects, 158 (8.1%) had latex glove-allergic symptoms, a positive latex CAP assay result, or both. In 1,003 subjects who reported latex glove use, 915 (91.4%) used nonpowdered gloves. A total of 133 subjects reported latex glove allergic symptoms, and 36 subjects had positive CAP assay results. Latex sensitization was correlated with atopy, race, and latex glove exposure. Latex symptoms were correlated with atopy, a positive CAP assay result, and latex glove exposure. Of the 133 subjects with latex glove allergic symptoms, only 11 had positive CAP assay results, giving a prevalence of confirmed latex glove allergy of 0.6%., Conclusions: Symptoms attributed to latex gloves and/or latex sensitization occurred in 8.1% of the employee population, with exposure, race, and atopy being the major risk factors. Few symptomatic individuals were sensitized to latex (0.6%). This low rate of confirmed latex glove allergy may have been related to nonpowdered glove use.

Background: The hygiene hypothesis proposes that declining exposure to infections is implicated in the rising trend of allergy and asthma., Objective: We sought to test this hypothesis by examining the relationship of hay fever, asthma, and atopic sensitization with markers of infection in a large general population sample of the United States., Methods: We analyzed the data of 33,994 US residents recorded in a public database of a nationally representative cross-sectional survey (Third National Health and Nutrition Examination Survey, 1988-1994). The variables examined were sociodemographic information, lifetime diagnosis and age at first diagnosis of hay fever or asthma, current skin sensitization to 9 airborne allergens and peanut, and current serology for Toxoplasma gondii, herpes simplex viruses type 1 and 2, and hepatitis A, B, and C viruses., Results: Hay fever (adjusted odds ratio, 0.27; 95% CI, 0.18-0.41; P <.001) and asthma (adjusted odds ratio, 0.45; 95% CI, 0.31-0.66; P <.001) were less frequent in subjects seropositive for hepatitis A virus (HAV), T gondii, and herpes simplex virus 1 versus seronegative subjects after adjusting for age, sex, race, urban residence, census region, family size, income, and education. Skin sensitization to peanut and to all the airborne allergens examined, except for cockroach, was less frequent among HAV-seropositive versus HAV-seronegative subjects younger than 40 years of age. The prevalence of hay fever and asthma diagnosed at or before 18 years of age in HAV-seronegative subjects increased progressively from 2.7% (95% CI, 0.7%-4.7%) and 0.4% (95% CI, 0.1%-1.6%), respectively, in cohorts born before 1920 to 8.5% (95% CI, 7.3%-9.7%) and 5.8% (95% CI, 4.8%-6.8%), respectively, in cohorts born in the 1960s, whereas they remained constant at around 2% in all cohorts of HAV-seropositive subjects., Conclusion: In the United States serologic evidence of acquisition of certain infections, mainly food-borne and orofecal infection, is associated with a lower probability of having hay fever and asthma. Third National Health and Nutrition Examination Survey data support the hypothesis that hygiene is a major factor contributing to the increase in hay fever, asthma, and atopic sensitization in westernized countries.

Background: Despite careful avoidance measures, food allergic patients have a significant risk of anaphylactic episodes. Risk situations need to be identified for more efficient preventive measures., Methods: Responders to an internet-based survey on the awareness of food anaphylaxis were invited to relate the circumstances of their most severe reaction following the diagnosis of IgE-mediated food allergy. Items of the questionnaire included the circumstances of the reaction and the treatment, as well as questions related to reactions occurring at specific categories of sites (i.e. home, schools, or restaurants)., Results: Fifty-one of the returned questionnaires (34.1%) corresponded to the study criteria. The median age of the subjects was 7 years (range 0.5-61), with 33/51 (64.7%) being less than 16 years of age. Reactions were reported to peanuts (24/51; 47.1%), milk (12/51; 23.5%), tree nuts (6/51; 11.8%), fish and shellfish (5/51; 9.8%), and others (3/51; 5.8%). Reactions occurred at home (13/51; 25.5%), in restaurants (9/51; 17.6%), at school or daycare or kindergarten (8/51; 15.7%), at a relative or friend's home (7/51; 13.7%), at sites of leisure activities (6/51; 11.8%), at work (3/51; 5.9%), in church or a hospital ward (2/51; 3.9% each), or in a food store (1/51; 2.0%). In severe reactions (37/51; 72.5%) epinephrine was administered in 28/37 (75.7%) of the responders. Finally, while most reactions happened after ingestion of the food (40/51; 78.4%), others were reported after skin contact exclusively (8/51; 16%), or after inhalation (3/51; 5.9%)., Conclusion: Food induced-anaphylaxis in patients aware of their allergy happens most often at sites considered as safe (i.e. home, schools, workplace, hospitals). Better strategies to avoid accidental reactions include clear labelling of forbidden foods and increased information at all levels. These might dramatically reduce the risk of food-induced anaphylaxis in food allergy sufferers.

Allergic reactions to Hymenoptera stings range from large local reactions to life-threatening anaphylaxis. Over the last 20 years, significant progress has been made using venom extracts in the diagnosis and treatment of Hymenoptera allergy. Despite these advances, there is still room for improvement in increasing the sensitivity of venom allergen skin testing. The venom allergic patient with negative skin tests poses special problems in management. It is important to note their increased risk with a subsequent sting. Guidelines to be used in determining the duration of venom immunotherapy are still evolving. Knowledge of the risks of discontinuing venom immunotherapy and risk factors associated with anaphylaxis with subsequent stings are required to form an individualized approach to treatment.

Latex allergy has become the epidemic of the 1990s for health care workers, as indicated by a remarkable increase in its prevalence. This literature review provides a brief background to the latex problem, strategies for prevention and management, a cost analysis of glove substitution in a clinical setting, and the implications for the military environment. Primary care providers must recognize the financial, medico-legal, occupational, and personal ramifications of latex allergy. Risk managers should realize that moving to a latex-free environment will reduce liability.

Allergies to antibiotics, mainly the beta-lactam antibiotics (penicillins and cephalosporins), are a common, costly, and potentially dangerous clinical problem encountered in everyday practice. Although studies on the role of non-beta-lactam antibiotics in allergic diseases, particularly the development of specific diagnostic tests and the immunochemical identification of allergenic structures, have been too few and relatively superficial, the situation with the beta-lactam antibiotics is much more advanced. Good progress has been made in identifying the spectra of allergenic determinants recognized by IgE antibodies in the sera of subjects sensitized to penicillins and cephalosporins, and this is aiding the development of an appropriate battery of drug conjugates for use as diagnostic agents. Patient-sensitivity responses to the beta-lactam antibiotics are frequently heterogeneous, and this factor must be taken into account for any diagnostic strategy or future therapy with a penicillin or cephalosporin.

This case is presented to: a) emphasize the importance of a careful history, including interviewing witnesses and considering a complete differential diagnosis when evaluating aviators with a history of an episode of altered consciousness; and b) demonstrate an appropriate use of literature review, subspecialty consultations, and U.S. Air Force Aeromedical Guidelines to arrive at an aeromedical disposition for an unusual case. A military aviator experienced an episode of syncope/near syncope, initially felt to be caused by a primary seizure or an arrhythmia. Subsequent thorough evaluation included careful history taking, extensive interviewing of witnesses, subspecialty consultations, review of appropriate literature and deliberation by a board of experienced military aeromedical physicians. Cardiac and neurologic diagnoses were considered but careful history and witness interviews revealed that the aviator had sustained an insect sting just minutes before the episode. Evaluation by allergy specialists, including skin testing, identified him as being hypersensitive to Hymenoptera stings. A diagnosis of hypersensitivity reaction to a Hymenoptera sting was determined to be the cause of the altered consciousness episode. Review of the literature revealed that immunotherapy for Hymenoptera sensitivity reduces the risk of future anaphylaxis to only 1-2% after maintenance dose is achieved. Consideration of the risk of future events and the success of rush immunotherapy resulted in a recommendation for a waiver to return the aviator to unrestricted flying duties. The importance of diligent history taking must never be forgotten. In this aviator it led to the correct diagnosis and definitive therapy. In addition, appropriate consideration of the literature and knowledge of outcome rates allowed a return to unrestricted flying for this aviator. If the original diagnosis of seizure or arrhythmia had been accepted, this aviator would have been disqualified without waiver and a valuable flying asset would have been lost.

The authors investigated the prevalence of immediate (Type I) hypersensitivity to gloves made from natural rubber latex, or NRL, by performing skin-prick tests on 2,166 dental workers over the course of a two-year period (with two one-year intervals). The investigator used two separate eluents made from different brands of natural rubber latex gloves. The study, conducted in 1994 and 1995 as part of the American Dental Association's Annual Health Screening Program, found that 6.2 percent of the participants (dentists, hygienists and assistants) tested positive for Type I hypersensitivity to NRL proteins.

Background: It has been hypothesized that asthma-related health problems are most severe among children in inner-city areas who are allergic to a specific allergen and also exposed to high levels of that allergen in bedroom dust., Methods: From November 1992 through October 1993, we recruited 476 children with asthma (age, four to nine years) from eight inner-city areas in the United States. Immediate hypersensitivity to cockroach, house-dust-mite, and cat allergens was measured by skin testing. We then measured major allergens of cockroach (Bla g 1), dust mites (Der p 1 and Der f 1), and cat dander (Fel d 1) in household dust using monoclonal-antibody-based enzyme-linked immunosorbent assays. High levels of exposure were defined according to proposed thresholds for causing disease. Data on morbidity due to asthma were collected at base line and over a one-year period., Results: Of the children, 36.8 percent were allergic to cockroach allergen, 34.9 percent to dust-mite allergen, and 22.7 percent to cat allergen. Among the children's bedrooms, 50.2 percent had high levels of cockroach allergen in dust, 9.7 percent had high levels of dust-mite allergen, and 12.6 percent had high levels of cat allergen. After we adjusted for sex, score on the Child Behavior Checklist, and family history of asthma, we found that children who were both allergic to cockroach allergen and exposed to high levels of this allergen had 0.37 hospitalization a year, as compared with 0.11 for the other children (P=0.001), and 2.56 unscheduled medical visits for asthma per year, as compared with 1.43 (P<0.001). They also had significantly more days of wheezing, missed school days, and nights with lost sleep, and their parents or other care givers were awakened during the night and changed their daytime plans because of the child's asthma significantly more frequently. Similar patterns were not found for the combination of allergy to dust mites or cat dander and high levels of the allergen., Conclusions: The combination of cockroach allergy and exposure to high levels of this allergen may help explain the frequency of asthma-related health problems in inner-city children.

The frequency of positive delayed hypersensitivity skin test reactions to tetanus toxoid in 47 healthy volunteers was 80%. The frequency of immediate hypersensitivity was low (8%) and there was less discomfort than with streptokinase or PPD. There was good correlation between leukocyte migration inhibition and delayed hypersensitivity skin testing, and a quantitative relationship was demonstrated between diameter of cutaneous reaction and degree of leukocyte migration inhibition. No relationship was demonstrated between any measures of immune responsiveness and the interval from the last booster immunization. It was concluded that tetanus toxoid is a valuable antigen for assessment of delayed hypersensitivity in man.