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Infants at high risk for developing a food allergy have either an atopic condition (such as eczema) themselves or an immediate family member with such a condition. Breastfeeding should be promoted and supported regardless of issues pertaining to food allergy prevention, but for infants whose mothers cannot or choose not to breastfeed, using a specific formula (i.e., hydrolyzed formula) is not recommended to prevent food allergies. When cow's milk protein formula has been introduced in an infant's diet, make sure that regular ingestion (as little as 10 mL daily) is maintained to prevent loss of tolerance. For high-risk infants, there is compelling evidence that introducing allergenic foods early-at around 6 months, but not before 4 months of age-can prevent common food allergies, and allergies to peanut and egg in particular. Once an allergenic food has been introduced, regular ingestion (e.g., a few times a week) is important to maintain tolerance. Common allergenic foods can be introduced without pausing for days between new foods, and the risk for a severe reaction at first exposure in infancy is extremely low. Pre-emptive in-office screening before introducing allergenic foods is not recommended. No recommendations can be made at this time about the role of maternal dietary modification during pregnancy or lactation, or about supplementing with vitamin D, omega 3, or pre- or probiotics as means to prevent food allergy., (© 2022. The Author(s).)

Background: Oral immunotherapy (OIT) is an emerging approach to the treatment of patients with IgE-mediated food allergy and is in the process of transitioning to clinical practice., Objective: To develop patient-oriented clinical practice guidelines on oral immunotherapy based on evidence and ethical imperatives for the provision of safe and efficient food allergy management., Materials and Methods: Recommendations were developed using a reflective patient-centered multicriteria approach including 22 criteria organized in five dimensions (clinical, populational, economic, organizational and sociopolitical). Data was obtained from: (1) a review of scientific and ethic literature; (2) consultations of allergists, other healthcare professionals (pediatricians, family physicians, nurses, registered dieticians, psychologists, peer supporters), patients and caregivers; and patient associations through structured consultative panels, interviews and on-line questionnaire; and (3) organizational and economic data from the milieu of care. All data was synthesized by criteria in a multicriteria deliberative guide that served as a platform for structured discussion and development of recommendations for each dimension, based on evidence, ethical imperatives and other considerations., Results: The deliberative grid included 162 articles from the literature and media reviews and data from consultations involving 85 individuals. Thirty-eight (38) recommendations were made for the practice of oral immunotherapy for the treatment of IgE mediated food allergy, based on evidence and a diversity of ethical imperatives. All recommendations were aimed at fostering a context conducive to achieving objectives identified by patients and caregivers with food allergy. Notably, specific recommendations were developed to promote a culture of shared responsibility between patients and healthcare system, equity in access, patient empowerment, shared decision making and personalization of OIT protocols to reflect patients' needs. It also provides recommendations to optimize organization of care to generate capacity to meet demand according to patient choice, e.g. OIT or avoidance. These recommendations were made acknowledging the necessity of ensuring sustainability of the clinical offer in light of various economic considerations., Conclusions: This innovative CPG methodology was guided by patients' perspectives, clinical evidence as well as ethical and other rationales. This allowed for the creation of a broad set of recommendations that chart optimal clinical practice and define the conditions required to bring about changes to food allergy care that will be sustainable, equitable and conducive to the well-being of all patients in need., Competing Interests: Competing interestsDirect competing interests related to the topic of the guidelines P. Bégin and J. Upton are non-remunerated investigators on an investigator-instigated trial sponsored by the Canadian Institutes of Health on the use of omalizumab in oral immunotherapy (in-kind contribution of investigative drug product by Novartis worth > $100,000 CAD). They were excluded from the room for the discussion and deliberations on recommendations related to the use of omalizumab in oral immunotherapy. M. Ben-Shoshan was a principal investigator on a trial on the use of pharmaceutical peanut flour preparations in OIT sponsored by Aimmune Therapeutics (> $100,000 CAD in grant support). J. Upton was a non-remunerated sub-investigator on clinical trial sponsored by Aimmune Therapeutics on the use of pharmaceutical peanut flour preparations in OIT. They were excluded from the room for the discussion and deliberations on recommendations related to the use of pharmaceutical food products in OIT. Direct competing interests unrelated to the topic of the guidelines P. Begin reports speaker and/or advisor fees from Food Allergy Canada, Novartis, Pfizer, Sanofi, ALK and Aralez Pharmaceuticals, as well as research grant support from Canadian Institutes for Health Research, Fonds de Recherche en Santé du Québec, Canadian Allergy, Asthma and Immunology Foundation, DBV technologies, CHU Ste-Justine Foundation, Regeneron and Sanofi outside the submitted work. M. Ben-Shoshan reports advisor fees from Food Allergy Canada, as well as research grant support from Canadian Institutes for Health Research, Fonds de recherché en Santé du Québec and Canadian Foundation of Allergy and Clinical Immunology outside the submitted work. S. B. Cameron reports an unrestricted educational grant from Pfizer outside the submitted work. S. Carr reports speaker and/or advisor fees from Aralez, Pfizer, Nutricia, Meda (Mylan), Sanofi, GSK, ALK, and Pediapharm. E. S. Chan reports speaker and/or advisor fees from Pfizer, Kaleo, Food Allergy Canada, Pediapharm, Leo and DBV technologies as well as research grant support from DBV Technologies outside the submitted work. D. Fischer reports speaker and/or advisor fees from ALK, AstraZeneca, Aralez, Bausch Health, Merck, Mylan, Pfizer, Novartis, Pediapharm, Sanofi and Teva outside the submitted work. A. Haynes reports advisor fees from Sanofi outside the submitted work. S. Kapur reports speaker and/or advisor fees from Pediapharm and has been a member of advisory boards for, Bausch, Kaleo, Mylan, Novartis, Pediapharm, Pfizer, and Sanofi outside the submitted work. He also holds shares in ABK Biomedical, who are not involved in the field of allergy. H. Kim reports speaker and/or advisor fees for ALK-Abelló, Aralez, Astra Zeneca, CSL Behring, Shire, Novartis, Pediapharm, Stallergenes, Kaleo, Sanofi, Pfizer, and Mylan outside the submitted work. M. N. Primeau reports speaker and/or advisor fees from ALK, Allergie Québec, Aralez, Bausch Health, Food Allergy Canada, Mead Johnson, Mylan, Novartis, Nutricia, Pediapharm and Pfizer outside the submitted work. J. Upton reports advisor fees from Food Allergy Canada, ALK-Abelló, Kaleo, as well as research grant support from Toronto SickKids Foundation, DBV technologies and Regeneron outside the submitted work. T. K. Vander Leek reports speaker and/or advisor fees from Pediapharm, Pfizer and Aralez outside the submitted work. Other authors and members of the deliberative committee declared no financial conflicts of interest. Indirect competing interests related to the topic of the guidelines E. M. Abrams is a pediatric allergist currently offering OIT in clinic. She has contributed to a national cohort study published on the topic. She is on the national advisory board of Food Allergy Canada. P. Begin is an adult-trained allergist currently offering OIT in the academic setting. He pursues clinical research projects on OIT. He is the director of a pilot public OIT program funded through philanthropy and government support. He collaborates with a parent committee doing fundraising for a public-funded OIT program in the province of Quebec. He is a clinician-scientist with a research program including clinical trials, epidemiologic and health technology assessment studies on food allergy and OIT. He has published original research as well as editorials and review articles on the topic of OIT. He is a member of the advisory board for Food Allergy Canada. He has given public and scientific lectures on the topic of OIT. M. Ben-Shoshan is a pediatric allergist currently not offering OIT outside research. He is a clinician-scientist with a research program including clinical trials OIT. He has previously published on the topic of OIT. He is on the national advisory board of Food Allergy Canada. A. Boisvert is a peer-supporter at byebyeallergies.ca and Food Allergy Canada. M. J. Cadieux, is a peer-supporter at Déjouer-les-allergies. S. B. Cameron is a pediatric allergist currently offering OIT in clinic. He has contributed to a national cohort study and a review published and has given scientific lectures on the topic. S. Carr is a pediatric allergist currently offering OIT in clinic. He has contributed to a national cohort study and a review published and has given scientific lectures on the topic. E. S. Chan is a pediatric allergist currently offering OIT in the academic setting. He collaborates with a parent committee doing fundraising for a public-funded OIT program in Vancouver. He as contributed to a national cohort study published on the topic. He is a member of the advisory board for Food Allergy Canada, is an eosinophilic esophagitis guideline member for the Joint Task Force/American Gastroenterological Association, and was an expert panel and coordinating committee member of the National Institute of Allergy and Infectious Diseases–sponsored Guidelines for Peanut Allergy Prevention. D. Fischer is an adult-trained allergist currently not offering OIT in clinic. He has given scientific lectures on the topic. B. Francoeur is a family physician from a region without allergist with a practice focus on allergy. He currently follows patients on OIT but does not initiate treatment himself. H. Kim is an adult-trained allergist currently offering OIT in clinic. He has published an editorial on the topic of OIT. He is the president of Canadian Society of Allergy and Clinical Immunology. A. Haynes is a pediatric allergist currently not offering OIT in clinic. S. Kapur is a pediatric allergist currently offering OIT in clinic. He has previously contributed to a national cohort study published on the topic. G. Parizeault is a pediatrician with a practice focus on allergy in a region without allergist. He is currently offering OIT in clinic. S. Pernice, is a registered dietician practicing in an academic allergy clinic offering OIT. M.N. Primeau is a pediatric allergist currently not offering OIT in clinic. J. Upton is an adult-trained allergists currently not offering OIT outside research. She is a clinician with a research program including clinical trials OIT. She is on the national advisory board of Food Allergy Canada. She has given public and scientific lectures on the topic of OIT. C. Vaillancourt is a family physician with a practice focus on allergy in a region without allergist. He is currently offering OIT in clinic. T. K. Vander Leek is a pediatric allergists currently offering OIT in clinic. He has previously contributed to a national cohort study published on the topic. Other authors and members of the deliberative committee declared no indirect conflicts of interest., (© The Author(s) 2020.)

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.

Allergic conditions in children are a prevalent health concern in Canada. The burden of disease and the societal costs of proper diagnosis and management are considerable, making the primary prevention of allergic conditions a desirable health care objective. This position statement reviews current evidence on dietary exposures and allergy prevention in infants at high risk of developing allergic conditions. It revisits previous dietary recommendations for pregnancy, breastfeeding and formula-feeding, and provides an approach for introducing solid foods to high-risk infants. While there is no evidence that delaying the introduction of any specific food beyond six months of age helps to prevent allergy, the protective effect of early introduction of potentially allergenic foods (at four to six months) remains under investigation. Recent research appears to suggest that regularly ingesting a new, potentially allergenic food may be as important as when that food is first introduced. This article has already been published (Paediatr Child Health. 2013 Dec;18(10):545-54), and is being re-published with permission from the original publisher, the Canadian Paediatric Society.

The diagnosis of peanut allergy (PA) can be complex especially in children never exposed to peanut or with an uncertain history. The aim of the study is to determine which diagnostic algorithms are used by Canadian allergists in such children. Children 1-17 yrs old never exposed to peanut or with an uncertain history having an allergist-confirmed diagnosis of PA were recruited from the Montreal Children's Hospital (MCH) and allergy advocacy organizations. Data on their clinical history and confirmatory testing were compared to six diagnostic algorithms: I. Skin prick test (SPT) >or=8 mm or specific IgE >or=5 kU/l or positive food challenge (+FC); II. SPT >or=8 or IgE >or=15 or +FC; III. SPT >or=13 or IgE >or=5 or +FC; IV. SPT >or=13 or IgE >or=15 or +FC; V. SPT >or=3 and IgE >or=5 or IgE >or=5 or +FC; VI. SPT >or=3 and IgE >or=15 or IgE >or=15 or +FC. Multivariate logistic regression analysis was used to identify factors associated with the use of each algorithm. Of 497 children recruited, 70% provided full data. The least stringent algorithm, algorithm I, was applied in 81.6% (95% CI, 77-85.6%) of children and the most stringent, algorithm VI, in 42.6% (95% CI, 37.2-48.1%).The factor most associated with the use of all algorithms was diagnosis made at the MCH in those never exposed to peanut. Other factors associated with the use of specific diagnostic algorithms were higher paternal education, longer disease duration, and the presence of hives, asthma, eczema, or other food allergies. Over 18% (95% CI, 14.4-23.0%) of children were diagnosed with PA without fulfilling even the least stringent diagnostic criteria., ((c) 2010 John Wiley & Sons A/S.)

Background: Because influenza vaccine contains some residual egg protein, there is a theoretic risk of anaphylaxis when vaccinating patients with egg allergy. The objective of this study was to estimate the risk of anaphylaxis in children with egg allergy administered an adjuvanted monovalent 2009 pandemic influenza A/H1N1 influenza vaccine (Arepanrix; GlaxoSmithKline, Mississauga, Ontario, Canada)., Methods: Patients with confirmed egg allergy with a history of respiratory or cardiovascular reactions after egg ingestion were vaccinated in 2 divided doses (10% and 90%) administered at a 30-minute interval, whereas children with other types of egg-induced allergic reactions were vaccinated with a single dose. All patients remained under observation for 60 minutes after vaccination. A 24-hour follow-up telephone call was made to detect any delayed reaction. The main outcome was the occurrence of an anaphylactic reaction according to criteria specified by the Brighton Collaboration., Results: Among the 830 patients with confirmed egg allergy, only 9% required the vaccine to be administered in divided doses. No patient had an anaphylactic reaction. Nine patients had minor allergic symptoms treated with an antihistamine (1 in the 60 minutes after vaccination and 8 in the following 23 hours), and 3 others received salbutamol (1 in the first 60 minutes after vaccination). Further vaccination of more than 3600 other children with reported egg allergy caused no anaphylaxis based on the criteria of the Brighton Collaboration, although 2 patients received epinephrine for symptoms compatible with allergy., Conclusion: Although anaphylaxis after influenza immunization is a theoretic risk, vaccination of patients with egg allergy with an adjuvanted monovalent pH1N1 influenza vaccine resulted in no cases of anaphylaxis and on that basis appears safe., (Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Little is known about the impact of food labeling on the allergic consumer., Objective: To determine the proportion of food-allergic individuals attributing an accidental exposure to inappropriate labeling, failure to read a food label, or ignoring a precautionary statement and to identify factors associated with accidental exposures., Methods: Food-allergic individuals or their caregivers were recruited from a Canadian registry of individuals with a physician-confirmed diagnosis of peanut allergy and from allergy awareness organizations. Participants completed questionnaires regarding accidental exposures due to specific food labeling issues. The association between accidental exposures and characteristics of food-allergic individuals or their caregivers was estimated using multivariate logistic regression models., Results: Of 1,862 potential participants, 1,454 (78.1%) responded. Of the 47.8% (95% confidence interval [CI], 45.1%-50.5%) of respondents who experienced an accidental exposure, 47.0% (95% CI, 43.1%-50.9%) attributed the event to inappropriate labeling, 28.6% (95% CI, 25.1%-32.2%) to failure to read a food label, and 8.3% (95% CI, 6.3%-10.7%) to ignoring a precautionary statement. Food-allergic individuals who were allergic to peanut, tree nut, fish, or shellfish were less likely to experience an accidental exposure due to the allergen not being identified in plain language., Conclusions: A considerable proportion of accidental exposures are attributed to inappropriate labeling, failure to read labels, and ignoring precautionary statements. Clear and consistent labeling of food allergens combined with increased consumer education is necessary to improve consumer confidence and compliance and to reduce accidental exposures.

Annual influenza immunization of children is highly recommended and is usually well tolerated. We report the first case of chickenpox exanthema localized to the influenza vaccination site in a boy with known egg allergy.

Gastric lesions in primary constitutive immune deficiencies include multifocal atrophic gastritis, erosive pangastritis, and a pattern of gastric lesions reminiscent of graft-versus-host disease. We describe the genetic anomalies in 2 monozygotic twins with an X-linked lymphoproliferative disease (XLP; MIM 308240), a rare familial setting of high susceptibility to Epstein-Barr virus (EBV). Since early childhood, both twin brothers exhibited a severe chronic active atrophic pangastritis. A germline screening of the SH2D1A (MIM 300490) and BIRC4 (MIM 300079) genes was performed, and also a high-resolution whole-genome SNP profiling (Infinium Sentrix Human-1 Genotyping BeadChip, Illumina). A 3 Megabase deletion in the Xq25 region, encompassing the SH2D1A gene, was defined by SNP array genotyping. Histologic analysis of yearly or twice yearly gastric biopsies in both children showed a Helicobacter pylori-negative, Epstein-Barr virus-negative chronic active atrophic pangastritis, with superficial ulcer formation, foveolar hyperplasia, glandular dilatation and ultimately pseudopyloric and intestinal metaplasia. No such chronic active inflammatory gastric lesions have been reported to date in XLP. The similarities between XLP and common variable immunodeficiency (MIM 240500) underscore the need for early recognition and close monitoring of these gastric lesions, with special regard to their neoplastic potential. No infectious cause was determined. We favor a dysimmune mechanism in the development of this chronic atrophic gastritis, presenting a striking similarity to the recently described atrophic autoimmune pangastritis.

Background: Soy lecithin is widely used as an emulsifier, not only in topical skin care products but also in various drugs administered either topically, orally, or intravenously or by inhalation. Patients strongly allergic to soy and/or peanuts can develop an anaphylactic reaction when exposed to soy lecithin., Method: We report a 3-year-old asthmatic boy, allergic to peanuts, who was treated at the emergency department for an exacerbation of asthma following an upper respiratory tract infection. Within an hour after receiving the second of two inhalations of an ipratropium bromide (Atrovent) metered dose inhaler, he developed respiratory distress and generalized urticaria, an adverse event that regressed within 48 hours of withdrawal of the suspected drug. Soy lecithin, contained as an excipient in the metered dose inhaler, was strongly suspected of being responsible for this reaction., Conclusion: Drug products containing soy lecithin can cause severe allergic reactions in patients allergic to peanuts or soy. Physicians should be aware that adverse drug reactions can be due to both the active medical component and the excipient ingredients.

Background: There have been reports that some children with autistic spectrum disorders have abnormal immune function. However, data in this area remain scarce and conflicting., Objective: To evaluate the immune function of a series of autistic children in the context of this proposed association., Methods: We prospectively collected data on 24 autistic children who, between January 1, 1996, and September 30, 1998, were referred unsolicited to an immunology clinic. We examined the clinical history and evaluated immunoglobulin levels; specific antibody titers to diphtheria, tetanus, and Haemophilus influenzae; T- + B-cell numbers; T-cell proliferation; and complement studies., Results: Seven of the 24 children had a history of recurrent infections. Only 2 patients had immunoglobulin levels that were outside the age-adjusted reference ranges, 1 of whom was subsequently diagnosed as having common variable immune deficiency. All the patients had normal in vitro T-cell function and complement study results, and only 2 of 24 patients had subtle derangements in T-cell numbers. Elevated levels of IgE were found in 5 patients, which correlated with a clinical history of atopy. Low diphtheria or tetanus antibody levels were found in 12 patients, but in 11 of these, vaccination status was not up-to-date., Conclusions: Most of the autistic children studied had normal immune function, suggesting that routine immunologic investigation is unlikely to be of benefit in most autistic children and should be considered only when there is a history suggestive of recurrent infections.

Background: Bronchial, nasal, and conjunctival challenges are useful for clarifying discordant clinical history (Hx) and skin and/or serologic tests and in assessing semiquantitative changes in biologic sensitivity over time. The objective of this study was to determine the safety and reproducibility of repeated latex-allergen challenges with a hooded exposure chamber (HEC)., Methods: The HEC system comprises a powered forced-air respirator with a fitted face shield and hood that uses glove-derived latex-allergen associated cornstarch particles (LAC) to expose simultaneously the conjunctiva, nose, and lungs. Serial control and incremental LAC challenges are conducted until an endpoint based on upper and/or lower respiratory tract symptoms and peak expiratory flow rates is reached. Six latex-allergic (Hx and puncture skin test [PST]- and 5/6 radioallergosorbent test [RAST]-positive) subjects were challenged on three separate occasions at least 2 weeks apart. Serial latex PST midpoints and serum anti-latex IgE by RAST were monitored at each visit and at a fourth follow-up visit., Results: All subjects responded to LAC, but not to air or control cornstarch administered as controls. All responses were confined to mild symptoms of allergic rhinoconjunctivitis and/or asthma that either resolved spontaneously or were reversed with inhaled albuterol. No subject experienced a systemic or delayed reaction. There were no significant changes in the endpoint LAC doses over the three challenge visits (P>0.2). The mean coefficient of variation for log2 endpoints within-subjects was 17.3+/-17.2% (SD). The serum latex-specific IgE was not significantly boosted by the three challenges (P>0.2). The concentration of latex extract necessary to produce an 8-mm wheal by PST was not significantly changed during the study (P>0.1), indicating that latex sensitivity was not affected by the repeated LAC exposures., Conclusions: The results of this study indicate that repeated HEC latex-allergen challenges are both reproducible and safe, and do not increase latex sensitivity.

The diagnosis of immunologic drug reactions is based primarily on a detailed clinical history and historical data on relative immunogenicity of the culprit drugs. Except for a few standardized skin tests, most of the other methods for diagnosing drug allergy have unproven diagnostic or predictive clinical utility. Many tests for drug-specific immune responses are suggestive if positive, but have unknown negative predictive values. The present review addresses the most recent published literature regarding the diagnosis of drug allergy. Recent advances in the use of the lymphocyte transformation test, and delayed intradermal skin tests and patch tests for the diagnosis of delayed cutaneous reactions to penicillins suggest that these tests may have clinical utility, although confirmatory reports are still missing. For the diagnosis of acute vaccine reactions, gelatin-specific IgE as measured by radioallergosorbent test has now been shown to be reliably associated with allergic reactions to gelatin-containing vaccines.

Background: The release of allergenic proteins from natural rubber vial closures (stoppers) into aqueous pharmaceuticals may induce allergic reactions in individuals with latex allergy (LA) receiving medications from such vials., Objective: The goal of this study was to determine whether solutions stored in vials containing natural rubber closures release allergenic proteins detectable by skin testing of subjects with LA., Methods: Five pharmaceutical vial closures (2 natural rubber and 3 synthetic) were coded, inserted onto vials containing phenol-saline-human serum albumin, and stored in an inverted position before use. Twelve volunteers with and 11 volunteers without LA underwent skin testing with solutions from each of the 5 vials, either those not punctured (0P) or those punctured 40 times with a 21-gauge needle 12 to 24 hours before testing (40P)., Results: All intradermal skin test responses in the group without LA were negative. Two and 5 of the 12 subjects with LA had positive intradermal skin reactions to 0P and 40P solutions, respectively, from vials containing rubber closures. Two subjects with LA had inexplicable, positive, nonreproducible intradermal skin test reactions to solutions from vials containing bromobutyl but not vials with isoprene synthetic closures. In vitro inhibition analysis detected 6 to 7 AU/g latex allergen in extracts of cut natural rubber containing closures but not in extracts of synthetic closures., Conclusion: Natural rubber vial closures released allergenic latex proteins into the tested solutions in direct contact during storage in sufficient quantities to elicit positive intradermal skin reactions in some individuals with LA. These data support a recommendation to eliminate natural rubber from closures of pharmaceutical vials.