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Background Oral immunotherapy (OIT) is a management strategy for food allergies, typically one at a time, with maintenance doses ≥ 300 mg protein. However, 30% of allergic children have multiple trigger foods, and large maintenance doses are associated with side effects. If efficacious, Very Low‐Dose OIT (VLOIT) may enhance safety in multi‐OIT. Methods Eighteen children with allergies to 2–5 nuts (tree nuts, peanuts) were enrolled (NCT03799328). Oral food challenge (OFC)‐confirmed allergies to their nut mix at ≤ 444 mg protein each nut followed by initiation of an open‐label mix of 4 mg protein/nut with dose increases every 2 months up to a maintenance dose of 30 mg protein/nut. After 18 months, an exit‐OFC assessed allergic threshold changes, with a maximum of 2040 mg protein/nut. Efficacy was evaluated using pre‐post treatment and proportional analyses (Wilcoxon signed‐ranks, two‐tailed Fisher's test). Results The median age at enrollment was 5.0 years (IQR 3.13–9.62). The baseline median tolerated dose was 10 mg protein/nut (IQR 3–100 mg). Three withdrew, one did not reach the target maintenance but was invited for the exit OFC, resulting in 15/18 eligible for exit OFC. The median tolerated dose at exit OFC was 1000 mg (IQR 300–1000 mg), with a significant difference from baseline (p < 0.0001). Ten out of 15 participants tolerated the maximum dose (p < 0.0001). Intention‐to‐treat analysis showed that 14/18 children met pre‐defined efficacy measures: tolerated 5X their baseline dose or ≥ 300 mg (p < 0.001). No patients required epinephrine during treatment. Conclusions VLOIT led to a significant increase in the tolerated dose to multiple nuts.

Chronic spontaneous urticaria affects 1% to 3% of people It is not an allergy and carries no risk of anaphylaxis, but is a chronic type 2 inflammatory disease driven by autoimmune mast cell activation. Noncausal, aggravating factors include stress, skin pressure, infections, and nonsteroidal anti-inflammatory drugs. The diagnosis is based on clinical findings Features include itchy hives lasting less than 24 hours, or angioedema without systemic symptoms or bruising, over a period of more than 6 weeks. A complete blood count, C-reactive protein levels, and erythrocyte sedimentation rate can rule out other causes. Painful or persistent hives, bruising, fever, isolated angioedema, or evidence of systemic inflammation should raise concern for urticarial vasculitis, bullous pemphigoid, bradykinin-mediated angioedema, or auto-inflammatory syndromes. Allergy testing is not routinely indicated. In select cases, skin biopsy or C1 esterase inhibitor testing may be needed for diagnostic clarification. Treatment should be taken daily for prevention. Doses may be increased weekly up to fourfold as tolerated. Higher doses carry risks of sedation and QT prolongation. Oral corticosteroids can be used for 5 days or less, but not long term. They do not alter disease course and should not delay escalation of first-line treatment.

Introduction Data is sparse on drug‐induced anaphylaxis (DIA) and there have not been studies assessing the differences in clinical characteristics and management of DIA between adults and children. Objective We assessed the percentage, diagnosis, and management of DIA among all anaphylaxis visits in three pediatric and one adult emergency departments (ED) across Canada. Methods Children presenting to the Montreal Children's Hospital (MCH), British Columbia Children's Hospital (BCCH), and Children's Hospital at London Health Sciences Center and adults presenting to Hôpital du Sacré‐Coeur with anaphylaxis were recruited as part of the Cross‐Canada Anaphylaxis Registry. A standardized data form documenting the reaction and management was completed and patients were followed annually to determine assessment by allergist and use of confirmatory tests. Results From June 2012 to May 2016, 51 children were recruited from the pediatric centers and 64 adults from the adult center with drug‐induced anaphyalxis. More than half the cases were prospectively recruited. The percentage of DIA among all cases of anaphylaxis was similar in all three pediatric centers but higher in the adult center in Montreal. Most reactions in children were triggered by non‐antibiotic drugs, and in adults, by antibiotics. The majority of adults and a third of children did not see an allergist after the initial reaction. In those that did see an allergist, diagnosis was established by either a skin test or an oral challenge in less than 20% of cases. Conclusions Our results reveal disparities in rate, culprit, and management of DIA in children versus adults. Further, most cases of suspected drug allergy are not appropriately diagnosed. Guidelines to improve assessment and diagnosis of DIA are required. Data is sparse on drug‐induced anaphylaxis and there have not been studies assessing the differences in clinical characteristics and management of drug‐induced anaphylaxis between adults and children. The percentage of drug‐induced anaphylaxis among all cases of anaphylaxis was similar in all three pediatric centers but higher in the adult center in Montreal. The majority of adults and a third of children did not see an allergist after the initial reaction, revealing that most cases of suspected drug allergy are not appropriately diagnosed.

Urticaria (hives) is a common disorder that may be associated with angioedema (swelling that occurs beneath the skin). It is generally classified as acute or chronic, and chronic urticaria is further classified as spontaneous or inducible Second-generation, non-sedating histamine type 1 (H1)-receptor antihistamines represent the mainstay of therapy for both acute and chronic urticaria. Second-line treatment for uncontrolled chronic urticaria includes omalizumab (a monoclonal anti-immunoglobulin E [IgE] antibody). In this article, we review the causes, diagnosis and management of urticaria (with or without angioedema). Key take-home messages Urticaria is a common disorder characterized by recurrent, pruritic (itchy) lesions with pale centers (wheals) that usually subside within 48 h; it can be associated with angioedema. Mast cells are the primary effector cells in urticaria. Urticaria is classified as acute (lesions for < 6 weeks) or chronic (lesions for ≥ 6 weeks). Chronic urticaria can be further classified as spontaneous or inducible. The diagnosis of urticaria is based primarily on a thorough clinical history and physical exam; however, diagnostic tests may be helpful in some instances. Second-generation, non-sedating H1-receptor antihistamines are the mainstay of therapy for urticaria. Omalizumab and cyclosporine can be used for more severe, chronic cases. Referral to an allergy specialist or dermatologist should be considered in the following situations: failure of or difficulty tolerating first-line second-generation antihistamine treatments; need for specialized treatment; and the presence of severe symptoms and/or atypical features.

The vast majority of individuals labelled as allergic are not deemed truly allergic upon appropriate assessment by an allergist. A label of beta-lactam allergy carries important risks for individual and public health. This article provides an overview of beta-lactam allergy, implications of erroneous beta-lactam allergy labels and the impact that can be provided by structured allergy assessment. We provide recommendations on how to stratify risk of beta-lactam allergy, beta lactam challenge protocols as well as management of patients at high risk of beta-lactam allergy.

Chronic urticaria (CU) is associated with debilitating symptoms such as pruritic wheals and/or angioedema, which can significantly affect patients' sleep, productivity and quality of life. Chronic spontaneous urticaria (CSU) is defined in cases in which no triggering factor is identified. Various guidelines directing the optimal management of CU in the adult population were published and updated over the recent years with the most accepted and widely used being the EAACI/GA LEN/EDF/WAO 2017 guidelines. Meanwhile, guidelines specific to the pediatric population are scarce, mainly due to the fact that high quality evidence is lacking for many treatment options in this age group. The objective of this article is to review and synthesize the existing literature regarding the management of pediatric CSU. Our review highlights evidence supporting the EAACI/GA LEN/EDF/WAO 2017 treatment guidelines with non-sedating second-generation antihistamines (sgAHs) as the mainstay of treatment for pediatric CSU, considering their demonstrated efficacy and reassuring safety profile. Additionally, the use of omalizumab in adolescents is well supported by the current literature. There is limited data available regarding the updosing of sgAHs, omalizumab in children with CSU under 12 years of age and the treatment with cyclosporine and leukotriene receptor antagonists (LTRAs) in pediatric patients of all ages. However, the results from currently available case series and case reports are promising for omalizumab and cyclosporine use in children with CSU, although large and well-designed randomized control trials (RCTs) assessing these treatment options are needed in order to formulate strong recommendations for their use. First-generation antihistamines (fgAHs) remain commonly used in pediatric CSU treatment despite a lack of studies assessing their efficacy and safety in the pediatric population and their widely known inferior safety profile compared to sgAHs.

Sesame is an important global allergen affecting ~0.1% of the North American population. It is a major cause of anaphylaxis in the Middle East and is the third most common food allergen in Israel. We conducted a systematic review of original articles published in the last 10 years regarding the diagnosis and management of sesame allergy. Skin prick testing appears to be a useful predictor of sesame allergy in infants, although data are less consistent in older children and adults. The diagnostic capacity of serum-specific immunoglobulin E is poor, especially in studies that used oral food challenges to confirm the diagnosis. Double-blind, placebo-controlled food challenge thus remains the diagnostic gold standard for sesame allergy. The cornerstone of sesame allergy management is allergen avoidance, though accidental exposures are common and patients must be prepared to treat the consequent reactions with epinephrine. Novel diagnostic and treatment options such as component-resolved diagnostics, basophil activation testing, and oral immunotherapy are under development but are not ready for mainstream clinical application.

Delayed drug T-cell immune-mediated hypersensitivity reactions have a large clinical heterogeneity varying from mild maculopapular exanthema (MPE) to severe cutaneous adverse reactions (SCARs) such as acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) and severe skin necrosis and blistering as seen in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Given the knowledge gaps related to the immunopathogenesis of these conditions, the absence of validated diagnostic tools and the significant associated morbidity and mortality, patients with SCARs often have limited drug choices. We performed a comprehensive review aiming to evaluate in vivo diagnostic tools such as delayed intradermal skin and patch testing and ex vivo/in vitro research assays such as the lymphocyte transformation test (LTT) and the enzyme-linked ImmunoSpot (ELISpot) assay. We searched through PubMed using the terms “drug allergy,” “ in vivo ” and “ ex vivo ” for original papers in the last 10 years. A detailed meticulous approach adapted to the various clinical phenotypes is recommended for the diagnostic and management of delayed drug hypersensitivity reactions. This review highlights the current diagnostic tools for the delayed drug hypersensitivity phenotypes.

Introduction In chronic spontaneous urticaria (CSU), interleukin (IL)-4 and IL-13 may promote mast cell activation directly via IL-4 receptor expression, or indirectly via upregulated immunoglobulin E (IgE) production. Dupilumab significantly improved CSU signs and symptoms in the phase 3, randomized, placebo-controlled LIBERTY-CSU CUPID Study A. This analysis explores the impact of dupilumab on CSU signs and symptoms and serum IgE levels in patients from LIBERTY-CSU CUPID Study A with serum total IgE above and below 100 IU/mL at baseline. Methods Patients with H1-antihistamine-refractory CSU received dupilumab ( n  = 70) or placebo ( n  = 68) for 24 weeks. Efficacy endpoints were change from baseline to weeks 12 and 24 in serum total IgE levels, Itch Severity Score over 7 days (ISS7), Urticaria Activity Score over 7 days (UAS7), and Hives Severity Score over 7 days (HSS7) in dupilumab- or placebo-treated patients with serum total IgE above and below 100 IU/mL at baseline. Results Dupilumab treatment significantly reduced median (interquartile range) IgE levels at week 12 [dupilumab: −31.9% (−41.9; −22.6); placebo: −6.3% (−21.3; 14.9)] and week 24 [dupilumab: −48.2% (−56.8; − 39.5); placebo: − 6.3% (−34.5; 14.8)]. Similar IgE reductions relative to baseline were observed in dupilumab-treated patients regardless of baseline IgE level. Dupilumab treatment improved ISS7, UAS7, and HSS7 over 12 and 24 weeks, regardless of baseline serum IgE level (interaction p  ≥ 0.59 for all treatment by subgroup comparisons), with weak correlations ( r  < 0.2) observed between IgE level changes and ISS7, UAS7, and HSS7 outcomes. Conclusions Dupilumab significantly improved CSU signs and symptoms and reduced serum IgE, regardless of baseline IgE levels. In the current analysis, baseline total IgE had no predictive value as a dupilumab treatment response biomarker in CSU. Downregulation of IgE, a key mediator of mast cell activation and histamine release, may at least partially explain the effectiveness of dupilumab in reducing CSU signs and symptoms. Trial Registration ClinicalTrials.gov Identifier: NCT04180488.