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Paclitaxel is one of the first-line treatments for breast, ovarian, and lung cancers. However, its use is limited by the high frequency of hypersensitivity reactions. In this retrospective chart review at Memorial Sloan Kettering Cancer Center, we assess clinical factors associated with immediate and delayed hypersensitivity reactions to paclitaxel and characterize delayed hypersensitivity reactions to paclitaxel in patients with breast cancer. 12,274 patients were treated with paclitaxel. 6,165 had breast cancer and 1,233 were seen by a dermatologist. 734 patients (11.9%) developed an immediate hypersensitivity reaction. Age ( p  < 0.001), race ( p  < 0.001), and prior history of allergy ( p  = 0.05) were associated with immediate hypersensitivity reactions. 147 patients (4.0%) had a rash of interest. The most common phenotypes were maculopapular (52%) and urticaria (36%). Race ( p  < 0.001) and history of allergy ( p  < 0.001) were associated with development of a cutaneous reaction. Patients with an immediate hypersensitivity reaction were more likely to have developed a delayed cutaneous reaction (OR = 1.80). Risk factors for development of immediate hypersensitivity reactions in this study were younger age, race, and history of allergy. Patients who developed an immediate hypersensitivity reaction were more likely to develop a delayed hypersensitivity reaction. Risk factors for development of the rash included Asian race and history of allergy. Identification of risk factors is critical to guide care coordination. Awareness of these clinical factors which are associated with development of a rash could guide providers in choosing treatment with paclitaxel or nab-paclitaxel. If the cutaneous reactions are bothersome to the patient, the transition of treatment from paclitaxel to nab-paclitaxel may be warranted, or a consideration of re-challenge or desensitization may be discussed.

The management of patients with immediate hypersensitivity reactions (IHSR) to COVID-19 vaccines and their components, polyethylene glycol (PEG) 2000 and polisorbate 80 (PS80), has evolved since the beginning of the vaccination campaign. Despite the end of the pandemics, ensuring safe access to COVID-19 vaccination remains critical, especially for individuals with underlying health conditions. In this retrospective study, we evaluated 333 patients who underwent a standardized allergy work-up, including skin testing (ST) with vaccine components, to assess their eligibility for COVID-19 vaccination. 155 patients had a history of IHSRs to PEG-containing drugs, and 178 reported a IHSR following a prior vaccine dose. The majority (92 %) tested negative and were safely vaccinated. Among the 8 % tested positive, 66.7 % tolerated re-vaccination without any reactions. These findings highlight the overall safety of COVID-19 vaccination, even in patients considered at risk for allergic reactions, and challenge the necessity of routine ST for vaccine eligibility. Moreover, the observation that most reactions occurred after the first dose, and that patients with prior IHSRs were often safely re-vaccinated – frequently with the same vaccine — question the role of an IgE-mediated mechanism of the reactions and confirm the safety of vaccination. In conclusion, patients deemed at risk for COVID-19 vaccine-related IHSRs were safely vaccinated, supporting a more selective approach to allergy work-up and the importance of evidence-based risk assessment.

Classic atopic dermatitis is complicated by asthma, allergic rhinitis, and food allergies, cumulatively referred to as atopic diseases. Recent discoveries of mutations in the filaggrin gene as predisposing factors for atopic diseases have refocused investigators' attention on epidermal barrier dysfunction as a causative mechanism. The skin's barrier function has three elements: the stratum corneum (air-liquid barrier), tight junctions (liquid-liquid barrier), and the Langerhans cell network (immunological barrier). Clarification of the molecular events underpinning epidermal barrier function and dysfunction should lead to a better understanding of the pathophysiological mechanisms of atopic diseases.

Among traditional Chinese medicine injections, intravenous Shuang-Huang-Lian (IV-SHL) has the highest incidence of injection-induced immediate hypersensitivity reactions (IHRs). The precise mechanisms of IV-SHL-induced IHRs remain ambiguous. In this study, we investigated the mechanisms of SHL injection (SHLI)-induced IHRs. Our data showed that serum total IgE and mouse mast cell protease 1 (MMCP1) levels were higher in the SHLI antiserum; however, these effects of SHLI disappeared in the antibiotic-treated mice. SHLI caused intraplantar vasopermeability and shock during the first local or systemic injection. SHLI-induced nonallergic IHRs were attributed to its intermediate fraction F2 (the extract of Lonicerae Japonicae Flos and Fructus forsythiae ), and could be blocked by antagonists for histamine or C5a, rather than PAF or C3a. Eight constituents of F2 were able to directly activate C5 to promote local vasopermeability at the mg/mL level. In conclusion, SHLI-induced IHRs are not mediated by IgE. SHLI or its F2 can directly activate blood C5. Subsequently, C5a is likely to provoke histamine release from its effector cells (e.g., mast cells and basophils), indicating that histamine is a principal effector of IHRs induced by SHLI.

T helper 9 (Th9) cells are specialized for the production of IL-9, promote allergic inflammation in mice, and are associated with allergic disease in humans. It has not been determined whether Th9 cells express a characteristic transcriptional signature. In this study, we performed microarray analysis to identify genes enriched in Th9 cells compared with other Th subsets. This analysis defined a transcriptional regulatory network required for the expression of a subset of Th9-enriched genes. The activator protein 1 (AP1) family transcription factor BATF (B cell, activating transcription factor–like) was among the genes enriched in Th9 cells and was required for the expression of IL-9 and other Th9-associated genes in both human and mouse T cells. The expression of BATF was increased in Th9 cultures derived from atopic infants compared with Th9 cultures from control infants. T cells deficient in BATF expression had a diminished capacity to promote allergic inflammation compared with wild-type controls. Moreover, mouse Th9 cells ectopically expressing BATF were more efficient at promoting allergic inflammation than control transduced cells. These data indicate that BATF is a central regulator of the Th9 phenotype and contributes to the development of allergic inflammation.

Background: Proton pump inhibitors (PPIs) are identified to cause immediate hypersensitivity reactions and cross-reactivity among them. In this study, we aimed to describe the clinical features of immediate-type hypersensitivity reactions caused by PPIs, the results of drug tests performed with PPIs, and the cross-reactivity between PPIs. There are immediate hypersensitivity reactions with PPIs and there may be cross-reactivity between PPIs. In this study, we aimed to describe the clinical features of immediate-type hypersensitivity reactions caused by PPIs, the results of drug tests performed with PPIs and the cross-reactivity between PPIs. Methods: Adult patients who described an immediate hypersensitivity reaction to PPIs between March 1, 2017 and March 1, 2023 were evaluated. Results: Of the 47 patients included in the study, 89.4% were females, and the suspected PPI in 68% of the patients was lansoprazole. Anaphylaxis accounted for 72.3% of reactions, and the most common reaction was grade 2 (42.6%) according to Ring Messmer. Those who had two or more reactions to the same or different PPI were 51.1% of patients. A positivity rate of 43.8% was observed in the skin prick test with the suspected drug, 33.3% in the intradermal test, and 100% in the provocation test. There is varying potential for cross-reactivity among five different PPIs. Conclusions: İmmediate hypersensitivity reactions are observed among PPIs, particularly to lansoprazole, with the majority of reactions being anaphylaxis. Multiple life-threatening reactions can be prevented by increasing awareness of allergies to PPIs. Cross-reactivities among PPIs are variable, and further studies are needed to elucidate cross-reactivity with PPIs.

Drug hypersensitivity reactions have multiple implications for patient safety and health system costs, thus it is important to perform an accurate diagnosis. The diagnostic procedure includes a detailed clinical history, often unreliable; followed by skin tests, sometimes with low sensitivity or unavailable; and drug provocation testing, which is not risk-free for the patient, especially in severe reactions. In vitro tests could help to identify correctly the responsible agent, thus improving the diagnosis of these reactions, helping the physician to find safe alternatives, and reducing the need to perform drug provocation testing. However, it is necessary to confirm the sensitivity, specificity, negative and positive predictive values for these in vitro tests to enable their implementation in clinical practice. In this review, we have analyzed these parameters from different studies that have used in vitro test for evaluating drug hypersensitivity reactions and estimated the added value of these tests to the in vivo diagnosis.

Objective To determine whether dietary n-3 long chain polyunsaturated fatty acid (LCPUFA) supplementation of pregnant women with a fetus at high risk of allergic disease reduces immunoglobulin E associated eczema or food allergy at 1 year of age.Design Follow-up of infants at high hereditary risk of allergic disease in the Docosahexaenoic Acid to Optimise Mother Infant Outcome (DOMInO) randomised controlled trial.Setting Adelaide, South Australia.Participants 706 infants at high hereditary risk of developing allergic disease whose mothers were participating in the DOMInO trial.Interventions The intervention group (n=368) was randomly allocated to receive fish oil capsules (providing 900 mg of n-3 LCPUFA daily) from 21 weeks’ gestation until birth; the control group (n=338) received matched vegetable oil capsules without n-3 LCPUFA.Main outcome measure Immunoglobulin E associated allergic disease (eczema or food allergy with sensitisation) at 1 year of age.Results No differences were seen in the overall percentage of infants with immunoglobulin E associated allergic disease between the n-3 LCPUFA and control groups (32/368 (9%) v 43/338 (13%); unadjusted relative risk 0.68, 95% confidence interval 0.43 to 1.05, P=0.08; adjusted relative risk 0.70, 0.45 to 1.09, P=0.12), although the percentage of infants diagnosed as having atopic eczema (that is, eczema with associated sensitisation) was lower in the n-3 LCPUFA group (26/368 (7%) v 39/338 (12%); unadjusted relative risk 0.61, 0.38 to 0.98, P=0.04; adjusted relative risk 0.64, 0.40 to 1.02, P=0.06). Fewer infants were sensitised to egg in the n-3 LCPUFA group (34/368 (9%) v 52/338 (15%); unadjusted relative risk 0.61, 0.40 to 0.91, P=0.02; adjusted relative risk 0.62, 0.41 to 0.93, P=0.02), but no difference between groups in immunoglobulin E associated food allergy was seen.Conclusion n-3 LCPUFA supplementation in pregnancy did not reduce the overall incidence of immunoglobulin E associated allergies in the first year of life, although atopic eczema and egg sensitisation were lower. Longer term follow-up is needed to determine if supplementation has an effect on respiratory allergic diseases and aeroallergen sensitisation in childhood.Trial registration Australian New Zealand Clinical Trials Registry ACTRN12610000735055 (DOMInO trial: ACTRN12605000569606).

House dust mites are an unsurpassed cause of atopic sensitization and allergic illness throughout the world. The major allergenic dust mites Dermatophagoides pteronyssinus, Dermatophagoides farinae, Euroglyphus maynei, and Blomia tropicalis are eight-legged members of the Arachnid class. Their approximately 3-month lifespan comprises egg, larval, protonymph, tritonymph, and adult stages, with adults, about one fourth to one third of a millimeter in size, being at the threshold of visibility. The geographic and seasonal distributions of dust mites are determined by their need for adequate humidity, while their distribution within substrates is further determined by their avoidance of light. By contacting the epithelium of the eyes, nose, lower airways, skin, and gut, the allergen-containing particles of dust mites can induce sensitization and atopic symptoms in those organs. Various mite allergens, contained primarily in mite fecal particles but also in shed mite exoskeletons and decaying mite body fragments, have properties that include proteolytic activity, homology with the lipopolysaccharide-binding component of Toll-like receptor 4, homology with other invertebrate tropomyosins, and chitin-cleaving and chitin-binding activity. Mite proteases have direct epithelial effects including the breaching of tight junctions and the stimulation of protease-activated receptors, the latter inducing pruritus, epithelial dysfunction, and cytokine release. Other components, including chitin, unmethylated mite and bacterial DNA, and endotoxin, activate pattern recognition receptors of the innate immune system and act as adjuvants promoting sensitization to mite and other allergens. Clinical conditions resulting from mite sensitization and exposure include rhinitis, sinusitis, conjunctivitis, asthma, and atopic dermatitis. Systemic allergy symptoms can also occur from the ingestion of cross-reacting invertebrates, such as shrimp or snail, or from the accidental ingestion of mite-contaminated foods. Beyond their direct importance as a major allergen source, an understanding of dust mites leads to insights into the nature of atopy and of allergic sensitization in general.

BackgroundAlthough women with severe non-allergic asthma may represent a substantial proportion of adults with asthma in clinical practice, gender differences in the incidence of allergic and non-allergic asthma have been little investigated in the general population.MethodsGender differences in asthma prevalence, reported diagnosis and incidence were investigated in 9091 men and women randomly selected from the general population and followed up after 8–10 years as part of the European Community Respiratory Health Survey. The protocol included assessment of bronchial responsiveness, IgE specific to four common allergens and skin tests to nine allergens.ResultsAsthma was 20% more frequent in women than in men over the age of 35 years. Possible under-diagnosis of asthma appeared to be particularly frequent among non-atopic individuals, but was as frequent in women as in men. The follow-up of subjects without asthma at baseline showed a higher incidence of asthma in women than in men (HR 1.94; 95% CI 1.40 to 2.68), which was not explained by differences in smoking, obesity or lung function. More than 60% of women and 30% of men with new-onset asthma were non-atopic. The incidence of non-allergic asthma was higher in women than in men throughout all the reproductive years (HR 3.51; 95% CI 2.21 to 5.58), whereas no gender difference was observed for the incidence of allergic asthma.ConclusionsThis study shows that female sex is an independent risk factor for non-allergic asthma, and stresses the need for more careful assessment of possible non-allergic asthma in clinical practice, in men and women.