P>Studies based on skin and challenge tests have shown that 12-60% of children with suspected betalactam hypersensitivity were allergic to betalactams. Responses in skin and challenge tests were studied in 1865 children with suspected betalactam allergy (i) to confirm or rule out the suspected diagnosis; (ii) to evaluate diagnostic value of immediate and non-immediate responses in skin and challenge tests; (iii) to determine frequency of betalactam allergy in those children, and (iv) to determine potential risk factors for betalactam allergy. The work-up was completed in 1431 children, of whom 227 (15.9%) were diagnosed allergic to betalactams. Betalactam hypersensitivity was diagnosed in 50 of the 162 (30.9%) children reporting immediate reactions and in 177 of the 1087 (16.7%) children reporting non-immediate reactions (p < 0.001). The likelihood of betalactam hypersensitivity was also significantly higher in children reporting anaphylaxis, serum sickness-like reactions, and (potentially) severe skin reactions such as acute generalized exanthematic pustulosis, Stevens-Johnson syndrome, and drug reaction with systemic symptoms than in other children (p < 0.001). Skin tests diagnosed 86% of immediate and 31.6% of non-immediate sensitizations. Cross-reactivity and/or cosensitization among betalactams was diagnosed in 76% and 14.7% of the children with immediate and non-immediate hypersensitivity, respectively. The number of children diagnosed allergic to betalactams decreased with time between the reaction and the work-up, probably because the majority of children with severe and worrying reactions were referred for allergological work-up more promptly than the other children. Sex, age, and atopy were not risk factors for betalactam hypersensitivity. In conclusion, we confirm in numerous children that (i) only a few children with suspected betalactam hypersensitivity are allergic to betalactams; (ii) the likelihood of betalactam allergy increases with earliness and/or severity of the reactions; (iii) although non-immediate-reading skin tests (intradermal and patch tests) may diagnose non-immediate sensitizations in children with non-immediate reactions to betalactams (maculopapular rashes and potentially severe skin reactions especially), the diagnostic value of non-immediate-reading skin tests is far lower than the diagnostic value of immediate-reading skin tests, most non-immediate sensitizations to betalactams being diagnosed by means of challenge tests; (iv) cross-reactivity and/or cosensitizations among betalactams are much more frequent in children reporting immediate and/or anaphylactic reactions than in the other children; (v) age, sex and personal atopy are not significant risk factors for betalactam hypersensitivity; and (vi) the number of children with diagnosed allergy to betalactams (of the immediate-type hypersensitivity especially) decreases with time between the reaction and allergological work-up. Finally, based on our experience, we also propose a practical diagnostic approach in children with suspected betalactam hypersensitivity.
Hypersensitivity pneumonitis (HP) is an interstitial lung disease with a better prognosis, on average, than idiopathic pulmonary fibrosis (IPF). We compare survival time and pulmonary function trajectory in patients with HP and IPF by radiologic phenotype. HP (n = 117) was diagnosed if surgical/transbronchial lung biopsy, BAL, and exposure history results suggested this diagnosis. IPF (n = 152) was clinically and histopathologically diagnosed. All participants had a baseline high-resolution CT (HRCT) scan and FVC % predicted. Three thoracic radiologists documented radiologic features. Survival time is from HRCT scan to death or lung transplant. Cox proportional hazards models identify variables associated with survival time. Linear mixed models compare post-HRCT scan FVC % predicted trajectories. Subjects were grouped by clinical diagnosis and three mutually exclusive radiologic phenotypes: honeycomb present, non-honeycomb fibrosis (traction bronchiectasis and reticulation) present, and nonfibrotic. Nonfibrotic HP had the longest event-free median survival (> 14.73 years) and improving FVC % predicted (1.92%; 95% CI, 0.49-3.35; = .009). HP with non-honeycomb fibrosis had longer survival than IPF (> 7.95 vs 5.20 years), and both groups experienced a significant decline in FVC % predicted. Subjects with HP and IPF with honeycombing had poor survival (2.76 and 2.81 years, respectively) and significant decline in FVC % predicted. Three prognostically distinct, radiologically defined phenotypes are identified among patients with HP. The importance of pursuing a specific diagnosis (eg, HP vs IPF) among patients with non-honeycomb fibrosis is highlighted. When radiologic honeycombing is present, invasive diagnostic testing directed at determining the diagnosis may be of limited value given a uniformly poor prognosis.
Abstract Background. Propofol is thought to be a potential cause of allergic reactions in patients allergic to egg, soy or peanut, since current formulations contain an emulsion that includes egg lecithin and soybean oil. However, other than six case reports lacking in confirmatory evidence of an allergic reaction, there is no evidence linking the two types of allergies. The aim of this study was to examine the frequency of propofol allergy and to investigate if patients with specific immunoglobulin E (IgE) to egg, soy or peanut tolerated propofol. Methods. Study A examined the frequency of propofol allergy in 273 patients systematically investigated for suspected perioperative allergic reactions. Of these, 153 had been exposed to propofol and underwent skin tests and intravenous provocation. Study B retrospectively investigated propofol exposure and tolerance in 520 adult patients with a positive specific IgE to egg, soy or peanut. Results. Four of the 153 propofol-exposed patients (2.6%) investigated in study A were diagnosed with propofol allergy. Of these, three tested positive only on intravenous provocation. None of the four had allergic symptoms when eating egg, soy or peanut and none had detectable levels of specific IgE to egg or soy in their serum. In study B we found no signs of allergic reactions towards propofol in 171 retrieved anaesthetic charts from 99 patients with specific IgE to egg, soy or peanut. Conclusion. No connection between allergy to propofol and allergy to egg, soy or peanut was found. The present practice of choosing alternatives to propofol in patients with this kind of food allergy is not evidence based and should be reconsidered.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAID-induced respiratory symptoms in population across Europe and to assess its association with upper and lower respiratory tract disorders. The GA2 LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15-74 from their general population, and in three centers (Athens, Munich, Oslo), a younger population was sampled. Questionnaires including questions about age, gender, presence of symptoms of asthma, allergic rhinitis, chronic rhinosinusitis, smoking status, and history of NSAID-induced hypersensitivity reactions were sent to participants by mail. Totally, 62 737 participants completed the questionnaires. The mean prevalence of NSAID-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%), and Lodz (4.4%)] and lowest in Skopje, (0.9%), Amsterdam (1.1%), and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants with chronic rhinosinusitis symptoms (Odds Ratio 2.12; 95%CI 1.78-2.74), asthma symptoms in last 12 months (2.7; 2.18-3.35), hospitalization due to asthma (1.53; 1.22-1.99), and adults vs children (1.53; 1.24-1.89), but was not associated with allergic rhinitis. Our study documented significant variation between European countries in the prevalence of NSAID-induced respiratory hypersensitivity reactions, and association with chronic airway diseases, but also with environmental factors
Pain hypersensitivity at the site of inflammation as a result of chronic immune diseases, pathogenic infection, and tissue injury is a common medical condition. However, the specific contributions of the innate and adaptive immune system to the generation of pain during inflammation have not been systematically elucidated. We therefore set out to characterize the cellular and molecular immune response in two widely used preclinical models of inflammatory pain: ( ) intraplantar injection of complete Freund’s adjuvant (CFA) as a model of adjuvant- and pathogen-based inflammation and ( ) a plantar incisional wound as a model of tissue injury-based inflammation. Our findings reveal differences in temporal patterns of immune cell recruitment and activation states, cytokine production, and pain in these two models, with CFA causing a nonresolving granulomatous inflammatory response whereas tissue incision induced resolving immune and pain responses. These findings highlight the significant differences and potential clinical relevance of the incisional wound model compared with the CFA model. By using various cell-depletion strategies, we find that, whereas lymphocyte antigen 6 complex locus G (Ly)6G⁺CD11b⁺ neutrophils and T-cell receptor (TCR) β⁺ T cells do not contribute to the development of thermal or mechanical pain hypersensitivity in either model, proliferating CD11b⁺Ly6G⁻ myeloid cells were necessary for mechanical hypersensitivity during incisional pain, and, to a lesser extent, CFA-induced inflammation. However, inflammatory (CCR2⁺Ly6C ) monocytes were not responsible for these effects. The finding that a population of proliferating CD11b⁺Ly6G⁻ myeloid cells contribute to mechanical inflammatory pain provides a potential cellular target for its treatment in wound inflammation.
Background Severe anaphylaxis to honeybee or vespid stings is associated with a variety of risk factors, which are poorly defined. Objective Our aim was to evaluate the association of baseline serum tryptase concentrations and other variables routinely recorded during patient evaluation with the frequency of past severe anaphylaxis after a field sting. Methods In this observational multicenter study, we enrolled 962 patients with established bee or vespid venom allergy who had a systemic reaction after a field sting. Data were collected on tryptase concentration, age, sex, culprit insect, cardiovascular medication, and the number of preceding minor systemic reactions before the index field sting. A severe reaction was defined as anaphylactic shock, loss of consciousness, or cardiopulmonary arrest. The index sting was defined as the hitherto first, most severe systemic field-sting reaction. Relative rates were calculated with generalized additive models. Results Two hundred six (21.4%) patients had a severe anaphylactic reaction after a field sting. The frequency of this event increased significantly with higher tryptase concentrations (nonlinear association). Other factors significantly associated with severe reactions after a field sting were vespid venom allergy, older age, male sex, angiotensin-converting enzyme inhibitor medication, and 1 or more preceding field stings with a less severe systemic reaction. Conclusion In patients with honeybee or vespid venom allergy, baseline serum tryptase concentrations are associated with the risk for severe anaphylactic reactions. Preventive measures should include substitution of angiotensin-converting enzyme inhibitors.
Aims Intravenous iron supplementation is widely used to treat iron deficiency and iron deficiency anemia when oral iron administration is ineffective or poorly tolerated. Hypersensitivity reactions (HSRs) during infusions are rare, but can be life-threatening. This study aimed to compare the risk for HSRs with the intravenous administration of iron isomaltoside-1000 and ferric carboxymaltose for the treatment of iron deficiency and iron deficiency anemia. Methods This was a single-centre cohort study. Nurses and physicians were instructed to fill out an HSR registration form with every administration of intravenous iron. HSRs were distinguished into serious and non-serious HSRs using the Ring and Messmer classification. Results HSRs occurred in 18/836 (2.1%) ferric carboxymaltose and 43/496 (8.7%) iron isomaltoside-1000 administrations. The crude risk for HSRs was 75% lower after ferric carboxymaltose treatment (RR = 0.248, 95% CI: 0.145-0.426, P < 0.0001). The risk for grade II HSRs was 88% lower after ferric carboxymaltoside (RR = 0.123, 95% CI: 0.051-0.294). The likelihood of HSRs was 3.4 times higher after the administration of iron isomaltoside-1000 (95% CI: 1.910-6.093, P < 0.0001). Regardless of the type of intravenous iron, patients with comorbidities have a factor 3.6 higher risk (95% CI: 1.899-6.739, P < 0.0001). Conclusions Ferric carboxymaltose is associated with a 75% lower risk for HSRs compared with iron isomaltoside-1000 in our population. The presence of a comorbidity raises the likelihood of an HSR by a factor of three regardless of the type of intravenous iron infusion. Further research is needed to clarify the underlying mechanism in various patient groups.