Safety of direct oral provocation test to delabel reported mild beta-lactam allergy in infants.

BACKGROUND: Around 10% of people report a drug allergy and avoid some medications because of fear of allergic reactions. However, only after a proper diagnostic workup can some of these reactions be confirmed as allergic or nonallergic hypersensitivities. Beta-lactams (BLs) are the most common medication suspected of being involved in drug hypersensivity reactions (DHRs) in children. Recently, direct oral provocation tests (DPT) with BLs gained popularity within pediatric populations as a tool for delabeling children with suspected BL allergies. This study aimed to evaluate the safety of direct provocation tests in infants with mild cutaneous non-immediate reactions to BLs. METHODS: The authors retrospectively analyzed the data of 151 infants between 2015 and 2022, referred for evaluating a suspected allergy to BLs that occurred before age 24 months. RESULTS: The mean age of the children, including 55% male kids, at the suspected reaction was 15.9 months and the mean age at the time of the DPT was 39.6 months. In most cases, antibiotics were prescribed to treat common upper respiratory infections, such as acute otitis (54.3%) and acute tonsillitis (27.2%). Amoxicillin was considered the culprit drug in 62.9% of the cases, and the combination of amoxicillin-clavulanic acid in the case of 33.8% of children. The most frequent associated cutaneous clinical manifestations were maculopapular exanthema in 74.8% and delayed urticaria/angioedema in 25.2%. Of the 151 infants evaluated, parents of 149 infants agreed for a direct DPT, and only three had a positive test (2%). Symptoms resulting from the DPT were mild and easily treatable. CONCLUSIONS: A direct DPT without prior tests is a safe and effective procedure to delabel BL allergy, even in infants. The authors wish to emphasize the importance of properly validating BL allergy suspicions by promoting appropriate diagnostic procedures in infants as, in most cases, DHRs can be excluded and there is no need for further therapeutic restrictions.

What determines health professionals' COVID-19 vaccine hesitancy? A nationwide study.

INTRODUCTION: To contain the COVID-19 pandemic, higher vaccination rates are essential. However, as vaccine hesitancy is a reality, it is important to understand what drives health professionals to refuse getting vaccinated against COVID-19, who have been in the frontline of this pandemic since its beginning and may be key actors to improve vaccine coverage among their patients. PURPOSE: This study aims to assess the factors associated with vaccine hesitancy (VH) among health professionals (physicians, nurses, pharmacists and dentists). METHODS: A nationwide cross-sectional study was conducted through an online survey, with 890 Portuguese health professionals. A logistic regression analysis was used to determine the adjusted odds ratio (OR) of the independent variables (perceptions, knowledge and attitudes) per 1-point increase in the Likert scale and VH. RESULTS: Complacency, communications, confidence and convenience were strongly associated with VH probability. Concerns about vaccines' efficacy (ORPhysicians  = 8.33, 95% CI: 4.51-15.36) and safety (ORNurses  = 11.07, 95% CI: 4.12-29.77) increase the risk of VH on all health professional groups. A reduction of VH probability is associated with higher risk perceptions of getting infected (1/ORNurses  = 2.76, 95% CI: 1.52-5.02) and suffering complications (1/ORNurses  = 33.72, 95% CI: 8.48-134.13), higher confidence in the effectiveness of COVID-19 vaccines (1/ORDentists  = 12.29, 95% CI: 2.91-51.89), risk perception of getting infected if vaccinated (1/ORPhysicians  = 14.92, 95% CI: 6.85-32.50), risk of suffering from complications after getting vaccinated, and higher trust levels on the information transmitted by competent authorities (1/ORDentists  = 17.76, 95% CI: 3.83-82.22). CONCLUSIONS: To reduce COVID-19 VH, which appears to be highly influenced by perceptions, knowledge and attitudes, it is essential to promote interventions directed to transforming these potentially modifiable determinants.

Allergies and COVID-19 vaccines: An ENDA/EAACI Position paper.

BACKGROUND: Anaphylaxis, which is rare, has been reported after COVID-19 vaccination, but its management is not standardized. METHOD: Members of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interested in drug allergy participated in an online questionnaire on pre-vaccination screening and management of allergic reactions to COVID-19 vaccines, and literature was analysed. RESULTS: No death due to anaphylaxis to COVID-19 vaccines has been confirmed in scientific literature. Potential allergens, polyethylene glycol (PEG), polysorbate and tromethamine are excipients. The authors propose allergy evaluation of persons with the following histories: 1-anaphylaxis to injectable drug or vaccine containing PEG or derivatives; 2-anaphylaxis to oral/topical PEG containing products; 3-recurrent anaphylaxis of unknown cause; 4-suspected or confirmed allergy to any mRNA vaccine; and 5-confirmed allergy to PEG or derivatives. We recommend a prick-to-prick skin test with the left-over solution in the suspected vaccine vial to avoid waste. Prick test panel should include PEG 4000 or 3500, PEG 2000 and polysorbate 80. The value of in vitro test is arguable. CONCLUSIONS: These recommendations will lead to a better knowledge of the management and mechanisms involved in anaphylaxis to COVID-19 vaccines and enable more people with history of allergy to be vaccinated.

Perceptions, knowledge and attitudes about COVID-19 vaccine hesitancy in older Portuguese adults.

BACKGROUND: Coronavirus 2019 (COVID-19) has become a public-health emergency of international concern. Most efforts to contain the spread and transmission of the virus rely on campaigns and interventions targeted to reduce Vaccine Hesitancy and Refusal (VHR). OBJECTIVE: this study aims to assess the major factors associated with VHR in the older population in Portugal. METHODS: a nation-wide cross-sectional study was conducted in the older Portuguese population (≥65 years old) through computer-assisted telephone interviewing. Logistic regression was used to determine the adjusted odds ratio (OR) of the independent variables (perceptions, knowledge and attitudes) and of the outcome (VHR). RESULTS: the response rate was 60.1% (602/1,001). Perceptions, knowledge and attitudes were strongly associated with VHR probability. A 1-point Likert scale increase in concerns about the vaccines' efficacy and safety increased the risk of VHR by 1.96 (95% confidence interval [CI]: 1.40-6.28) and 3.13 (95%CI: 2.08-8.22), respectively. A reduction of VHR probability for 'reliability of the information released by social media' (OR = 0.34, 95%CI: 0.16-0.70) and for 'trust in national and international competent authorities' (OR = 0.34, 95%CI: 0.17-0.69) is also observed per 1-point increase. CONCLUSIONS: as VHR seems to be strongly associated with perceptions, knowledge and attitudes, the design and promotion of vaccination campaigns/educational interventions specifically targeted at changing these potentially modifiable determinants may help to tackle COVID-19 VHR and achieve a wider vaccine coverage.

The influence of protected fat in supplements on the performance and carcass characteristics of Nellore beef bulls in tropical pasture.

The finishing stages for uncastrated Nellore beef cattle on tropical pasture often produce high yielding carcasses with minimal fat cover. This study aimed to evaluate the performance and carcass characteristics of uncastrated Nellore beef bulls fed a diet containing rumen-protected fat during the rainy period for 210 days. Eighty Nellore beef bulls with 28 months of age, and an initial live weight of 416 kg ± 16 kg, were allocated into eight paddocks (7.0 ha), totaling 56 ha, at 10 animals/paddock, in a continuous-grazing system. The pasture characteristics, performance production, loin-eye area (cm2), subcutaneous fat thickness (mm), and rump fat thickness were evaluated. There was no effect (P > 0.05) on the average total weight gain (203.00 kg) and average daily gain (0.98 kg/day). On the other hand, the subcutaneous fat thickness and rump fat thickness were 42.8% and 49.5% greater, respectively, when the animals were fed a diet containing rumen-protected fat inclusion (P < 0.05). Supplementation with rumen-protected fat provided a thicker fat layer in the carcass of Nellore beef bulls grazing on tropical pasture during the rainy period.

Ruminal kinetics and nutritive value of Zuri grass silage harvested at different ages and added with powder molasses.

This study aimed to evaluate the effect of regrowth ages and the use of powdered molasses on nutritional characteristics of Zuri grass (Megathyrsus maximus) silages. A completely randomized design was used, in a 3 × 3 factorial scheme: three regrowth ages (65, 80, and 95 days) and three inclusion levels of powdered molasses of sugarcane (0, 20, and 40 g), with four replications. The chemical composition, fermentation parameters, in vitro digestibility, and in vitro degradation kinetics of the silages were evaluated. Greater dry matter (DM) contents were observed in silages with 95 days with 40 g of molasses. The 65 days of regrowth silages with 40 g of molasses had greater in vitro digestibility of dry matter compared to other treatments. However, lower pH values, N-NH3, DM losses, gas losses, and density were observed in silages with 95 days of regrowth with 40 g of molasses. It is recommended to cut the Zuri grass in the range of 80 to 95 days of regrowth with the addition of 40 g/kg of molasses in powders for the production of silages.

An EAACI Task Force report on allergy to beta-lactams in children: Clinical entities and diagnostic procedures.

Beta-lactam (BL) allergy suspicion is common in children and constitutes a major public health problem, with an impact on patient's health and on medical costs. However, it has been found that most of these reactions are not confirmed by a complete allergic workup. The diagnostic value of the currently available allergy tests has been investigated intensively recently by different groups throughout the world. This has led to major changes in the management of children with a suspected BL allergy. Particularly, it is now well accepted that skin tests can be skipped before the drug provocation test in children with a benign non-immediate reaction to BL. However, there is still a debate on the optimal allergic workup to perform in children with a benign immediate reaction. In addition, management of children with severe cutaneous adverse drug reactions remains difficult. In this review, based on a selection of the most relevant studies found in the literature, we will review and discuss the diagnosis of different forms of BL allergy in children.

Delayed hypersensitivity to antiepileptic drugs in children.

BACKGROUND: Antiepileptic drugs (AEDs) are widely used for the treatment of epilepsy, but they can be associated with the development of mainly delayed/non-immediate hypersensitivity reactions (HRs). Although these reactions are usually cutaneous, self-limited, and spontaneously resolve within days after drug discontinuation, sometime HR reactions to AEDs can be severe and life-threatening. AIM: This paper seeks to show examples on practical management of AED HRs in children starting from a review of what it is already known in literature. RESULTS: Risk factors include age, history of previous AEDs reactions, viral infections, concomitant medications, and genetic factors. The diagnostic workup consists of in vivo (intradermal testing and patch testing) and in vitro tests [serological investigation to exclude the role of viral infection, lymphocyte transformation test (LTT), cytokine detection in ELISpot assays, and granulysin (Grl) in flow cytometry. Treatment is based on a prompt drug discontinuation and mainly on the use of glucocorticoids. CONCLUSION: Dealing with AED HRs is challenging. The primary goal in the diagnosis and management of HRs to AEDs should be trying to accurately identify the causal trigger and simultaneously identify a safe and effective alternative anticonvulsant. There is therefore an ongoing need to improve our knowledge of HS reactions due to AED medications and in particular to improve our diagnostic capabilities.

Anaphylaxis in children and adolescents: The Portuguese Anaphylaxis Registry.

BACKGROUND: Anaphylaxis is increasing at pediatric age; however, its characterization is hampered by underdiagnosis and underreporting. The aim of this study was to identify the causes of anaphylaxis in children and adolescents in Portugal, thus contributing to a better knowledge of its etiology, clinical manifestations, and management. METHODS: During a 10-year period, a nationwide notification system for anaphylaxis was implemented, with voluntary reporting by allergists. Data on 533 patients under 18 years of age with anaphylaxis were included. RESULTS: Mean age was 8.5 ± 4.9 years, 61% were male; 45% had asthma. Mean age at the first anaphylaxis episode was 5.3 ± 4.7 years (ranging from 1 month to 17 years of age), 63% at pre-school age. Most reactions occurred at home (57%). Food-induced anaphylaxis was the leading cause (77%). The main culprit foods were cow's milk (32%), tree nuts (16%), shellfish (13%), egg (12%), fresh fruits (11%), fish (8%), and peanut (8%). Other causes included drugs (11%), insect sting (5%), cold-induced anaphylaxis (4%), exercise-induced anaphylaxis (2%), latex (1%), and idiopathic anaphylaxis (1%). Most patients (83%) were admitted to the emergency department; only 46% received adrenaline treatment. Recurrence of anaphylaxis occurred in 41% of the patients (3 or more episodes in 21%). An adrenaline autoinjector was used in 9% of the patients. CONCLUSIONS: In the Portuguese pediatric population, food is the leading cause of anaphylaxis. Undertreatment with adrenaline and high recurrence of anaphylaxis highlight the need to improve both the diagnosis and the therapeutic management of this life-threatening entity.

Drug-Induced Anaphylaxis: An Update on Epidemiology and Risk Factors.

Drug hypersensitivity is one of the most frequent causes of anaphylaxis, particularly in adults and in hospitalized patients. Drug-induced anaphylaxis (DIA) is also associated with more severe outcomes than other anaphylaxis triggers, and drugs are responsible for the majority of deaths due to anaphylaxis. We here review the current knowledge on the incidence, prevalence, drugs involved, mortality, and mortality risk factors for DIA. The incidence of both anaphylaxis and DIA seems to be increasing worldwide. Antibiotics and analgesics are the most frequently reported triggers of DIA. However, the importance of other drug groups should be taken into account, especially in particular settings (e.g., peri-operative and oncology). The identification of risk factors, geographical variables, and drugs associated with higher risk for DIA may improve the outcomes of this entity.

Diagnosis and management of drug-induced anaphylaxis in children: An EAACI position paper.

Drug hypersensitivity reactions (DHR) constitute a major and common public health problem, particularly in children. One of the most severe manifestations of DHR is anaphylaxis, which might be associated with a life-threatening risk. During those past decades, anaphylaxis has received particularly a lot of attention and international consensus guidelines have been recently published. Whilst drug-induced anaphylaxis is more commonly reported in adulthood, less is known about the role of drugs in pediatric anaphylaxis. Betalactam antibiotics and non-steroidal anti-inflammatory drugs are the most commonly involved drugs, probably related to high prescription rates. Diagnosis relies on the recognition of symptoms pattern and is based on complete allergic workup, particularly including skin tests and/or specific IgE. However, the real diagnostic value of those tests to diagnose immediate reactions in children remains not well defined for a significant number of the drugs. Generally, a drug provocation test is discussed to confirm or exclude an immediate-onset drug-induced hypersensitivity. Although avoidance of the incriminated drug (and related drug) is the rule, rapid desensitization is useful in selected subgroups of patients. There is a need for large, multicentric studies, to evaluate the real diagnostic value of the currently available skin tests. Moreover there is also a need to develop new diagnostic tests in the future to improve the management of these children.

EAACI/ENDA Position Paper: Diagnosis and management of hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) in children and adolescents.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in the pediatric population as antipyretics/analgesics and anti-inflammatory medications. Hypersensitivity (HS) reactions to NSAID in this age group, while similar to adults, have unique diagnostic and management issues. Although slowly accumulating, published data in this age group are still relatively rare and lacking a unifying consensus. This work is a summary of current knowledge and consensus recommendations utilizing both published data and expert opinion from the European Network of Drug Allergy (ENDA) and the Drug Hypersensitivity interest group in the European Academy of Allergy and Clinical Immunology (EAACI). This position paper summarizes diagnostic and management guidelines for children and adolescents with NSAIDs hypersensitivity.

Vaccination and allergy: EAACI position paper, practical aspects.

Immunization is highly effective in preventing infectious diseases and therefore an indispensable public health measure. Allergic patients deserve access to the same publicly recommended immunizations as non-allergic patients unless risks associated with vaccination outweigh the gains. Whereas the number of reported possible allergic reactions to vaccines is high, confirmed vaccine-triggered allergic reactions are rare. Anaphylaxis following vaccination is rare, affecting <1/100 000, but can occur in any patient. Some patient groups, notably those with a previous allergic reaction to a vaccine or its components, are at heightened risk of allergic reaction and require special precautions. Allergic reactions, however, may occur in patients without known risk factors and cannot be predicted by currently available tools. Unwarranted fear and uncertainty can result in incomplete vaccination coverage for children and adults with or without allergy. In addition to concerns about an allergic reaction to the vaccine itself, there is fear that routine childhood immunization may promote the development of allergic sensitization and disease. Thus, although there is no evidence that routine childhood immunization increases the risk of allergy development, such risks need to be discussed.

Frequency of self-reported drug allergy: A systematic review and meta-analysis with meta-regression.

BACKGROUND: Patients reporting drug allergy are treated with second-line therapies, with possible negative clinical and health consequences. OBJECTIVE: To assess the prevalence of self-reported drug allergy. METHODS: We performed a systematic review of observational studies assessing the prevalence of self-reported drug allergy. We searched 4 electronic databases. From selected studies, we extracted data on self-reported drug allergy prevalence, study design, participants' demographic characteristics, reported clinical manifestations, and suspected culprit drugs. We performed a random-effects meta-analysis followed by a meta-regression. RESULTS: Fifty-three studies were included in the systematic review, assessing a total of 126,306 participants, of whom 8.3% (range across studies 0.7-38.5%) self-reported drug allergy. Cutaneous manifestations were reported by 68.2% of participants, and anaphylactic or systemic reactions were reported by 10.8%. Antibiotics, nonsteroidal anti-inflammatory drugs, and anesthetics were the most frequently reported culprit drug classes. The frequency of self-reported drug allergy was higher in female (11.4%) than in male (7.2%) patients, adults (10.0%) than in children (5.1%), and in studies in the medical setting (15.9% in inpatients, 11.4% in outpatients) than in the general population (5.9%). The meta-analysis rendered a pooled prevalence of 7.9% (95% confidence interval 6.4-9.6), and the meta-regression identified study region, participants' age group, and study setting as factors associated with significant heterogeneity. Confirmation tests (including skin, in vitro, and drug provocation tests) were performed in only 3 studies. CONCLUSION: The prevalence of self-reported drug allergy is highly variable and is higher in female patients, adults, and inpatients. To overcome this variability, further studies using confirmation tests are needed.

Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs among Adults: Clinical Features and Risk Factors for Diagnosis Confirmation.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDS) are among the most common causes of drug hypersensitivity (HS) reactions. The diagnosis is based on a careful clinical history, and provocation tests are considered the gold standard for diagnosis. Skin tests have some value to study reactions to pyrazolones. Laboratory investigations are mostly used for research purposes. Different phenotypes have been described. OBJECTIVE AND METHODS: Our aim was to describe the most common clinical manifestations of NSAID HS in a large population of adult patients, the drugs involved, the association with previously described risk factors, and the outcome of diagnostic procedures. The classification of reactions proposed by the European Academy of Allergy and Clinical Immunology (EAACI) Drug Allergy Interest Group was adopted. RESULTS: Acetylsalicylic acid was the drug most often involved in reactions (34%), isolated cutaneous symptoms were the most reported (60%), and immediate reactions (58%) were the most common. There was an overall female predominance (64%) and 35% of the patients were atopic. HS to NSAIDs was confirmed in 21% of the patients. The most common phenotypes encountered among HS patients were NSAID-induced urticaria/angioedema and single-NSAID-induced urticaria/angioedema or anaphylaxis. Logistic regression analysis showed that gender and atopy were not significant risk factors for HS confirmation, but diagnosis depended on the number of previous reactions, the type of reaction, and the time interval between drug intake and reaction. CONCLUSION: Only 21% of suspected HS reactions were confirmed after diagnostic workup. Patients describing >1 previous reaction and suffering immediate reactions had a higher probability of a positive investigation.

Managing a child with possible allergy to vaccine.

Similarly to other medications, vaccines may be responsible for allergic reactions. Although IgE-mediated allergies to vaccine are extremely rare, they are clearly overdiagnosed. Indeed, accurate diagnosis of vaccine allergy is important not only to prevent serious or even life-threatening reactions, but also to avoid unnecessary vaccine restriction. Systematic approaches have been proposed and, if implemented, will likely reduce the number of children being inappropriately labeled as allergic to vaccine. In diagnosis of vaccine allergy, the patient's history is central although not sufficient. In case of suspicion of an allergy, the child should be referred to an allergist in order to perform a complete allergy workup, based primarily on skin tests and/or specific IgE. Highlighting the most recent literature, this article will address the management of children with a possible allergy to vaccine.

Hypersensitivity reactions to non-betalactam antibiotics in children: an extensive review.

In contrast to hypersensitivity reactions (HSRs) to ß-lactam antibiotics in children, studies about HSR to non-ß-lactam antibiotics (NBLAs) such as sulfonamides, macrolides, quinolones, and antituberculosis agents are scarce, and information is generally limited to case reports. The aim of this extensive review was to summarize our present knowledge on clinical characteristics, evaluation, and management of HSR to NBLAs in children based on the literature published between 1980 and 2013. NBLAs have been reported to induce a wide spectrum of HSRs from mild eruptions to severe, and sometimes fatal, systemic drug reactions, especially in some high-risk groups. The diagnosis relied upon history and remained unconfirmed by allergological tests in most of the cases. Obtaining a detailed history is valuable in the diagnosis of suspected reactions to NBLAs. Diagnostic in vivo and in vitro tests for NBLAs lack validation, which makes the diagnosis challenging. The definitive diagnosis of NBLA hypersensitivity frequently depends upon drug provocation tests. Studies including children showed that only 7.8 to 36% of suspected immediate and delayed HSRs to NBLAs could be confirmed by skin and/or provocation tests. Therefore, a standardized diagnostic approach and management strategy should be developed and employed for pediatric patients in the evaluation of suspected HSRs to NBLAs, some of which may be critical and unreplaceable in certain clinical situations.

Validation of control of allergic rhinitis and asthma test for children (CARATKids)--a prospective multicenter study.

BACKGROUND: Control of Allergic Rhinitis and Asthma Test for Children (CARATKids) is the first questionnaire that assesses simultaneously allergic rhinitis and asthma control in children. It was recently developed, but redundancy of questions and its psychometric properties were not assessed. This study aimed to (i) establish the final version of the CARATKids questionnaire and (ii) evaluate its reliability, responsiveness, cross-sectional validity, and longitudinal validity. METHODS: A prospective observational study was conducted in 11 Portuguese centers. During two visits separated by 6 wk, CARATKids, visual analog scale scales and childhood asthma control test were completed, and participant's asthma and rhinitis were evaluated by his/her physician without knowing the questionnaires' results. Data-driven item reduction was conducted, and internal consistency, responsiveness analysis, and associations with external measures of disease status were assessed. RESULTS: Of the 113 children included, 101 completed both visits. After item reduction, the final version of the questionnaire has 13 items, eight to be answered by the child and five by the caregiver. Its Cronbach's alpha was 0.80, the Guyatt's responsiveness index was -1.51, and a significant (p < 0.001) within-patient change of CARATKids score in clinical unstable patients was observed. Regarding cross-sectional validity, correlation coefficients of CARATKids with the external measures of control were between 0.45 and -0.69 and met the a priori predictions. In the longitudinal validity assessment, the correlation coefficients between the score changes of CARATKids and those of external measures of control ranged from 0.34 to 0.46. CONCLUSION: CARATKids showed adequate psychometric properties and is ready to be used in clinical practice.