Botanical Impurities in the Supply Chain: A New Allergenic Risk Exacerbated by Geopolitical Challenges.

BACKGROUND: The supply chains of food raw materials have recently been heavily influenced by geopolitical events. Products that came from, or transited through, areas currently in conflict are now preferentially supplied from alternative areas. These changes may entail risks for food safety. METHODS: We review the potential allergenicity of botanical impurities, specifically vegetable contaminants, with particular attention to the contamination of vegetable oils. We delve into the diverse types of botanical impurities, their sources, and the associated allergenic potential. Our analysis encompasses an evaluation of the regulatory framework governing botanical impurities in food labeling. RESULTS: Unintended plant-derived contaminants may manifest in raw materials during various stages of food production, processing, or storage, posing a risk of allergic reactions for individuals with established food allergies. Issues may arise from natural occurrence, cross-contamination in the supply chain, and contamination at during production. The food and food service industries are responsible for providing and preparing foods that are safe for people with food allergies: we address the challenges inherent in risk assessment of botanical impurities. CONCLUSIONS: The presence of botanical impurities emerges as a significant risk factor for food allergies in the 2020s. We advocate for regulatory authorities to fortify labeling requirements and develop robust risk assessment tools. These measures are necessary to enhance consumer awareness regarding the potential risks posed by these contaminants.

Perspectives in precautionary allergen labelling of prepackaged foods after the FAO/WHO consultation.

PURPOSE OF REVIEW: The purpose of this review is to provide an overview of the perspectives regarding precautionary allergen labelling (PAL) of prepackaged foods following the consultation conducted by the Food and Agriculture Organization (FAO) and the WHO. RECENT FINDINGS: The FAO/WHO consultation provided a comprehensive assessment of the current status and practices of PAL implementation worldwide. One of the key findings highlighted by the Expert Committee was the need for improvement in existing PAL systems. It was noted that many countries lacked uniformity in PAL practices, leading to inconsistencies in labelling and potentially misleading information for consumers. Furthermore, the consultation emphasized the importance of PAL being risk-based, taking into account both the amount and frequency of unintended allergen presence (UAP) in food products. SUMMARY: The FAO/WHO consultation shed light on various perspectives and challenges associated with PAL of prepackaged foods. Key findings emphasized the need for improvement in existing PAL systems, including the adoption of a risk-based approach, standardized regulations, and enhanced transparency. Moving forward, collaborative efforts between regulatory agencies, food manufacturers, and consumer advocacy groups will be essential in developing effective PAL strategies that prioritize consumer safety and well being.

Drug-Induced Anaphylaxis in Children.

Drug-induced anaphylaxis in children is less common than in adults and primarily involves beta-lactams and nonsteroidal anti-inflammatory drugs. Epidemiological studies show variable prevalence, influenced by age, gender, and atopic diseases. The pathophysiology includes IgE-mediated reactions and non-IgE mechanisms, like cytokine release reactions. We address drug-induced anaphylaxis in children, focusing on antibiotics, nonsteroidal anti-inflammatory drugs, neuromuscular blocking agents, and monoclonal antibodies. Diagnosis combines clinical criteria with in vitro, in vivo, and drug provocation tests. The immediate management of acute anaphylaxis primarily involves the use of adrenaline, coupled with long-term strategies, such as allergen avoidance and patient education. Desensitization protocols are crucial for children allergic to essential medications, particularly antibiotics and chemotherapy agents.

Local Anesthetic Hypersensitivity Reactions in Pediatric Patients: Recognition and Management.

Local anesthetics (LAs) are commonly used in all medical specialties, particularly in association with surgery, obstetrics, dentistry, and emergency departments. Most individuals, starting from young children, are exposed to LAs during life. LA hardly induces adverse events when used in recommended doses and with proper injection techniques. However, immediate anaphylactic reactions to LA injections may be a rare but life-threatening manifestation. A comprehensive report of the event and performing a specialist examination are crucial to prevent further episodes. The diagnosis should be based on history, medical records, skin and challenge tests.

Reactivity to allergenic food contaminants: A study on products on the market.

BACKGROUND: The frequency and severity of reactions in food-allergic consumers exposed to unintentional food allergen contamination during production is unknown. To warn allergic consumers, it has been suggested for pre-packaged foods to be precautionary labelled when the food allergen contamination may exceed the amount to which 1%-5% of the population could react (ED01-ED05). ED01 for hazelnut and milk have been estimated at 0.1 and 0.2 mg, respectively, by the Voluntary Incidental Trace Allergen Labelling (VITAL) initiative. The respective reference doses recommended by the FAO/WHO Codex consultation are 3 and 2 mg. We evaluated the reactivity to potential traces of milk and hazelnut allergens in allergen-free pre-packaged products by children affected by severe allergies to milk and hazelnuts. METHODS: Oral Food Challenges with commercially available hazelnut-free wafer biscuits and milk-free chocolate pralines were administered to patients with severe food allergies to hazelnut and cow's milk, respectively. Contamination levels of milk or hazelnut allergens were measured using chromatographic separation interfaced with triple quadrupole mass spectrometry. RESULTS: No hazelnut allergic patient showed allergic reactions to exposure to biscuits, nor any milk allergic patient displayed allergic reactions to the dark chocolate praline. While no hazelnut trace was detected in biscuits, the praline was found to be contaminated by milk at concentrations ranging between 8 and 35 mg total protein/kg food. In our dose model, these amounts exceeded 1.5-10 times the VITAL ED01 and reached the threshold suggested by the FAO/WHO Codex consultation. CONCLUSIONS: Upon the consumption of food products available on the market, many patients with severe food allergies tolerate significantly higher doses of allergen than reference doses indicated in the VITAL system used for precautionary allergen labelling. These doses support the safety of the FAO/WHO recommended reference doses.

Evaluation and Updated Classification of Acute Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): NSAID-Exacerbated or -Induced Food Allergy.

BACKGROUND: There are hypersensitivity reactions (HRs) to foods in which nonsteroidal anti-inflammatory drugs (NSAIDs) act as aggravating factors (NSAID-exacerbated food allergy [NEFA]) or cofactors (NSAID-induced food allergy [NIFA]), often misdiagnosed as HRs to NSAIDs. Urticarial/angioedematous and/or anaphylactic reactions to two or more chemically unrelated NSAIDs do not meet current classification criteria. However, they may be considered part of a cross-reactive type of acute HR, which is NSAID-induced urticaria/angioedema with or without respiratory or systemic symptoms of anaphylaxis. OBJECTIVE: To evaluate patients reporting acute HRs to NSAIDs and classify them according to updated criteria. METHODS: We prospectively studied 414 patients with suspected HRs to NSAIDs. For all whom met these criteria, NEFA/NIFA was diagnosed: (1) mild reactions to (NEFA) or tolerance of (NIFA) the suspected foods without taking NSAIDs; (2) cutaneous and/or anaphylactic reactions to the combination foods plus NSAIDs; (3) positive allergy tests to the suspected foods; and (4) negative drug challenges (DCs) with the NSAIDs involved. RESULTS: A total of 252 patients were given the diagnosis of NSAID hypersensitivity (60.9%), 108 of whom had NSAID-induced urticaria/angioedema with or without respiratory or systemic symptoms of anaphylaxis. We excluded NSAID hypersensitivity in 162 patients (39.1%) who tolerated DCs with the suspected NSAIDs, nine of whom received a diagnosis of NEFA, and 66 of NIFA. Pru p 3 was implicated in 67 of those 75 patients who received a diagnosis of NEFA or NIFA. CONCLUSIONS: NEFA and NIFA account for about 18% of patients reporting HRs to NSAIDs, in which Pru p 3 is the main responsible food allergen. Therefore, patients with cutaneous and/or anaphylactic reactions to NSAIDs should be carefully questioned about all foods ingested within 4 hours before or after NSAID exposure, and targeted food allergy tests should be considered in the diagnostic workup of these patients. If testing is positive, DCs with the suspected NSAIDs should also be considered.

The Combined Use of Chronological and Morphological Criteria in the Evaluation of Immediate Penicillin Reactions: Evidence From a Large Study.

BACKGROUND: Immediate hypersensitivity reactions to penicillins are often labeled on the basis of a similar set of symptoms, but a key feature of these reactions that can be reproduced in diagnostic testing may be the timing of a reaction in relation to the dose administration. OBJECTIVE: To determine whether the timing of a reaction in response to the last dose of a penicillin would predict the results of diagnostic testing. METHODS: We evaluated 1074 patients by performing skin tests, serum specific IgE assays (ImmunoCAP), and challenges. Patients who were evaluated by us more than 6 months after their reactions and found negative were reevaluated within 2 to 4 weeks. RESULTS: Patients who had reacted within 1 hour after the first dose, within 1 hour after subsequent doses, more than 1 hour to within 6 hours after the first dose, or more than 1 hour to within 6 hours after subsequent doses were classified as group A (758 individuals), B (92), C (67), or D (157), respectively. Penicillin hypersensitivity was diagnosed in 707 patients (65.8%) by skin tests (407 patients, 57.6%), ImmunoCAP (47, 6.6%), both tests (232, 32.8%), or challenges (21, 3%). A conversion to allergy-test positivity occurred in 7 of 10 patients with anaphylactic reactions and in 1 of 28 patients with other reactions who were reevaluated after negative challenges. The rate of penicillin-allergic patients in groups A, B, C, and D was 85%, 35.9%, 35.8%, and 3.8%, respectively. Only 1 of 107 patients reporting cutaneous reactions lasting more than 1 day had positive results to allergy tests. CONCLUSIONS: IgE-mediated hypersensitivity can be diagnosed by skin tests in about 70% of subjects who react within 1 hour (eg, patients from groups A and B). This hypersensitivity can be lost over time, as demonstrated by the negativization of allergy tests in follow-up studies. In subjects with anaphylactic reactions, however, it is advisable to not consider this phenomenon definitive. In fact, a conversion to allergy test positivity can be observed in up to 20% of such subjects retested after negative challenges.

Down Syndrome in FPIES: An Overwhelming and Unexpected Prevalence.

Down syndrome (DS) is one of the most common chromosomal anomalies. Gastrointestinal disorders in DS are predominantly related to anatomical anomalies and celiac disease. In 2015, the first two cases of non-IgE-mediated food allergy in patients with DS were described. However, gastrointestinal symptoms experienced by subjects with DS have never been related to a possible non-IgE-mediated food allergy and a Food Protein-induced Enterocolitis syndrome (FPIES). A retrospective descriptive single-center study was conducted. Subjects included were children with acute FPIES who entered our institutional follow-up protocol between January 2013 and January 2020. Among the 85 patients (forty-nine boys-57.6%), ten (11.76%) were children with DS. In our population, the FPIES triggers included different foods (such as milk, egg, fruit, fish, wheat, soy, beef, etc.). Nine patients with DS showed FPIES reactions after ingesting cow's milk (one even with beef and three with soy), while the last one was affected by FPIES to fish. Considering the subgroup of patients affected by cow's milk FPIES (40 subjects overall), 22.5% had a diagnosis of DS. Patients with DS experienced acute FPIES reactions with a severity degree slightly higher than that reported in other patients, ranging from mild-moderate to severe or very severe. During the acute reactions, the patients with DS showed increased white blood cell production, absolute neutrophil count and C-reactive protein levels. This series provides a starting point for novel hypothesis-testing clinical research and possible specific immunological alterations in FPIES children with or without DS.

Detection of Serum-Specific IgE by Fluoro-Enzyme Immunoassay for Diagnosing Type I Hypersensitivity Reactions to Penicillins.

Diagnosis of type I hypersensitivity reactions (IgE-mediated reactions) to penicillins is based on clinical history, skin tests (STs), and drug provocation tests (DPTs). Among in vitro complementary tests, the fluoro-enzyme immunoassay (FEIA) ImmunoCAP® (Thermo-Fisher, Waltham, MA, USA) is the most widely used commercial method for detecting drug-specific IgE (sIgE). In this study, we aimed to analyze the utility of ImmunoCAP® for detecting sIgE to penicillin G (PG) and amoxicillin (AX) in patients with confirmed penicillin allergy. The study includes 139 and 250 patients evaluated in Spain and Italy, respectively. All had experienced type I hypersensitivity reactions to penicillins confirmed by positive STs. Additionally, selective or cross-reactive reactions were confirmed by DPTs in a subgroup of patients for further analysis. Positive ImmunoCAP® results were 39.6% for PG and/or AX in Spanish subjects and 52.4% in Italian subjects. When only PG or AX sIgE where analyzed, the percentages were 15.1% and 30.4%, respectively, in Spanish patients; and 38.9% and 46% in Italian ones. The analysis of positive STs showed a statistically significant higher percentage of positive STs to PG determinants in Italian patients. False-positive results to PG (16%) were detected in selective AX patients with confirmed PG tolerance. Low and variable sensitivity values observed in a well-defined population with confirmed allergy diagnosis, as well as false-positive results to PG, suggest that ImmunoCAP® is a diagnostic tool with relevant limitations in the evaluation of subjects with type I hypersensitivity reactions to penicillins.

Cow's milk and egg protein threshold dose distributions in children tolerant to beef, baked milk, and baked egg.

BACKGROUND: The use of eliciting doses (EDs) for food allergens is necessary to inform individual dietary advice and food allergen risk-management. The Eliciting Dose 01 (ED01) for milk and egg, calculated from populations of allergic subjects undergoing oral food challenges (OFCs), are 0.2 mg total protein. The respective Eliciting Dose 05 (ED05) is 2.4 mg for milk and 2.3 mg for egg. As about 70% children allergic to such foods may tolerate them when baked, we sought to verify the EDs of that subpopulation of milk and egg-allergic children. METHODS: We retrospectively assessed consecutive OFC for fresh milk and egg between January 2018 and December 2020 in a population of baked food-tolerant children. RESULTS: Among 288 children (median age 56 - IQR 36-92.5 months, 67.1% male) included, 87 (30.2%) returned positive OFC results, 38 with milk and 49 with egg. The most conservative ED01 was 0.3 mg total protein (IQR 0.03-2.9) for milk and 14.4 mg total protein (IQR 3.6-56.9) for egg. The respective ED05 was 4.2 (IQR 0.9-19.6) mg for milk and 87.7 (IQR 43-179) mg for egg. Such thresholds are, respectively, 1.5 (milk ED01), 1.75 (milk ED05), 72 (egg ED01), and 38.35 (egg ED05) times higher than the currently used thresholds. CONCLUSIONS: The subpopulation of children allergic to milk and egg, but tolerant to baked proteins, displays higher reactivity thresholds than the general population of children allergic to milk and egg. Their risk stratification, in both individual and population terms, should consider this difference. In baked milk-tolerant children, milk causes reactions at lower doses than egg in our group of egg-tolerant children. This could be associated with the relative harmlessness of egg compared with milk in the determinism of fatal anaphylactic reactions in children.

Threshold of Reactivity and Tolerance to Precautionary Allergen-Labelled Biscuits of Baked Milk- and Egg-Allergic Children.

Extremely sensitive food-allergic patients may react to very small amounts of allergenic foods. Precautionary allergen labelling (PAL) warns from possible allergenic contaminations. We evaluated by oral food challenge the reactivity to a brand of PAL-labelled milk- and egg-free biscuits of children with severe milk and egg allergy. We explored the ability of proteomic methods to identify minute amounts of milk/egg allergens in such biscuits. Traces of milk and/or egg allergens in biscuits were measured by two different liquid-chromatography-mass spectrometry methods. The binding of patient's serum with egg/milk proteins was assessed using immunoblotting. None of the patients reacted to biscuits. Egg and milk proteins were undetectable with a limit of detection of 0.6 µg/g for milk and egg (method A), and of 0.1 and 0.3 µg /g for milk and egg, respectively (method B). The immunoblots did not show milk/egg proteins in the studied biscuits. Milk/egg content of the biscuits is far lower than 4 µg of milk or egg protein per gram of product, the minimal doses considered theoretically capable of causing reactions. With high sensitivity, proteomic assessments predict the harmlessness of very small amount of allergens in foods, and can be used to help avoiding unnecessary PAL.

Urticaria: The 1-1-1 Criterion for Optimized Risk Stratification in ß-Lactam Allergy Delabeling.

BACKGROUND: A spurious label of ß-lactam allergy compromises antibiotic stewardship. Delabeling protocols based on direct challenges (ie, not preceded by allergy tests) can be applied in low-risk patients. OBJECTIVE: This study aims at determining the significance of the characteristics of urticaria in the risk stratification for delabeling. METHODS: The characteristics of urticarial eruptions that had occurred during therapeutic courses with a ß-lactam, namely the time interval between the exposure and onset, the dose (first or subsequent) after which urticaria appeared, and the duration of the eruption, were correlated to the results of a systematic allergy workup (skin tests, specific IgE measurements, and challenges). Data from 410 patients enrolled in 3 allergy centers (Rome and Troina, Italy, and Antwerp, Belgium) were analyzed. A multivariable logistic regression was performed, which included appearance within 1 hour after the first dose and regression within 1 day: a model that can be summarized as the "1-1-1" urticaria criterion. RESULTS: An urticarial eruption that had appeared within 1 hour after the first dose and had regressed within 1 day was more frequently reported in the group with a positive allergy workup, with odds ratios of 17 (95% confidence interval [CI]: 9-31), 11 (95% CI: 6-20), and 48 (95% CI: 14-157), respectively (P < .005). The 1-1-1 criterion displayed a sensitivity and specificity of 85%, and a negative predictive value and a positive predictive value of 80% and 90%, respectively. CONCLUSION: Patients with urticaria meeting the 1-1-1 criterion should be considered at high risk and referred for an allergy workup with skin testing and specific IgE measurement before challenging.

Gut Microbiota Profile in Children with IgE-Mediated Cow's Milk Allergy and Cow's Milk Sensitization and Probiotic Intestinal Persistence Evaluation.

Food allergy (FA) and, in particular, IgE-mediated cow's milk allergy is associated with compositional and functional changes of gut microbiota. In this study, we compared the gut microbiota of cow's milk allergic (CMA) infants with that of cow's milk sensitized (CMS) infants and Healthy controls. The effect of the intake of a mixture of Bifidobacterium longum subsp. longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 on gut microbiota modulation of CMA infants and probiotic persistence was also investigated. Gut microbiota of CMA infants resulted to be characterized by a dysbiotic status with a prevalence of some bacteria as Haemophilus, Klebsiella, Prevotella, Actinobacillus and Streptococcus. Among the three strains administered, B.longum subsp. infantis colonized the gastrointestinal tract and persisted in the gut microbiota of infants with CMA for 60 days. This colonization was associated with perturbations of the gut microbiota, specifically with the increase of Akkermansia and Ruminococcus. Multi-strain probiotic formulations can be studied for their persistence in the intestine by monitoring specific bacterial probes persistence and exploiting microbiota profiling modulation before the evaluation of their therapeutic effects.

ß-Lactam Allergy and Cross-Reactivity: A Clinician's Guide to Selecting an Alternative Antibiotic.

ß-Lactams which include penicillins, cephalosporins, carbapenems, and monobactams are the most common antibiotic classes reported to cause allergic reactions to drugs. This review is mainly about published studies assessing the cross-reactivity among ß-lactams in penicillin- or cephalosporin-allergic subjects by carrying out diagnostic tests with alternative ß-lactams and, if appropriate, graded challenges. Several studies demonstrated that cross-reactivity connected with the ß-lactam ring, causing positive responses to allergy tests with all ß-lactams, is infrequent in subjects with an IgE-mediated allergy and anecdotal in those with a T-cell-mediated allergy. Identities or similarities of ß-lactam side-chain structures are mainly responsible for cross-reactivity among these antibiotics. For example, in aminopenicillin-allergic subjects, cross-reactivity with aminocephalosporins could possibly be over 30%. On the other hand, in a few prospective studies of penicillin-allergic individuals, less than 1% of cases show a cross-reactivity between penicillins and both aztreonam and carbapenems. Particular patterns of allergy-test positivity observed in some studies that assessed cross-reactivity among ß-lactams seem to indicate that prior exposures may be responsible for coexisting sensitivities. Therefore, pre-treatment skin tests with the related ß-lactams are suggested before administering them via graded challenges to ß-lactam-allergic patients who need alternative ß-lactams.

Beta-lactam-induced immediate hypersensitivity reactions: A genome-wide association study of a deeply phenotyped cohort.

BACKGROUND: ß-lactam antibiotics are associated with a variety of immune-mediated or hypersensitivity reactions, including immediate (type I) reactions mediated by antigen-specific IgE. OBJECTIVE: We sought to identify genetic predisposing factors for immediate reactions to ß-lactam antibiotics. METHODS: Patients with a clinical history of immediate hypersensitivity reactions to either penicillins or cephalosporins, which were immunologically confirmed, were recruited from allergy clinics. A genome-wide association study was conducted on 662 patients (the discovery cohort) with a diagnosis of immediate hypersensitivity and the main finding was replicated in a cohort of 98 Spanish cases, recruited using the same diagnostic criteria as the discovery cohort. RESULTS: Genome-wide association study identified rs71542416 within the Class II HLA region as the top hit (P = 2 × 10-14); this was in linkage disequilibrium with HLA-DRB1∗10:01 (odds ratio, 2.93; P = 5.4 × 10-7) and HLA-DQA1∗01:05 (odds ratio, 2.93, P = 5.4 × 10-7). Haplotype analysis identified that HLA-DRB1∗10:01 was a risk factor even without the HLA-DQA1∗01:05 allele. The association with HLA-DRB1∗10:01 was replicated in another cohort, with the meta-analysis of the discovery and replication cohorts showing that HLA-DRB1∗10:01 increased the risk of immediate hypersensitivity at a genome-wide level (odds ratio, 2.96; P = 4.1 × 10-9). No association with HLA-DRB1∗10:01 was identified in 268 patients with delayed hypersensitivity reactions to ß-lactams. CONCLUSIONS: HLA-DRB1∗10:01 predisposed to immediate hypersensitivity reactions to penicillins. Further work to identify other predisposing HLA and non-HLA loci is required.

Evaluating Immediate Reactions to Cephalosporins: Time Is of the Essence.

BACKGROUND: Few studies have assessed the diagnostic value of cephalosporin skin tests in patients with immediate reactions to these ß-lactams. OBJECTIVE: To evaluate the usefulness of skin tests and challenges in assessing such subjects. METHODS: We conducted a prospective study of 236 consecutive subjects who had suffered 249 immediate reactions (mostly anaphylaxis) to cephalosporins. Skin tests were performed with penicillin reagents and suspected cephalosporins. Serum specific IgE assays (ImmunoCAP) were also carried out for penicillins and cefaclor. Subjects with negative results underwent challenges with the suspected cephalosporins; patients with negative results who had been assessed more than 6 months after their reactions were reevaluated. RESULTS: In the first allergy workup, an IgE-mediated hypersensitivity to cephalosporins was diagnosed in 164 (69.5%) of the 236 patients on the basis of skin test (162 patients) or cefaclor ImmunoCAP positivity (2 patients). Of the 72 patients with negative results, 55 underwent cephalosporin challenges; 3 reacted. Twenty subjects were reevaluated after cephalosporin negative challenges, with a conversion to cephalosporin skin test positivity occurring in 5 of the 6 subjects who had had anaphylactic reactions and in none of the remaining 14 subjects with other reactions. Overall, an immediate hypersensitivity to cephalosporins was diagnosed in 172 patients (of whom it was diagnosed in 5 after retesting). CONCLUSIONS: Most immediate reactions to cephalosporins are IgE-mediated. Cephalosporin skin testing is a useful tool for evaluating these reactions. IgE-mediated cephalosporin hypersensitivity may be a transient condition; therefore, allergy examinations should be repeated in patients with negative results who experienced anaphylaxis more than 6 months before the allergy workup, including challenges.

SIRM-SIAAIC consensus, an Italian document on management of patients at risk of hypersensitivity reactions to contrast media.

Hypersensitivity reactions (HRs) to contrast media (CM) can be distinguished in immune-mediated (including allergic reactions) and non-immune-mediated reactions, even if clinical manifestations could be similar. Such manifestations range from mild skin eruptions to severe anaphylaxis, making it important for radiologists to know how to identify and manage them. A panel of experts from the Società Italiana di Radiologia Medica e Interventistica (SIRM) and the Società Italiana di Allergologia, Asma e Immunologia Clinica (SIAAIC) provided a consensus document on the management of patients who must undergo radiological investigations with CM. Consensus topics included: the risk stratification of patients, the identification of the culprit CM and of a safe alternative by an allergy workup, as well as the use of premedication and the correct procedure to safely perform an elective (i.e., scheduled) or urgent examination. The most important recommendations are: (1) in all patients, a thorough medical history must be taken by the prescribing physician and/or the radiologist to identify at-risk patients; (2) in patients with hypersensitivity reactions to CM, the radiologist must consider an alternative, non-contrast imaging study with a comparable diagnostic value, or prescribe a different investigation with another class of CM; (3) if such options are not feasible, the radiologist must address at-risk patients to a reference centre for an allergy evaluation; (4) if timely referral to an allergist is not viable, it is recommended to use a CM other than the responsible one, taking into account cross-reactivity patterns; in the case of patients with histories of severe reactions, the presence of an anesthesiologist is also recommended and a premedication is suggested.

Food protein-induced enterocolitis syndrome epidemiology, diagnosis, and treatment.

PURPOSE OF REVIEW: In the last years, the interest of the scientific community toward food protein-induced enterocolitis syndrome (FPIES) has grown exponentially. We review here the peculiar characteristics of this syndrome. RECENT FINDINGS: The recent publication of the First International Consensus Guidelines allowed a positive interaction between different research groups with the aim of improving the diagnosis and management of patients affected by FPIES. SUMMARY: Several fixed points have been placed on the diagnosis and management, but further studies are needed to clarify the many shadows that still surround different aspects of the syndrome, especially regarding the pathophysiology.

Tolerability of Cefazolin and Ceftibuten in Patients with IgE-Mediated Aminopenicillin Allergy.

BACKGROUND: Side-chain similarities or identities constitute the predominant factor for cross-reactivity between penicillins and cephalosporins, whereas differences in the side-chain structure seem to account for the absence of such cross-reactivity. OBJECTIVE: We sought to assess the cross-reactivity between penicillins and 2 cephalosporins (ie, cefazolin and ceftibuten) that have side chains different from those of penicillins, as well as to evaluate the possibility of using these cephalosporins in penicillin-allergic subjects. METHODS: We conducted a prospective study of 131 consecutive subjects who had suffered 170 immediate reactions (mostly anaphylaxis) to penicillins and had positive skin test results to at least 1 penicillin reagent. All patients underwent skin tests with cefazolin and ceftibuten. Patients with negative results were challenged with them. RESULTS: One participant had positive skin test results to cefazolin and ceftibuten, as well as to all other reagents tested, including aztreonam and carbapenems. All 129 subjects who underwent challenges with cefazolin and ceftibuten tolerated them. One subject refused cephalosporin challenges. CONCLUSIONS: Subjects with an IgE-mediated hypersensitivity to penicillins could be treated with cephalosporins such as cefazolin and ceftibuten, which are among the cephalosporins that have side-chain determinants different from those of penicillins. Nevertheless, in patients with such hypersensitivity who need these alternative ß-lactams, pretreatment skin tests are advisable because of the possibility of coexisting sensitivities or, much less frequently, of a sensitivity to an antigenic determinant of the common ß-lactam ring.