Approach for delabeling beta-lactam allergy in children.

A considerable number of pediatric patients treated with beta-lactam (BL) antibiotics develop delayed onset of skin rashes during the course of treatment. Although the most frequent cause of these symptoms is infectious, many cases are labeled as allergic reactions to these drugs. BL allergy labels could have a negative impact, as they imply avoidance of this group of drugs and the use of second-line antibiotics, leading to a potential increase in adverse effects and the utilization of less effective therapies. This constitutes a major public health concern and economic burden, as the use of broad-spectrum antibiotics can result in multidrug-resistant organisms and prolonged hospital stays. Therefore, it is crucial to delabel patients during childhood to avoid false labeling in adult life. Although the label of BL allergy is among the most frequent causes of allergy referral, its management remains controversial, and new diagnostic perspectives are changing the paradigm of managing BL allergies in children. Traditionally, drug provocation testing (DPT) was exclusively performed in patients who had previously obtained negative results from skin tests (STs). However, the sensitivity of STs is low, and the role of in vitro testing in the pediatric population is not well defined. Recent studies have demonstrated the safety of direct DPT without prior ST or serum tests for pediatric patients who report a low-risk reaction to BLs, which is cost-effective. However, there is still a debate on the optimal allergic workup to be performed in children with a benign immediate reaction and the management of children with severe cutaneous adverse drug reactions. In this review, we will discuss the impact of the label of BL allergy and the role of the different tools currently available to efficiently address BL allergy delabeling in children.

Deconstructing adverse reactions to Amoxicillin-Clavulanic Acid: the importance of time of onset.

BACKGROUND: Amoxicillin-clavulanic acid (AX-CL) is the most consumed betalactam antibiotic worldwide. We aimed to establish the different phenotypes of betalactam allergy in those referring a reaction with AX-CL and to investigate the differences between immediate and non-immediate onset. METHODS: Cross-sectional retrospective study performed at Hospital Clínico San Carlos (HCSC) and Hospital Regional Universitario de Málaga (HRUM) in Spain. Patients reporting reactions with AX-CL who completed the allergy workup between 2017 and 2019 were included. Data of reported reaction and allergy workup were collected. Reactions were classified as immediate and non-immediate with 1hour cut-off point. RESULTS: We included 372 patients (HCSC 208, HRUM 164). There were 90 (24.2%) immediate, 252 (67.7%) non-immediate reactions, and 30 (8.1%) with unknown latency. Allergy to betalactams was ruled-out in 266 (71.5%) and confirmed in 106 patients (28.5%). The final main diagnosis in the overall population were allergy to aminopenicillins (7.3%), to CL (7%), to penicillin (6.5%) and to betalactams (5.9%). Allergy was confirmed in 77.2% and 14.3% of immediate and non-immediate reactions respectively, with a relative risk of 5.06 (95%CI 3.64-7.02) of an allergy diagnosis in those reporting immediate reactions. Only 2/54 patients with late-positive intradermal test (IDT) to CL were diagnosed of CL allergy. CONCLUSION: Allergy diagnosis was confirmed in a minority of the whole study population, but 5 times more frequently in those reporting immediate reactions, making this classification useful in risk stratification. Late-positive IDT for CL has no diagnostic value and its late reading could be retrieved from the diagnosis work-up.

Corrigendum: Approach for delabeling beta-lactam allergy in children.

[This corrects the article DOI: 10.3389/falgy.2023.1298335.].

Local allergic rhinitis: Implications for management.

A significant proportion of rhinitis patients without systemic IgE-sensitisation tested by skin prick test and serum allergen-specific IgE (sIgE) display nasal reactivity upon nasal allergen provocation test (NAPT). This disease phenotype has been termed local allergic rhinitis (LAR). LAR is an underdiagnosed entity affecting children and adults from different parts of the world, with moderate-to-severe symptoms, impairment of quality of life and rapid progression to symptom worsening. LAR is a stable phenotype and not merely an initial state of AR. Allergic rhinitis and LAR share many clinical features including a positive NAPT response, markers of type 2 nasal inflammation including sIgE in nasal secretions and a significant rate of asthma development. LAR should be considered as a differential diagnosis in those subjects of any age with symptoms suggestive of AR but no evidence of systemic atopy. Although LAR pathophysiology is partially unknown, in some patients sIgE can be demonstrated directly in the nasal secretions and/or indirectly via positive responses in basophil activation test (BAT). LAR can coexist with other rhinitis phenotypes, especially AR. The diagnosis currently relies on the positivity of NAPT to a single or multiple allergens. NAPT has high sensitivity, specificity and reproducibility, and it is considered the gold standard. BAT and the measurement of nasal sIgE can also contribute to LAR diagnosis. LAR patients benefit from the same therapeutic strategies than AR individuals, including the avoidance of allergen exposure and the pharmacotherapy. Moreover, several recent studies support the effectiveness and safety of allergen immunotherapy for LAR, which opens a window of treatment opportunity in these patients.

Local allergic rhinitis is an independent rhinitis phenotype: The results of a 10-year follow-up study.

BACKGROUND: The knowledge about the natural history of local allergic rhinitis (LAR) is limited. One unmet question is to demonstrate whether LAR should be considered the first step in the development of allergic rhinitis (AR) or an independent phenotype. The aim of this study was to prospectively evaluate the natural history of a population with LAR, the potential conversion to AR with systemic atopy and the development of asthma during 10 years. METHODS: This is the second phase of a 10-year follow-up study of a cohort of 176 patients with LAR of recent onset and 115 age- and sex-matched healthy controls prospectively evaluated from 2005 to 2016. Clinical-demographic questionnaire, spirometry, skin prick test and specific IgE were evaluated yearly. Nasal allergen provocation tests (NAPT) with Dermatophagoides pteronyssinus, Alternaria alternata, Olea europaea and grass pollen were performed at baseline, and after 5 and 10 years. RESULTS: After 10-year LAR, patients experienced a significant and clinically relevant worsening of the rhinitis, with increase in emergency assistance, development of asthma, loss of allergen tolerance and impairment of the quality of life. This worsening became significant after 5 years and progressed throughout 10 years. A similar rate of development of AR with systemic atopy was detected in patients and controls (9.7% vs 7.8%, log-rank P=.623). In 5 patients, conversion to systemic atopy occurred >10 years (3%). CONCLUSIONS: LAR is a well-differentiated clinical entity with a low rate of development of systemic atopy, a natural evolution towards worsening and a risk factor for suffering asthma.

The clinical and immunological effects of Pru p 3 sublingual immunotherapy on peach and peanut allergy in patients with systemic reactions.

BACKGROUND: The peach non-specific lipid transfer protein, Pru p 3, is the primary sensitizer in fruits and responsible for severe reactions in the Mediterranean area. Peach allergy is frequently associated with other allergies such as peanut. Therefore, it is important to assess how specific immunotherapy to Pru p 3 could affect both peach and peanut tolerance. OBJECTIVES: To evaluate peach and peanut desensitization and immunological changes after 1 year of Pru p 3 sublingual immunotherapy (SLIT) in patients with systemic allergic reactions to peach and/or peanut. METHODS: Forty-eight peach allergic patients, 36 treated with SLIT and 12 non-treated, were monitored for 12 months. Treated patients were subclassified as peanut allergic (Group A), sensitized (Group B) or tolerant (Group C). SLIT effect was evaluated by skin prick test (SPT) reactivity and food challenge. Immunological changes were evaluated by monitoring sIgE and sIgG4 levels and basophil reactivity. RESULTS: After 1 year of SLIT, the weal area in SPT significantly decreased and a significant increase in peach threshold in treated patients was observed (P < 0.001). Patients in Group A showed a significant decrease in peanut SPT weal area and an increase in peanut threshold (P < 0.001). Immunological changes were observed in treated patients only, with a significant decrease in sIgE and a parallel increase in sIgG4, sIgG4/sIgE and basophil reactivity for both Pru p 3 and Ara h 9. CONCLUSIONS AND CLINICAL RELEVANCE: After 1 year, Pru p 3 SLIT induces both desensitization and immunological changes not only for peach but also for other food allergens relevant in the induction of severe reactions such as peanut.

Natural evolution in patients with nonsteroidal anti-inflammatory drug-induced urticaria/angioedema.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequent triggers of drug hypersensitivity with NSAIDs-induced urticaria/angioedema (NIUA) the most common phenotype. Loss of hypersensitivity has been reported for IgE-mediated reactions; however, it has not been assessed in nonimmunological reactions such as NIUA. We evaluated NSAID-hypersensitivity over time in NIUA patients. METHODS: Patients confirmed as NIUA by positive drug provocation test (DPT) with acetylsalicylic acid (ASA) during 2005-2012 (V1) were included (n=38). Subjects were prospectively re-evaluated by DPT with ASA/other NSAIDs at two time points between 2013 and 2015 (V2 and V3). Atopy was assessed by skin prick test (SPT) using inhalant and food allergens. RESULTS: Patients were evaluated at V1 and re-evaluated after 60 months (V2; IR:48-81) and a further 18 months (V3; IR:14-24). At V2, the majority (24; 63.15%) tolerated ASA and other NSAIDs (Group A) while 14 (36.84%) still reacted (Group B). At V3, all Group A patients remained tolerant; all Group B patients remained hypersensitive. The number of previous episodes reported at V1 and the percentage of reactions induced by ASA/ibuprofen were significantly lower in Group A (P=.005 and P=.006, respectively). Group A patients developed tolerance 72 months (IR:45-87) after their last evaluated reaction (V1); this interval was shorter in nonatopics (P=.003), patients who experienced reactions over 1 hour after NSAIDs administration (P=.001), and those who experienced isolated urticaria after NSAID intake (P=.024). CONCLUSIONS: NIUA patients may develop tolerance to NSAIDs over time, a process that seems to be influenced by atopy and type of clinical reaction.

Nonallergic rhinitis and lower airway disease.

In the past years, several investigators have demonstrated the existence of local nasal responses in some patients with typical allergic rhinitis symptoms but without atopy and have defined a new phenotype called local allergic rhinitis (LAR) or 'entopy'. In a percentage of LAR subjects, the upper airway disease is also associated with lower airway symptoms. After the description of this phenotype, the differential diagnosis between LAR and nonallergic rhinitis (NAR) has become a challenge for the clinician. To correctly identify LAR patients is of high importance for treatment and management of these patients, and for an appropriate inclusion of patients in clinical trials and genetics studies. The treatment of LAR patients, in contrast with NAR, is oriented to allergen avoidance and specific treatment. Allergen immunotherapy, the aetiological treatment for allergic respiratory diseases, has demonstrated to be an effective and safe treatment in LAR, increasing immunological tolerance, and reducing the clinical symptoms and the use of medication. In this article, the important and novel aspects of LAR in terms of mechanisms, diagnosis and treatment will be discussed. Also, the involvement of the lower airway and the potential role of IgE in the bronchial disease will be also reviewed.

Anaphylaxis to 2 NSAIDs in a patient who tolerated ASA

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