Clinical Relevance of Specific IgE in Penicillin Allergy Investigation.

INTRODUCTION: Patients with immediate type allergic reactions to penicillins are at risk of anaphylaxis on reexposure. Diagnostic gold standard is drug provocation test (DPT) if allergy is not diagnosed by other means, such as skin testing or in vitro testing with measurement of specific IgE. Specific IgE testing carries low risk for the patient and blood sampling can be performed in primary care, but it is reported to have low sensitivity. The aim of this study was to evaluate if clinical characteristics of patients with suspected allergic reactions to penicillin and elevated specific IgE to penicillins, differed from patients without specific IgE, to identify predictors for elevated specific IgE to penicillins. METHODS: Levels of specific IgE to five penicillins (penicillin G, penicillin V, amoxicillin, ampicillin, and penicillin minor determinants) were available for 9,100 patients. Using multiple logistic regression, clinical data from 430 patients in this group who had elevated specific IgE to one or more penicillins were compared to data from 4,094 patients without specific IgE to penicillins, who had undergone DPT with a penicillin. RESULTS: In total 5.2% of patients had elevated specific IgE to one or more penicillins. Significantly more patients with elevated specific IgE had a history of immediate type reactions (<2 h) (OR = 4.34, p < 0.001); circulatory symptoms (OR = 1.63, p = 0.03) or angioedema (OR = 1.46, p = 0.005). Also, significantly more patients with elevated specific IgE had been treated with adrenaline (OR = 2.21, p = 0.005), steroids (OR = 1.76, p < 0.001), or antihistamines (OR = 1.83, p < 0.001). CONCLUSION: A history of an immediate type reaction requiring treatment, combined with elevated specific IgE to one or more penicillins is suggestive of an IgE mediated penicillin allergy and further allergy investigations may not be needed. Specific IgE to penicillins may be used early in allergy investigation of patients with severe immediate type reactions to penicillins.

Penicillin allergy delabeling has a significant impact on subsequent antibiotic use in primary care.

Efforts to delabel penicillin allergic patients are important as the majority of suspected penicillin allergy can be ruled out by relevant allergy testing. The aim is to change the antibiotic pattern in delabeled patients to minimize use of unnecessary broad-spectrum antibiotics, reducing the risk of antimicrobial resistance and making treatment more cost effective. However, published information on subsequent antibiotic use is scarce. To evaluate the effect of delabeling on subsequent antibiotic use in primary care, a cohort of 2911 patients tested for penicillin allergy was compared to a matched control group of 14,522 individuals from the background population. In total 86.4% of the tested patients were delabeled. For delabeled patients, penicillin use increased from 0.07 prescriptions per patient year before allergy investigation, to 0.53 prescriptions per patient year post investigation (p < 0.001). The use of fluoroquinolones and macrolides was reduced and reached a level comparable to the background population. This study shows that penicillin allergy delabeling has significant positive impact on subsequent antibiotic use in primary care, and that penicillin use increases to levels similar to the background population. Penicillin allergy delabeling should be prioritized as an important and efficient element in antimicrobial stewardship initiatives.

The shape of and applied weight on skin prick lancets critically affect the wheal size in the skin prick test.

The global application of the skin prick test (SPT) is attributed to the low costs, easy execution, and in vivo approach. Still, the healthcare professionals' technique and the lancet shape may challenge the standardization of the method. Thus, we investigated the influence of the shape of the lancet and the applied weight on the wheal size of SPT. Two allergic and one non-allergic individual were tested with allergens (Dermatophagoides pteronyssinus and Phleum pratense) and histamine solution (positive control), respectively. Horizontally (HS) and diagonally (DS) shouldered lancets with the same tip length (1 mm) were tested under two different conditions: either 60 g or 120 g weight pressure. The wheal size induced by the 4 different combinations was measured. The higher-weight device (120 g) induced a significantly larger and less variable wheal response with the tested allergens and histamine. However, the shape of the lancet affected the wheal size more than the applied weight. The least variable response was measured to histamine for the horizontal-shouldered lancet combined with the higher weight, whereas the same lancet with the lower weight resulted in a significant number of false negative results.

Delabeling of Penicillin Allergy: Room for Improvement.

BACKGROUND: Penicillin allergy labels have been shown to be associated with suboptimal treatment, negative health outcomes, and increased antibiotic resistance. Many inpatients claim to have penicillin allergy, but studies show that allergy can be disproved and the label removed in up to 90% of cases. OBJECTIVES: The purpose of the study was to investigate the proportion of patients with a penicillin allergy label in a Danish hospital and to classify patients according to the risk of having penicillin allergy in "no risk," low, and high risk. METHODS: For 22 days, inpatients with penicillin allergy labels were interviewed, had their dispensed penicillin prescriptions examined, and were subsequently categorized into risk groups based on the risk evaluation criteria in national guidelines. RESULTS: In total, 260 patients had a penicillin allergy label (10% of the inpatients). Out of 151 included patients, 25 were "no risk" patients (17%), who could potentially have their penicillin allergy label removed without testing. 42 were low-risk patients (28%). 10 "no risk" patients and 20 low-risk patients had been prescribed and dispensed one or more penicillins despite an allergy label. CONCLUSION: Ten percent of inpatients have a penicillin allergy label in a Danish hospital. 17% of these could potentially have their penicillin allergy label removed without allergy testing.

Safe De-Labeling of Patients at Low Risk of Penicillin Allergy in Denmark.

INTRODUCTION: Penicillin allergy is suspected in 10% of hospital inpatients but can be disproved in 90% of cases. Direct oral provocation without preceding tests among low-risk patients has proven to be safe in studies of both children and adults and is gaining use across the world. The aims of this study were to investigate the rate of severe allergic reactions to direct oral drug provocation, without preceding tests, in penicillin allergy patients stratified to be at low risk, as well as to examine if these patients have barriers to penicillin allergy de-labeling and future use of penicillins. METHODS: Adult patients referred to a university hospital allergy clinic with a suspected penicillin allergy were prospectively risk evaluated. Patients stratified to be at low risk were offered a direct oral provocation with a single-dose amoxicillin followed by 4 days of continued treatment. The same risk stratification criteria were applied to a larger retrospective cohort. RESULTS: In the prospective study population, 202 patients had a direct oral drug provocation and 20 (10%) were positive. There were no cases of anaphylaxis or severe delayed hypersensitivity. Fifteen reactions were benign rashes with onset >1 day after initial dosing, and 13 of these were maculopapular rashes. The same low-risk criteria were applied retrospectively to patients in a drug provocation database, and 1,759 patients fulfilled the criteria; of these, 10% had positive provocations, and there were no cases of anaphylaxis or severe delayed hypersensitivity. De-labeled patients in the prospective study reported not to fear future penicillin intake, after prolonged provocation. CONCLUSION: The risk stratification criteria for identifying low-risk patients for the oral drug provocation test without prior skin testing were safe in terms of avoiding anaphylaxis or severe delayed hypersensitivity. Benign delayed skin reactions still occurred, and access to allergy advice and follow-up is necessary.

Intradermal Testing Identifies 1 in 4 Patients with Nonimmediate Penicillin Allergy.

BACKGROUND: Intradermal testing with delayed reading (IDTdr), used routinely in many centers, may identify delayed reactions to penicillins. However, few studies have compared the results of IDTdr with drug provocation test (DPT). The aim of this study was to examine the proportion of provocation-positive patients testing positive on IDTdr. METHODS: Fifty-seven patients with a positive DPT occurring >2 h after intake of penicillin V, dicloxacillin, pivampicillin, or amoxicillin had an IDTdr with penicillin G, amoxicillin, ampicillin, and dicloxacillin. A control group included 18 patients with negative DPTs with the suspected penicillin. RESULTS: In total 25% (n = 14) of provocation-positive patients tested positive on IDTdr. Among patients with positive IDTdr, 9/14 (64%) versus 11/43 (26%) in the IDTdr negative group (p < 0.05) had required oral steroids to treat skin reactions following DPT. No other differences between IDTdr positive and negative groups were found. No controls had a positive IDTdr. CONCLUSION: Investigating with IDTdr would have identified 25% of patients with a DPT-verified allergy with delayed reactions. It is difficult to target subgroups who will test positive on IDTdr. There were more patients who tested positive on IDT who had received oral steroids after DPT, and this may be an indication that skin reaction severity plays a role in skin testing diagnostics. Further potential predictors for positivity of IDTdr, such as duration of skin symptoms, should be assessed in large studies in order to optimize the investigations of nonimmediate drug allergic reactions.

[Work-up of penicillin allergy].

Up to 10% of hospitalised patients are registered as penicillin allergic. However, 80-90% will tolerate penicillin after evaluation. New Danish guidelines suggest criteria for evaluation of patients based on risk stratification according to the severity of the index reaction. The allergy label can be removed immediately, if allergy can be ruled out using the criteria presented in this review, but all other patients should be referred for evaluation in a specialist allergy department. Specific IgE measurement should only be done in adult patients with an immediate reaction (onset less-than 2 h after intake of a tablet) or urticaria.

Intradermal Tests With Drugs: An Approach to Standardization.

Background: Intradermal tests (IDTs) are performed and interpreted differently in drug allergy centers making valid comparison of results difficult. Objective: To reduce method-related and intercenter variability of IDTs by the introduction of a standardized method. Materials and methods: In 11 centers of the European Network for Drug Allergy, IDTs were prospectively performed with saline and with amoxicillin (20 mg/ml) using (1) the local method and (2) the standardized European Network in Drug Allergy (ENDA) method (0.02 ml). The diameters of the initial injection wheal (Wi) for the different volumes and sites injected obtained from each center were analyzed. Results: The most reproducible method was to fill a syringe with test solution, then expel the excess fluid to obtain exactly 0.02 ml. The median Wi diameter with 0.02 ml injection using the standardized method was 5 mm [range 2-10 mm; interquartile range (IQR) 5-5 mm; n = 1,096] for saline and 5 mm (range 2-9 mm; IQR = 4.5-5 mm; n = 240) for amoxicillin. IDT injection sites did not affect the Wi diameter. Training improved precision and reduced the variability of Wi diameters. Conclusion: Using the standardized IDT method described in this multicenter study helped to reduce variability, enabling more reliable comparison of results between individuals and centers.

A EAACI drug allergy interest group survey on how European allergy specialists deal with ß-lactam allergy.

An accurate diagnosis of ß-lactam (BL) allergy can reduce patient morbidity and mortality. Our aim was to investigate the availability of BL reagents, their use and test procedures in different parts of Europe, as well as any differences in the diagnostic workups for evaluating subjects with BL hypersensitivity. A survey was emailed to all members of the EAACI Drug Allergy Interest Group (DAIG) between February and April 2016, and the questionnaire was meant to study the management of suspected BL hypersensitivity. The questionnaire was emailed to 82 DAIG centres and answered by 57. Amoxicillin alone or combined to clavulanic acid were the most commonly involved BL except in the Danish centre, where penicillin V was the most frequently suspected BL. All centres performed an allergy workup in subjects with histories of hypersensitivity to BL: 53 centres (93%) followed DAIG guidelines, two national guidelines and two local guidelines. However, there were deviations from DAIG recommendations concerning allergy tests, especially drug provocation tests. A significant heterogeneity exists in current practice not only among countries, but also among centres within the same country. This suggests the need to re-evaluate, update and standardize protocols on the management of patients with suspected BL allergy.

Risk of Immediate-Type Allergy to Local Anesthetics Is Overestimated-Results from 5 Years of Provocation Testing in a Danish Allergy Clinic.

BACKGROUND: Local anesthetics (LAs) are used in many health care settings and exposure during a lifetime is almost inevitable. Immediate-type allergy to LAs is considered rare among allergy experts but is commonly suspected by health care workers from other specialties, and by patients. OBJECTIVE: The main aim of this study was to investigate the incidence of immediate-type allergy to LAs in our regional allergy clinic over the 5-year period 2010 to 2014. METHODS: This was a retrospective single-center study of patients referred to a regional allergy clinic (excluding patients with perioperative reactions) with suspected immediate allergy to LAs, who had undergone subcutaneous provocation with 1 or more LAs. Patients were identified in the hospital clinical coding system and clinical information about the reaction and investigation results was obtained from their medical records. RESULTS: A total of 164 patients (123 women/41 men; median age, 56 years; range, 7-89 years) who had 189 provocations with LAs were included over the 5-year period 2010 to 2014. All 164 patients had negative subcutaneous provocations to all 189 tests with LAs (95% CI, 0%-1.83%). Another allergen was identified in 10% (n = 17) of the patients. CONCLUSIONS: None of the 164 patients with suspected immediate-type allergy to LAs reacted on provocation. Thus, no patients have been diagnosed with an immediate allergy to LAs in our regional allergy clinic in the 5-year period studied, and allergy to LAs must be considered very rare. Alternative mechanisms should be considered, but if symptoms are consistent with allergy, other potential allergens should be investigated.

Erratum to: Allergen immunotherapy for insect venom allergy: protocol for a systematic review.

[This corrects the article DOI: 10.1186/s13601-016-0095-x.].

The Importance of Prolonged Provocation in Drug Allergy - Results From a Danish Allergy Clinic.

BACKGROUND: Drug provocation is the "Gold Standard" in drug allergy investigation. Recent studies suggest that a negative drug provocation on first dose should be followed by a prolonged provocation over several days. OBJECTIVE: To evaluate drug allergy investigations on the basis of drug provocation, including prolonged provocation. METHODS: Data from adult patients investigated for drug allergy in a Danish Allergy Clinic during the period 2010 to 2014 were entered into a database. Data included clinical details and results of provocations with suspected culprit drug (for penicillins performed only in specific IgE-negative patients). If provocation was negative on first dose, treatment was continued for 3 to 10 days. RESULTS: A total of 1,913 provocations were done in 1,659 patients, median age 46 years, of whom 1,237 (74.6%) were females. Drugs investigated were antibiotics, 1,776 (92.8%), of which 1,590 (89.5%) were penicillins; analgesics, 59 (3.1%); local anesthetics, 33 (1.7%); and other drugs, 45 (2.4%). In total, 211 of 1,913 (11.0%) provocations were positive. Causes were antibiotics, 198 (93.8%), of which 167 (84.3%) were penicillins; analgesics, 7 (3.3%); local anesthetics, 0; and other drugs, 6 (2.8%). Only 43 (20.4%) provocations were positive on first dose, whereas 95 (45.0%) turned positive more than 3 days later. CONCLUSIONS: Only 11.0% of the provocations were positive. Importantly, only 1 of 5 patients tested positive on the first dose, indicating that prolonged exposure should always be considered when drug provocation is included in allergy investigations. Most provocations were with penicillins, reflecting the pattern of antibiotic use in Denmark, which differs from that in other countries, especially outside Northern Europe.

High occurrence of rhinitis symptoms in hairdressing apprentices.

BACKGROUND: Little is known about the occurrence of respiratory symptoms among hairdressing apprentices during their training. Therefore, in this study, we examined whether hairdressing apprentices are at increased risk of rhinitis and asthma symptoms when compared with other young adults from the general population. METHODS: A questionnaire was completed by 504 hairdressing apprentices and 1400 control participants from the general population with a similar age, gender, and geographic distribution. RESULTS: The 1-year prevalence of rhinitis symptoms was higher in hairdressing apprentices than in controls (58.1% vs 46.6%; odds ratio, 1.59; 95% confidence interval, 1.30-1.98), and the prevalence was higher among hairdressing apprentices in the last years of training compared with apprentices in the first year of training (62.4% vs 41.8%, p = 0.003). Current smoking was more common in hairdressing apprentices (28.4% vs 17.2%, p < 0.001). Asthma symptoms were equally common in the 2 groups; however, hairdressing apprentices had a later age of onset of wheezing than did the controls (18 years vs 14 years, p < 0.00001) and a decreased risk of wheezing (odds ratio, 0.72; 95% confidence interval, 0.54 to 0.95) after adjusting for smoking, education level, and degree of rurality. Bleaching products were the most frequently reported cause of rhinitis and asthma symptoms in hairdressing apprentices. CONCLUSIONS: Hairdressing apprentices seem to have an increased risk of occupational rhinitis, and bleaching products are the main cause of respiratory symptoms. In addition, our findings suggest that a healthy worker effect exists in relation to asthma among hairdressing apprentices.

Insect Sting Reactions and Specific IgE to Venom and Major Allergens in a General Population.

BACKGROUND: Insect sting reactions are frequently reported, but population studies documenting the frequency and the relation to IgE-sensitization and serum tryptase are scarce. METHODS: Questionnaire data and results from measurements of specific IgE against venom, major allergens and cross-reacting carbohydrate determinants (CCDs) were collected from 2,090 adult participants in a cross-sectional survey. RESULTS: 13% of the population reported symptoms of sting reactions and about half were systemic in nature. In all, 15% were sensitized to venom but only 31% of these had reacted to stings and only 38% of those with reactions had IgE to venom. In addition, 12% with IgE to venom were double-sensitized (DS), i.e. to both bee and wasp venom. Among DS IgE to major venom allergens, rApi m 1, rVes v 1 and rVes v 5 were negative and of no help in 31%, but 59% could be identified as likely sensitized to bee or wasp. IgE to CCDs occurred in only 0.7%, but 80% of these were DS. Finally, 36% with IgE to CCDs had had symptoms, mostly local. Serum tryptase was not associated with a history of sting reactions. CONCLUSIONS: In a temperate climate, self-reported insect sting reactions and sensitization to venom are frequent, but in most cases, these are not seen in the same individual. In DS individuals, measurements of IgE to major allergens can be helpful in some but not all cases and additional analyses are needed. IgE to CCDs may have some clinical relevance.

Efficacy and safety of SQ house dust mite (HDM) SLIT-tablet treatment of HDM allergic asthma.

INTRODUCTION: In the treatment of house dust mite (HDM) respiratory allergic disease, allergy immunotherapy constitutes an add-on treatment option targeting the underlying immunological mechanisms of allergic disease. However, for the treatment of HDM allergic asthma, the use of subcutaneous allergy immunotherapy (SCIT) has been limited by the risk of systemic adverse events. Thus, sublingually administered allergy immunotherapy (SLIT) has been investigated as a treatment option with an improved tolerability profile that allows for safer treatment of patients with HDM allergic asthma. AREAS COVERED: In this Drug Profile, we provide a review of the clinical data behind the SQ HDM SLIT-tablet, which was recently approved for the treatment of HDM allergic asthma and allergic rhinitis by regulatory authorities in several European countries. Expert commentary: The SQ HDM SLIT-tablet is the first allergy immunotherapy to be tested prospectively in patients with asthma, and to favorably modify patient relevant end points such as requirement for inhaled corticosteroid (ICS) or the time to first asthma exacerbation upon ICS reduction, suggesting that SQ HDM SLIT-tablet treatment may contribute to improving overall asthma control.