Local anesthetics allergy in children: Evaluation of diagnostic tests with Real-Life data.

BACKGROUND: Local anesthetic (LA) drugs are commonly used in clinical practice to provide effective analgesia, including in dentistry and minor surgical procedures. The perception of a high risk of allergy in daily applications leads to the referral of atopic patients and those with other drug allergies to allergy clinics for the evaluation of allergic reactions to LA. The aim of this study was to determine who should be referred to the allergy clinic for LA allergy testing, assess the frequency of LA allergy in pediatric patients, and identify the negative predictive value of skin tests in diagnosis. METHODS: January 2017-July 2023, the clinical and laboratory data, as well as the results of drug allergy tests, of patients referred to our pediatric allergy clinic by dentists and physicians performing minor surgical procedures with suspected LA allergy were retrospectively evaluated. RESULTS: Our study included a total of 153 patients, comprising 84 girls (54.9%) and 69 boys (45.1%), with a mean age of 8.9 (±3.3) years. The most common reason for referral was a history of non-LA drug allergies (n = 66, 43.2%), followed by asthma (n = 25, 16.3%). Hypersensitivity reactions (HRs) with LA were most commonly associated with articaine (n = 7, 4.8%), followed by lidocaine (n = 6, 4.1%). When intradermal tests were evaluated, 17 patients (11.1%) had a positive test result. The positivity for lidocaine was 70.6% (n = 12), and prilocaine was 29.4% (n = 5). Subcutaneous provocation was administered to 109 patients (71.2%), and one patient exhibited local erythema and swelling with prilocaine. CONCLUSION: Although LA allergy is a rare occurrence, consultations of this nature are frequently requested from allergy clinics in real life. Considering the negative predictive value of skin tests performed with LA drugs, the reaction rate appears to be low in patients with atopy or other drug allergies. It is crucial for all relevant healthcare professionals to be knowledgeable about the appropriate approach to suspected LA allergies to avoid unnecessary tests. To the best of our knowledge, our study is the most comprehensive work in the literature that evaluates the results of diagnostic tests in children referred with a suspicion of LA allergy.

A prospective study evaluating the correlation between local weather conditions, pollen counts and pruritus of dogs with atopic dermatitis.

BACKGROUND: Canine atopic dermatitis (cAD) is a hereditary, generally pruritic and predominantly T-cell-driven inflammatory skin disease, involving an interplay between skin barrier abnormalities, allergen sensitisation and microbial dysbiosis. The individual immunological response is predominantly against environmental allergens, including mite antigens; mould spores; and pollen from grasses, trees and weeds. Airborne pollens show fluctuating patterns during the year. OBJECTIVE: The aim of this prospective study was to evaluate the influence of local pollen concentrations and weather conditions on the clinical signs of atopic dogs, and to investigate any possible correlations with the results of intradermal testing (IDT). MATERIALS AND METHODS: Thirty-seven privately owned atopic dogs in Bavaria were surveyed from 1 April to 30 November 2021. Owners were asked to record pruritus using a validated Visual Analog Scale (PVAS) score and the weekly medication of their dog. Furthermore, weather data, including pollen count, rainfall, relative humidity, hours of sunshine and temperature from the dog's location were collected daily. RESULTS: Of the evaluated parameters, only humidity and medication scores correlated positively with the PVAS scores of the atopic dogs. There was no correlation between specific pollen counts and PVAS scores of dogs with positive IDT reactions to that pollen. CONCLUSION AND CLINICAL RELEVANCE: The outcome of this study highlights the importance of a careful interpretation of positive IDT results in dogs with cAD and questions the validity of airborne pollen trap methodology in representing pollen exposure for dogs at ground level.

Cutaneous anaphylactoid reaction to polyoxyethylene hydrogenated castor oil in dogs.

BACKGROUND: Polyoxyethylene hydrogenated castor oil (HCO ethoxylates) is a nonionic surfactant used as an excipient for ointments and injections in human and veterinary drugs. Several polyethylene glycol (PEG) derivatives can be obtained depending on the number of moles of ethylene oxide (EO). HCO ethoxylates have the potential to cause anaphylactoid reactions. There is little published information about these types of reactions in dogs. OBJECTIVE: To determine the potential for HCO-ethoxylate-containing drugs to cause anaphylactoid reactions in dogs, employing intradermal testing (IDT) with various concentrations of HCO ethoxylates (HCO-25, -40, -60 and -80). ANIMALS: Four healthy male laboratory dogs. MATERIALS AND METHODS: We performed IDT with drugs containing HCO ethoxylates and HCO ethoxylates alone to determine threshold concentrations. The IDT scores and threshold concentrations were compared. Analysis of skin biopsies from IDT sites was used to measure the percentage of degranulated mast cells. The effect of histamine at IDT sites was investigated by pre-treatment with an antihistamine. RESULTS: All HCO-ethoxylate-containing drugs caused a wheal-and-flare reaction. The threshold concentrations (0.001% and 0.00001%) of each HCO-ethoxylate depended on the number of moles of EO (p < 0.05). Mast cell degranulation was enhanced by all HCO ethoxylates. The HCO-60-induced reaction was suppressed by an oral antihistamine. CONCLUSIONS AND CLINICAL RELEVANCE: The threshold concentration can serve as a consideration for developing safe new drug formulations and for clinical decision-making around using drugs containing PEG derivatives. IDT is useful to predict the risk of adverse effects. Antihistamines could demonstrate a prophylactic effect.

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.

Delayed hypersensitivity reactions to iodinated contrast media: A diagnostic approach by skin tests.

BACKGROUND: Adverse drug reactions to iodinated contrast media (ICM) have risen due to their increasing use in x-ray-based imaging modalities. Delayed hypersensitivity reactions are mainly caused by nonionic monomeric compounds and represent an issue impacting the diagnostic-therapeutic pathways of cancer, cardiology and surgery patients. OBJECTIVES: To prospectively evaluate the usefulness of skin tests in delayed hypersensitivity reactions to ICM and to evaluate the tolerability of iobitridol, a monomeric nonionic low osmolality compound, as a possible safe alternative. METHODS: Patients with delayed hypersensitivity reactions to ICM referred to us from 2020 to 2022 were prospectively enrolled in the study. All patients underwent patch test and, if negative, intradermal test with the culprit ICM and iobitridol as alternative. RESULTS: A total of 37 patients (females 24, 64.9%) were enrolled in the study. Iodixanol and iomeprol were the most frequently involved ICM (48.5% and 35.2%, respectively); 62.2% of patients presented maculopapular eruption, while 37.8% reported delayed urticaria-like rash. Skin tests resulted positive to the culprit ICM in 19 patients (51.4%), 16 to patch test and 3 to intradermal test. Skin tests with iobitridol, tested as alternative, resulted positive in 3/19 patients (15.8%). All 16 patients with negative results to iobitridol were administered this ICM and tolerated it. CONCLUSIONS: In at least half of patients, delayed-type hypersensitivity was demonstrated by skin tests, particularly by patch test. This diagnostic approach resulted simple, cost-effective and safe, not only to confirm the culprit ICM but also to identify iobitridol as feasible alternative.

Remimazolam Anaphylaxis during Induction of General Anesthesia Confirmed by Provocation Test-A Case Report and Literature Review.

Background: Remimazolam besylate, a newly developed drug, is linked to various anaphylaxis cases. We present a case of remimazolam anaphylaxis confirmed using a provocation test. Case: A 51-year-old female patient was scheduled for humeral pinning. General anesthesia was induced using remimazolam, rocuronium, and remifentanil. After tracheal intubation, the patient experienced decreased blood pressure, increased heart rate, and a systemic rash. Epinephrine was administered repeatedly, and the patient's vital signs stabilized. Acute phase tryptase levels were within normal limits. After four weeks, intradermal test results were negative. When remimazolam was administered intravenously for the provocation test, facial swelling, flushing, and coughing occurred, which improved with epinephrine. The culprit drug was identified as remimazolam using a provocation test. Conclusions: When anaphylaxis occurs during anesthesia induction, remimazolam should not be ruled out as the causative drug. If the skin test result for remimazolam is negative, a provocation test should be considered. The provocation test should be initiated cautiously at a low dose under careful patient monitoring.

COVID vaccination can be performed in patients with a history of allergic reactions to the vaccines or their components: experience from a specialist clinic in South Australia.

BACKGROUND: The development of vaccines against SARS-CoV2 has been a key public health response to the COVID-19 pandemic. However, since their introduction, there have been reports of anaphylactic reactions to vaccines in individuals with history of allergic reactions to other vaccines, excipients or to COVID vaccines. AIM: A dedicated adult COVID vaccine allergy clinic with a standardised allergy testing protocol was set up to investigate safety and suitability of available COVID vaccines in Australia. METHODS: Patients referred to a state-wide COVID-19 vaccine allergy clinic between March and August 2021 with a history of allergy underwent skin-prick testing and intradermal testing to both available vaccine formulations (BNT162b2 and ChAdOx1-S), excipients (polyethylene glycol and polysorbate 80), excipient-containing medications and controls. Basophil activation testing was conducted in few subjects with convincing history of immediate type reactions. RESULTS: Fifty-three patients underwent testing for possible excipient allergy (n = 19), previous non-COVID vaccine reaction (n = 13) or previous reaction to dose 1 of COVID-19 vaccine (n = 21). Patients were predominantly female (n = 43, 81%), aged 18-83 (median 54) years. Forty-four patients tested negative and 42 of these received at least their first dose of a COVID-19 vaccine. Nine patients tested positive to excipients or excipient-containing medication only (n = 3), or vaccines (n = 6). Five patients were positive to just BNT162b2, 3/5 have been vaccinated with ChAdOx1-S. One who was skin test positive to both vaccines, but negative BAT to ChAdOx1-S was successfully vaccinated with ChAdOx1-S. CONCLUSION: Even in a high-risk population, most patients can be vaccinated with available COVID-19 vaccines. This paper reports local experiences using a combined allergy testing protocol with skin testing and BAT during the pandemic.

Diagnosis of non-immediate hypersensitivity to amoxicillin in children by skin test and drug provocation tests: A retrospective case-series study.

BACKGROUND: Skin rash often occurs upon oral administration of amoxicillin in children, due to non-immediate hypersensitivity. However, information on delayed hypersensitivity to amoxicillin is scarce. Moreover, the appropriate diagnostic method and actual diagnostic rate of delayed hypersensitivity to amoxicillin among Japanese children are unclear. We conducted intradermal tests (IDTs) and drug provocation tests (DPTs) and retrospectively investigated the proportion of children with a definitive diagnosis of non-immediate hypersensitivity to amoxicillin. We then evaluated the characteristics of patients with a positive allergic workup. METHODS: We enrolled children referred for suspected findings of mild or moderate non-immediate hypersensitivity to amoxicillin between August 2018 and March 2020. If the IDT in the delayed phase was negative, DPT with amoxicillin (60-90 mg/kg/day) was performed for 7 days. Non-immediate hypersensitivity to amoxicillin was defined when IDT or DPT was positive. We evaluated the potential of the drug-induced lymphocyte stimulation test (DLST) to reveal hypersensitivity to amoxicillin. RESULTS: This study enrolled 27 children. Fourteen children (52%) had hypersensitivity to amoxicillin, of whom 12 had positive IDTs and two had positive DPTs. No differences in age, sex, history of allergic disease, days from oral use to symptom onset, type of rash at symptom onset, generalized rash, and DLST results were observed between the hypersensitivity and non-hypersensitivity groups. CONCLUSIONS: Examination should be performed for children with mild or moderate reactions because positive cases have no significant features and half of the suspected cases are negative.

Radiocontrast Media Hypersensitivity Reactions in Children.

Hypersensitivity reactions to radiocontrast media seem to be rare in children. Furthermore, the use of radiocontrast media in children remains quite safe in terms of the severity of reactions. Since pediatric guidelines are lacking, the diagnostic workup employed in adults could be adapted to children, taking into account that results have not yet been validated in this age group. Specific protocols for risk stratification and management of severe reactions have been proposed so far.

Clarithromycin hypersensitivity in children: Is there a link with ß-lactam hypersensitivity?

BACKGROUND: Clarithromycin hypersensitivity is reported as the most common cause of non-ß-lactam antibiotic allergy in children. Clarithromycin is frequently prescribed in cases of suspected ß-lactam hypersensitivity. Oral provocation tests stand as the gold standard to confirm drug hypersensitivity as diagnostic value of skin tests is variable. We analyzed the frequency of true clarithromycin hypersensitivity ratio and its relationship with ß-lactam allergy among children with suspected clarithromycin hypersensitivity and evaluated the diagnostic value of skin tests. METHODS: The study included 160 children referred with suspected clarithromycin hypersensitivity. Clinical history and allergy workups including skin tests or/and oral provocation tests were retrieved from medical records. RESULTS: Oral provocation test confirmed clarithromycin hypersensitivity rate was 5.6% (n = 9/160). Skin tests with clarithromycin showed positivity in 32.6% (n = 29/89) of the tested patients. The sensitivity of clarithromycin skin tests was negligible, and specificity was 73.9% (95% confidence interval [CI], 64.7-81.8). Eighty-eight of the patients (55%) reported that they had previously tolerated a ß-lactam antibiotic. ß-lactam hypersensitivity was suspected in 40% (n = 64/160) of the patients (simultaneous [n = 10], sequential [n = 19], distant form [n = 35]) in relation with clarithromycin usage. ß-lactam hypersensitivity (95% CI, 2.1-70.6, p = .005) and sequential usage of clarithromycin after the development of a rash with amoxicillin-clavulanic acid (95% CI, 2.0-96.4, p = .007) were found as risk factors for confirmed clarithromycin hypersensitivity. CONCLUSION: The frequency of confirmed clarithromycin hypersensitivity was found low among suspected patients. Oral provocation test is crucial for definite diagnosis. Confirmed ß-lactam allergy may be attributed as a risk factor for clarithromycin hypersensitivity, particularly clarithromycin treatment after a developing rash with amoxicillin-clavulanic acid in sequential usage.

Autoimmune progesterone dermatitis.

Autoimmune progesterone dermatitis (APD) is an exceptional condition affecting young women of childbearing age with a high prevalence during the third decade of life. The diagnosis should be confirmed using an intradermal skin test to progesterone, during the follicular phase of the menstrual cycle. APD represents an early manifestation of autoimmune disease. A case of APD is presented who after curative treatment did not develop other autoimmune diseases during a 6-year follow-up. Dermatologists, gynecologists and obstetricians should be aware of this rare but highly invalidating entity.

Should patients with risk factors be tested for hypersensitivity to contrast media: a prospective study.

BACKGROUND: Previous hypersensitivity reactions to contrast media (CM), atopy, atopic disease, drug allergy, and age (20-29 or >55) are risk factors for CM hypersensitivity reactions. Our aim was to evaluate whether these risk factors should prompt skin testing for diagnosing CM allergy. METHODS: The study was conducted among patients referred for allergy testing with CM. Skin tests were performed with non ionic or gadolinium CM, recommended by a radiologist. After completion of tests patients were telephonically queried on their symptoms of reactions. RESULTS: 151 risk patients (53 men, 98 women; mean age 55.2) were included in the study. Only 13 (9 %) had a history of hypersensitivity reaction to CM. Compared with the other patients, atopy was significantly more common in patients with a history of CM hypersensitivity reactions. Female gender and mean age were also higher, but not significant. All of the tests with CMs were negative. Only one patient reported urticaria within 1-2 min after administration of CM (telephonically). CONCLUSIONS: Atopy can increase the risk of CM allergy. However, skin tests with CMs may be inefficient, unnecessary, and time-consuming, except in cases with a history of CM allergy. Premedication protocols appear to be beneficial in patients with a history of CM allergy and cannot be recommended for patients with well-controlled asthma, rhinitis, atopic dermatitis or history of drug allergy.

Recombinant allergen-based provocation testing.

Over the last 25 years, recombinant allergens from all important allergen sources have been cloned and are now available as recombinant proteins. These molecules can be produced in practically unlimited amounts without biological or batch-to-batch variability. It has been shown in provocation tests that recombinant allergens have similar clinical effects as their natural counterparts. With the help of these tools it is possible to reveal the precise reactivity profiles of patients and to uncover and differentiate cross-reactivity from genuine sensitization to an allergen source. Although it has been shown some time ago that it would be possible to replace crude allergen extracts with recombinant allergens for skin prick testing, and even though the use of allergen components can improve routine diagnosis, these tools are still not available for clinical routine applications. The use of provocation tests is a crucial step in the development of new, hypoallergenic vaccines for therapy of allergic disease. Here we describe important provocation methods (skin prick test, intradermal test, atopy patch test, nasal provocation, colonoscopic provocation test) and give an overview of the clinical provocation studies which have been performed with recombinant allergens so far.