Drug Provocation Test Research Articles

Antibiotic allergy de-labeling in the intensive care unit: The prospective ADE-ICU study

PurposeCritically ill patients in the intensive care unit (ICU) are frequently prescribed antibiotics, with many reporting an antibiotic allergy label, predominantly to penicillin. Mislabeling contributes to suboptimal antibiotic use, increasing multidrug-resistant organisms and Clostridium difficile infections, and increased hospital length of stay. This prospective study implemented an antibiotic allergy assessment and testing program in the ICU, independently of clinical immunology/allergy services. Materials and methodsTrained ICU staff prospectively identified and risk assessed eligible patients as having a non-immune mediated drug reaction, or a low, intermediate or high risk antibiotic allergy. Non-immune mediated reactions were directly de-labeled. Low-risk allergies underwent direct drug provocation testing, while intermediate-risk allergies included skin testing followed by drug provocation testing. High-risk allergies were confirmed without testing. ResultsOf 71 eligible patients, 62 underwent assessment. Antibiotic allergy de-labeling occurred in 48 of 51 patients (94 %) with a non-immune, low or intermediate risk allergy. High risk allergies were confirmed in 11 patients (18 %). The study resulted in increased penicillin use and decreased broad-spectrum antibiotic use. No adverse events occurred from testing. ConclusionsThis study shows the feasibility of ICU led antibiotic allergy assessment and testing, highlighting a potential model for implementation in settings lacking immunology/allergy services.

Assessment of the Safety of Alternative Antibiotics in Children with Confirmed Beta-Lactam Antibiotic Allergy

Introduction: Beta-lactam antibiotics (BLAs) are the most common cause of drug hypersensitivity reactions in children, and it is important to find safe alternative antibiotics for these children. This study evaluates the selection, safety to alternative antibiotics in patients with confirmed BLA allergies based on diagnostic tests. Methods: At the Pediatric Immunology and Allergy Clinic of Ankara Bilkent City Hospital, a retrospective evaluation of diagnostic tests (including skin prick, intradermal, and drug provocation tests) was conducted to identify alternative antibiotics for patients with confirmed BLA. Patients were also contacted by telephone to assess their use of these alternative drugs. Results: The study included 80 patients with confirmed beta-lactam allergy (BLA). The BLAs causing reactions were categorized into two groups: penicillins (75%, n = 60) and cephalosporins (25%, n = 20). Among the penicillins, amoxicillin-clavulanic acid (ACA) was the most common at 68.8%, while among the cephalosporins, ceftriaxone was the most common at 16.3%. Of the 55 patients with ACA allergy, 53 underwent controlled administration with clarithromycin, with 52 showing no reaction. In addition, no reaction was observed in patients who received DPT with cefuroxime (n: 16), phenoxymethyl penicillin (n: 9), cefdinir (n: 1), and cefixime (n: 1), while there was no reaction in the controlled administration with clindamycin. Alternative treatments were tested in 13 patients with a confirmed ceftriaxone allergy. No adverse reactions were observed in 9 patients who underwent DPT with ACA and in 10 patients who were exposed to clarithromycin under controlled conditions. Finally, 54 of the 80 patients (67.5%) were successfully contacted and none reported a reaction to the alternative drugs. Conclusion: For patients with confirmed BLA, macrolides may be considered as preferred alternatives. In addition, beta-lactams with different side chains may be safe alternatives after diagnostic evaluation, taking into account the risk of cross-reactivity.

NSAID Allergy Labels Associated With Mortality and Cardiovascular Outcomes in Stroke.

Mislabeled drug allergy can restrict future prescriptions and medication use, but its prevalence and impact among patients with stroke remain unknown. This study investigated the prevalence of the most commonly labeled drug allergies, their accuracy, and their impact among patients with stroke. In this combined longitudinal and cross-sectional study, we compared the prevalence of allergy labels among the general population and patients with ischemic stroke between 2008 and 2014 from electronic health care records in Hong Kong. Outcomes between patients with stroke with or without the most prevalent labels (ie, NSAID) were compared. Rate of mislabeled NSAID allergy was confirmed by provocation testing. Compared with the general population (n=702 966), patients with stroke had more labels (n=235) to cardiovascular and hematopoietic system (prevalence, 19.5% versus 9.2%; odds ratio [OR], 2.4 [95% CI, 1.74-3.32]; P<0.001) and radiographic and diagnostic agents (prevalence, 4.2% versus 0.9%; OR, 4.82 [95% CI, 2.56-9.08]; P<0.001). The most common labels were to NSAID (prevalence, 1.8%). Patients with NSAID allergy labels were significantly less likely to be prescribed aspirin after acute stroke (OR, 0.24 [95% CI, 0.09-0.60]; P=0.003) and on follow-up (OR, 0.22 [95% CI, 0.08-0.56]; P=0.002). The median duration of follow-up was 6.7 years (6499±2.49 patient-years). Patients with stroke with NSAID allergy labels also experienced significantly higher mortality (OR, 7.44 [95% CI, 2.44-23.18]; P<0.001), peripheral vascular disease (OR, 9.35 [95% CI, 1.95-44.86]; P=0.005), and major adverse cardiovascular events (OR, 6.09 [95% CI, 2.00-18.58]; P=0.001) in the poststroke period. Patients with NSAID allergy labels (who remained alive and could consent) were referred for allergist assessment and offered drug provocation testing. The majority (80%; 4/5) had negative provocation tests and were delabeled. NSAID allergy labels were significantly more prevalent among patients with stroke, associated with excessive mortality, peripheral vascular disease, and major adverse cardiovascular events. Given the high rate of mislabeled allergies, multidisciplinary neuro-allergy interventions could have the potential to improve patient outcomes.

The safety of initial single therapeutic dose challenge with a 5-day prolonged drug provocation test in children with a history of low-risk non-immediate reactions to beta-lactam antibiotics.

Background: Although the gold standard for diagnosing beta-lactam antibiotic (BLA) allergy is the drug provocation test (DPT), there is no standardized protocol for children. Objective: We aimed to evaluate the clinical features and DPT results of children with a history of low-risk non-immediate reactions (NIR) to BLA who underwent initial direct single therapeutic dose challenge with a 5-day prolonged DPT. Methods: We retrospectively evaluated children ages 0-18 years with a history of low-risk NIRs to BLAs. On the first day of provocation, a single-dose DPT protocol without any skin test was administered at the clinic. The therapeutic dose was adjusted to not exceed the maximum single-unit dose (MSUD) for age and weight. The DPT protocol was administered with 100% of MSUD. To identify children with delayed reactions, the parents or caregivers were told to continue giving the medication at home for 5 days. Results: One hundred and nine children were included in this study. The median (interquartile range) age of the children was 62.5 months (26.5-94 months). Of the suspected drugs, the main culprit drug was amoxicillin-clavulanic acid for 89 children (81.7%). The most common clinical manifestation was maculopapular exanthema, which occurred in 85 children (78%), and 8 (7.3%) had a positive DPT result. Three children (2.8%) developed a reaction after the first DPT dose. The remaining children continued to use the suspected BLA at home. Five children (4.7%) developed a reaction while using the drug at home. All the children with positive DPT results developed mild cutaneous signs and presented with a reaction to amoxicillin-clavulanic acid. None had a systemic or severe cutaneous reaction. Conclusion: Initial direct single therapeutic dose challenge with a 5-day prolonged DPT is a useful and safe way to assess low-risk NIRs to BLAs in children.

Assessment of pediatric patients with suspected nonsteroidal anti-inflammatory drug hypersensitivity.

Background: Beta-lactam antibiotics are the most common cause of hypersensitivity reactions to medications, followed by nonsteroidal anti-inflammatory drugs (NSAID). Objective: The aim of this study was to classify children with hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAID-H) according to the latest updates. Methods: ENDA recommendations were used to evaluate all patients with suspected NSAID-H. Children were classified as either selective responders (SR) or cross-intolerant based on the results of the drug provocation test (DPT). Results: Sixty-seven patients with suspected NSAID-H were evaluated in this study. NSAID-H was confirmed in 20 patients (29.9%). Among the 20 patients diagnosed with NSAID-H, 15 were classified according to the 2018 EAACI/ENDA Position Paper. Twelve patients (80%) were classified as cross-intolerant and 3 (20%) as SRs. NSAID-H was confirmed in 4 of 37 patients (10.8%) ages <10 years and 16 of 30 patients (53.3%) ages >10 years (p < 0.001). Twelve patients ages >10 years were classified. Cross-intolerance was detected in nine patients (66.6%). In patients >10 years of age, NSAID-induced urticaria/angioedema (NIUA) (16.7%) was the most common type in the group with classifiable cross-intolerant. In addition, NSAID-exacerbated respiratory disease was detected in one patient. Conculsion: Ibuprofen is the most common NSAID-H drug used in children. NIUA is the most common reaction. In pediatric allergy, hypersensitivity to NSAIDs is a challenging diagnostic issue. Hypersensitivity to NSAIDs poses a challenging diagnostic issue in pediatric allergies. The oral challenge test is the main diagnostic tool; however, in clinical practice, performing multiple challenge tests is difficult.

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.

Severe exacerbation of facial dermatitis with swelling following introduction of abrocitinib in a patient with atopic dermatitis

BackgroundAbrocitinib, an oral small-molecule Janus kinase 1 (JAK1) inhibitor, has been widely accepted for the treatment of moderate-to-severe atopic dermatitis (AD). Currently there is a paucity of data on the adverse events (AEs) after abrocitinib treatment, especially on rare events such as exacerbation of facial dermatitis, and their causal relationship and subsequent management remains poorly elucidated.Case presentationA 43-year-old female patient with moderate AD received dupilumab after failure of topical treatments. Facial dermatitis persisted and became refractory after dupilumab treatment, and the patient changed treatment to oral abrocitinib. Fifteen hours after the first dose of abrocitinib, she developed exacerbation of facial dermatitis with swelling. The patient was initially diagnosed as abrocitinib-induced hypersensitivity. However, a score of 3 of the Naranjo adverse drug reaction assessment indicates week correlation between abrocitinib therapy and exacerbation of facial dermatitis, and negative results from subsequent drug provocation test further suggests no causal relationship.ConclusionsThe present case report highlights the necessity of careful determination of abrocitinib-induced hypersensitivity, which should not be diagnosed simply based on the time sequence between drug exposure and symptom occurrence. In addition, caution should be exercised for drug withdrawal, especially when confirmative evidence is absent. Drug provocation test can be helpful and effective treatments could be continued unless severe AEs occur.

Negative Predictive Value of Single-Day Drug Provocation Test for Immediate and Non-Immediate Beta-Lactam Hypersensitivity Reactions in Children

Introduction: Beta-lactam antibiotics (BLAs) commonly cause hypersensitivity reactions in children. These reactions are categorized into immediate reactions, which include urticaria, angioedema, bronchospasm, and anaphylaxis, and non-immediate reactions, such as maculopapular rashes and delayed-onset urticaria/angioedema. Rashes in children, often caused by infections, may be misdiagnosed as BLA allergy. However, over 90% tolerate the medication following an allergic evaluation. Methods: We aimed to evaluate patients with negative single-day drug provocation test (sdDPT) results for subsequent reactions and to determine the negative predictive value (NPV) of sdDPT for immediate (less than 1 h) and non-immediate (more than 1 h) suspected BLA allergy. In addition, non-immediate reactions were assessed by classifying them as occurring within 1–6 h or after 6 h. Patients who underwent sdDPT for suspected BLA allergy and tested negative between 2019 and 2023 were included in the study. They were questioned via telephone interviews about their reuse of the tested drug. Results: 404 patients who underwent sdDPT for suspected BLA allergy were evaluated. The NPV of BLA sdDPT was determined to be 97.3%. When patients were categorized based on the time interval between the last dose and the reaction, the NPV was 97% for those experiencing a reaction within the first hour of drug use and 96.7% for reactions occurring after more than 1 h. Non-immediate reactions were further evaluated, revealing an NPV of 98.7% for reactions occurring between 1 and 6 h, and 92.5% for reactions occurring after 6 h. Conclusion: Our findings demonstrate that sdDPT has a high NPV for both immediate and non-immediate reactions. However, the NPV of sdDPT was lower for reactions occurring more than 6 h after the last dose.

Basophil activation test is a complementary tool in the diagnosis of immediate reactions to platinum salts and taxanes.

Delabelling pathways offer confirmatory diagnosis and can prevent unnecessary second-line therapies or drug desensitization procedures after chemotherapeutic hypersensitivity reactions (CHT-HSRs). However, these pathways rely on risky invivo tests. Data on whether invitro tests could be helpful are scarce. We assessed the role of basophil activation test (BAT) in the diagnosis of HSRs to platin salts (PSs) and taxanes (TXs) in a well-defined population featuring varied endophenotypes and severities of HSRs. We conducted a 3-year-long multicentric, prospective study with 121 suspected-immediate CHT-HSR patients. The allergy workup included clinical history (initial reaction based on Type I, cytokine release syndrome, and mixed phenotype's symptoms and if unable to fit in any of these, as "indeterminate"), skin testing (ST), and drug provocation testing (DPT), provided risk assessment was favorable. Final diagnosis classified patients as "hypersensitive," "non-hypersensitive," or "inconclusive." We performed BAT using CD63 and CD203c as activation markers in patients and controls. Patients underwent DPT regardless of BAT results to prevent bias. ST positivity significantly correlated with skin involvement, Type I phenotype, cancer recurrence, and lifetime exposures before reactions. DPTs were negative in all indeterminate phenotype patients (p = .02) and those considered low-risk, whereas they were negative in 62% moderate-risk patients. 55% were confirmed as hypersensitive (mainly Type I reactions, p < .0001), 24% as non-hypersensitive (mainly TXs and indeterminate phenotypes), and 21% as inconclusive. BAT showed 79% sensitivity in Type I IgE-mediated reactions to PSs with a high correlation to ST. BAT is a promising tool for delabelling and endotyping CHT-HSRs, especially Type I reactions to PSs, possibly identifying patients at risk of positive DPT. ST seems useful in confirming CHT-HSRs, especially PS-induced reactions, and DPT remains the gold standard, being essential even in moderate-risk patients.

Bibliometric analysis of the trends and evolution in β-lactam allergy research

BackgroundBeta-lactams remain the most reported drug allergy globally, with the volume and diversity of related drug allergy research continuing to accumulate. Recognizing evolving research trends can help inform future directions and encourage synergistic collaborations. ObjectiveWe conducted a comprehensive bibliometric analysis of all publications relevant to beta-lactam allergy, with a focus on longitudinal publication rates, international collaborations and keyword/ trend analysis. MethodsMeta-data from all original articles, letters and reviews relevant to beta-lactam allergy on the Web of Science Core Collection up till 31-Dec-2023 were analysed. ResultsFrom 1966-2023, there were 4451 records (3536 articles, 631 reviews, 284 letters) from 78 countries. There was an exponential increase in publications, especially during the last decade, with half of all publications on beta-lactam allergy published during this time (50.6%, 2252/4452). Overall, 18.1% (805/4452) involved international co-authorships, with significant increase since the last decade (12.7% vs. 23.3%, p<0.001). The most frequent keywords, in the first published half of articles were “skin testing” (84/1919), “IgE” (57/1919) and “anaphylaxis” (49/1919); in contrast to “skin testing” (137/3351), “drug provocation test” (121/3351), “antimicrobial resistance” (120/3351) and “antimicrobial stewardship” (118/3351) in the latter. ConclusionThere has been a surge in publications, international collaboration and shifting paradigms in beta-lactam allergy research. The field has evolved beyond focusing on “in vitro tests” or “desensitization”, toward “antimicrobial stewardship”. However, there is still seems to relatively fewer collaborations with non-Western countries. Further international collaborations to harmonize delabelling strategies against the threat of mislabelled beta-lactam allergy should be encouraged.

Bullous Drug Eruption.

A 63-year-old woman presented at our emergency department with a disseminated dermatosis that developed after undergoing a cardiac catheterization procedure. Her past medical history included an end-stage renal disease undergoing hemodialysis. Clinical examination revealed erosions and hemorrhagic crusts located on her lips and along the arteriovenous fistula. Additionally, we observed five hyperpigmented macules on her left hand's dorsum and palm and multiple hypopigmented macules in the genital area. Upon medical record review, we discovered the occurrence of prior bullous eruptions following contrast administration. A fixed drug eruption (FDE) due to radiocontrast was diagnosed based on clinical history, clinical examination, eruption timeframe, and positive drug provocation test. Intravenous contrast media reactions can be immediate or delayed, with delayed hypersensitivity reactions (DHR) occurring one hour to seven days post-administration. DHRs often present as maculopapular rashes. FDEs are rare. Skin tests are used to identify culprit agents. Ideally, intradermal tests, with delayed readings, and patch tests are combined for optimal sensitivity. Despite lacking standardized protocols, premedication with corticosteroids may mitigate reaction severity.

Different phenotypes of nonsteroidal anti-inflammatory drug hypersensitivity in children and negative predictive value of drug provocation test

This is the first study trying to correlate the clinical history of patients' previous NSAIDs in terms of the culprit drug, the frequency of reactions and the clinical manifestations with the risk for being diagnosed with a specific phenotype.

Cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs, manifested as urticaria and/or angioedema, anaphylaxis

BACKGROUND: The main mechanism of drug hypersensitivity to non-steroidal anti-inflammatory drugs is associated with inhibition of cyclooxygenase type 1, which leads to cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs from various subgroups of different chemical structures. Clinically, cross-hypersensitivity usually manifests in the form of urticaria and/or angioedema. AIM: To characterize a group of patients with cross-hypersensitivity to non-steroidal anti-inflammatory drugs manifesting as urticaria / angioedema / anaphylaxis. MATERIALS AND METHODS: To achieve this aim a prospective single-center study was conducted. Patients with a presumptive diagnosis of drug hypersensitivity to non-steroidal anti-inflammatory drugs (n=307) were consulted. A group of patients (n=237) with high probability of such reactions was identified, of which cross-hypersensitivity manifested as urticaria / angioedema / anaphylaxis was observed in 127 patients. This group was divided into 2 phenotypes: a group with concomitant chronic urticaria (n=67) and without it (n=60). We assessed demographic data, drug triggers, clinical manifestations, concomitant atopy, and compared these indicators between both groups. Selected patients underwent a drug provocation test with selective or predominantly selective non-steroidal anti-inflammatory drugs and paracetamol. RESULTS: Cross-hypersensitivity reactions manifested as urticaria / angioedema / anaphylaxis is the most common phenotype of immediate-type drug cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs (75.6%). Women develop this condition 2.5 times more frequently than men, and are more likely to develop cross-drug hypersensitivity with concomitant chronic urticaria with the onset of approximately 16 years later than men. Mild manifestations of cross-hypersensitivity (urticaria/angioedema) develop more frequently than severe ones (anaphylaxis). Angioedema in children, urticaria in adults with concomitant chronic urticaria and angioedema in adults without concomitant chronic urticaria are it's main manifestations. The most frequent non-steroidal anti-inflammatory drugs triggers are metamizole, acetylsalicylic acid and propionic acid derivatives. Non-steroidal anti-inflammatory drugs with the lowest risk of developing drug hypersensitivity are coxibs, paracetamol, and to a lesser extent ― meloxicam, nimesulide. CONCLUSION: The data obtained allowed us to expand our understanding of cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs presenting as urticaria/angioedema or anaphylaxis. Selective cyclooxygenase type 2 inhibitors and paracetamol are drugs with the highest safety profile.

Diagnostic evaluation of hypersensitivity reactions to arylpropionic acid derivatives: a descriptive observational study focusing on clinical characteristics and potential risk factors in children.

Arylpropionic acid derivatives (APs) are the main triggers of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. Data on clinical patterns and risk factors for AP hypersensitivity in children are quite limited. To assess the clinical characteristics and potential risk factors for proven AP hypersensitivity in children. Patients with a history of AP hypersensitivity were retrospectively assessed using a standardized diagnostic algorithm. Children with confirmed hypersensitivity were defined as selective responders or cross-intolerants based on the result of drug provocation tests and further categorized according to the EAACI/ENDA classification. A multivariable logistic regression analysis was performed to analyze the potential risk factors for proven AP hypersensitivity. A total of 166 patients (51.2% male, median age of six years) with a history of AP hypersensitivity were included. Ibuprofen (89.2%) was the most frequently reported AP in the patients' histories. The reported hypersensitivity of 40 (22.4%) patients was confirmed by diagnostic testing: eight (13.6%) patients with a history of reaction only to APs and 32 (29.9%) patients with a history of reactions to multiple NSAIDs, including chemically unrelated NSAIDs in addition to APs. Five (12.5%) patients were classified as selective respondersand 35 (87.5%) were cross-intolerants. Overall, five (12.5%) of the confirmed cases could not be categorized according to the EAACI/ENDA classification. Older age (aOR: 1.11, 95% CI 1.02-1.21, p = 0.015), chronic urticaria as an underlying disease (aOR: 2.87, 95% CI 1.09-7.54, p = 0.033) and a history of anaphylaxis (aOR: 7.84, 95% CI 1.86-33.04, p = 0.005) were related to confirmed AP hypersensitivity. Almost a quarter of children and adolescents were confirmed to have AP hypersensitivity. Older age, the presence of chronic urticaria and a history of anaphylaxis were potential risk factors for proven AP hypersensitivity.

Prospective, Multicenter, Head-to-Head Comparison Between Allergists Versus Nonallergists in Low-Risk Penicillin Allergy Delabeling: Effectiveness, Safety, and Quality of Life (HK-DADI2)

BackgroundPenicillin “allergy” labels are prevalent but frequently misdiagnosed. Mislabelled allergies are associated with adverse outcomes and increased antimicrobial resistance. With an urgent need to delabel the overwhelming number of mislabelled allergies, non-allergist evaluations have been advocated for low-risk individuals. Despite growing interest in non-allergist-led initiatives; evidence on their effectiveness, safety, and impact by direct comparisons are lacking. ObjectiveWe assessed the comparative outcomes of penicillin allergy evaluations conducted by allergists vs. non-allergists. MethodsA prospective, multi-centre, pragmatic study was conducted at four tertiary hospitals (one allergist- vs. three non-allergist-led) for low-risk penicillin allergy patients in Hong Kong – the Hong Kong Drug Allergy Delabelling Initiative 2 (HK-DADI2). ResultsAmong 228 low-risk patients who underwent testing (32.9% by allergists, 67.1% by non-allergists), only 14 (6.1%) had positive penicillin allergy testing. Delabelling rates (94.1% vs. 93.3%, p=0.777), positive skin tests (2.6% vs. 2.7%, p=1.000) and drug provocation tests (3.3% vs. 2.7%, p=1.000) were similar between allergists and non-allergists. There were no systemic reactions in either cohort. All patients had significant improvements in health-related quality-of-life (DrHy-Q scores −5.00 vs. −8.33, p=0.072). Non-allergist evaluations had shorter waiting times (0.57 vs. 15.7 months, p<0.001), while allergists required fewer consultations with higher rate of completing evaluations within a single-visit (OR=0.04, p<0.001). ConclusionWith training and support, non-allergists can independently evaluate low-risk penicillin allergies. Compared to allergists, evaluation of low-risk penicillin allergy by non-allergists can be comparably effective, safe, and impactful on quality-of-life. More multi-disciplinary partnerships to empower non-allergists to conduct allergy evaluations, should be encouraged.

Gradual drug provocation tests in the evaluation of suspected delayed drug hypersensitivity reactions

Gradual drug provocation tests in the evaluation of suspected delayed drug hypersensitivity reactions

Specific IgE and Basophil Activation Test by Microarray: A Promising Tool for Diagnosis of Platinum Compound Hypersensitivity Reactions.

Drug hypersensitivity reactions (DHRs) to platinum-based compounds (PCs) are on the rise, and their personalized and safe management is essential to enable first-line treatment for these cancer patients. This study aimed to evaluate the usefulness of the basophil activation test by flow cytometry (BAT-FC) and the newly developed sIgE-microarray and BAT-microarray in diagnosing IgE-mediated hypersensitivity reactions to PCs. A total of 24 patients with DHRs to PCs (20 oxaliplatin and four carboplatin) were evaluated: thirteen patients were diagnosed as allergic with positive skin tests (STs) or drug provocation tests (DPTs), six patients were diagnosed as non-allergic with negative STs and DPTs, and five patients were classified as suspected allergic because DPTs could not be performed. In addition, four carboplatin-tolerant patients were included as controls. The BAT-FC was positive in 2 of 13 allergic patients, with a sensitivity of 15.4% and specificity of 100%. However, the sIgE- and BAT-microarray were positive in 11 of 13 DHR patients, giving a sensitivity of over 84.6% and a specificity of 90%. Except for one patient, all samples from the non-allergic and control groups were negative for sIgE- and BAT-microarray. Our experience indicated that the sIgE- and BAT-microarray could be helpful in the endophenotyping of IgE-mediated hypersensitivity reactions to PCs and may provide an advance in decision making for drug provocation testing.

Polyethylene glycol hypersensitivity, patient outcomes in a 7-year retrospective study

BackgroundImmediate IgE-mediated hypersensitivity reactions to polyethylene glycol (PEG) are rare. Our understanding of PEG hypersensitivity is limited. ObjectiveTo evaluate the clinical characteristics and investigation outcomes of the largest cohort of patients with PEG allergy reported. MethodsA total of 44 patients investigated for suspected PEG allergy across 4 United Kingdom tertiary allergy centers between October 2013 and December 2020 were studied. Clinical characteristics, index reaction, and approaches to and outcomes of allergy investigations were analyzed. ResultsPEG hypersensitivity was confirmed in 42 of 44 cases. Macrogol laxatives were the most common index drugs reported (23%), followed by depo-medroxyprogesterone (19%), oral penicillin V (10%), and depo-methylprednisolone (10%). In general, 61% experienced grade III anaphylaxis. Intradermal testing (IDT) increased the diagnostic sensitivity from 51% to 85%. Five patients experienced systemic reactions during IDT. Of the 5 patients, 2 were skin prick test positive to a high molecular weight PEG. Three patients with negative skin test results had positive drug provocation test results. Seven patients with PEG allergy reported tolerance to H1-antihistamines containing PEG. Administration of messenger RNA COVID-19 or Oxford/AstraZeneca COVID-19 vaccines was tolerated in all 16 patients to whom they were administered. ConclusionPEG hypersensitivity is an uncommon cause of drug-induced anaphylaxis. Four index drugs accounted for two-thirds of the cases, and reactions to these drugs should prompt PEG hypersensitivity investigations. PEG IDT increases diagnostic yield. The role of skin prick test with higher molecular weight PEGs requires further attention. Further studies are required to understand PEG thresholds and PEG equivalent doses of various administration routes. COVID-19 vaccines were tolerated by all exposed.

Intradermal testing of iodinated contrast media: Should we test up to pure or with diluted compounds only?

Intradermal testing (IDT) with iodinated contrast media (ICMs) is an established diagnostic tool in patients with ICM hypersensitivity. Currently, it is unclear which test concentration is the more useful one, up to pure or up to 1:10 diluted ICMs. We searched the literature database PubMed for eligible papers dealing with ICM allergy and their IDT results. We analyzed the data presented by the papers and compared the pooled groups tested with diluted and undiluted ICMs. We identified 29 eligible original papers, and extracted data of 1137 patients that formed the study population. Although in the cohort tested with diluted ICMs the number of tested ICMs was greater, the percentage of positive tests was significantly less (9.0% vs. 24.7%; P < 0.0001; OR 0.30 [0.26-0.34]). The frequency of positive tested culprit ICMs was also lesser in the group tested with diluted ICMs (31.0% vs. 72.5%; P < 0.0001; OR 0.17 [0.12-0.23]). The number of drug provocation tests (DPTs) was greater in patients with diluted IDTs (374 vs. 89; P < 0.0001; OR 2.54 [1.93-3.36]). We detected an increased sensitivity in patients with undiluted tests (0.774 vs. 0.282) and a nearly identical specificity in both groups (1 vs. 0.983). For the first time, we show that IDT up to pure ICM concentrations is superior to using diluted ICMs only. Possibly, we can reduce the number of DPTs when performing IDTs with pure ICMs. In the undiluted group, there were no hints for skin irritations or unspecific test reactions.

Clinical Profile of Patients with Lichenoid Drug Eruption: A Observational Study.

Lichenoid drug eruption (LDE) is an uncommon cutaneous adverse drug reaction, where a variety of drugs used in day-to-day clinical practice have been implicated. To describe the clinico-demographic characteristics of patients with LDE and to identify the most likely drugs involved. In this prospective, observational study, consecutive patients with LDE presenting to the dermatology department of a tertiary teaching hospital were included. The clinico-demographic profile of patients with LDE and implicated drugs was noted. Treatment of drug reaction along with outcome was also documented. Naranjo adverse drug reaction probability scale was used for causality assessment of the drug reactions. A thorough literature review on LDE was also undertaken due to the paucity of existing literature. A total of 15 patients (11 males and 4 females) with LDE were evaluated. Their age ranged from 37 to 61 years, with a mean of 51.53 ± 7.59 years. Anti-hypertensive medications (40%) were the most common culprit agent, followed by antitubercular drugs (33.4%), anti-diabetic agents (13.3%), and others (13.3%). The latent period (time from drug initiation to the appearance of a cutaneous eruption) varied from 15 days to 6 months (mean 2.2 months). Cutaneous involvement was generalized in 73.4% and photo-distributed lesions in 26.6%. Drug provocation test was done to identify the culprit drug. According to the Naranjo adverse drug reaction probability scale, one-third of LDEs were "definite," whereas two-thirds were designated as "probable." LDE is more common in the elderly population. The latent period is comparatively longer in LDE than in other common drug reactions. Prompt recognition and withdrawal of suspected drug are essential to minimize disease morbidity.