Drug Challenge Research Articles

Non-steroidal anti-inflammatory drug-induced anaphylaxis infrequent in 388 patients with mastocytosis: A two-center retrospective cohort study.

Anaphylaxis is a well-known feature of mastocytosis, particularly in relation to hymenoptera venom stings. It is therefore hypothesized that mastocytosis patients may also be predisposed to severe hypersensitivity reactions to certain medications including non-steroidal anti-inflammatory drugs (NSAIDs). For this reason, these patients are usually discouraged from using these drugs. The current study aimed to determine the prevalence and evaluate the severity of NSAID-related hypersensitivity reactions among patients with mastocytosis. A retrospective study was conducted among a total of 388 (≥18 years old) consecutive patients from two independent European mastocytosis centers, in Sweden and Italy. Patients underwent a thorough allergy work-up where self-reported NSAID-hypersensitivity reactions were re-evaluated by an allergist in the first cohort (202 patients) and results were validated in the second cohort (186 patients). Overall frequency of NSAID-hypersensitivity was 11.3% in the total study cohort. Most patients reacted with cutaneous symptoms (89%), whereas severe hypersensitivity reactions were infrequent with only 11 patients (2.8%) experiencing anaphylaxis. All NSAID-related hypersensitivity reactions had occurred before mastocytosis was diagnosed. There was no difference between the groups regarding gender, baseline tryptase levels or presence of atopy, asthma/rhinitis. Our study indicates an approximate 4-fold increased prevalence of NSAID hypersensitivity among mastocytosis patients compared to the general population. However, most NSAID reactions were limited to the skin as the prevalence of overall anaphylaxis was infrequent. Our results support that mastocytosis patients with a known tolerance to NSAIDs can continue using these medications without special precautions, whereas those with a prior reaction to NSAIDs should undergo thorough allergy work-up, including drug challenges.

HPR64 Opportunities and Challenges for Innovative Drugs in China

China’s near-universal drug coverage has limitations due to high out-of-pocket costs for patients and poor coverage of innovative, premium-priced medicines. To increase access to high-cost innovative drugs, national drug price negotiations were introduced in 2015. The objective was to describe current opportunities and challenges for innovative drugs in China based on recent evidence from the new reimbursement decision making processes.

Self-assumed Neurologic Related Condition Deviated Metoclopramide-Induced Acute Dystonic of Oculogyric Crisis in a Woman of Childbearing Age: A Case Report

A 26-year-old Malaysian woman (childbearing age) attended a private primary care clinic with a known case of gastroesophageal reflux disease (GERD) and complained of persistent nausea and a few episodes of vomiting. She had no known drug allergy, no surgical history, no hospitalization in the last two years, was a non-smoker, and no history of drug or alcohol abuse. The patient was prescribed Tab metoclopramide 10 mg TDS and Tab ranitidine 150 mg BD for five days. About 30 min after oral administration of both medicines, her eyes rolled involuntary upward, leading to lateral deviation of the eyes, and mouth jaws clenched as if “dislocated jaws.” The patient was immediately brought into an emergency department (ED) of a public tertiary care hospital. A drug challenge test was done which resulted in the withdrawal of metoclopramide. The accompanied sister later disclosed that the patient had taken metoclopramide and ranitidine from a private clinic earlier in the day. The patient self-assumed to have a sudden seizure, due to excessive hot weather and dehydration. A slow intravenous infusion of 50 mg/mL diphenhydramine hydrochloride in 0.9% w/v NaCl 100 mL was administered stat. Consequently, the symptoms vanished after approximately 30 min of the therapy, devoid of relapse. The patient was discharged from ED post 8 hours of monitoring with complete recovery. Physicians frequently prescribe metoclopramide to treat nausea and vomiting, which may cause adverse drug reaction of acute dystonic oculogyric crisis (OGC). Due to its unwanted and unpredictable extrapyramidal symptoms, metoclopramide should be prescribed and dispensed with caution. Thorough history taking at ED is imperative for correct early diagnosis and treatment, as metoclopramide-induced dystonic OGC has a high probability of confusion with other causes of dystonia such as conversion and seizures, encephalitis, tetanus, and hypercalcemic tetany.

An In Vivo Definition of Brain Histamine Dynamics Reveals Critical Neuromodulatory Roles for This Elusive Messenger.

Histamine is well known for mediating peripheral inflammation; however, this amine is also found in high concentrations in the brain where its roles are much less known. In vivo chemical dynamics are difficult to measure, thus fundamental aspects of histamine's neurochemistry remain undefined. In this work, we undertake the first in-depth characterization of real time in vivo histamine dynamics using fast electrochemical tools. We find that histamine release is sensitive to pharmacological manipulation at the level of synthesis, packaging, autoreceptors and metabolism. We find two breakthrough aspects of histamine modulation. First, differences in H3 receptor regulation between sexes show that histamine release in female mice is much more tightly regulated than in male mice under H3 or inflammatory drug challenge. We hypothesize that this finding may contribute to hormone-mediated neuroprotection mechanisms in female mice. Second, a high dose of a commonly available antihistamine, the H1 receptor inverse agonist diphenhydramine, rapidly decreases serotonin levels. This finding highlights the sheer significance of pharmaceuticals on neuromodulation. Our study opens the path to better understanding and treating histamine related disorders of the brain (such as neuroinflammation), emphasizing that sex and modulation (of serotonin) are critical factors to consider when studying/designing new histamine targeting therapeutics.

Improving drug allergy label accuracy by supervised safety- and protocol-driven evaluation

Drug allergies are often self-reported but of unknown accuracy. We carried out a prospective study to examine the utility and safety of formal allergology evaluation, and to identify factors associated with accurate drug allergy labels. All patients who underwent drug allergy evaluation in our clinic during the study period were recruited. Baseline demographics, characteristics of index hypersensitivity reaction and outcomes of evaluation were recorded. A total of 331 patients from March 2019 to June 2021 completed drug allergy evaluation to index drugs of concern. There were 123 (37%) male patients, and the mean age was 49 years (standard deviation 17). There were 170 beta-lactam antibiotics, 53 peri-operative drugs, 43 others, 38 non steroidal anti-inflammatory drugs, and 27 non-beta-lactam antibiotic evaluations. Index reaction occurred within 5 years in 165 (50%) patients, with latency of less than 4 hours in 125 (38%) patients. The most common index reactions were rash, angioedema and urticaria. There were 57 (17%) evaluations stratified as low risk, 222 (67%) moderate risk, and 52 (16%) high risk based on multidisciplinary consensus. Allergy label was found to be false (negative drug evaluation) in 248 (75%) patients, while 16/237 (7%) skin tests, 44/331 (13%) in-clinic graded challenge, and 23/134 (17%) home prolonged challenges were positive (true drug allergy). The most common evaluation reactions were rash and urticaria. No cases of anaphylaxis were elicited. Seventy-five percent of drug allergy labels are inaccurate. Risk-stratified, protocolised allergy evaluation is safe. Prolonged drug challenge increases the sensitivity of drug allergy evaluation and should therefore be performed when indicated.

Safety of oral graded challenges as a diagnostic approach hypersensitivity reaction to anti-tuberculosis drugs: a case report

Tuberculosis (TB) still becomes a significant health problem in developing countries, especially in Indonesia. Allergy to antitubercular drugs is a real hindrance to the management of TB. The first-line anti-TB drug (ATD) is still the most effective TB drug, but it can have some side effects. One of these side effects is drug hypersensitivity reactions (DHR) which can affect a patient's compliance. The recommended diagnostic approach to DHR is a graded challenge by introducing drugs safely and optimally under a threshold dose until the usual daily dose is reached. We present a case of DHR to ATB drug and oral graded challenge as the diagnosis approach.

Evaluation of Neonatal and Paediatric Vancomycin Pharmacokinetic Models and the Impact of Maturation and Serum Creatinine Covariates in a Large Multicentre Data Set.

Infants and neonates present a clinical challenge for dosing drugs with high interindividual variability due to these patients' rapid growth and the interplay between maturation and organ function. Model-informed precision dosing (MIPD), which can account for interindividual variability via patient characteristics and Bayesian forecasting, promises to improve individualized dosing strategies in this complex population. Here, we assess the predictive performance of published population pharmacokinetic models describing vancomycin in neonates and infants, and analyze the robustness of these models in the face of clinical uncertainty surrounding covariate values. The predictive precision and bias of nine pharmacokinetic models were compared in a large multi-site data set (N = 2061 patients, 5794 drug levels, 28 institutions) of patients aged 0-365 days. The robustness of model predictions to errors in serum creatinine measurements and gestational age was assessed by using recorded values or by replacing covariate values with 0.3, 0.5 or 0.8 mg/dL or with 40 weeks, respectively. Of the nine models, two models (Dao and Jacqz-Aigrain) resulted in predicted concentrations within 2.5 mg/L or 15% of the measured values for at least 60% of population predictions. Within individual models, predictive performance often 2 differed in neonates (0-4 weeks) versus older infants (15-52 weeks). For preterm neonates, imputing gestational age as 40 weeks reduced the accuracy of model predictions. Measured values of serum creatinine improved model predictions compared to using imputed values even in neonates ≤1 week of age. Several available pharmacokinetic models are suitable for MIPD in infants and neonates. Availability and accuracy of model covariates for patients will be important for guiding dose decision-making.

Azobenzene derivatives with activity against drug-resistant Candida albicans and Candida auris.

Increasing resistance against antimycotic drugs challenges anti-infective therapies today and contributes to the mortality of infections by drug-resistant Candida species and strains. Therefore, novel antifungal agents are needed. A promising approach in developing new drugs is using naturally occurring molecules as lead structures. In this work, 4,4'-dihydroxyazobenzene, a compound structurally related to antifungal stilbene derivatives and present in Agaricus xanthodermus (yellow stainer), served as a starting point for the synthesis of five azobenzene derivatives. These compounds prevented the growth of both fluconazole-susceptible and fluconazole-resistant Candida albicans and Candida auris strains. Further in vivo studies are required to confirm the potential therapeutic value of these compounds.

Basophil Activation Test Shows Poor Sensitivity in Immediate Amoxicillin Allergy

In light of the pandemic of spurious penicillin allergy, correct diagnosis of amoxicillin (AX) allergy is of great importance. The diagnosis of immediate hypersensitivity reactions relies on skin tests and specific IgE, and although reliable, these are not absolutely predictive. Therefore, drug challenges are needed in some cases, which contain the risk of severe reactions. Safe invitro diagnostics as an alternative for the drug challenge in the diagnostic workup of AX allergy would be more than welcome to fill this gap. In this respect, the basophil activation test (BAT) has shown potential, but its clinical reliability is doubtful. To investigate the reliability of the BAT to AX and determining its exact place in the diagnostic algorithm of AX allergy. BAT for AX was performed in 70 exposed control individuals and 66 patients diagnosed according to the European Academy of Allergy and Clinical Immunology guidelines for AX allergy. Upregulation of both CD63 and CD203c was flow-cytometrically assessed. Analyses revealed that 1370 μmol/L and 685 μmol/L were the most discriminative stimulation concentrations for CD63 and CD203c upregulation, respectively, and a diagnostic threshold of 9% for positivity for both markers was identified. At these concentrations, sensitivity and specificity for CD63 upregulation were 13% and 100%, respectively, and for CD203c upregulation, 23% and 98%. BAT with dual analysis of CD63 and CD203c is of poor performance to document AX allergy. The sensitivity is too low to let it occupy a prominent role in the diagnostic algorithm.

Patenting and patent challenges in South Korea after introducing a patent linkage system

BackgroundSouth Korea introduced the patent linkage system in 2015 as part of the implementation of free trade agreements with the United States. This study assessed trends in brand-name drug patenting and generic patent challenges in South Korea after the introduction of the system.MethodsFrom 2012–19, we constructed a novel dataset that combines information about listed patents with their corresponding brand-name drugs and patent challenges against these brand-name drugs. We analyzed brand-name drug patenting and generic patent challenges and elucidated factors in timely patent challenges using event history analysis.ResultsDuring the study period, 659 brand-name drugs listed their patents in the K-Orange Book and patent challenges against 95 brand-name drugs were initiated. The number of listed patents and their nominal patent term varied by the characteristics of the brand-name drugs. Patent challenges of generic drugs were marginal in South Korea even though the surge of patent challenges of generics were noticed right after the introduction of the patent linkage system.ConclusionsPatenting and patent challenges are critical factors when introducing generic drugs into the market under the patent linkage system. However, the impact of the patent linkage system on patenting and patent challenges could be varied by the specific form of the patent linkage system and the contexts of pharmaceutical markets.

Abstract 12307: Exercise-Induced Ventricular Fibrillation in Patients with Brugada Syndrome Phenotype

Introduction: Ventricular fibrillation (VF) in Brugada syndrome (BS) patients are thought to be triggered by vagal nerve activation, which leads to sudden cardiac arrest (SCA) at rest or while asleep. Generally, exercise is not considered as trigger of SCA in BS patients. Aim: To report 2 rare cases of patients with BS phenotype developing exercise-induced ventricular (VF). Case reports: Case 1: 48 year-old male developed SCA during marathon running and was successfully resuscitated with cardiopulmonary resuscitation (CPR). The stored automatic external defibrillator (AED) electrogram (ECG) showed VF. The 12-lead ECG did not show abnormal morphology, however sodium channel blocker challenge test (intravenous injection of pilsicainide, a pure sodium channel blocker 1mg/Kg) unmasked typical type-1 BS ECG. The treadmill stress test induced single premature ventricular contraction by Bruce protocol, and ventricular tachycardia by a flat-out dash without a run-up. Genetic analysis did not show mutation of SCN5A gene. Case 2: 18 year-old male experienced SCA while playing basketball and was successfully resuscitated with CPR. The stored ECG record of AED showed VF. The 12-lead ECG showed normal result, then we performed the drug challenge test. Pilsicainide unmasked typical type-1 BS ECG. He also had exercise-induced atrial fibrillation (AF) and experienced inappropriate shock delivery from implantable cardioverter defibrillator. The treadmill stress test by Bruce protocol did not induce any ventricular arrhythmias. We avoided a flat-out dash protocol because of possibility of exercise-induced AF. Genetic analysis did not show SCN5A mutation. Conclusion: These 2 rare cases of drug-induced BS phenotype developing exercise-induced VF highlight important role of exercise testing as risk stratification tool in certain BS patients.

Genetically-encoded BRET probes shed light on ligand bias–induced variable ion selectivity in TRPV1 and P2X5/7

Whether ion channels experience ligand-dependent dynamic ion selectivity remains of critical importance since this could support ion channel functional bias. Tracking selective ion permeability through ion channels, however, remains challenging even with patch-clamp electrophysiology. In this study, we have developed highly sensitive bioluminescence resonance energy transfer (BRET) probes providing dynamic measurements of Ca2+ and K+ concentrations and ionic strength in the nanoenvironment of Transient Receptor Potential Vanilloid-1 Channel (TRPV1) and P2X channel pores in real time and in live cells during drug challenges. Our results indicate that AMG517, BCTC, and AMG21629, three well-known TRPV1 inhibitors, more potently inhibit the capsaicin (CAPS)-induced Ca2+ influx than the CAPS-induced K+ efflux through TRPV1. Even more strikingly, we found that AMG517, when injected alone, is a partial agonist of the K+ efflux through TRPV1 and triggers TRPV1-dependent cell membrane hyperpolarization. In a further effort to exemplify ligand bias in other families of cationic channels, using the same BRET-based strategy, we also detected concentration- and time-dependent ligand biases in P2X7 and P2X5 cationic selectivity when activated by benzoyl-adenosine triphosphate (Bz-ATP). These custom-engineered BRET-based probes now open up avenues for adding value to ion-channel drug discovery platforms by taking ligand bias into account.

Improving antimicrobial stewardship with penicillin allergy testing: a review of current practices and unmet needs.

Penicillin allergy, the most frequently reported drug allergy, has been associated with suboptimal antibiotic therapy, increased antimicrobial resistance, increased rates of Clostridioides difficile colonization and infection, as well as extended hospital length of stay and increased cost. Although up to 10% of all patients may report penicillin allergy, most penicillin allergies are not confirmed. As such, most patients with a penicillin allergy can still safely use penicillin and related drugs following a more precise assessment. Herein, we review the current practices and unmet needs in penicillin allergy testing. The diagnostic algorithm is mostly based on a clinical history assessment followed by in vivo testing, i.e. skin test and/or drug challenge. As these tests are labour and resource intensive, there is increased interest in point-of-care penicillin allergy de-labelling solutions incorporated into Antimicrobial Stewardship Programmes including digital assessment tools. These can be locally parameterized on the basis of characteristics of target populations, incidence of specific allergies and local antibiotic usage to perform clinical risk stratification. Safely ruling out any residual risk remains essential and in vivo drug challenge and/or skin testing should be systematically encouraged. Gradual understanding and convergence of the risk stratification of the clinical presentation of penicillin allergy is enabling a wider implementation of this essential aspect of antimicrobial stewardship through digitalized decision tools and in vivo testing. More research is needed to deliver point of care in vitro diagnostic tools to democratize this de-labelling practice, which would be highly beneficial to patient care. This progress, together with better education of patients and clinicians about the availability, efficacy and safety of penicillin allergy testing, will increase the dissemination of penicillin allergy assessment as an important component of Antimicrobial Stewardship Programmes.

Anti-Cocaine IgA Rather Than IgG Mediates Vaccine Protection from Cocaine Use.

In developing a vaccine for fentanyl use disorder, we observed that IgA was the best correlate of vaccine-mediated protection from injected drug challenge, rather than IgG or binding affinity. Recent evidence shows that IgA secreting cells line the blood-brain barrier that capture pathogens and could prevent drug antigens from penetrating the brain. We assayed IgA and IgG antibodies from an anti-cocaine vaccine clinical trial and categorized each subject's antibody levels using half-log cut-points for IgA: <1000, <5000, <10,000 and >10,000; and for IgG: <10,000 to >100,000. We compared these antibody groups on urine toxicology in 130 subjects at week 9 after 3 booster vaccinations. We also provided relevant data on benzoylecgonine (BE, cocaine metabolite) from this study's placebo patients. BE urine levels were lowest for the highest IgA category; however, levels did not differ across IgG groups. Our findings linking IgA to protection from cocaine and fentanyl in mice, rats and humans are novel and suggest an increasingly recognized role of IgA in vaccine efficacy.

A SYMPATHETIC CASE OF MULTIPLE INHALER INTOLERANCES

<h3>Introduction</h3> Drug reactions account for a large proportion of complaints evaluated in allergy/immunology clinic. Determining the cause for these drug reactions can often be difficult. In this case, we discuss a rare cause for repeated adverse reactions to multiple inhalers. <h3>Case Description</h3> A 57-year-old male veteran with COPD presented for evaluation of drug allergy. His COPD was previously well-controlled with ipratropium and albuterol inhalers. Over the last several weeks, he has experienced flushing, lightheadedness, and shortness of breath following use of both inhalers. He tolerated inhaled fluticasone and cromolyn for several days before having the same symptoms following each use. Initial testing included skin prick testing to the offending agents, which was negative (Table 1). Drug challenge with budesonide, omalizumab, and albuterol revealed intense flushing, hypertension, and sense of doom within 30 mins. Serum catecholamines, urine metanephrines, urine 5-HIAA, and serum tryptase were normal. 24hr urine cortisol was slightly elevated. Dexamethasone suppression test was normal. In collaboration with endocrinology, he was diagnosed with <i>pseudopheochromocytoma</i> and advised to start an SSRI given the frequency of his paroxysms, which he declined. <h3>Discussion</h3> Non-immunologic drug reactions are suspected when drugs from multiple drug classes incite symptoms. Determining the underlying process is important to allow patients to continue taking life-saving medications. Pseudopheochromocytoma is a rare but important cause of drug reactions that present with paroxysms of hypertension, headache, palpitations, lightheadedness, flushing, and diaphoresis due to somatic sympathetic surges. Treatment includes antidepressants and biofeedback therapy.

TWO-STEP NONSTEROIDAL ANTI-INFLAMMATORY DRUG CHALLENGE DURING PREGNANCY: A CASE SERIES

<h3>Introduction</h3> Preeclampsia is a multi-system disorder associated with serious maternal and fetal morbidity and mortality, and low-dose aspirin is recommended for prevention in high-risk women. However, up to 2.5% of women of childbearing age report allergy to nonsteroidal anti-inflammatory drugs (NSAIDs), which may preclude aspirin use. We have previously shown that 2-step NSAID challenges can be safely performed in the outpatient setting. <h3>Case Description</h3> Three pregnant women were referred for NSAID allergy evaluation between 2021-2022: a 33-year-old with twin pregnancy and history of skin flushing with aspirin use >30 years prior; a 34-year-old with twin pregnancy and history of delayed facial angioedema and rash after aspirin ingestion within the past year; a 40-year-old with elevated BMI and history of lip angioedema with ibuprofen use >10 years prior. Two patients had well-controlled asthma, and none had history of chronic spontaneous urticaria. After risk-benefit discussion of drug challenge versus desensitization, all three underwent outpatient 2-step oral graded challenge (aspirin, aspirin, and ibuprofen, respectively) in the second trimester. All challenges were negative with no subjective symptoms or objective signs of a reaction elicited. <h3>Discussion</h3> For pregnant women with history of NSAID hypersensitivity and an indication for aspirin use, empiric aspirin desensitization can be performed but is time and resource intensive and requires subsequent daily administration to prevent risk of re-sensitization. For women with history of a prior mild reaction, we propose that a 2-step drug challenge may be considered in select patients after a risk-benefit discussion with the patient and obstetrician.

ANAPHYLACTIC REACTION TO OMEPRAZOLE AFTER NEGATIVE PANTOPRAZOLE ALLERGY TESTING

<h3>Introduction</h3> Proton pump inhibitors (PPIs) are widely used inhibitors of gastric acid secretion. PPIs are generally well tolerated with very few side effects and hypersensitivity reactions are rarely described. Here we present an adult man who reports anaphylaxis upon treatment with oral omeprazole. <h3>Case Description</h3> A 56-year-old man presented with symptoms of skin rash with pruritus of the skin upon treatment with oral omeprazole in treating Helicobacter pylori on two separate occasions. The reaction occurred after the first dose of the drug. Allergy skin testing (SKT) to pantoprazole was negative, and the patient tolerated the graded oral challenge to Pantoprazole. To treat the H. pylori infection, the patient took Talicia (amoxicillin, rifabutin, and omeprazole) and developed generalized pruritus, itchy tongue, throat, and bilateral hand swelling within 20 minutes of taking this medication. He also experienced chest tightness, shortness of breath, abdominal pain, dizziness, and vomiting. The patient was taken to the emergency department and received IV Benadryl (25 mg), famotidine (20 mg), methylprednisolone (125 mg), and intravenous fluids (1L NS), with an improvement in his symptoms. Upon follow-up for this anaphylactic reaction, allergy SKT and challenge to penicillin were performed which were negative. <h3>Discussion</h3> This case reinforces the importance of performing SKTs and oral drug challenges for each medication within the PPI drug class. The cross-reactivity between different PPIs is not currently well described, and other PPIs should be avoided unless an SKT and oral drug challenge are performed under close observation. Further studies are needed to provide more information on cross-reactivity among PPIs.

A RARE CAUSE OF URTICARIA IN AN NSAID TOLERANT PATIENT

<h3>Introduction</h3> Acetaminophen is one of the most used anti-pyretics to mitigate fever. Few cases have been reported of hypersensitivity reactions to acetaminophen without non-steroidal anti-inflammatory drug (NSAID) intolerance. It is recommended that if there is suspected drug hypersensitivity then the patient should undergo an oral drug challenge. <h3>Case Description</h3> A 49-year-old male presented for evaluation of urticaria that occurred with acetaminophen ingestion. He reported several episodes where he developed diffuse urticaria within 15 minutes of ingestion, but no other symptoms concerning for anaphylaxis. He was unsure of the dose. He also noted urticaria with Excedrin migraine, which contains acetaminophen, aspirin, and caffeine. He tolerated NSAIDs alone. An oral drug challenge was performed. He was administered 250mg of acetaminophen, which he tolerated. After taking his second dose of 250mg, he developed pruritus and 4 urticarial lesions within 30 minutes. He did not have any other signs of anaphylaxis. He was treated with 20mg of loratadine. Upon re-evaluation, he had more diffuse urticarial lesions, but no other symptoms and he remained hemodynamically stable. He was serially monitored every 15 minutes for a total of 90 minutes, with near resolution of his urticaria. <h3>Discussion</h3> Pseudoallergy is an immediate systemic reaction that resembles anaphylaxis but is non IgE-mediated. NSAIDs are a common cause of pseudoallergy. There are cases of acetaminophen hypersensitivity reactions in NSAID intolerant patients due to cross-reactivity. If a patient is NSAID tolerant and develops symptoms with acetaminophen, it is more likely to be IgE-mediated. Acetaminophen challenge should be done with caution and avoided if positive.

TO CHALLENGE OR AVOID? POSSIBLE ASPIRIN ALLERGY IN PATIENTS WITH CHRONIC IDIOPATHIC URTICARIA AND ANGIOEDEMA

<h3>Introduction</h3> Aspirin remains an important component of dual antiplatelet therapy following percutaneous coronary intervention (PCI). Despite studies showing safety in discontinuing aspirin post PCI through use of P2Y12 inhibitor therapy plus anticoagulation, no large, randomized trials evaluate an initial aspirin-free regimen post PCI without systemic anticoagulation. Aspirin intolerances occur in 20% of patients, with only 2% being true allergies. Most aspirin intolerances are linked to asthma, rhinitis, and chronic idiopathic urticaria (CIU). Differentiating this population is important for optimizing care. <h3>Case Description</h3> C.P. is a 54-year-old male with CIU referred for evaluation of aspirin allergy prior to coronary angiography with possible PCI. In 2001, C.P. developed right periorbital edema an hour after his third dose of daily aspirin therapy. Antihistamines reduced the swelling within hours, however due to reaction, his physician recommended discontinuing aspirin. He noted taking aspirin as a child and ibuprofen as an adult without incident. An in-clinic open oral drug challenge to aspirin was conducted. The patient was given 1/10^th of the full dose, followed by the remaining dose then monitored for 1 hour. The patient was diagnosed with NSAID exacerbated CIU and discharged with aspirin and antihistamines for control. <h3>Discussion</h3> Without clear guidelines for managing NSAID induced CIU, many physicians recommend avoidance, resulting in suboptimal care. 20-40% of CIU patients have flares triggered by NSAIDs, and many are misdiagnosed with an aspirin allergy. Our case demonstrates that through careful history and oral challenge, aspirin exacerbated CIU can be effectively managed without forgoing quality care.

ILLICIT DRUGS: CHALLENGES AND TENACITIES

This paper examines the global phenomenon of drug addiction, analyzes the historical trajectory of drug abuse, examines its categories, and considers response mechanisms in conjunction with local and international initiatives intended to reduce substance abuse. The paper emphasizes the role of legal institutions at the local level and the way international actors and stakeholders collaborate to curb the threat. The research presented here presents opportunities for drug control through programs, rehabilitation sessions, and policy initiatives. It sketches a comprehensive and well-defined program that focuses on the role of legal institutions in preventing and treating drug addiction. It explores the challenges of drugs as a global hazard and provides policy frameworks for collective responses in place of government and non-government interventions. In this study, a doctrinal approach is employed along with an exploratory approach. This paper would contribute considerably to the understanding of the subject.