History Of Drug Hypersensitivity Reaction Research Articles

Drug-induced hypersensitivity reactions in a Lebanese outpatient population: A decade-long retrospective analysis (2012-2021)

Drug hypersensitivity reactions (DHRs) are becoming more common as a result of increasing prevalence and case complexity. Allergists and clinical immunologists worldwide are challenged daily to adequately diagnose and manage these reactions. Data in the literature regarding DHR outpatient consultations are scarce worldwide, limited in the Middle East, and currently unavailable in Lebanon. This retrospective study aimed to evaluate the characteristics of all reported DHRs over 10 years in a tertiary-care allergy clinic in Lebanon. We conducted a decade-long (2012-21) retrospective analysis of the archived medical records of patients with a history of DHRs. Demographics, clinical history, diagnostic tools, and characteristics of the DHRs were collected and analyzed. A total of 758 patients experienced DHRs to therapeutic molecules provided for ambulatory care. Our results identified 72 medications. The most frequently implicated drug classes included β-lactam antibiotics (53.8%), followed closely by nonsteroidal anti-inflammatory drugs (48.9%). Of the 758 patients, 32.6% reported DHRs to multiple molecules, and 11.8% reported concomitant DHRs to 1 or several molecules provided in the perioperative setting. Of those, opioids and neuromuscular blocking agents were the 2 most common therapeutic classes. Furthermore, we evaluated the cross-reactivity between molecules of the same class. In neuromuscular blocking agents, rocuronium and cisatracurium were the most commonly cross-reactive, and for opioids, the most common association we recorded was with morphine and pethidine. Our findings constitute the first step toward a more comprehensive evaluation of the clinical characteristics of DHRs in Lebanon.

Allergic reactions to local anesthetics: should we test those with drug allergies and atopy history?

Aim: Many patients are referred to allergy clinics for allergy tests to local anesthetics. The aim of this study was to evaluate the effect of a history of atopy and drug hypersensitivity on allergy tests made with local anesthetics. Materials and Methods: A retrospective review was made of the records of patients referred to our clinic within a 5-year period because of a suspicion of allergy to local anesthetics, and who were applied with skin tests and subcutaneous challenge tests. Results: Evaluation was made of a total of 138 patients, comprising 114 (82.6%) females and 24 (17.4%) males with a mean age of 45.35 ± 14.13 years. A reaction during a dental procedure was reported in 99 (71.7%) patients. Mepivacaine was the most tested local anesthetic (n = 66, 40.2%). A positive reaction was determined in the skin tests made with local anesthetics in 6 (4.3%) patients. Lidocaine was the local anesthetic most often showing a positive reaction (n = 3, 50%). A history of atopy was present in 30 (21.7%) patients. No correlation was determined between atopy history and the development of a positive reaction to local anesthetics (p = 0.086). In the cases determined with a positive reaction to local anesthetics, there was a greater rate of history of hypersensitivity to drugs other than local anesthetics (p = 0.012). Conclusion: Patients with a history of drug hypersensitivity reaction should be tested in respect of local anesthetic allergy prior to a procedure to be made with local anesthetics.

Outcomes of drug provocation tests in Korean children with suspected drug hypersensitivity reaction

Purpose: Drug provocation tests (DPT) are the gold standard for confirming the diagnosis of drug hypersensitivity reactions (DHRs). However, there are little studies of DPT in children. The purpose of this study was to evaluate DPT results and safety as diagnostic methods of DHR in Korean children. Methods: We reviewed the medical records of 39 children under 18 years of age with a suspected DHR and performed DPT be tween January 2010 and May 2016 at Asan Medical Center. Results: Total 110 DPT were performed in 39 children (20 boys and 19 girls) with a history of DHR. Clinical presentation of DHR in cluded skin rash (n=7), pruritus (n=3), urticaria (n=18), angioedema (n=19), dyspnea (n=5), hoarseness (n=1), hypothermia (n=1), and anaphylaxis (n=5). The median age at the time of DPT was 9 years. Positive DPT were observed in 21 of 39 children (53.8%) and 28 of 110 cases (25.5%). Drugs causing positive reactions were acetaminophen in 50% (9 of 18), nonsteroidal anti-in flammatory drugs in 29.2% (14 of 48), cephalosporin in 9.1% (1 of 11), trimethoprim/sulfamethoxazole in 50% (1 of 2), local anes thetics in 10% (1 of 10), and others (levodropropizine and idursulfase) in 15.4% (2 of 13). There was no statistical difference between children who had positive and negative results in sex, age, personal and parental history of allergic disease, eosinophil count, or to tal IgE level. Children with positive DPT did not develop anaphylaxis during the DPT procedure. Conclusion: Drug provocation test is safe, and it can be considered in children with suspected DHRs. (Allergy Asthma Respir Dis 2018;6:26-33)

Local anesthetics allergy: who should be tested?

Objective. To document the test results of patients referred to our clinic for testing with local anesthetics (LAs) in real life conditions and provide data related to the necessity of these tests. Methods. All consecutive subjects who were referred to be evaluated for LA allergy during a two-year follow up were included in the analysis. All subjects underwent skin prick / intradermal tests followed by a subcutaneous provocation test with the LAs tested. Results. A total of 228 subjects were included. The main referral reason was the presence of a history of drug hypersensitivity reaction (DHR) to drugs other than LAs (n = 128; 56%), whereas a history of LA allergy constituted the second most common referral reason (n = 64, 28.1%). In the majority of cases (n = 39; 60.9%), the culprit LA was not known by the patients. Asthma was the third most common referral reason, presented in 49 cases (21.5%). Ten cases had positivity to the tested LA in skin testing / challenges. Nine out of 10 patients had a history of DHR to drugs other than LA, whereas 5 of them had also a history of DHR to LA. Six of the 10 patients had a history of multiple DHR. None of the asthma patients without any DHR history were positive in the LA tests. Eight out of 10 cases who underwent skin testing / challenge with an alternative LA, tolerated the alternative LA. Conclusion. The most common referral reason for testing with LA was a history of DHR to drugs other than LAs, whereas asthma was the third most common referral reason. Patients with a history of multiple DHR may be considered for testing with LAs. Asthmatics and those with other allergic diseases without a history of drug / LA allergy do not need to be tested with LA.

Characteristics of drug-induced anaphylaxis in children and adolescents.

Although data on anaphylaxis in the general population exist for different allergens, there is still lack of detailed etiologic data on drug-induced anaphylaxis (DIA), particularly in children. To define the etiology of DIA, to determine the accuracy of drug-related anaphylaxis histories, along with the severity and culprit drug associations among individuals <18 years old. Patients with a history of drug hypersensitivity reaction (DHR) referred to our center between January 2012 and February 2016 were included. After the collection of European Network for Drug Allergy questionnaire results, initial skin tests and/or provocation tests were performed for the offending drug. Among 561 children and adolescents referred due to a suspected DHR, 113 (19%) (median age [interquartile range], 9.6 years [5.4-13.8 years]; 55% boys) had anaphylaxis in their history. At the end of diagnostic evaluation of the patients, 84 (74% of the patients with a history of DIA) were actually hypersensitive to the offending drug. Major drugs that resulted in DIA were antibiotics (33%), nonsteroidal anti-inflammatory drugs (25%), and chemotherapeutics (19%). The majority of patients reported grade 2 (moderate) (45%) and grade 3 (severe) (33%) anaphylactic reactions. A history of systemic illness (41.7 versus 7.1%; p = 0.001), concomitant intake of other drugs regularly (36.9 versus 10.3%; p = 0.007), and the use of chemotherapeutics as the culprit drug (19 versus 0%; p = 0.011) were more frequent, whereas the use of antibiotics was less frequent (34.5 versus 75.9%; p < 0.001) among patients with actual DIA compared to drug tolerant patients. Three-fourths of the children and adolescents referred due to a suspected history of DIA were found to actually be drug hypersensitive. Prediagnosed systemic illness and different types of drugs would have an impact on the risk of DIA; however, atopic disease or a family history of drug hypersensitivity did not have an impact on actual DIA.

Development of a modified lymphocyte transformation test for diagnosing drug-induced liver injury associated with an adaptive immune response

Drug-induced liver injury (DILI) is a growing problem. Diagnostic methods to differentiate DILI caused by an adaptive immune response from liver injury of other causes or to identify the responsible drug in patients receiving multiple drugs, herbals and/or dietary supplements (polypharmacy) have not yet been established. The lymphocyte transformation test (LTT) has been proposed as a diagnostic method to determine if a subject with an apparent hypersensitivity reaction has become sensitized to a specific drug. In this test, peripheral blood mononuclear cells (PBMC) collected from a subject are incubated with drug(s) suspected of causing the reaction. Cell proliferation, measured by the incorporation of [3H]-thymidine into new DNA, is considered evidence of a drug-specific immune response. The objectives of the current studies were to: (1) develop and optimize a modified version of the LTT (mLTT) and (2) investigate the feasibility of using the mLTT for diagnosing DILI associated with an adaptive immune response and identifying the responsible drug. PBMC collected from donors with a history of drug hypersensitivity reactions to specific drugs (manifested as skin rash) were used as positive controls for assay optimization. Following optimization, samples collected from 24 subjects enrolled in the U.S. Drug-Induced Liver Injury Network (DILIN) were tested in the mLTT. Using cytokine and granzyme B production as the primary endpoints to demonstrate lymphocyte sensitization to a specific drug, most samples from the DILIN subjects failed to respond. However, robust positive mLTT responses were observed for two of four samples from three DILIN subjects with hepatitis due to isoniazid (INH). We conclude that the mLTT, as performed here on frozen and thawed PBMC, is not a reliable test for diagnosing DILI caused by all drugs, but that it may be useful for confirming the role of the adaptive immune response in DILI ascribed to INH.

Basal serum tryptase is not a risk factor for immediate-type drug hypersensitivity during childhood.

High serum basal tryptase (sBT) levels have been identified as a risk factor for both venom- and food-induced severe allergic reactions. The aim of this study was to compare sBT levels in children with different severity of actual drug hypersensitivity reactions (DHRs) with those of age- and sex-matched controls without any history of DHRs. Patients between 0 and 18 years of age with a history of immediate-type DHRs manifested in 0-6 h after the culprit drug intake were included. Following ENDA (European Network for Drug Allergy) inquiries, patients were evaluated with skin and/or provocation tests to define the actual drug-hypersensitive patients. Serum BT levels were determined for both patients and controls. Of 345 children, 106 patients (30.7%) [(58.5% male), median age (interquartile range) 8.0 years (4.2-12.2)] were diagnosed as drug hypersensitive. Ninety-eight controls were also included. The sBT levels of drug-hypersensitive patients with and without anaphylaxis and the control group were similar [2.6 (2.0-3.6) μg/l vs. 2.8 (1.6-4.3) μg/l vs. 2.6 (1.8-3.6) μg/l, respectively, (p > 0.05)]. The sBT levels of the patients with sole cutaneous symptoms 2.8 (1.6-4.3) μg/l, mild anaphylaxis 3.0 (1.9-4.9) μg/l, and moderate-to-severe anaphylaxis 2.6 (2.0-3.6) μg/l were also comparable (p > 0.05). The onset of DHRs [those occurring in 1 h (n = 87) or in 1-6 h (n = 19) after the drug intake], positive results with skin tests with the culprit drug, or the classification of the patients according to different age groups [(0-2 years), (2-6 years), (6-12 years), (12-18 years)] did not correlate with sBT levels. The sBT levels in children with actual drug hypersensitivity would not be a risk factor for severe systemic reactions on the contrary to children with allergic reactions to food or insect venom.

Comprehensive Allergy Evaluation Is Useful in the Subsequent Care of Patients with Drug Hypersensitivity Reactions During Anesthesia

For patients with a history of drug hypersensitivity reaction (HSR) during anesthesia, strategies to minimize risk with subsequent anesthesia are unclear. Identification of the cause of HSR during anesthesia remains challenging. To determine the success of a comprehensive allergy evaluation and management plan for patients with HSR during anesthesia, including identification of the causative agent and review of outcomes during subsequent anesthesia exposure. We performed chart reviews of patients referred for the evaluation of HSR during anesthesia between 2003 and 2012. Data collection included patient characteristics, signs/symptoms of HSR during anesthesia, and subsequent outcomes. Patients underwent comprehensive allergy evaluation including skin testing for identifying potential culprit agents, and the results were used to provide recommendations for any subsequent anesthesia. Over the 10-year study period, 73 patients with HSR during anesthesia were referred for further evaluation. Thirteen patients (18%) had positive skin test results to a drug received during anesthesia. One patient with a positive skin test result was diagnosed with mastocytosis. The causative agents identified in these 13 patients included latex, β-lactam antibiotics, neuromuscular blockers, tetracaine, odansetron, and fentanyl. On follow-up, 47 of the 73 patients (64%) subsequently underwent procedures requiring anesthesia. Using our recommendations from evaluation and testing, 45 of these 47 patients (96%) successfully tolerated subsequent anesthesia. The 2 patients who developed recurrent HSR during anesthesia were later diagnosed with mast cell disorders. Our comprehensive evaluation and management plan minimizes risk with subsequent anesthesia even when the cause of HSR could not be identified. Baseline tryptase levels may be helpful in this patient population to diagnose mast cell disorders.

Determinants of nocebo effect during oral drug provocation tests

BackgroundA “nocebo” effect is defined as troublesome symptoms after the administration of placebo. The aim of this study was to determine characteristics of nocebo responses and related factors. MethodsPatients with a reliable history of drug-induced hypersensitivity reactions subjected to placebo-controlled oral drug provocation tests and reacted to placebo, were consecutively included in this case–control study. Controls consisted of the randomly selected subjects who had a history of drug hypersensitivity reaction but did not react to placebo. A structured questionnaire was performed by an allergy specialist. ResultsThere were 137 subjects (mean age: 43.10±12.65 years), with nocebo and 91 subjects (42.38±12.18 years) without any reaction to placebo. Most nocebo reactions (71.5%, n=98) were classified as subjective, with local pruritus as the most common finding. A minority of nocebo reactions (11.7%, n=16) were objective as cutaneous reactions including flushing and urticaria. Factors related with nocebo risks were university graduation (OR: 2.96, 95% CI: 1.27–6.93, p=0.012) and non-atopy (OR: 2.12, 95% CI: 1.02–4.40, p=0.043). In terms of the time of first and last historical reaction to drugs, each 1-unit (a month) increase in first reaction time (OR: 1.008, 95% CI: 1.00–1.02, p=0.001) and last reaction time (OR: 1.019, 95% CI: 1.01–1.03, p<0.001) were associated with increased nocebo risk. ConclusionIn conclusion, subjects with high education, non-atopy, and older drug hypersensitivity reactions history seem to be more likely to experience nocebo effect during oral drug provocation tests. These risk factors should be considered and managed accordingly to complete the drug provocation procedure successfully.

Results of Drug Provocation Tests in Patients with a History of Drug Hypersensitivity Reaction

The diagnosis of drug hypersensitivity is often based upon history without further diagnostic evaluation.However,several studies indicated that history alone is unreliable.Although drug provocation testing is the gold standard for a diagnosis there are very few reports of DPTs in Thailand.The purpose of this study was to present the results of DPT in patients with suspected drug hypersensitivity.