History Of Hypersensitivity Reactions Research Articles

Formulation and Evaluation of Diclofenac Transdermal Gel

Diclofenac sodium gel is a widely used nonsteroidal anti-inflammatory drug (NSAID) formulation designed for topical application, primarily targeting local pain and inflammation. This wok aims to provide a comprehensive analysis of the anti-inflammatory activity of diclofenac sodium gel, focusing on its mechanism of action, efficacy, safety profile, and clinical applications. Several clinical studies have investigated the efficacy of diclofenac sodium gel in various inflammatory conditions, including osteoarthritis, rheumatoid arthritis, and soft tissue injuries. Results consistently demonstrate significant reductions in pain, swelling, and functional impairment, validating the gel's anti-inflammatory properties. The safety profile of diclofenac sodium gel is generally favorable, with local skin reactions being the most commonly reported adverse events. Systemic absorption is low, reducing the risk of gastrointestinal complications and other systemic side effects associated with oral NSAIDs. However, caution should be exercised in individuals with a history of hypersensitivity reactions or skin disorders.

Healthcare Providers’ knowledge, attitudes and practice in relation to drug hypersensitivity reactions at King Abdulaziz Medical City in Riyadh

BackgroundDrug hypersensitivity reactions (DHRs) are immune-mediated responses triggered by exposure to a drug. DHRs are responsible for serious adverse drug reactions (ADRs) and are considered the fifth leading cause of death. This study aims to assess and evaluate the knowledge, practice, and attitudes of healthcare providers (HCPs) towards DHRs. MethodsA cross-sectional survey was conducted at King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia. Healthcare providers, including pharmacists, physicians, and nurses, were recruited using a convenience sampling method to complete the survey. The survey comprised three domains: knowledge (14 items), attitudes (5 items), and practices (6 items), utilizing a standardized self-administered questionnaire. ResultsThe survey was completed by 373 healthcare providers. The respondents were predominantly female (72.1 %) with a mean age of 33.8 ± 7.8 years. Of the respondents, 64 % were nurses, 25 % pharmacists, and 11.3 % physicians. Educational levels varied, with 53 % holding a bachelor's degree, 22 % an associate degree, and 25 % a master's degree or higher. The median knowledge score was 48. Female healthcare providers, those with advanced levels of education, and physicians had higher knowledge scores compared to male and nurse participants (p < 0.05). One-third of the respondents (33 %) were satisfied with their knowledge of DHRs, and 42 % believed HCPs should receive more advanced training in DHR management. Less than a quarter of HCPs reported inquiring about patients' histories of hypersensitivity reactions. ConclusionsThe study revealed that healthcare workers had a relatively low level of knowledge about drug hypersensitivity reactions and lacked a consensus on DHR management. While displaying a positive attitude towards DHRs, they often did not translate this attitude into consistent clinical practice.

Acetylsalicylic acid challenge or desensitization in sensitive patients with cardiovascular disease

Abstract Background The use of acetylsalicylic acid (ASA) is problematic in subjects with histories of hypersensitivity reactions (HRs) to it or with cross-reactive types of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. Purpose To evaluate the efficacy of low-dose ASA challenge (LDAC) and desensitization to allow ASA therapy at an antiplatelet dose in patients with atherosclerotic cardiovascular disease (ASCVD) or multiple related risk factors and histories of HRs to ASA or ≥ 2 chemically unrelated NSAIDs. Methods We studied prospectively all patients with such histories and ≥ 3 risk factors for ASCVD (group I), chronic coronary syndrome (CCS, group II), and acute coronary syndrome (ACS) with indication for ASA desensitization (group III). Patients from groups I and II underwent LDACs (cumulative dose of 110 mg), while those from group III were desensitized (cumulative dose of 100.1 mg). Results We evaluated 103 patients: 62 from group I, 24 from group II, and 17 from group III. Eighty-two of the 86 patients from the first two groups underwent LDACs and 2 reacted. Subsequently, 22 (27.5%) of the 80 patients with negative LDACs were administered dual antiplatelet therapy with ASA after successful percutaneous coronary interventions, thus sparing desensitizations. The remaining 4 patients with CCS and all 17 patients from group III were successfully desensitized. Conclusions LDAC proved to be a safe and reliable diagnostic tool for identifying patients with histories of HRs to ASA or ≥ 2 different NSAIDs who can tolerate ASA at antiplatelet doses. Routine LDAC is advisable in all patients at high risk for ASCVD or with CCS who report HRs to ASA or ≥ 2 NSAIDs. ASA desensitization remains a safe and effective option in patients with ACS.

Relevance of the diagnosis of hypersensitivity reactions to antineoplastic and biological agents: experience with drug provocation test.

Background. Evidence regarding drug provocation test (DPT) with chemotherapeutic agents is scarce. The aim of our study is to describe the experience of DPT in patients with a history of hypersensitivity reactions (HSRs) to antineoplastic and biological agents. Methods. This was an eight-year retrospective, observational, descriptive study of patients with a history of HSRs to chemotherapy who were submitted to DPT. Anamnesis, skin tests (ST) and DPT were analyzed. Patients with a negative DPT were submitted to at least one regular supervised administration (RSA). Patients with positive DPT or HSR during RSA were offered rapid drug desensitization (RDD). Results. A total of 54 patients were submitted to DPT. The most common suspected drugs were platins (n = 36), followed by taxanes (n = 11). Most initial reactions were classified as grade II (n = 39) according to Brown's grading system. ST with platinum (n = 35), taxanes (n = 10) and biological agents (n = 4) were negative, except for one intradermal test with paclitaxel, which was positive. A total of 64 DPTs were performed. Eleven percent of all DPTs were positive (platins (n = 6), doxorubicin (n = 1)). Of the 57 RSA with the culprit drugs, 2 were positive (platins). The diagnosis of hypersensitivity was confirmed by DPT/RSA in 9 patients. All patients with positive DPT/RSA presented HSRs of equal or less severity than the initial one. Conclusions. DPT followed by RSA allowed to exclude HSRs in 45 patients (55 culprit drugs). DPT before desensitization prevents non-hypersensitivity patients from undergoing RDD. In our study DPT was safe, all reactions were managed by an allergist.

Acetylsalicylic acid challenge or desensitization in sensitive patients with cardiovascular disease.

The use of acetylsalicylic acid (ASA) is problematic in subjects with histories of hypersensitivity reactions (HRs) to it or with cross-reactive types of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. We sought to evaluate the efficacy of low-dose ASA challenge (LDAC) and desensitization to allow ASA therapy at an antiplatelet dose in patients with atherosclerotic cardiovascular disease (ASCVD) or multiple related risk factors and histories of HRs to ASA or ≥ 2 chemically unrelated NSAIDs. We studied prospectively all patients with such histories and ≥ 3 risk factors for ASCVD (group I), chronic coronary syndrome (CCS, group II), and acute coronary syndrome (ACS) with indication for ASA desensitization (group III). Patients from groups I and II underwent LDACs (cumulative dose of 110mg), while those from group III were desensitized (cumulative dose of 100.1mg). We evaluated 103 patients: 62 from group I, 24 from group II, and 17 from group III. Eighty-two of the 86 patients from the first two groups underwent LDACs and 2 reacted. Subsequently, 22 (27.5%) of the 80 patients with negative LDACs were administered dual antiplatelet therapy with ASA after successful percutaneous coronary interventions, thus sparing desensitizations. The remaining 4 patients with CCS and all 17 patients from group III were successfully desensitized. In this pragmatic study,LDAC proved to be a safe and reliable diagnostic tool for identifying patients with histories of HRs to ASA or ≥ 2 different NSAIDs who can tolerate ASA at antiplatelet doses. Routine LDAC is advisable in all patients at high risk for ASCVD or with CCS who report HRs to ASA or ≥ 2 NSAIDs. ASA desensitization remains a safe and effective option in patients with ACS. Study flow-chart. ASCVD atherosclerotic cardiovascular disease; CCS chronic coronary syndrome; ACS acute coronary syndrome; ASA acetylsalicylic acid; DAPT dual antiplatelet therapy; PCI percutaneous coronary intervention; NSAIDs nonsteroidal anti-inflammatory drugs; NERD NSAID-exacerbated respiratory disease; NECD NSAID-exacerbated cutaneous disease; NIUAA NSAID-induced urticaria-angioedema or anaphylaxis; SNIUAA single NSAID-induced urticaria-angioedema or anaphylaxis; SNIDHR single NSAID-induced delayed hypersensitivity reaction.

Toxicity management and efficacy of carboplatin desensitization therapy for recurrent epithelial ovarian carcinoma: A real-world study.

Epithelial Ovarian cancer (EOC) is the most lethal gynecologic cancer worldwide. Carboplatin (CP) is the main chemotherapeutic agent in the treatment of ovarian cancer. However, the development of a hypersensitivity reaction (HSR) in 10% to 15% of patients with EOC is an important limiting factor for the clinical use of CP. Herein, we aimed to investigate the efficacy and safety of CP-desensitization (CP-D) therapy in the treatment of recurrent patients with EOC. Forty-seven ovarian cancer cases treated with CP-desensitization at the Istanbul University Oncology Institute were retrospectively analyzed between 01.01.2017 and 01.01.2022. The decision for CP-D was based on the patients' history of HSR and/or a positive skin test. For all patients, a 6-hour 12-step rapid drug desensitization protocol with a 30-minutes premedication regimen was used. Forty-seven patients were included in this study, and the median age at diagnosis was 53 years (range; 27-80). Twenty-one (43.7%) patients had 1 or more comorbid diseases, and 12.7% had a previous history of drug allergy. On average, HSR due to carboplatin was identified after 9 (7-16) cycles, and carboplatin was administered n = 11 (range, 3-36) times to patients. The overall survival from the first desensitization procedure (0S2) was 42.2 months (range: 25.3-59.1), and the 1-, 2-, and 5-years survival rates were 92.6%, 75.6%, and 47.2%, respectively. The objective response rate (ORR) was 78.5%. Cumulatively, 496 CP-D procedures were performed, of which 478 (96.3%) were successfully completed. None of the patients included in this study developed severe (grade 3-4) HSR during CP administration (no adrenaline was used, no need for intensive care). No deaths due to CP-D were noted. CP-D is a beneficial and safe method in treating platinum-sensitive recurrent EOC patients with CP-induced HSR.

The Whitening, Moisturizing, Anti-aging Activities, and Skincare Evaluation of Selenium-Enriched Mung Bean Fermentation Broth

Selenium-enriched mung bean (Se-MB) is a combination of mung bean (MB) and selenium (Se), which have a variety of potential biological activities. However, little is known about the skincare activity of Se-MB. The chemical composition of Se-MB fermentation broth (Se-MBFB) was analyzed to investigate the whitening, moisturizing, and anti-aging activities of Se-MBFB. The tyrosinase inhibition, anti-melanogenic in melanocytes (B16F10 cells), and moisturizing effect in human dermal fibroblasts (HDFs) were analyzed. Besides, the free radical scavenging activity of Se-MBFB was assessed in vitro. To verify the in vivo effects and the potential of practical applications of Se-MBFB, a clinical trial was conducted on the participants: 31 Chinese women aged 25–60 years, with no pigmentation disorder, no illness, no history of hypersensitivity reaction, and no use of skincare product on the face. The participants used an Se-MBFB masque for 15-20 min after cleaning the face. The measurement points were Week 0, 2, and 4 (W0, W2, and W4) after using the masque, and target sites were cheek and canthus. The following parameters were recorded on the target sites at each visit: melanin index, skin color, cuticle moisture content, transepidermal water loss, and crow's feet. The results demonstrated that Se-MBFB was rich in polyphenols, peptides, and γ-aminobutyric acid (GABA), displayed significant free radical scavenging and tyrosinase inhibiting activities, decreased the synthesis of melanin, and upregulated the aquaporin-3 (AQP3) expression. The test of the Se-MBFB mask showed that after 4 weeks of using the Se-MBFB facemask, the faces of the participants became whiter with reduced wrinkles and increased moisture content. Se-MB possessed the excellent whitening, moisturizing, and antioxidant efficacy, which could lay a scientific foundation for utilization and development of skincare products of Se-MB and its related industrial cosmetics products.

Oral Challenge without Penicillin Skin Tests in Children with Suspected Beta-Lactam Hypersensitivity

AbstractObjective A misdiagnosed “penicillin allergy” is a common problem in childhood. Recently, skipping skin tests (STs) and performing a direct oral challenge test (OCT) have become an increasingly common approach in children with suspected β-lactam (BL) allergy. In our study, we aimed to evaluate the safety and efficacy of OCT without using ST in children who had a history of hypersensitivity reactions with BL antibiotics.Materials and Methods We retrospectively evaluated direct OCT outcomes in children with both nonimmediate and immediate-type reaction history with BL antibiotics. STs were not performed before the challenge test. The patients were monitored for 4 hours after the challenge and continued using the drug in two divided doses for 3 days at home.Results In this study, 72 patients were included, with median age of 7 years (interquartile range: 4; min: 1 year to max: 16 years), and of these, 56% were male. Forty-five subjects (63%) reported immediate-type adverse reactions. The most common clinical manifestation was urticaria/angioedema (51%, n: 37) and maculopapular exanthema in 46% (n: 33) of patients, respectively. The most commonly suspected drug was 71% amoxicillin-clavulanate. A 3-day OCT without preceding ST was performed in all patients. Only three patients (4.2%) showed a positive response to the oral drug challenge test. None of these reactions observed was more severe than index reactions.Conclusion Performing OCT without STs is a safe and convenient method to exclude BL hypersensitivity in the pediatric age group.

Clinical significance of plasma PAF acetylhydrolase activity measurements as a biomarker of anaphylaxis: Cross-sectional study.

IntroductionPlatelet-activating factor (PAF) has a direct role as a mediator in the pathogenesis of various disorders with an inflammatory component, including those with allergic aetiology. The peripheral blood concentration of PAF is dynamically regulated by plasma PAF acetylhydrolase (PAF-AH). Previous research suggest that low activity of plasma PAF-AH could be a predictive marker for increased severity of some types of allergic hypersensitivity reactions–especially anaphylaxis. The purpose of the study was to evaluate the association between plasma PAF-AH activity and severity in patients with anaphylactic reactions following a wasp or bee sting.Materials and methodsThe study group of 89 patients was divided into two subgroups depending on the increasing severity of the most severe anaphylactic reaction in the past, which was assessed according to the Müller’s scale. The first subgroup included participants with a history of hypersensitivity reactions up to grade II. The second subgroup consisted of patients who have experienced at least one grade III or IV reactions in the past. A control group of 20 people was established. Plasma PAF-AH activity was measured using a colorimetric method.ResultsIt has been observed that plasma activity of platelet-activating factor acetylhydrolase was significantly lower in patients with anaphylaxis history compared to the control group with negative atopic history (on average 21.38 nmol/min/ml for the control group, 9.47 nmol/min/ml for the first subgroup and 10.16 nmol/min/ml for the second subgroup, in both cases p < 0.0001).ConclusionThe plasma activity of PAF-AH is a promising parameter that can help to distinguish a group of patients not threatened with development of anaphylaxis and not requiring laborious or expensive prophylactic procedures.

Evaluation of skin test indications for general anesthetics in real life: a prospective cohort study

BackgroundIn daily practice, atopic patients and those who have other drug allergies are referred to allergy clinics for evaluation of possible general anesthetic allergy despite the fact that it is not recommended in recent guidelines. ObjectiveThe aim of this prospective study is to determine the negative predictive value of skin tests for common general anesthetic drugs prior to general anesthesia in atopic patients and in patients who had drug allergies by including the data of those who had previously tolerated or reacted to general anesthesia. MethodsA database program was constituted to collect the preoperative skin test data of patients referred to our clinic between 2013 and 2018. Demographic and clinical history, medications implemented during perioperative period, reactions, and results of skin tests performed with anesthetic drugs and latex were evaluated. ResultsFour hundred fifty-nine out of the total 1167 patients referred fulfilled the inclusion criteria for further evaluation. Nearly 75% of the patients were female and mean age was 46.3 ± 14.3 years. History of hypersensitivity reactions (HRs) due to NSAIDs and/or antibiotics, radiocontrast agents, local anesthetics, and food were present in the 53.1%, 4.1%, 1.5%, and 2.0%, respectively. The negative predictive values of skin tests for general anesthetics were in the range of 80–100%. Only 4 patients (0,87%) experienced HRs during operation. ConclusionThese real-life data reveal high rates of negative predictive value of skin tests with general anesthetic drugs and a low reaction rate in atopic patients and in patients with allergy to other drugs.

SARS-CoV-2 Vaccines: Much Accomplished, Much to Learn

As COVID vaccines roll out, internists and other health care providers are being turned to as trusted sources of information for patients and communities. Here, experts from NIAID outline the current state of knowledge regarding such vaccines. They contrast vaccine platforms, summarize clinical trial data regarding efficacy and safety, and comment on key questions including the ability of current vaccines to protect against infection and to decrease the prevalence of virus in the community.

Influence of Antihistamines on Basophil Activation Test in Food Allergy to Milk and Egg.

Background: The basophil activation test (BAT) is used to improve the accuracy of food allergy diagnosis. To date, the influence of antiallergic drugs on BAT reactivity is poorly investigated. The aim of the study was to investigate if BAT results were influenced by antihistamine intake for 3 months in a cohort of patients with IgE-mediated food allergy to milk or egg. Methods: A retrospective, single-center, observational study was performed. We enrolled subjects with history of hypersensitivity reaction after specific food ingestion, positive skin prick tests and specific IgEs, concomitant allergic rhinitis, and, contraindication to the double-blind, placebo-controlled food challenge due to personal history of systemic reactions related to the ingestion of culprit food. Validated allergens (α-lactoalbumin, β-lactoglobulin, casein, egg white, and yolk) for BAT were used. Results: Thirty-nine patients with well-documented food symptoms and positive allergological workup were included in the study. BAT was positive in 29 patients. The mean percentages of CD63+ expression to specific culprit allergen did not change after the administration of drugs. Conclusions: This was the first study assessing the effects of oral antihistamines on basophil reactivity in cow’s milk and egg food allergy. Antihistamines do not interfere with BAT results.

Oral Immunotherapy for Hazelnut Allergy: A Single-Center Retrospective Study on 100 Patients

Oral immunotherapy (OIT) protects patients with IgE-mediated food allergies from food-induced allergic reactions due to accidental exposure and may improve their quality of life. This approach has never been evaluated for hazelnut, a major cause of food allergy in Europe. To determine the proportion of hazelnut-desensitized patients after 6 months of OIT and to identify predictors of successful desensitization. In a retrospective single-center study, we included patients younger than 18 years who underwent at least 6 months of hazelnut OIT for IgE-mediated allergy, defined by history of hypersensitivity reaction after hazelnut ingestion, positive hazelnut skin prick test result or specific IgE, and positive double-blind, placebo-controlled food challenge. Patients able to tolerate 1635 mg of hazelnut protein (∼8 hazelnuts) were considered to be hazelnut desensitized. We determined the proportion of desensitized patients after 6 months of OIT, searched for associations between baseline variables and successful desensitization, and estimated the frequency and severity of OIT-related adverse reactions. One hundred patients were included (64% males; median age, 5 years). History of severe reactions was noted in 7% of cases. At 6 months, the proportion of desensitized patients was 34% (95% CI, 25-44). The median eliciting dose (defined as the amount of hazelnut protein provoking a hypersensitivity reaction during the double-blind, placebo-controlled food challenge) increased from 106 mg (interquartile range, 51-249) at baseline to 523 mg (interquartile range, 190-1635) after 6 months of OIT (P < .0001). With longer therapy, the proportion of desensitized patients increased. Using multivariate analysis, successful desensitization was associated with older age (odds ratio [OR], 1.5; 95% CI, 1.2-2.2), smaller hazelnut skin prick test wheal diameter (OR, 0.61; 95% CI, 0.4-0.8), lower hazelnut specific IgE level (OR, 0.86; 95% CI, 0.72-0.98), and absence of cashew allergy (OR, 0.42; 95% CI, 0.12-0.64). Adverse reactions occurred in 30% of patients; none were severe. In a cohort of 100 patients aged 3 to 9 years, our results show for the first time that hazelnut OIT is associated with hazelnut desensitization and may be safe in most patients undergoing this therapy.

Abstract 3078: Tesetaxel, a novel, oral taxane, crosses intact blood-brain barrier (BBB) at therapeutically relevant concentrations

Abstract Background: Central nervous system (CNS) metastases in cancers such as breast and lung cancer are common and associated with poor outcomes. The taxanes paclitaxel (P) and docetaxel (D) do not significantly cross the BBB (brain to plasma exposure of only 1% and 8%, respectively), making them ineffective in treating CNS metastases. Tesetaxel (T) is a novel, orally administered taxane currently in a Phase 3 study in patients with advanced breast cancer (aBC; NCT03326674). Several properties make it unique, including: oral administration with a low pill burden; a long (~8-day) terminal plasma half-life in humans, allowing infrequent dosing; no history of hypersensitivity reactions; significant activity against chemo-resistant tumors; and, unlike P and D, minimal efflux by the P-glycoprotein pump, a key element of the BBB. The in vivo tissue distribution of tesetaxel was previously investigated in mice treated with 14C-T at 4 mg/kg and sacrificed between 1-168 hours. We now report 2 additional studies in dogs and monkeys. Methods: Dogs and monkeys were dosed at 0.6 mg/kg and 1 mg/kg of 14C-T, respectively, and tissue distribution was assessed at 336 hours. These doses equate to ~44% of the 27 mg/m2 dose in the ongoing Phase 3 study. In vivo radioactivity concentrations in the cerebrum were compared to plasma concentrations and mean tumor GI50 (concentration resulting in 50% tumor growth inhibition) determined by MTT assay in 23 tumor cell lines. Results: The absolute brain concentrations of T in dogs and monkeys far exceeded both the respective plasma concentrations and the tumor GI50 (Table 1). Conclusions: In dogs and monkeys, T brain concentrations far exceed its tumor GI50 for a sustained period when administered at therapeutically relevant concentrations. The inclusion criteria for the ongoing Phase 3 study of T in patients with aBC allows for CNS metastases. Table 1:Tesetaxel CNS Levels Far Exceed Human GI50a in Dogs and Monkeys14C-T Radioactivity Concentration (ng eq./g or mL) bCerebrum Concentration/ Tumor GI50 cNCerebrum (Mean ± SD)Plasma (Mean ± SD)Cerebrum/ PlasmaDog d310.9 ± 4.00.9 ± 0.112x18xMonkey e36.5 ± 3.80.9 ± 0.27x11xaConcentration of drug required to inhibit growth by 50%b14 days after dosingcMean GI50 for T across 23 tumor cells lines = 0.6 ng/mLdSingle dose of 0.6 mg/kg (equivalent to 44% of a human dose of 27 mg/m2)eSingle dose of 1 mg/kg (equivalent to 44% of a human dose of 27 mg/m2) Citation Format: Joyce James, Kevin Tang, Thomas Wei. Tesetaxel, a novel, oral taxane, crosses intact blood-brain barrier (BBB) at therapeutically relevant concentrations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3078.

A new non-dilution rapid desensitization protocol successfully applied to all-grade platinum hypersensitivity.

Desensitization is a safe alternative for patients with hypersensitivity reactions (HSRs) to platinum-based chemotherapeutic agents and widely used in real practice by employing stepwise administration of multiple serial dilutions of the culprit drugs. However, its labor-intensive nature has required a simpler protocol that is easier to prepare and perform. We performed an observational study of patients with platinum HSR who underwent a new non-dilution one-bag desensitization protocol. Premedication consisted of Montelukast as well as H1 and H2 blockers. The outcomes and safety profiles of a new protocol were assessed. A total of 36 patients were recruited (oxaliplatin 23, carboplatin 9, and cisplatin 4) and the most common grade of HSR presented was grade 2 (61.1%), followed by grade 3 (25%), and grade 1 (13.9%). Of 175 desensitization procedures, all cases were successfully completed in re-administration of culprit chemotherapeutic platinum agents; 146 (83.4%) had no breakthrough reactions (BTRs) while 29 (16.6%) did. Most BTRs were mild reactions (grade 1, 51.7%) or moderate reactions (grade 2, 44.8%) of Brown's Scale. Although there was one case of asymptomatic mild hypotension (grade 3, 3.5%), categorized as severe reaction, dyspnea, desaturation, and anaphylaxis did not occur. The proportion of severe HSRs was significantly lower than that of initial HSRs (3.5% vs. 25%, P = 0.0167). The new non-dilution desensitization protocol was safe and effective for re-administration of culprit platinum agents in patients with a history of HSRs. Therefore, this new protocol can be used as an alternative to existing protocols using multiple serial dilutions.

Oxaliplatin desensitization after hypersensitivity reaction: A single-center experience on more than 300 procedures.

610 Background: Oxaliplatin is an essential drug in gastrointestinal oncology. Hypersensitivity reactions (HSR) occur frequently (incidence varying from 10% to 25%), leading to permanent treatment discontinuation. The present study aimed to report our experience of oxaliplatin desensitization in patients with history of HSR to oxaliplatin. Methods: We retrospectively reviewed all patients who received at least one infusion of oxaliplatin according to a desensitization protocol after prior history of HSR to oxaliplatin, from June 2011 until June 2017. HSRs were classified from NCI CTC-AE grade 1 (transient rash, fever &lt; 38°C) to grade 4 (anaphylaxis). We applied in all cases a desensitization protocol in which the oxaliplatin infusion rate is gradually increased from 1mL/hr. to 150mL/hr., on an inpatient basis. Intravenous or hepatic arterial infusion was used depending on clinical setting. Results: Overall, 54 patients were included in this study, in whom HSR to oxaliplatin occurred after a median of 9 infusions (range, 1-31). The severity of HSRs was grade 1-2 in 33 patients (61%) and grade 3-4 in 21 patients (39%). A total of 305 oxaliplatin infusions according to a desensitization protocol were performed in these 54 patients (median, 5 infusions; range, 1-20). These infusions were by intravenous route in 42 patients (78%), by hepatic arterial route in 11 patients (18%), and both in 2 patients (4%). Infusions were well tolerated in 41 patients (76%), without new HSR. The remaining 13 patients (24%) experienced HSR recurrence (grade 2, 9 patients [69%]; grade 3, 4 patients [31%]). No anaphylaxis or oxaliplatin-related death occurred. In the 21 patients with a prior history of severe (grade 3-4) HSR, oxaliplatin desensitization procedure was effective and sustained in 16 patients (79%). Among 32 evaluable patients, 23 (72%) experienced disease control (14 partial responses, 9 stable diseases). Conclusions: Rechallenging Oxaliplatin desensitization procedure was successful in three out of four patients with prior history of HSR to oxaliplatin. Our retrospective study confirms that oxaliplatin desensitization is safe, and allows patients who developed HSR to continue an effective treatment.

Stratified premedication strategy for the prevention of contrast media hypersensitivity in high-risk patients

BackgroundAlthough the severity of hypersensitivity reactions to iodinated contrast media varies, it is well correlated with the severity of recurrent reactions; however, prophylaxis protocols are not severity-stratified. ObjectiveTo assess the outcomes of tailored prophylaxis according to the severity of hypersensitivity reactions to iodinated contrast media. MethodsOur premedication protocols were stratified based on the severity of previous reactions: (1) 4 mg of chlorpheniramine for mild reactions, (2) adding 40 mg of methylprednisolone for moderate reactions, and (3) adding multiple doses of 40 mg of methylprednisolone for severe index reactions. Cases of reexposure in patients with a history of hypersensitivity reactions were routinely monitored and mandatorily recorded. ResultsAmong a total of 850 patients who underwent enhanced computed tomography after severity-tailored prophylaxis, breakthrough reactions occurred in 17.1%, but most breakthrough reactions (89.0%) were mild and did not require medical treatment. Additional corticosteroid use did not reduce the breakthrough reaction rate in cases with a mild index reaction (16.8% vs 17.2%, P = .70). However, underpremedication with a single dose of corticosteroid revealed significantly higher rates of breakthrough reaction than did double doses of corticosteroid in cases with a severe index reaction (55.6% vs 17.4%, P = .02). Changing the iodinated contrast media resulted in an additional reduction of the breakthrough reaction rate overall (14.9% vs 32.1%, P = .001). ConclusionIn a total severity-based stratified prophylaxis regimens and changing iodinated contrast media can be considered in patients with a history of previous hypersensitivity reaction to iodinated contrast media to reduce the risk of breakthrough reactions.

Effectiveness of premedication for hypersensitivity reactions to radiocontrast media in one tertiary hospital

Results A total of 401 patients with a history of hypersensitivity reaction to RCM and were premedicated at re-exposure to RCM. Male was 177 (44.1%) and mean age was 55.83i¾11.92 years. Most common hypersensitivity symptom was urticaria (259, 64.6%), followed by itching (36.7%), rash (21.4%) and angioedema (13.2%). Hypotension was reported in 9 (2.2%) and syncope 5 (1.2%). Systemic steroid was prescribed in 143 patients (35.4%). After premedication, 139 patients (77.7%) had no hypersensitivity reactions to re-exposed RCM. Incidence of symptom after premedication such as uriticaria (12.4%), itching (5.6%), rash (5.1%), angioedema (2.2%) were significantly decreased compared with previous incidence (P 0.05) Conclusion The use of corticosteroid or antihistamine before administration of RCM may diminish the overall prevalence of reactions. Randomized controlled studies of the effects of pretreatment in patients with hypersensitivity reaction to RCM were needed.

Abstract 1188: BRCA 1/2 mutation status is correlated with increased hypersensitivity reactions to carboplatin.

Abstract Background: Carboplatin (Cp) has become the standard first-line chemotherapeutic agent for treatment of ovarian cancer (OvCa), and Cp-related hypersensitivity reaction (HSR) has been observed in 5-20% of patients (pts). The several known potential risk factors for HSR include age, # of prior platinum treatments/cycles, and longer duration of platinum-free interval (PFI). The role of BRCA mutation status has not been studied in the context of Cp HSR, although OvCa pts with BRCAmut+ are treated repeatedly with platinum-based chemotherapies. Methods: The medical records of 74 women who enrolled and initiated at least one cycle of Cp on two phase I clinical trials (NCT01237067 and NCT01445418) with Cp and olaparib (AZD2281) were reviewed. Cp was given with olaparib for a maximum of 8 cycles. Clinical characteristics including BRCA mutation status, history of HSR prior to or on study, and outcomes were analyzed. Results: Primary diagnoses of the 74 pts were ovarian (71), fallopian tube (1), and primary peritoneal (2) carcinomas. Pts had a median age of 56 years (27-80) and ECOG 0-1. 50/74 (68%) pts were BRCA mutation carriers (BRCA 1 [38], BRCA 2 [10], BRCA1/2 [1], BRCApro 68% [1]). All pts had received platinum-based therapy prior to enrollment, and the median # of prior platinum regimens and cycles were 2 (1-6) and 12 (2-42), respectively. The median PFI from the last prior platinum treatment to the first Cp infusion on study was 15.3 months (6-82). 15/74 (20%) pts had a documented history of HSR to Cp prior to enrollment and were pre-medicated with methylprednisolone, H1, and H2 blockers before a slow, incremental Cp infusion. 15/74 (20%) pts developed HSR on study (grade 1 [6], grade 2 [5], and grade 3 [4]), 4 of whom had prior history of Cp HSR. Taken together, the incidence of Cp HSR at any point in the pts’ oncologic history, either prior to or on study, was 35.1% (26/74); prior history of Cp HSR was not predictive of HSR on study. Age, median # of prior platinum cycles, and PFI for the 15 pts with HSR on study vs. those with no HSR history were 52 (27-73) vs. 56 (34-73), 12 (6-20) vs. 10 (2-42), and 21.2 (8-53) vs. 15.3 (6-82), respectively, all of which were not statistically significant. 4/15 (27%) pts with HSR on study (including 2/4 pts with prior history) stopped Cp treatment due to repeated HSR despite pre-medications, while 7/15 (47%) pts stopped therapy for other reasons. The remaining 4/15 (27%) pts successfully completed 8 cycles or are continuing therapy per protocol. BRCA mutation was significantly associated with increased risk of HSR (prior to or on study), 46% (23/50), vs. 11% (2/19) for pts with no BRCA mutation (p = 0.010). Conclusions: Cp re-treatment can be successful for OvCa pts despite prior history of HSR. Prior HSR history did not increase the risk of HSR on study. Being a BRCAmut+ carrier was associated with a statistically significantly greater risk of HSR and may serve as a clinical predictive biomarker of Cp hypersensitivity. Citation Format: Dominic H. Moon, John L. Hays, Christina M. Annunziata, Anne M. Noonan, Lori Minasian, Nicole Houston, Elise C. Kohn, Jung-min Lee. BRCA 1/2 mutation status is correlated with increased hypersensitivity reactions to carboplatin. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1188. doi:10.1158/1538-7445.AM2013-1188

Comprehensive Allergy Consultation Minimizes Risk of Hypersensitivity Reaction During Subsequent Anesthesia

In patients with a history of hypersensitivity reaction (HSR) during anesthesia, data are lacking on success of strategies to minimize risk with subsequent anesthesia. Identification of the specific cause of HSR to anesthesia remains challenging.