Use of Rapid Drug Desensitization in Delayed Hypersensitivity Reactions to Chemotherapy and Monoclonal Antibodies

Background:Rapid drug desensitization (RDD) allows first-line therapies in patients with immediate drug hypersensitivity reactions (DHR) to chemotherapeutic drugs (ChD) and monoclonal antibodies (mAb). Desensitization in delayed drug reactions has traditionally used slow protocols extending up to several weeks; RDD protocols have been scarcely reported.Patients and Method:We retrospectively analyzed the patients referred to the Allergy Department, who had experienced a delayed DHR (> 6 h) related to a ChD or mAb and underwent an RDD protocol. The rate of successful administration of the offending drug and the presence of adverse reactions were evaluated.Results:A total of 93 RDDs were performed in 11 patients (including 6 men and 5 women, with a median age of 61 years). The primary DHR were maculopapular exanthema (MPE) (8), generalized delayed urticaria (1), MPE with pustulosis and facial edema (1), and facial edema with desquamative eczema (1). The meantime for the onset of symptoms was 3 days (range 1–16 days). RDD was performed using a protocol involving 8–13 steps, with temozolomide (25), bendamustine (4), rituximab (9), infliximab (24), gemcitabine (23), and docetaxel (8), within 4.6–6.5 h. Sixteen breakthrough reactions were reported during the RDD (17.2 %) in 5 patients; all were mild reactions including 11 delayed and 5 immediate reactions. All patients completed their treatment.Conclusions:RDD is a potentially safe and effective procedure in patients suffering from delayed reactions to ChD and mAb. It allows them to receive full treatment in a short period, thereby reducing time and hospital visits.

Biocompatibility and Comfort during Extended Wear of Mel4 Peptide-Coated Antimicrobial Contact Lenses

(1) Purpose: This study aimed to investigate the effects of Mel4 antimicrobial contact lenses (MACL) on the ocular surface and comfort during extended wear. (2) Methods: A prospective, randomised, double-masked, contralateral clinical trial was conducted with 176 subjects to evaluate the biocompatibility of contralateral wear of MACL. The wearing modality was 14-day extended lens wear for three months. The participants were assessed at lens dispensing, after one night, two weeks, one month and three months of extended wear and one month after study completion. (3) Results: There were no significant differences (p > 0.05) in ocular redness or palpebral roughness between Mel4 and control eyes at any of the study visits. There was no significant difference (p > 0.05) in corneal staining between Mel4 and control eyes. There were no significant differences in front surface wettability or deposits or back surface debris (p > 0.05). No statistically significant differences (p > 0.05) were found in comfort, dryness, CLDEQ-8 scores lens or edge awareness. There was no evidence for delayed reactions on the ocular surface after cessation of lens wear. (4) Conclusion: The novel MACLs showed similar comfort to control lenses and were biocompatible during extended wear. Thus, these lenses were compatible with the ocular surface.

Delayed allergic skin reactions to vaccines

Background: Recent advances in vaccination against the severe acute respiratory syndrome coronavirus 2 pandemic have brought allergists and dermatologists to the forefront because both immediate and delayed hypersensitivity reactions have been reported. Objective: This literature review focused on delayed reactions to vaccines, including possible causative agents and practical information on how to diagnose, evaluate with patch testing, and manage subsequent dose administration. Methods: Currently published reviews and case reports in PubMed, along with data on vaccines from the Centers for Disease Control and Prevention web site. Relevant case reports and reviews that focused on delayed reactions to vaccines were selected. Results: Most delayed hypersensitivity reactions to vaccines include cutaneous manifestations, which vary from local persistent pruritic nodules to systemic rashes. The onset is usually within a few days but can be delayed by weeks. Multiple excipients have been identified that have been implicated in delayed vaccine reactions, including thimerosal, formaldehyde, aluminum, antibiotics, and gelatin. Treatment with antihistamines, topical corticosteroids, or systemic corticosteroids alleviates symptoms in most patients. Such reactions are generally not contraindications to future vaccination. However, for more-severe reactions, patch testing for causative agents can be used to aid in diagnosis and approach further vaccination. Conclusion: Delayed-type hypersensitivity reactions to vaccines are not uncommon. If needed, patch testing can be used to confirm agents, including antibiotics, formaldehyde, thimerosal, and aluminum. In most cases, delayed cutaneous reactions are not contraindications to further vaccine administration.

1093. Bypassing Penicillin Skin Testing in favor of Direct Oral Challenge: A Pharmacy-driven Inpatient Program

Background Patient interview, penicillin skin testing (PST) and/or an oral challenge can be used to evaluate penicillin allergies. Programs favor PST prior to oral challenge, but there is interest in bypassing PST and directly oral challenging for logistical and financial reasons. Data on the safety and efficacy of a direct challenge in the inpatient setting when the index reaction is moderate to severe (e.g. swelling of throat, angioedema, anaphylaxis) is lacking. Methods Adult patients (≥18 years) admitted with a penicillin allergy were evaluated for eligibility between September 2019 and June 2021. Pregnant patients were excluded, while critically ill patients and those on anti-histamine medications were evaluated if clinical need was high. Institutional protocols allowing for patients to be challenged without PST if reaction was more than 10 years ago were used. Data collected included the number of patients challenged and delabeled, number of patients who had moderate to severe index reactions, number of patients who were relabeled without cause, and number of patients who declined further testing. Results Two hundred twenty-five patients were evaluated; 11 patients declined testing. Two hundred four patients were delabeled (95%) among those fully evaluated. One hundred twelve patients were delabeled by interview and chart review alone (52%), 99 by oral challenge (46%), and 2 by PST and oral challenge (1%). Twenty-nine patients with moderate to severe reactions were challenged and 27 were delabeled. Ten patients could not be delabeled due to mild or delayed reactions to challenge or subsequent treatment, including 2 patients with severe index reactions who had mild challenge reactions and required no rescue medications. No patients required epinephrine during challenge. Five patients were relabeled and then delabeled again as no new reaction had occurred. Conclusion Penicillin allergies can be removed with a pharmacy-driven algorithm that prioritizes direct challenges when appropriate even when the index reaction was moderate to severe. Risks of a reaction are low, and reactions tend to be mild. Given well-documented benefits of delabeling patients for the patient and the institution, more hospitals should consider starting such services. Disclosures All Authors: No reported disclosures

‘Full cause of weeping’: Affective Failure in The Queen (2006) and The Crown (2019)

This article reads The Crown, Series Three, Episode Three, ‘Aberfan’, as an adaptation of The Queen, both of which were written by Peter Morgan. Each focuses on a crisis in public relations emerging from Elizabeth II’s delayed reaction to a tragedy: the mining disaster in The Crown and the death of Princess Diana in The Queen. Both are double portraits, in which the monarch’s affective failure is contrasted with the more humane response of the prime minister, Harold Wilson and Tony Blair respectively. And both texts explore the tension between private grief and public performance. By reading these texts in dialogue, their relevance to their contemporary contexts is magnified. The Queen uses Elizabeth II’s nadir in public relations to comment on Blair’s fall from grace as a result of the Iraq War, while ‘Aberfan’, by emphasising the avoidable nature of the disaster, comments on the Grenfell Tower fire of 2017. While neither text shrinks from criticising the monarch for her breakdown in empathy, the resonances between Aberfan and Grenfell allow the Queen’s immediate and humane response in 2017 to redeem her delayed reactions in the past. This demonstrates the capacity of fictional texts to intervene in the popular perception of their subjects.

Next-Generation Sequencing and Genotype Association Studies Reveal the Association of HLA-DRB3*02:02 With Delayed Hypersensitivity to Penicillins

Background: Nonimmediate (delayed) allergic reactions to penicillins are common and some of them can be life-threatening. The genetic factors influencing these reactions are unknown/poorly known/poorly understood. We assessed the genetic predictors of a delayed penicillin allergy that cover the HLA loci. Methods: Using next-generation sequencing (NGS), we genotyped the MHC region in 24 patients with delayed hypersensitivity compared with 20 patients with documented immediate hypersensitivity to penicillins recruited in Italy. Subsequently, we analyzed in silico Illumina Immunochip genotyping data that covered the HLA loci in 98 Spanish patients with delayed hypersensitivity and 315 with immediate hypersensitivity compared to 1,308 controls. Results: The two alleles DRB3*02:02:01:02 and DRB3*02:02:01:01 were reported in twenty cases with delayed reactions (83%) and ten cases with immediate reactions (50%), but not in the Allele Frequency Net Database. Bearing at least one of the two alleles increased the risk of delayed reactions compared to immediate reactions, with an OR of 8.88 (95% CI, 3.37–23.32; P <0.0001). The haplotype (ACAA) from rs9268835, rs6923504, rs6903608, and rs9268838 genetic variants of the HLA-DRB3 genomic region was significantly associated with an increased risk of delayed hypersensitivity to penicillins (OR, 1.7; 95% CI: 1.06–1.92; P=0.001), but not immediate hypersensitivity. Conclusion: We showed that the HLA-DRB3 locus is strongly associated with an increased risk of delayed penicillin hypersensitivity, at least in Southwestern Europe. The determination of HLA-DRB3*02:02 alleles in the risk management of severe delayed hypersensitivity to penicillins should be evaluated further in larger population samples of different origins.

Feline blood donation adverse reactions: classification and description of acute and delayed reactions in a donor population

Objectives This article aims to analyse the safety of feline blood donation by describing the frequency and nature of any adverse reactions and their causes, as well as propose measures to decrease the incidence of adverse reactions. Methods In this prospective study, any blood donor adverse reactions detected by the clinical staff during and immediately after donation were recorded. The owners of the cats were also surveyed by a veterinary practitioner or veterinary nurse 5 days after donation, using a predefined questionnaire to assess for any clinical or behavioural changes. Data were collected between January 2019 and March 2020 from blood donors enrolled in an animal blood bank programme. Results Of 3690 blood donations from 1792 feline donors assessed, post-donation reactions were reported in 1.14% (n = 42): 0.22% (n = 8) were acute reactions, which included weakness, pallor, tachypnoea and open-mouth breathing; and 0.92% (n = 34) were delayed post-donation reactions, with 0.16% involving cutaneous (haematomas and skin rashes, n = 6), 0.68% involving behavioural (n = 25) and 0.08% involving digestive (emesis and inappetence, n = 3) signs. Conclusions and relevance The low incidence of post-donation reactions in this study is encouraging, suggesting that a well-established protocol and competent staff can help to ensure a high level of safety in a feline donor programme and, in turn, increase the confidence of cat owners.

β-lactam exposure outcome among patients with a documented allergy to penicillins post-implementation of a new electronic medical record system and alerting rules

Background: Recent studies suggest that type I hypersensitivity cross-reactivity between β-lactam antibiotics is due to side chain similarity and not the common β-lactam ring. As a result, the prescriber-alerting rules of an electronic medical record (EMR) system were adjusted to only flag prescribers when prescribing penicillins or β-lactams with similar side chains (viz, cephalexin, cefadroxil, and cefoxitin) to patients with a documented allergy to penicillins. This study was conducted to assess and confirm the safety of the adjusted alerting rules; the primary outcome was the prevalence of anaphylaxis on β-lactam re-exposure. Methods: Retrospective chart review was conducted for patients who, under the reformed alerting rules, received a β-lactam antibiotic post-documentation of an allergy to penicillins in their EMR from April 2018 to July 2019 at a 268-bed community hospital. Given the volume of eligible patients, a 25% sample was randomly selected for review from initiation of the β-lactam antibiotic up to 30 days post-exposure to determine the prevalence of anaphylaxis. Results: Of the 325 charts reviewed, 300 (92.3%) received a β-lactam antibiotic with a different side chain than penicillins (not alerted on prescribing). Chart review of these 300 patients confirmed no reports of anaphylaxis secondary to β-lactam exposure (0%), and two patients developed non-anaphylactic delayed reactions (rash). Conclusions: There were no reports of immediate life-threatening anaphylaxis under the reformed alerting rules, despite 25 (7.7%) patients receiving an alerted drug, such as piperacillin–tazobactam. The reformed alerting rules better reflect current literature and reduce the risk of prescriber-alerting fatigue without compromising patient safety. The occurrence of delayed reactions reinforced the need to monitor for these reactions on β-lactam antibiotic prescribing.

Safety of subcutaneous daratumumab in the treatment of plasma-cell disorders: A single-center experience.

e20007 Background: Daratumumab (Dara) is a CD38-directed monoclonal antibody approved for the treatment of patients with multiple myeloma (MM) and light-chain amyloidosis (AL). Infusion-related reactions (IRRs) have been reported in 28-56% of individuals receiving the conventional intravenous (IV) formulation, necessitating slow infusions and frequent use of rescue medications to mitigate complications. Recently subcutaneous (SC) Dara received approval in MM, and randomized data suggests a lower rate of IRRs compared to IV Dara. Guidelines regarding post-injection monitoring with SC Dara are not well established. This retrospective study aims to evaluate the safety of SC Dara in patients with MM and AL, and to suggest guidelines for monitoring following SC Dara administration. Methods: This single-center retrospective study included patients treated with MM or AL receiving SC Dara between June 2020 and December 2020. The primary outcome of the study was incidence of IRRs. Secondary outcomes include timing and severity of IRRs based on CTCAE version 4.0. Results: A total of 82 patients received SC Dara during the study period. Of these 82, forty-nine (60%) had previously received Dara (Dara-exposed), and 33 patients (40%) were Dara-naïve. Eight of the 82 patients (9.8%) experienced an IRR. All were grade 1 (n=5, 63%) or grade 2 (n=3, 38%) in severity. Seven patients in the Dara-naïve group experienced an IRR (21%), and one patient in the Dara-exposed group (2%) experienced injection-site erythema with the second SC dose after transitioning from IV. Three patients experienced reactions immediately after SC Dara administration, and four patients experienced delayed reactions >4 hours after SC Dara administration (median 11.9 hours; range 5-24). Among those with delayed reactions, three experienced reactions after being discharged from the treatment area but symptoms resolved without any intervention. Conclusions: In this single-center study of patients receiving SC Dara, IRRs occurred in about 10% of patients, and were more likely with a patient’s first dose of SC Dara. All reactions were mild to moderate in severity and could be managed in the outpatient setting. We suggest that Dara-naïve patients receiving their 1st SC Dara dose be monitored for one hour after SC Dara administration. Monitoring does not appear necessary for patients transitioning from IV to SC Dara or receiving subsequent doses of SC Dara. [Table: see text]

Intradermal Testing Identifies 1 in 4 Patients with Nonimmediate Penicillin Allergy

<b><i>Background:</i></b> Intradermal testing with delayed reading (IDTdr), used routinely in many centers, may identify delayed reactions to penicillins. However, few studies have compared the results of IDTdr with drug provocation test (DPT). The aim of this study was to examine the proportion of provocation-positive patients testing positive on IDTdr. <b><i>Methods:</i></b> Fifty-seven patients with a positive DPT occurring &#x3e;2 h after intake of penicillin V, dicloxacillin, pivampicillin, or amoxicillin had an IDTdr with penicillin G, amoxicillin, ampicillin, and dicloxacillin. A control group included 18 patients with negative DPTs with the suspected penicillin. <b><i>Results:</i></b> In total 25% (<i>n</i> = 14) of provocation-positive patients tested positive on IDTdr. Among patients with positive IDTdr, 9/14 (64%) versus 11/43 (26%) in the IDTdr negative group (<i>p</i> &#x3c; 0.05) had required oral steroids to treat skin reactions following DPT. No other differences between IDTdr positive and negative groups were found. No controls had a positive IDTdr. <b><i>Conclusion:</i></b> Investigating with IDTdr would have identified 25% of patients with a DPT-verified allergy with delayed reactions. It is difficult to target subgroups who will test positive on IDTdr. There were more patients who tested positive on IDT who had received oral steroids after DPT, and this may be an indication that skin reaction severity plays a role in skin testing diagnostics. Further potential predictors for positivity of IDTdr, such as duration of skin symptoms, should be assessed in large studies in order to optimize the investigations of nonimmediate drug allergic reactions.