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.

Unusual Reactions to Hymenoptera Stings: Current Knowledge and Unmet Needs in the Pediatric Population

Hymenoptera stings are generally well-tolerated and usually cause limited local reactions, characterized by self-resolving erythema and edema associated with pain. However, Hymenoptera stings can induce immediate and delayed hypersensitivity reactions. In addition to these manifestations, unusual reactions to Hymenoptera stings have been reported. The latter are defined as unusual because of their atypical characteristics. They may differ from classical hypersensitivity reactions due to the stings' particular localization and the unusual involvement of one or more specific organs. Although unusual reactions to Hymenoptera stings are infrequent, it is essential for clinicians to know the possible related clinical manifestations. Here, we review the available literature and propose a diagnostic and management algorithm. At present, there are no defined guidelines for most of the unusual reactions to Hymenoptera stings, which should be managed in a tailored way according to the specifical clinical manifestations presented by the patients. Further studies are needed to better define these conditions and the underlying pathogenetic mechanisms to improve the diagnostic and therapeutic approach.

Severe delayed hypersensitivity reactions to IL-1 and IL-6 inhibitors link to common HLA-DRB1*15 alleles

ObjectivesDrug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, delayed hypersensitivity reaction (DHR). We observed DRESS to inhibitors of interleukin 1 (IL-1) or IL-6 in a small group of patients with Still’s disease with atypical lung disease. We sought to characterise features of patients with Still’s disease with DRESS compared with drug-tolerant Still’s controls. We analysed human leucocyte antigen (HLA) alleles for association to inhibitor-related DHR, including in a small Kawasaki disease (KD) cohort.MethodsIn a case/control study, we collected a multicentre series of patients with Still’s disease with features of inhibitor-related DRESS (n=66) and drug-tolerant Still’s controls (n=65). We retrospectively analysed clinical data from all Still’s subjects and typed 94/131 for HLA. European Still’s-DRESS cases were ancestry matched to International Childhood Arthritis Genetics Consortium paediatric Still’s cases (n=550) and compared for HLA allele frequencies. HLA association also was analysed using Still’s-DRESS cases (n=64) compared with drug-tolerant Still’s controls (n=30). KD subjects (n=19) were similarly studied.ResultsStill’s-DRESS features included eosinophilia (89%), AST-ALT elevation (75%) and non-evanescent rash (95%; 88% involving face). Macrophage activation syndrome during treatment was frequent in Still’s-DRESS (64%) versus drug-tolerant Still’s (3%; p=1.2×10−14). We found striking enrichment for HLA-DRB1*15 haplotypes in Still’s-DRESS cases versus INCHARGE Still’s controls (p=7.5×10-13) and versus self-identified, ancestry-matched Still’s controls (p=6.3×10−10). In the KD cohort, DRB1*15:01 was present only in those with suspected anakinra reactions.ConclusionsDRESS-type reactions occur among patients treated with IL-1/IL-6 inhibitors and strongly associate with common HLA-DRB1*15 haplotypes. Consideration of preprescription HLA typing and vigilance for serious reactions to these drugs are warranted.

143. Use of First-Generation Cephalosporins in Patients with Serious Penicillin Allergies

Background Penicillin allergies have a negative impact on patient outcomes due to utilization of second-line agents. Newer data suggests cephalosporins are well tolerated in penicillin allergies; however, none have solely evaluated anaphylactic penicillin allergies with first-generation cephalosporins. The purpose of this study was to evaluate the risk of any allergic reaction to first-generation cephalosporins compared to aztreonam in patients reporting anaphylaxis to an agent in the penicillin class. Methods This was a retrospective cohort study with patients who reported “anaphylaxis” to a penicillin agent and received cefazolin, cephalexin, or aztreonam. The final analysis included 220 patients: aztreonam (n=81), cefazolin (n=81), and cephalexin (n=58) (Figure 1). IgE-mediated reactions (within six hours of antibiotic administration) were defined as any one of the following: anaphylaxis, angioedema, urticarial rash, hypotension, immediate airway compromise, or receipt of epinephrine, hydrocortisone, or diphenhydramine. Non-IgE mediated reactions (within thirty days of antibiotic administration) included delayed hypersensitivity reactions and other dermatologic reactions. Figure 1: Patient Enrollment Patients admitted between January 1, 2013 to September 1, 2020 with a reported allergy of “anaphylaxis” to an agent in the penicillin class who received at least one dose of cefazolin, cephalexin, or aztreonam were screened for inclusion. Patients were excluded if the allergy was deleted from the electronic health record prior to antibiotic administration. All first-generation cephalosporin patients were included. Aztreonam patients were included in chronological order and limited to the number of included cefazolin patients. Results There were less allergic reactions in the first-generation cephalosporin group compared to the aztreonam group, but this was not statistically significant (7% vs. 14%, p=0.077). There were fewer IgE-mediated reactions in the cephalosporin group (6% vs. 14%, p=0.046). No difference in allergic reactions was observed when comparing those who received a single antibiotic dose versus multiple doses within the cephalosporin and aztreonam groups, respectively (3% vs. 11%, p=0.082, 20% vs. 12%, p=0.451). Because cephalexin has a similar R1 side chain to aminopenicillins, five patients with an aminopenicillin allergy who received cephalexin were evaluated separately; none had an allergic reaction (Table 1, Table 2, Figure 2). Table 1: Baseline Characteristics The median age was higher in the aztreonam group, and the majority of patients were female and Caucasian. There were significantly more pregnant females in the cephalosporin group, and the majority of patients reported a natural penicillin allergy. Table 2: Outcomes There were less allergic reactions (IgE or non-IgE mediated) in the first-generation cephalosporin group compared to the aztreonam group, but this was not statistically significant. Also, there were fewer IgE-mediated reactions in the cephalosporin group. There was no difference in allergic reactions in patients with two or more reported drug allergies compared to less than two drug allergies. No difference in allergic reactions was observed when comparing those who received a single antibiotic dose versus multiple doses within the cephalosporin and aztreonam groups. Of the five patients who received cephalexin and reported an aminopenicillin anaphylactic allergy, none had an allergic reaction. Additionally, there were not any patients readmitted within 30 days for delayed hypersensitivity reactions and no antibiotics were discontinued due to other documented adverse reactions. Figure 2: Occurrence of Allergic Reactions Of the patients who had allergic reactions in the cephalosporin and aztreonam groups, these included immediate airway compromise, hypotension with one patient in the aztreonam group receiving vasopressors within the pre-defined time frame, receipt of the non-standing rescue medication of diphenhydramine, and drug rash. Conclusion There was no difference in the incidence of allergic reactions between the aztreonam and first-generation cephalosporin group, and fewer serious allergic reactions occurred in the cephalosporin group. This study suggests that cefazolin and cephalexin can safely be used in patients who report anaphylaxis to an agent in the penicillin class. Disclosures Janessa Smith, PharmD, Merck & Co. (Employee)