Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome induced by ceftriaxone with successful treatment — A case report and literature review

Drug reaction with eosinophilia and systemic symptoms is a rare and potentially life threatening condition characterised by hypersensitivity reactions to a drug with prolonged latency, in the form of skin rashes, hyper eosinophilia and systemic features like fever, lymphadenopathy, leucocytosis, internal organ involvement (liver, kidney, lung). Though it can occur in response to many drugs but very few cases has been described in relation to one of the most commonly used antibiotic ceftriaxone. Here we have described a case of DRESS in a patient who has been treated with ceftriaxone outside our hospital for sore throat.

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.

Incidence and Risk Factors of Immediate Hypersensitivity Reactions and Immunisation Stress-related Responses with COVID-19 mRNA Vaccine

Background: With the implementation of mass vaccination campaigns against COVID 19, the safety of vaccine needs to be evaluated. Objective: We aimed to assess the incidence and risk factors for immediate hypersensitivity reactions (IHSR) and immunisation stress related responses (ISRR) with the Moderna COVID 19 vaccine. Methods: This nested case control study included recipients who received the Moderna vaccine at a mass vaccination centre, Japan. Recipients with IHSR and ISRR were designated as cases 1 and 2, respectively. Controls 1 and 2 were selected from recipients without IHSR or ISRR and matched (1:4) with cases 1 and cases 2, respectively. Conditional logistic regression analysis was used to identify risk factors associated with IHSR and ISRR. Results: Of the 614,151 vaccine recipients who received 1,201,688 vaccine doses, 306 recipients (cases 1) and 2,478 recipients (cases 2) showed 318 events of IHSR and 2,558 events of ISRR, respectively. The incidence rates per million doses were estimated as IHSR: 266 cases, ISRR: 2,129 cases, anaphylaxis: 2 cases, and vasovagal syncope: 72 cases. Risk factors associated with IHSR included female, asthma, atopic dermatitis, thyroid diseases, and history of allergy; for ISRR, they were younger age, female, asthma, thyroid diseases, mental disorders, and a history of allergy and vasovagal reflex. Conclusion: In the mass vaccination settings, the Moderna vaccine can be used safely owing to the low incidence rates of IHSR and anaphylaxis. However, providers should beware of the occurrence of ISRR. Risk factor identification may contribute to the stratification of high risk recipients for IHSR and ISRR.

Converter Phenotype: A New Profile That Is Not Exclusive to Taxanes

Introduction: Phenotype I hypersensitivity reactions are the most commonly reported drug reactions; however, precision medicine has made it possible to characterize new phenotypes. A recent communication proposed the existence of a “converter phenotype,” which would affect patients who present non-immediate hypersensitivity reactions and in subsequent exposures develop immediate hypersensitivity reactions. This study aimed to describe the clinical characteristics of converter phenotype reactions and their evolution during desensitization to chemotherapeutic drugs and monoclonal antibodies.Methods: We retrospectively reviewed our database of patients undergoing desensitization to chemotherapy or biological agents and selected those with a converter phenotype. Demographic and clinical characteristics of the patients, the results of skin tests, tryptase and IL-6 levels, and desensitization outcomes were assessed.Results: Of 116 patients evaluated, 12 (10.3%) were identified as having a converter phenotype. The median interval between drug exposure and reaction was 90.6 h (range 8-288 h). After the conversion, phenotype I was the most frequent (58.3%), followed by cytokine release reactions (33.3%). Fifty-one desensitizations were undertaken and all treatments completed, with 10 (19.6%) breakthrough reactions. No new changes in the phenotype were detected.Conclusions: The symptoms of non-immediate drug hypersensitivity reactions may indicate the need for an early allergological evaluation to assess the risk of future immediate drug reactions. Clinical characteristics, skin test results, and biomarkers can help predict responses to rapid drug desensitization, guiding clinicians on how to optimize therapy delivery while maintaining patient safety.

Incidence of Oxaliplatin Hypersensitivity Reaction Among Colorectal Cancer Patients: a 5-Year Retrospective Study

PurposeWe explored the clinical data of colorectal cancer patients treated with oxaliplatin-based regimen to determine the incidence, severity, and risk factors of oxaliplatin-related hypersensitivity reaction (HSR). MethodThis retrospective study investigated 245 colorectal cancer patients (1,690 treatment cycles) receiving care at King Chulalongkorn Memorial Hospital, Thai Red Cross society between January 1, 2015, and December 31, 2019. The patients’ demographic data, laboratory data, and clinical features suggesting hypersensitivity reactions to oxaliplatin were reviewed. The Fisher’s Exact test and unpaired t-test were used to determine the differences among patients with and without oxaliplatin HSR. The potential risk factors for oxaliplatin HSR were analyzed for statistical significance by logistic regression.Results A total of 245 colorectal cancer patients (1,690 treatment cycles) were included in this study. The incidence of oxaliplatin HSR was 37.96%, according to the NCI-CTCAE v.5, (grade 1, grade 2, and higher grades were 27.35% (67 patients), 6.53% (16 patients), and 4.08% (10 patients), respectively). The proportion of male patients and patients with history of prior exposure to platinum-based chemotherapy were statistically higher in the HSR group. The eosinophil count and serum creatinine level were also significantly greater in the HSR group. On the contrary, the total lymphocyte count and serum albumin level were significantly lower in the HSR group. The multivariate logistic regression found 5 risk factors with significant difference. Male gender, prior exposure to platinum-based chemotherapy, and elevated eosinophil count were associated with increased risk of oxaliplatin HSR, whereas elevated monocyte count and elevated serum albumin were protective factors for the development of oxaliplatin HSR. ConclusionColorectal cancer patients treated with oxaliplatin-based regimen with male gender, prior exposure to platinum-based chemotherapy, and elevated eosinophil count have a greater risk of oxaliplatin related hypersensitivity reactions.

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.

Allergic reactions to cephalosporin antibiotics in a 15-year-old population

Cephalosporin, along with penicillin, are among the least harmful antibiotics. It is widely prescribed for common infections such as bronchitis, otitis media, pneumonia and cellulitis. A contraindication for this agent is a history of penicillin allergy, due to possible cross-reactions of hypersensitivity to penicillin and cephalosporin. Hypersensitivity reactions can occur in any mode of administration and to almost all antibiotics. Hypersensitivity reactions to cephalosporin are very similar to those of penicillin. The purpose of the study was to determine whether exist reactions to cephalosporin in the study population, and to determine whether exist statistically significant differences in the occurrence of allergic reactions to cephalosporin between boys and girls of the same age and whether exist differences in the occurrence of allergic reactions between subjects in urban and rural areas. The sample consisted of 1605 respondents, the sample was randomly selected and stratified by sex, and all data were processed in the statistical program. The results of the research show that 9.1% of the total population of boys and girls aged 15 from the Tuzla Canton are allergic to some type of antibiotic. The percentage of allergic reactions to cephalosporin is statistically significantly higher in the total population of 15 - year - olds from suburban and urban settlements than among peers in rural areas. Allergic reactions to cephalosporin were not observed in the group of boys from urban and suburban settlements as well as girls from rural settlements. This research also showed that there are statistically significant differences in the occurrence of cephalosporin allergies between urban and rural respondents.

Genotyping for HLA Risk Alleles to Prevent Drug Hypersensitivity Reactions: Impact Analysis

Human Leukocyte Antigen (HLA) variants can be a risk factor for developing potentially fatal drug hypersensitivity reactions. Our aim was to estimate the potential impact of genotyping for the HLA risk alleles incorporated in the Dutch Pharmacogenetics Working Group (DPWG) guidelines in The Netherlands. We estimated the number of hypersensitivity reactions and associated deaths that can be avoided annually by genotyping for these HLA risk alleles. Additionally, the cost-effectiveness was estimated. Nationwide implementation of genotyping HLA risk alleles before initiating drugs with an actionable drug–gene interaction can potentially save the life of seven allopurinol initiators and two flucloxacillin initiators each year in The Netherlands. Besides these deaths, 28 cases of abacavir hypersensitivity, 24 cases of allopurinol induced SCARs, 6 cases of carbamazepine induced DRESS and 22 cases of flucloxacillin induced DILI can be prevented. Genotyping HLA-B*5701 in abacavir initiators has a number needed to genotype of 31 to prevent one case of abacavir hypersensitivity and is cost-saving. Genotyping HLA-B*5801 in allopurinol initiators has a number needed to genotype of 1149 to prevent one case of SCAR but is still cost-effective. Genotyping before initiating antiepileptic drugs or flucloxacillin is not cost-effective. Our results confirm the need for mandatory testing of HLA-B*5701 in abacavir initiators, as indicated in the drug label, and show genotyping of HLA-B*5801 in allopurinol initiators should be considered.