Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome usually presents two to six weeks after treatment with a drug implicated in this disorder. However, in some cases, it can present more than eight weeks after the initiation of an implicated medication. This is a type 4 drug hypersensitivity reaction in which any internal organ may be involved. While the liver is commonly involved, cardiac involvement is not unheard of. Comorbidities and multiorgan involvement may obscure the diagnosis, and Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) criteria are a useful diagnostic aid. It is best treated by withdrawing the offending agent and administering systemic steroids. Oxidative stress is high in DRESS syndrome. Hepatoprotection is a priority in all patients and yields a better prognosis.

UNASSIGNED: Data on the prevalence of allergic diseases in children with proven drug allergies are limited. We aim to evaluate the frequency of allergic comorbidity in children with proven common drug allergies.
UNASSIGNED: Children with drug hypersensitivity confirmed by diagnostic allergy tests at our center between January 2010 and December 2020 were screened retrospectively. Patients with the most common drug allergies (due to antibiotics, nonsteroidal antiinflammatory drugs [NSAIDs], and antiepileptic drugs) were selected for analysis. Age, sex, the culprit drug, initial reaction characteristics, diagnostic test results, and the study physician who diagnosed concomitant allergic diseases were noted.
UNASSIGNED: A total of 168 patients (boys, 51.2%) with a median age of 12 years (IQR = 8-16.3) were included in the study. The culprit drug was an antibiotic in 63% (n = 106), NSAID in 25% (n = 42) and anticonvulsant in 11.9 % (n = 20) of the patients. Drug hypersensitivity reactions were immediate in 74.4 % (n = 125) and delayed in 25.6 % (n = 43) of the patients. Seventy-five patients (44.6 %) had at least one allergic disease, most commonly rhinitis (27.3 %, n = 46) or asthma (25 %, n = 42). Fifty-five patients underwent skin prick tests with aeroallergens, producing a positive result in 60% (n = 31). The prevalence of allergic disease was not differing according to the culprit drug. The frequency of developing at least one concomitant allergic disease was 47.2% (n = 50/106) for antibiotic hypersensitivity, 52.4% (n = 22/42) for NSAID hypersensitivity, and 15% (n = 3/20) for anticonvulsant hypersensitivity (p < 0.00).Immediate drug hypersensitivity reactions were more frequent in children who had allergic diseases (80 % vs. 64.5 %; p = 0.027).
UNASSIGNED: Nearly half (44.6%) of the children with proven drug hypersensitivity had concomitant allergic diseases and immediate reactions were more common in this group. Children evaluated for drug hypersensitivity should be assessed for other allergic diseases.

Human granulocyte colony-stimulating factor (G-CSF) is a granulopoietic growth factor used in the treatment of neutropenia following chemotherapy, myeloablative treatment, or healthy donors preparing for allogeneic transplantation. Few hypersensitivity reactions (HRs) have been reported, and its true prevalence is unknown. We aimed to systematically characterize G-CSF-induced HRs while including a comprehensive list of adverse reactions. We reviewed articles published before January 2024 by searching in the PubMed, Embase, Cochrane Library, and Web of Science databases using a combination of the keywords listed, selected the ones needed, and extracted relevant data. The search resulted in 68 entries, 17 relevant to our study and 7 others found from manually searching bibliographic sources. A total of 40 cases of G-CSF-induced HR were described and classified as immediate (29) or delayed (11). Immediate ones were mostly caused by filgrastim (13 minimum), with at least 9 being grade 5 on the WAO anaphylaxis scale. Delayed reactions were mostly maculopapular exanthemas and allowed for the continuation of G-CSF. Reactions after first exposure frequently appeared and were present in at least 11 of the 40 cases. Only five desensitization protocols have been found concerning the topic at hand in the analyzed data. We believe this study brings to light the research interest in this topic that could benefit from further exploration, and propose regular updating to include the most recently published evidence.

Drug hypersensitivity reactions (DHRs) manifested as vasculitis are rare. Antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), sulphonamides, diuretics, immunosupressants and anticonvulsants are the most common culprits for drug-induced leukocytoclastic vasculitis (LCV) but there is scarce information about barbiturates. We present a case of 53-year-old female with severe vasculitis after phenobarbital- and NSAIDs-containing medications use. The preliminary diagnosis of drug-induced vasculitis was made based on anamnestic and clinical data. Further examinations confirmed the diagnosis of LCV and excluded other more common causes of vasculitis. The causative significance of used medications was assessed by long-term observation of the patient after the reaction, including the drug challenge series and Naranjo\'s Adverse Drug Reaction Probability Scale. It was concluded that phenobarbital is the most probable culprit drug. The patient\'s data were included in the Armenian Registry of Patients with Severe DHRs. Since then, the patient has avoided only barbiturate-containing drugs and no reactions were noted. Thus, the case indicates that even with limited diagnostic capabilities, the final diagnosis of rare drug-induced LCV and even rarer culprit drug can be established by comparing the available data. Awareness about phenobarbital and proper recording of the case are important in the management and prevention of DHRs manifested as vasculitis.

UNASSIGNED: There are limited data regarding the characteristics and management of drug hypersensitivity reactions (DHR) in hospitalized children. This study aims to determine the prevalence, clinical features, and management of DHRs in pediatric inpatients.
UNASSIGNED: Children who had pediatric allergy consultation for suspected DHR during hospitalization in Ankara Bilkent City Hospital between August 1, 2020, and July 30, 2021, were included. Patient and reaction characteristics, culprit drugs, and management strategies were recorded. When possible, diagnostic tests (skin or provocation tests) were performed after discharge.
UNASSIGNED: Among the 14,090 hospitalized children, 165 (72% male, median age: 106 months) underwent consultation for 192 suspected DHRs with 246 drugs. Cutaneous eruptions were the most common (94.3%). There was anaphylaxis in 40 patients and severe cutaneous adverse drug reaction in 4 patients (drug rash with eosinophilia and systemic symptoms in 3, acute generalized exanthematous pustulosis in 1). Antimicrobials were the leading cause (78.4%, n = 193/246). In 48 reactions, 60 (24%) culprit drugs could be readministered with close follow-up or desensitization (n = 12). In total, 186 suspected drugs were discontinued, and 115 were replaced with alternative drugs. After discharge, 38 provocation tests (2 positives) and 36 skin tests (1 positive prick test, 1 positive intradermal test, and 1 positive patch test) were performed.
UNASSIGNED: The incidence of suspected DHR among pediatric inpatients was approximately 1.1%. Skin symptoms were the most common manifestation. Twenty-four percent of suspected drugs could be continued during hospitalization. Patients with DHR during hospitalization should be evaluated with a drug allergy work-up unless there are contraindications to testing.

OBJECTIVE: To present the characteristics of drug hypersensitivity reactions (DHRs) among taxane recipients with non-small cell lung carcinoma (NSCLC), and to describe the results of rapid drug desensitization (RDD).
METHODS: A retrospective cross-sectional study included 45 patients who were treated with taxane for NSCLC and were found to be hypersensitive to taxane. All patients were administered the standard 3-bag, 12-step RDD protocol following the development of DHR. RDD success was evaluated separately for each cycle, and successful RDD was defined as the completion of the cycle with application of 12 steps of the desensitization protocol and the absence of early and/or late reactions afterwards.
RESULTS: Among 45 patients hypersensitive to taxane 43 (95.6%) successfully received taxane cycles with desensitization. Failed RDD occurred in only 2 (4.4%) patients. The total number of desensitization cycles was 183, of which 181 (98.9%) were successful. The mean age of patients with successful desensitization was 59.42 ± 10.48 years and 37 (86.0%) of them were male.
CONCLUSIONS: RDD is a reliable procedure that enables effective administration and completion of first-line taxane treatments in taxane-sensitive patients.

Across all settings, women self-report more drug allergies than do men. Although there is epidemiologic evidence of increased drug allergy labeling in postpubertal females, the evidence base for female sex as a risk factor for true immune-mediated drug hypersensitivity reactions (DHRs), particularly in fatal drug-induced anaphylaxis, is low. A focus on the known immunologic mechanisms described in immediate and delayed DHR, layered on known hormonal and genetic sex differences that drive other immune-mediated diseases, could be the key to understanding biological sex variations in DHR. Particular conditions that highlight the impact of drug allergy in women include (1) pregnancy, in which a drug allergy label is associated with increased maternal and fetal complications; (2) multiple drug intolerance syndrome, associated with anxiety and depression; and (3) female-predominant autoimmune medical conditions in the context of mislabeling of the drug allergy or increased underlying risk. In this review, we describe the importance of drug allergy in the female population, mainly focusing on the epidemiology and risk, the mechanisms, and the associated conditions and psychosocial factors. By performing a detailed analysis of the current literature, we provide focused conclusions and identify existing knowledge gaps that should be prioritized for future research.

Drug hypersensitivity reactions (DHRs) are adverse drug reactions (ADRs) that are particularly impactful on health-related quality of life (HRQoL) and mental health. Although the role of HRQoL as an important patient-reported outcome has been recognized in past years, HRQoL and mental health in patients with ADRs are still poorly investigated.
To evaluate the prevalence, severity, and risk factors of HRQoL and mental health in DHRs, with a particular focus on drug-induced anaphylaxis.
We searched the MEDLINE, Scopus, and American Psychological Association PsycArticles databases to identify all studies up to December 31, 2022 that included subjects with at least one episode of DHR and assessments of mental health and/or quality of life. Results were reported as qualitative and quantitative analyses, with meta-analyses after assessment for risk of bias and heterogeneity.
A total of 45 observational studies were included. Overall, a high prevalence of depression (up to 51.4%; odd ratio = 2.94; 95% CI, 1.42-6.10) and anxiety (up to 48%; odd ratio = 3.92; 95% CI, 1.91-8.05) were reported compared with healthy subjects. The HRQoL was significantly affected, especially in the case of drug-induced anaphylaxis (mean score, +5.88; 95% CI, 0.77-10.98).
Despite the scarce and heterogeneous studies on this topic, the review shows that HRQoL and mental health are markedly affected after ADRs. A better assessment of HRQoL and characterization of patients\' mental status may improve the efficacy of therapeutic strategies, which should include psychological support.

Drug hypersensitivity reactions induced by small molecule drugs encompass a broad spectrum of adverse drug reactions with heterogeneous clinical presentations and mechanisms. These reactions are classified into allergic drug hypersensitivity reactions and non-allergic drug hypersensitivity reactions. At present, the hapten theory, pharmacological interaction with immune receptors (p-i) concept, altered peptide repertoire model, and altered T-cell receptor (TCR) repertoire model have been proposed to explain how small molecule drugs or their metabolites induce allergic drug hypersensitivity reactions. Meanwhile, direct activation of mast cells, provoking the complement system, stimulating or inhibiting inflammatory reaction-related enzymes, accumulating bradykinin, and/or triggering vascular hyperpermeability are considered as the main factors causing non-allergic drug hypersensitivity reactions. To date, many investigations have been performed to explore the underlying mechanisms involved in drug hypersensitivity reactions and to search for predictive and preventive methods in both clinical and non-clinical trials. However, validated methods for predicting and diagnosing hypersensitivity reactions to small molecule drugs and deeper insight into the relevant underlying mechanisms are still limited.

BACKGROUND: Severe drug hypersensitivity reactions (DHRs) refer to allergic reactions caused by drugs and usually present with severe skin rashes and internal damage as the main symptoms. Reporting of severe DHRs in hospitals now solely occurs through spontaneous reporting systems (SRSs), which clinicians in charge operate. An automatic identification system scrutinizes clinical notes and reports potential severe DHR cases.
OBJECTIVE: The goal of the research was to develop an automatic identification system for mining severe DHR cases and discover more DHR cases for further study. The proposed method was applied to 9 years of data in pediatrics electronic health records (EHRs) of Beijing Children\'s Hospital.
METHODS: The phenotyping task was approached as a document classification problem. A DHR dataset containing tagged documents for training was prepared. Each document contains all the clinical notes generated during 1 inpatient visit in this data set. Document-level tags correspond to DHR types and a negative category. Strategies were evaluated for long document classification on the openly available National NLP Clinical Challenges 2016 smoking task. Four strategies were evaluated in this work: document truncation, hierarchy representation, efficient self-attention, and key sentence selection. In-domain and open-domain pretrained embeddings were evaluated on the DHR dataset. An automatic grid search was performed to tune statistical classifiers for the best performance over the transformed data. Inference efficiency and memory requirements of the best performing models were analyzed. The most efficient model for mining DHR cases from millions of documents in the EHR system was run.
RESULTS: For long document classification, key sentence selection with guideline keywords achieved the best performance and was 9 times faster than hierarchy representation models for inference. The best model discovered 1155 DHR cases in Beijing Children\'s Hospital EHR system. After double-checking by clinician experts, 357 cases of severe DHRs were finally identified. For the smoking challenge, our model reached the record of state-of-the-art performance (94.1% vs 94.2%).
CONCLUSIONS: The proposed method discovered 357 positive DHR cases from a large archive of EHR records, about 90% of which were missed by SRSs. SRSs reported only 36 cases during the same period. The case analysis also found more suspected drugs associated with severe DHRs in pediatrics.