Different phenotypes of Non-Steroidal Anti-Inflammatory drugs hypersensitivity in children and negative predictive value of drug provocation test.

CLINICAL IMPLICATIONS BOX: This is the first study trying to correlate the clinical history of patients' previous NSAIDs in terms of the culprit drug, the frequency of reactions and the clinical manifestations with the risk for being diagnosed with a specific phenotype.

New Approaches for Basophil Activation Tests Employing Dendrimeric Antigen-Silica Nanoparticle Composites.

In vitro cell activation through specific IgE bound to high-affinity receptors on the basophil surface is a widely used strategy for the evaluation of IgE-mediated immediate hypersensitivity reactions to betalactams. Cellular activation requires drug conjugation to a protein to form a large enough structure displaying a certain distance between haptens to allow the cross-linking of two IgE antibodies bound to the basophil's surface, triggering their degranulation. However, no information about the size and composition of these conjugates is available. Routine in vitro diagnosis using the basophil activation test uses free amoxicillin, which is assumed to conjugate to a carrier present in blood. To standardize the methodology, we propose the use of well-controlled and defined nanomaterials functionalized with amoxicilloyl. Silica nanoparticles decorated with PAMAM-dendrimer-amoxicilloyl conjugates (NpDeAXO) of different sizes and amoxicilloyl densities (50-300 µmol amoxicilloyl/gram nanoparticle) have been prepared and chemically characterized. Two methods of synthesis were performed to ensure reproducibility and stability. Their functional effect on basophils was measured using an in-house basophil activation test (BAT) that determines CD63+ or CD203chigh activation markers. It was observed that NpDeAXO nanocomposites are not only able to specifically activate basophils but also do so in a more effective way than free amoxicillin, pointing to a translational potential diagnosis.

Pseudoephedrine-induced Fixed Drug Eruption in a Scuba Diver With Recurrent Palmoplantar Exfoliation.

Objectives: This report presents a case of pseudoephedrine-induced nonpigmented bullous fixed drug eruption (NBFDE) manifesting as recurrent palmoplantar exfoliation in a scuba diver. It emphasizes the importance of considering drug allergies in the differential diagnosis when divers present with peeling hands and soles. Methods: A 38-year-old female scuba diver experiencing recurrent palmoplantar exfoliation underwent a clinical evaluation, patch testing, an interferon-gamma enzyme-linked immunospot (ELISpot) assay, and graded drug challenges with pseudoephedrine and phenylephrine. Results: Patch testing yielded negative results; however, the ELISpot assay indicated a strong immune response to pseudoephedrine. A graded challenge involving pseudoephedrine successfully reproduced the symptoms, confirming a diagnosis of pseudoephedrine-induced NBFDE. Subsequently, a challenge with phenylephrine elicited a milder reaction, suggesting it as a potential alternative medication for the patient. Conclusions: This case highlights NBFDE as a potential cause of skin peeling in scuba divers who are allergic to pseudoephedrine. It emphasizes the importance of considering drug allergies when diagnosing palmoplantar exfoliation in divers and underscores the need for a thorough evaluation of medication use in this group. Alternative medications and management strategies should be considered for divers with a pseudoephedrine allergy to prevent ear barotrauma while minimizing the risk of adverse skin reactions.

Successful case of deferasirox slow desensitization in adults.

INTRODUCTION: When deferasirox is used in iron chelation therapy, maculopapular rash occurs in 10% of patients, but there is no accepted and implemented protocol for the management of these drug reactions in adults. CASE REPORT: A 23-year-old woman diagnosed with thalassemia major is presented. She had taken 1,500 mg oral deferasirox for 1 week. Five hours after the last dose, a pruritic maculopapular rash developed on the body, face, and hands. The rash spread to the whole body within 3 days. The absolute necessity for the patient to take the drug was clarified by the hematology department. The patient's history was evaluated. A delayed-type hypersensitivity reaction due to deferasirox was considered. MANAGEMENT: The slow desensitization protocol described in the literature and applied on a case-by-case basis in pediatric patients was modified to shorten the duration by determining appropriate doses for the current preparation. The desensitization process was started with 1/100,000 of the total dose and the therapeutic dose was reached with a 2- to 2.5-fold increase in dose. No pre-medication was applied. During the procedure, at a low dose of 0.1 mg, local flushing and erythema was observed around the auricle on the face. The reaction did not progress. CONCLUSION: Slow desensitization protocol for oral deferasirox was successfully applied in an adult patient.

Clinical characteristics, treatment and outcome of clindamycin induced acute generalized exanthematous pustulosis.

Acute generalized exanthematous pustulosis (AGEP) is a serious and rare adverse reaction to clindamycin. This study investigated the clinical features of clindamycin-induced AGEP and provided reference for the prevention and treatment of AGEP. Case reports, case series and clinical studies of clindamycin-induced AGEP were collected by retrieving English and Chinese database from inception until May 31, 2024. Of the 35 patients included, 25 (71.4%) were female, and the median age was 57 years (1.6-88 years). The duration of AGEP onset is 2 days (range 0.04,13) after initial administration. The main clinical morphology of AGEP is a non-follicular pustular on an erythematous base, which may be accompanied by fever (54.3%) and pruritus (40.0%). These lesions mainly involved extremities and trunk. The median elevated neutrophil count was 13.3 × 109/L (range 10.3, 31.4). Histologic features of AGEP are characterized by intracorneal, subcorneal, and/or intraepidermal pustules with papillary dermal edema containing neutrophilic, lymphocytic, andeosinophilic infiltrates. Patients gradually recovered after the withdrawal of clindamycin and supportive therapy with a median time of 9 days (range 2, 30). Clinicians should be aware of AGEP as a rare adverse effect of clindamycin. When clindamycin is prescribed, it should be stopped in time when AGEP occurs, and active systemic treatment should be given. AGEP is a self-limiting disease with a good prognosis.

Leveraging implementation science theories to develop and expand the use of a penicillin allergy de-labeling intervention.

BACKGROUND: Penicillin allergy is the most frequently reported drug allergy, yet most patients can tolerate the drug if challenged. Despite this discrepancy, large scale penicillin allergy de-labeling interventions have not been widely implemented in many health care systems. The application of a multi-method implementation science approach can provide key tools to study this evidence to practice gap and provide insight to successfully operationalize penicillin allergy evaluation in real-world clinical settings. METHODS: We followed a four-step process that leverages qualitative analysis to design evidence-based, actionable strategies to develop an intervention. First, we specified the clinician-perceived barriers to penicillin allergy de-labeling (intervention targets). We then mapped intervention targets onto Theoretical Domains Framework (domains and constructs) and found the root causes of behavior. Next, we linked root causes of behavior with intervention functions (BCW). In the final step, we synthesized participants' suggestions for process improvement with implementation strategies aligning with the intervention functions. RESULTS: Evidence-based strategies such as focused education and training in penicillin allergy evaluation can address knowledge and confidence barriers reported by frontline clinicians. Other key strategies involve developing a system of champions, improving communications systems, and restructuring the healthcare team. Implementation mapping can provide a powerful multi-method framework to study, design, and customize intervention strategies. CONCLUSION: Empowering clinicians beyond allergy specialists to conduct penicillin allergy assessments requires designing new workflows and systems and providing additional knowledge to those clinicians.

Impact of a drug allergy education course for non-specialists: Findings from ADAPT-A randomized crossover trial.

BACKGROUND: The consequences of drug allergy remain a global health concern. Drug allergy is often a neglected topic and many non-specialists lack sufficient knowledge or confidence in evaluating or managing this common condition. Evidence-based interventions to better equip non-specialists to tackle drug allergy are needed. The aim of the study is to evaluate the effectiveness of an intensive educational course on drug allergy knowledge and practice of non-specialists. METHODS: A randomized crossover trial (NCT06399601) was conducted among practicing physicians and nurses participating in an intensive drug allergy course-Advances in Drug Allergy & Penicillin Testing (ADAPT). Participants' baseline knowledge and self-reported practices were assessed with standardized questionnaires (scored from 0 to 100, with "satisfactory" defined as ≥60/100). Participants were randomized into two cohorts and attended ADAPT at different time points. Serial responses before and after the course were compared within and between cohorts. RESULTS: Seventy participants (25 physicians, 45 nurses) randomized into two groups completed the course. Baseline drug allergy knowledge (58.0 ± 19.9) and self-reported practice (36.9 ± 24.3) were unsatisfactory among non-specialists, with significantly lower scores from nurses than physicians in both domains (knowledge: 49.0 ± 17.4 vs. 74.0 ± 12.7; practice: 32.1 ± 21.3 vs. 53.3 ± 23.1; all p < 0.001). Following completion of ADAPT, participants demonstrated significant improvements in knowledge (58.0 ± 19.9 vs. 77.7 ± 15.9, p < 0.001) and self-reported practice (36.9 ± 24.3 vs. 71.0 ± 20.2, p < 0.001). All participants (100%) and 99% of participants agreed that the course improved their clinical knowledge and practice, respectively. CONCLUSIONS: ADAPT, an intensive drug allergy educational course was effective in improving drug allergy knowledge and practice for non-specialists. Further longitudinal studies are required to evaluate long-term impact.

A Skin Testing Strategy for Non-IgE-mediated Reactions Associated with Vancomycin.

BACKGROUND: Vancomycin infusion reaction (VIR), reportedly mediated through Mas-Related G Protein-Coupled Receptor-X2 (MRGPRX2), is the primary vancomycin-induced immediate drug reaction (IDR). Clinically, distinguishing the underlying drug-induced IDR mechanisms is crucial for future treatment strategies, including drug restriction, re-administration, and pretreatment considerations. However, the lack of validated diagnostic tests makes this challenging, often leading to unnecessary drug restriction. OBJECTIVE: To determine if intradermal tests (IDTs) and, separately, the basophil activation test (BAT) differentiate VIR from vancomycin-tolerant subjects. METHODS: Cross-sectional study of vancomycin-exposed adults with and without a history of VIR. Demographics, allergy-related comorbidities, history of vancomycin exposures, and VIR characteristics were collected. IDT with vancomycin was performed. IDT dose responses EC50, IDT-related local symptoms, and BAT were compared between groups. RESULTS: 11 VIR and 10 vancomycin-tolerant subjects were enrolled. The most reported VIR symptoms were pruritus (82%), flushing (82%), hives (46%), hives (46%), angioedema (27%), and dyspnea (19%). The IDT dose response mean EC50 was 328 µg/mL (95% CI 296, 367) in the VIR vs. 1,166 µg/mL (95% CI 1029, 1379) in the tolerant group (p<0.0001). All VIR subjects reported IDT-related local pruritus compared to 60% of tolerant subjects (p=0.0185). The %CD63+ basophils were consistently <2%, without significant differences between groups (p < 0.54). CONCLUSIONS: Variations in skin test methodologies could help identify other IDR mechanisms beyond IgE. This skin test protocol holds the potential for identifying VIR, particularly in cases where patients have received multiple drugs while BAT is insufficient. Future studies will validate and delineate its predictive value, assessing the risk of VIR.

Incidence of and risk factors for paediatric perioperative anaphylaxis in the USA.

BACKGROUND: Perioperative anaphylaxis is a serious and often life-threatening immediate hypersensitivity reaction. There are few published data on paediatric perioperative anaphylaxis (pPOA). We evaluated the incidence of and risk factors involved in the occurrence of pPOA within a large US national database. METHODS: Deidentified data from the US Nationwide Inpatient Sample from 2005 to 2014 were used to identify pPOA cases and to conduct a retrospective multivariate analysis of preselected independent variables. RESULTS: Among 3,601,180 surgeries and procedures in children aged 0-18 yr, 297 pPOA cases were identified for an incidence of one in 12,125 surgeries and procedures. Compared with controls, pPOA cases had an increased median length of stay (6 vs 2 days; P<0.001) and median hospital cost ($54 719 vs $5109; P<0.0001). The age groups between 6 and 12 yr (odds ratio [OR] 7.1; 95% confidence interval [CI] 3.9-12.9; P<0.001) and 13 and 17 yr (OR 8.5; 95% CI 4.7-15.2; P<0.001) were associated with increased odds of pPOA. Transplant (OR 46.3; 95% CI 20.8-102.9; P<0.001), cardiac (OR 16.4; 95% CI 7.5-35.9; P<0.001), and vascular (OR 15.2; 95% CI 7.5-30.7; P<0.001) procedures posed the highest risk for pPOA. Chronic pulmonary disease, coagulopathy, and fluid and electrolyte disorders were also associated with pPOA (OR 2.2; 95% CI 1.5-3.3; P<0.001). CONCLUSIONS: The incidence of pPOA was one in 12,125 cases. Risk factors included age, procedure type, and comorbidities.

Type I Kounis Syndrome: Allergic Myocardial Infarction Triggered by Ciprofloxacin.

Kounis syndrome (KS), known as allergic myocardial infarction (MI), is an uncommon but potentially life-threatening disease characterized by acute coronary artery disease (CAD) in the setting of allergic reactions. KS is most frequently triggered by medication, and ciprofloxacin-induced KS-I is rarely reported. Here, we present a case of KS-I triggered by ciprofloxacin in a young female with no prior CAD. A 35-year-old female presented with sudden onset chest pain, diaphoresis, and lightheadedness, accompanied by itching, confusion, and collapse, shortly after taking oral ciprofloxacin. Her electrocardiogram showed inferior wall MI with elevated cardiac troponin levels. Urgent coronary angiography was unremarkable. Her condition improved after sublingual nitroglycerine, methylprednisolone, and intramuscular injection of epinephrine. This case highlights the importance of recognizing drug-induced allergic reactions as a potential cause of acute coronary events, particularly in young patients without traditional risk factors.

Kounis Syndrome: Review of Clinical Cases.

BACKGROUND: Kounis syndrome is defined as a combination of acute coronary syndrome and allergic reactions. OBJECTIVE: In this review, we aim to describe the etiological, clinical, and diagnostic characteristics of Kounis syndrome. METHODS: A literature search using PubMed was conducted for the past 32 years using keywords, resulting in the selection of 761 scientific papers. From these, 217 articles describing 235 clinical cases were selected. Patients under 18 years of age or without a confirmed diagnosis were excluded. RESULTS: Among the 235 patients, type I Kounis syndrome was observed in 49.7%, type II in 27.2%, type III in 5.9%, and a combination of types I and II in 1.0%; in 16.2%, it was not possible to classify the type of Kounis syndrome. The median age was 57 years, and 68.5% of the patients were male. The most common causes were antibiotics (32.3%) and non-steroidal anti-inflammatory drugs (24.3%). The clinical features included chest pain (59.1%), hypotension (74.2%), itching (30.6%), and dyspnea (30.6%). Electrocardiographic monitoring revealed ST-segment elevation in 42.9% and was normal in only 5.5% of patients. Coronary angiography was performed in 80.4% of the patients, revealing unchanged coronary arteries in 50.3% of cases. Сonclusion: Allergic myocardial infarction is a serious complication of drug therapy.

Methotrexate might become the sole treatment option for leukemia following the occurrence of Stevens-Johnson syndrome.

INTRODUCTION: Severe cutaneous adverse reactions (SCARs) arising from drug interactions can carry life-threatening implications and result in lasting effects. SCARs can be triggered by various factors, with trimethoprim/sulfamethoxazole identified as a primary culprit. Anticonvulsants and antineoplastic agents have been noted as secondary triggers. Notably, antineoplastics linked to SCARs include immunomodulatory agents. The higher mortality rates among cancer patients with SCARs underscore the significance of comprehending cancer--specific risk factors. Our objective is to present the case of a boy with acute lymphocytic leukemia (ALL) who developed Stevens-Johnson syndrome (SJS) following MTX treatment. CASE REPORT: We present the case of a three-year-old male patient diagnosed with ALL who developed Stevens-Johnson syndrome (SJS) subsequent to the administration of MTX, following the "BFM 2009" protocol. He had undergone intrathecal MTX administration on six previous occasions. Our patient received IVIG at a dose of 2g/kg along with steroids, resulting in partial clinical improvement after 21 days. An innovative protocol was developed, involving IVIG before MTX infusion and dexamethasone before MTXi, with folinic acid rescue. Intravenous immunoglobulin (IVIG) mitigates SJS/TEN via type IV hypersensitivity down-regulation and apoptosis curbing. CONCLUSION: As far as we know, the prophylactic use of IVIG to counteract SCARs in a pediatric leukemia patient represents uncharted territory. Moreover, research into the immune system dynamics within these patients and the preservation of indispensable treatments should involve allergist-immunologists as part of the multidisciplinary team attending to neoplastic conditions.

Basophil Activation Test Predicts Cetuximab Anaphylaxis Severity in Alpha-Gal IgE-Positive Patients.

Upon first exposure to cetuximab, hypersensitivity reactions can occur. We aimed to assess the utility of the basophil activation test (BAT) to alpha-gal and cetuximab for predicting severe reactions. We prospectively recruited 38 patients and evaluated sIgE to alpha-gal in all patients before the first application of cetuximab. In all alpha-gal-sensitized patients, we evaluated skin tests to meat extracts, gelatine, and cetuximab and performed BAT with alpha-gal and cetuximab. In 24% (9/38) of patients, sIgE to alpha-gal was >0.10 kUA/L, and 8/9 reacted to the cetuximab. Basophil activation tests with alpha-gal were positive in all sensitized patients and were higher in those with severe reactions (18.3% in grade 4 [n = 4] vs. 1.8% in grade 2 [n = 3] or no reaction [n = 1] at 3.3 ng/mL of alpha-gal; p = 0.03). All patients with severe grade 4 reactions had a positive CD63 BAT response to cetuximab compared to patients with moderate or no reaction, who all had negative BAT (57.7% vs. 0.9% at 500 µg/mL, 63.2% vs. 4.1% at 100 µg/mL, 58.2% vs. 2.7% at 10 µg/mL, and 32.1% vs. 3.3% at 1 µg/mL of cetuximab, respectively; p ≤ 0.001). In summary, before initiating cetuximab treatment, sIgE to alpha-gal should be assessed in all patients. To predict the severity of the reaction and to assess the risk of cetuximab-induced anaphylaxis, we should perform BATs with alpha-gal or more discriminative BATs with cetuximab.

Penicillin Allergy in China: Consequences of Inappropriate Skin Testing Practices and Policies.

Penicillins are the most frequently prescribed class of medications worldwide and first-line antibiotic of choice for most bacterial infections. They are also commonly labelled as the culprit of drug 'allergy'; leading to obligatory use of second-line antibiotics, suboptimal antibiotic therapy and increased antimicrobial resistance. However, the majority of reported penicillin 'allergy' labels are found to be incorrect after allergy testing, emphasising the importance of proper drug allergy testing and evaluation. Penicillin skin testing (PST) remains an important component of drug allergy diagnosis; however, its practice and policies significantly differ across the world. Inappropriate and non-evidence-based PST practices can lead to consequences associated with allergy mislabelling. Even within different regions of China, with a population exceeding 1.4 billion, there are marked differences in the implementation, execution and interpretation of PST. This review aims to examine the differences in PST between Mainland China, Hong Kong and the rest of the world. We critically analyse the current practice of 'pre-emptive' PST in Mainland China, which has a significant false-positive rate leading to high levels of penicillin allergy mislabelling. Non-evidence-based practices further compound the high false-positive rates of indiscriminatory PST. We postulate that inappropriate PST policies and practices may exacerbate the mislabelling of penicillin allergy, leading to unnecessary overuse of inappropriate second-line antibiotics, increasing antimicrobial resistance and healthcare costs. We advocate for the importance of more collaborative research to improve the contemporary workflow of penicillin allergy diagnosis, reduce mislabelling and promote the dissemination of evidence-based methods for allergy diagnosis.

Optimizing preoperative antibiotic use through improved penicillin allergy documentation.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Penicillin allergy documentation in the electronic health record (EHR) lacks detail with regard to type of reaction, history of reaction, and other tolerated ß-lactams. Because of concern for penicillin allergy cross-reactivity with cefazolin, patients with a reported penicillin allergy are frequently prescribed suboptimal preoperative antibiotics, which have been associated with negative patient outcomes, including increased risk of surgical site infection. The purpose of this study was to increase preoperative use of cefazolin via improvement to the documentation of penicillin allergies in the EHR. METHODS: This single-center, quasi-experimental quality improvement study compared patients with a self-reported penicillin allergy admitted for select elective surgeries before and after implementation of a penicillin allergy questionnaire. The primary outcome was receipt of cefazolin for surgical prophylaxis. Secondary outcomes were the proportion of patients with detailed penicillin allergy documentation, the proportion of patients with surgical site infections occurring within 30 days of surgery, and the proportion of patients who received the full antibiotic dose before the first surgical incision. RESULTS: A total of 100 patients were included in the preintervention group, while 85 patients were included in the postintervention group. Cefazolin use was higher in the postintervention group (13.0% vs 41.2%; P < 0.001). The postintervention group also had a larger proportion of patients with detailed allergy documentation (2.0% vs 50.6%; P < 0.001) and who received the full preoperative antibiotic dose before the first incision (25.0% vs 48.2%; P = 0.001). There was no statistical difference between the groups in the incidence of surgical site infection at 30 days after surgery (3.0% vs 1.2%; P = 0.63). CONCLUSION: Preoperative cefazolin use was higher in patients with a reported penicillin allergy after implementation of a penicillin allergy questionnaire and EHR documentation tool.

Development and validation study of compact biophotonic platform for detection of serum biomarkers.

The application of advances in personalized medicine requires the support of in vitro diagnostic techniques aimed at the accurate, fast, sensitive, and precise determination of selected biomarkers. Herein, a novel optical centrifugal microfluidic device is developed for clinical analysis and point-of-care diagnostics. Based on compact disc technology, the integrated biophotonic system enables multiple immunoassays in miniaturized mode. The disposable microfluidic discs are made in cyclic olefin copolymer (COP), containing arrays of immobilized probes. In the developed approach, up to six patient samples can each be tested simultaneously. A portable instrument (<2 kg) controls the assay and the high-sensitive reproducible optical detection in transmission mode. Also, the instrument incorporates specific functionalities for personalized telemedicine. The device (analytical method, disc platform, reader, and software) has been validated to diagnose IgE-mediated drug allergies, such as amoxicillin and penicillin G. The total and specific IgE to ß-lactam antibiotics were determined in human serum from patients (25 µL). The excellent analytical performances (detection limit 0.24 ng/mL, standard deviation 7-20 %) demonstrated that the developed system could have the potential for a broader impact beyond the allergy field, as it applies to other IVD tests.

Association of HLA alleles with cephalosporin allergy in the Taiwanese population.

Cephalosporin antibiotics are widely used in clinical settings, but they can cause hypersensitivity reactions, which may be influenced by genetic factors such as the expression of Human leukocyte antigen (HLA) molecules. This study aimed to investigate whether specific HLA alleles were associated with an increased risk of adverse reactions to cephalosporins among individuals in the Taiwanese population. This retrospective case-control study analyzed data from the Taiwan Precision Medicine Initiative (TPMI) on 27,933 individuals who received cephalosporin exposure and had HLA allele genotyping information available. Using logistic regression analyses, we examined the associations between HLA genotypes, comorbidities, allergy risk, and severity. Among the study population, 278 individuals had cephalosporin allergy and 2780 were in the control group. Our results indicated that certain HLA alleles, including HLA-B*55:02 (OR = 1.76, 95% CI 1.18-2.61, p = 0.005), HLA-C*01:02 (OR = 1.36, 95% CI 1.05-1.77, p = 0.018), and HLA-DQB1*06:09 (OR = 2.58, 95% CI 1.62-4.12, p < 0.001), were significantly associated with an increased risk of cephalosporin allergy reactions. Additionally, the HLA-C*01:02 allele genotype was significantly associated with a higher risk of severe allergy (OR = 2.33, 95% CI 1.05-5.15, p = 0.04). This study identified significant associations between HLA alleles and an increased risk of cephalosporin allergy, which can aid in early detection and prediction of adverse drug reactions to cephalosporins. Furthermore, our study highlights the importance of HLA typing in drug safety and expanding our knowledge of drug hypersensitivity syndromes.

Maculopapular rash with multiple drug hypersensitivity to cotrimoxazole, amikacin, piperacillin/tazobactam, and meropenem in a patient with hairy cell leukemia.

We describe a rare case of a 54-year-old female with hairy cell leukemia, who following treatment for neutropenic sepsis, developed an extensive severe maculopapular exanthema with perifollicular hemorrhage. Cladribine, cotrimoxazole, allopurinol, domperidone, amikacin, piperacillin/tazobactam, and meropenem had all been given in the 9 days prior to eruption onset. Three months later, drug patch testing/delayed intradermal testing was positive to cotrimoxazole, trimethoprim, amikacin, piperacillin/tazobactam, and meropenem, with additional evidence of penicillin cross-reactivity. Drug challenge tests were negative to allopurinol and domperidone. She was diagnosed with multiple drug hypersensitivity to cotrimoxazole, amikacin, piperacillin/tazobactam, and meropenem. Multiple drug hypersensitivity is a novel syndrome mainly seen with severe delayed type IV drug eruptions, involving long-lasting strong T-cell reactivity to two or more structurally unrelated drugs.