暂无摘要。

BACKGROUND: Abnormal ventricular activation at rest is reported in Brugada syndrome (BrS).
OBJECTIVE: The aim of this study was to evaluate the usefulness of dynamic changes in ventricular activation during exercise to improve disease phenotyping and diagnosis of BrS.
METHODS: Digital 12-lead electrocardiograms during stress testing were analyzed retrospectively at baseline, peak exercise, and recovery in 53 patients with BrS and 52 controls. Biventricular activation was assessed from QRS duration (QRSd), whereas right ventricular activation was assessed from S wave duration in the lateral leads (I and V6) and terminal R wave duration in aVR. Exercise-induced changes in QRS parameters to predict a positive procainamide response were assessed in separate test and validation cohorts with suspected BrS.
RESULTS: Baseline electrocardiogram parameters were similar between BrS and controls. QRSd shortened with exercise in all controls but prolonged in all BrS (-6.1 ± 6.0 ms vs 7.1 ± 6.5 ms [P < 0.001] in V6). QRSd in recovery was longer in BrS compared with controls (90 ± 12 ms vs 82 ± 11 ms in V6; P = 0.002). Both groups demonstrated exercise-induced S duration prolongation in V6, with greater prolongation in BrS (8.2 ± 14.3 ms vs 1.2 ± 12.4 ms; P < 0.001). Any exercise-induced QRSd prolongation in V6 differentiated those with a positive vs negative procainamide response with 100% sensitivity and 95% specificity in the test cohort, and 87% sensitivity and 93% specificity in the validation cohort.
CONCLUSIONS: Exercise-induced QRSd prolongation is ubiquitous in BrS primarily owing to delayed right ventricular activation. This electrocardiogram phenotype predicts a positive procainamide response and may provide a noninvasive screening tool to aid in the diagnosis of BrS before drug challenge.

BACKGROUND: Ten percent of the population is labeled as allergic to penicillin(s), when in fact 90% of these labels are inappropriate. Recent studies have shown that inpatient delabeling by a direct drug challenge (dDC) is safe in low-risk patients. However, there is a need for outpatient and nonallergist delabeling.
OBJECTIVE: To assess the safety of delabeling low-risk adults by means of dDC in primary care.
METHODS: We searched the MEDLINE, Embase, and Cochrane Library databases from inception to March 15, 2022 (updated June 5, 2023) for studies performing dDC in adults in primary care or other outpatient settings. Two researchers independently screened studies for eligibility. The data extraction and critical appraisal were performed by 1 reviewer, and we pooled the results in a meta-analysis.
RESULTS: Of 2138 results, 12 studies (1070 participants) were eligible for inclusion. Three studies evaluated delabeling in primary care and 9 studies in an outpatient hospital setting. There were no critical adverse events during dDC. No reaction occurred in 97.13% of the 1070 patients, who previously labeled as penicillin-allergic, and were safely delabeled. Ten patients (<1%) developed an immediate reaction: 3 had self-limiting reactions and 7 needed antihistaminics, steroids, epinephrine, and/or salbutamol.
CONCLUSIONS: No serious allergic reactions are observed during direct amoxicillin challenge in adults in an outpatient setting. However, with the exception of 1 recent report, these studies are of low to moderate quality. Nonspecialist delabeling is promising, but further research is required on correct risk stratification and safety assessment in large cohort studies evaluating dDC in primary care.

BACKGROUND: In high HIV prevalence settings, first-line antituberculosis drug (FLTD)-associated drug reaction with eosinophilia and systemic symptoms (DRESS) poses therapeutic challenges. A sequential and additive drug challenge (SADC) of FLTDs best identifies offending drug(s), avoids unnecessary exclusions, and optimizes reinitiation of nonoffending drugs. However, SADC-associated reaction complexities limit its utility.
OBJECTIVE: We aimed to describe the characteristics of patients with FLTD-associated DRESS, their treatment-limiting SADC reactions, and related outcomes.
METHODS: Patients hospitalized with FLTD-associated DRESS from 2013 to 2023 in a South African tertiary hospital and enrolled (retrospectively or prospectively) in an existing registry were eligible.
RESULTS: SADC was undertaken in 41 patients. Overall, 47 classifiable reactions occurred. 34/47 (72%) reactions in 29/41 (71%) patients were treatment-limiting and 12 of 41(29%) patients reinitiated FLTDs uneventfully. Fifteen single and 8 multiple drug reactors were identified. Rifampicin in 13 of 23(57%) reactors was the most common individual offender. Ethambutol was most frequently involved in multiple drug reactors. The median (interquartile range) time to a detectable reaction was 24(12-120) hours, 6 of 34(18%) being immediate (<6 hours). Itch (65%), eosinophilia (56%), fever (41%), atypical lymphocytosis (41%), rash (38%), transaminitis (32%), and facial edema (18%) singly or in combination were the most common features. Three reactions, 1 epidermal necrolysis and 2 liver derangements, were Common Terminology Criteria for Adverse Events grade 4 (life-threatening) events. No predictors of multiple drug reactivity were identified, but multiple reactors were hospitalized significantly longer, 125(100-134) days versus 60(45-80) days.
CONCLUSIONS: SADC optimizes FLTD reinitiation. However, timing, clinical presentation, and severity of SADC-associated reactions after FLTD-associated DRESS are markedly heterogeneous. Additionally, multiple drug reactors are a complex group that require longer hospitalization. There are no routine biomarkers available to distinguish true multiple drug hypersensitivity from nonspecific flare-ups and to guide long-term drug avoidance strategies.

Allergy to penicillin can occur via any of the 4 types of Gel-Coombs hypersensitivity reactions, producing distinct clinical histories and physical examination findings. Treatments include penicillin discontinuation, and depending on the type of reaction, epinephrine, antihistamines, and/or glucocorticoids. Most beta-lactams may be safely used in penicillin-allergic patients, with the possible exception of first-generation and second-generation cephalosporins. Penicillin testing includes skin testing, patch testing, and graded challenge. The selection of the type of testing depends on the clinical setting, equipment availability, and type of hypersensitivity reaction. Desensitization may be used in some cases where treatment with penicillins is essential.

BACKGROUND: Approximately 10% of the US population self-reports a penicillin allergy history or are labeled as penicillin allergic. However, from 90% through 99% of these patients are not allergic on formal evaluation.
METHODS: Patients labeled as penicillin allergic receive broader-spectrum and sometimes less-effective antibiotics, thereby contributing to increased treatment failures, antibiotic resistance, and adverse drug reactions. Self-reported penicillin allergy can be eliminated or classified as low-, medium-, or high-risk after a careful review of patient history. This allows these patients to be delabeled; that is, having any reference to their penicillin allergy history or of having an allergy to penicillin eliminated from their health records.
CONCLUSIONS: Oral health care professionals are ideally placed to partner in both antibiotic stewardship interventions by means of recognizing pervasive mislabeling and aiding in the process of delabeling.

暂无摘要。

In drug hypersensitivity, drug provocation testing (DPT), also called drug challenge, is the gold standard for investigation. In recent years, risk stratification has become an important tool for adjusting the diagnostic strategy to the perceived risk, whilst still maintaining a high level of safety for the patient. Skin tests are recommended before DPT but may be omitted in low-risk patients. The task force suggests a strict definition of such low-risk patients in children and adults. Based on experience and evidence from studies of allergy to beta-lactam antibiotics, an algorithm on how to adjust DPT to the risk, and when to omit skin tests before DPT, is presented. For other antibiotics, non-steroidal anti-inflammatory drugs and other drugs, skin tests are poorly validated and DPT is frequently necessary. We recommend performing DPT with chemotherapeutics and biologicals to avoid unnecessary desensitization procedures and DPT with skin tests negative contrast media. We suggest DPT with anesthetics only in highly specialized centers. Specifics of DPT to proton pump inhibitors, anticonvulsants and corticosteroids are discussed. This position paper provides general recommendations and guidance on optimizing use of DPT, whilst balancing benefits with patient safety and optimizing the use of the limited available resources.

Few studies have evaluated allergy workup in fixed drug eruption (FDE) in a large population.
To evaluate the sensitivity of a standardized allergy workup for diagnosing the cause of FDE, with a focus on in situ repeated open application tests (ROATs).
In a retrospective multicenter study, we analyzed the practice of conducting a complete allergy workup for the etiological diagnosis of FDE. It consisted of 3 steps: in situ patch tests (PTs) for all cases except pure mucosal involvement, followed by in situ ROAT if in situ PT results were negative, and finally a drug challenge (DC). The in situ ROAT involved daily application of the suspected drug on a previously affected FDE site for 7 days.
Of 98 suspected FDE cases, 61 patients (median age 61 y; male-to-female ratio 1.8) with a complete allergy workup were included. In 4 cases, even the DC yielded negative results. Among the remaining 57 patients with a positive workup, implicated drugs included paracetamol (12 cases), β-lactams (11 cases), imidazoles (9 cases, including 5 with metronidazole), nonsteroidal anti-inflammatory drugs (8 cases), iodinated contrast media (4 cases), cotrimoxazole (3 cases), and various other drugs in 10 patients. The diagnosis was confirmed by in situ PT in 17 of 54 cases (31.5%), in situ ROAT in 14 of 40 cases (35%) (with 4 cases showing remote reactivation of FDE sites), and DC in 26 cases.
The sequential allergy workup involving successively in situ PT, in situ ROAT, and DC is a reliable and safe method for diagnosing the cause of FDE. In situ tests exhibited a sensitivity of over 50%.

There is no accepted grading system classifying the severity of immediate reactions to drugs.
The purpose of this article is to present a proposed grading system developed through the consensus of drug allergy experts from the United States Drug Allergy Registry (USDAR) Consortium.
The USDAR investigators sought to develop a consensus severity grading system for immediate drug reactions that is applicable to clinical care and research.
The USDAR grading scale scores severity levels on a scale of 0 to 4. A grade of no reaction (NR) is used for patients who undergo challenge without any symptoms or signs, and it would confirm a negative challenge result. A grade 0 reaction is indicative of primarily subjective complaints that are commonly seen with both historical drug reactions and during drug challenges, and it would suggest a low likelihood of a true drug allergic reaction. Grades 1 to 4 meet the criteria for a positive challenge result and may be considered indicative of a drug allergy. Grade 1 reactions are suggestive of a potential immediate drug reaction with mild symptoms. Grade 2 reactions are more likely to be immediate drug reactions of moderate severity. Grade 3 reactions have features suggestive of a severe allergic reaction, whereas grade 4 reactions are life-threatening reactions such as anaphylactic shock and fatal anaphylaxis.
This proposed grading schema for immediate drug reactions improves on prior schemata by being developed specifically for immediate drug reactions and being easy to implement in clinical and research practice.