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Immunology and Allergy Clinics of North... Aug 2023Drug hypersensitivity reactions are a diverse group of reactions mediated by the immune system after exposure to a drug. The Gell and Coombs classification divides... (Review)
Review
Drug hypersensitivity reactions are a diverse group of reactions mediated by the immune system after exposure to a drug. The Gell and Coombs classification divides immunologic DHRs into 4 major pathophysiologic categories based on immunologic mechanism. Anaphylaxis is a Type I hypersensitivity reaction that requires immediate recognition and treatment. Severe cutaneous adverse reactions (SCARs) are a group of dermatologic diseases that result from a Type IV hypersensitivity process and include drug reaction with eosinophilia and systemic symptom (DRESS) syndrome, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). Other types of reactions are slow to develop and do not always require rapid treatment. Emergency physicians should have a good understanding of these various types of drug hypersensitivity reactions and how to approach the patient regarding evaluation and treatment.
Topics: Humans; Drug Hypersensitivity; Stevens-Johnson Syndrome; Skin; Acute Generalized Exanthematous Pustulosis; Hypersensitivity, Delayed
PubMed: 37394254
DOI: 10.1016/j.iac.2022.10.005 -
JAMA Internal Medicine Sep 2023Fewer than 5% of patients labeled with a penicillin allergy are truly allergic. The standard of care to remove the penicillin allergy label in adults is specialized... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Fewer than 5% of patients labeled with a penicillin allergy are truly allergic. The standard of care to remove the penicillin allergy label in adults is specialized testing involving prick and intradermal skin testing followed by an oral challenge with penicillin. Skin testing is resource intensive, limits practice to specialist-trained physicians, and restricts the global population who could undergo penicillin allergy delabeling.
OBJECTIVE
To determine whether a direct oral penicillin challenge is noninferior to the standard of care of penicillin skin testing followed by an oral challenge in patients with a low-risk penicillin allergy.
DESIGN, SETTING, AND PARTICIPANTS
This parallel, 2-arm, noninferiority, open-label, multicenter, international randomized clinical trial occurred in 6 specialized centers, 3 in North America (US and Canada) and 3 in Australia, from June 18, 2021, to December 2, 2022. Eligible adults had a PEN-FAST score lower than 3. PEN-FAST is a prospectively derived and internationally validated clinical decision rule that enables point-of-care risk assessment for adults reporting penicillin allergies.
INTERVENTIONS
Patients were randomly assigned to either direct oral challenge with penicillin (intervention arm) or a standard-of-care arm of penicillin skin testing followed by oral challenge with penicillin (control arm).
MAIN OUTCOME AND MEASURE
The primary outcome was a physician-verified positive immune-mediated oral penicillin challenge within 1 hour postintervention in the intention-to-treat population. Noninferiority was achieved if a 1-sided 95% CI of the risk difference (RD) did not exceed 5 percentage points (pp).
RESULTS
A total of 382 adults were randomized, with 377 patients (median [IQR] age, 51 [35-65] years; 247 [65.5%] female) included in the analysis: 187 in the intervention group and 190 in the control group. Most patients had a PEN-FAST score of 0 or 1. The primary outcome occurred in 1 patient (0.5%) in the intervention group and 1 patient (0.5%) in the control group, with an RD of 0.0084 pp (90% CI, -1.22 to 1.24 pp). The 1-sided 95% CI was below the noninferiority margin of 5 pp. In the 5 days following the oral penicillin challenge, 9 immune-mediated adverse events were recorded in the intervention group and 10 in the control group (RD, -0.45 pp; 95% CI, -4.87 to 3.96 pp). No serious adverse events occurred.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, direct oral penicillin challenge in patients with a low-risk penicillin allergy was noninferior compared with standard-of-care skin testing followed by oral challenge. In patients with a low-risk history, direct oral penicillin challenge is a safe procedure to facilitate the removal of a penicillin allergy label.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04454229.
Topics: Adult; Humans; Female; Middle Aged; Male; Clinical Decision Rules; Penicillins; Drug Hypersensitivity; Risk Assessment; Hypersensitivity; Anti-Bacterial Agents
PubMed: 37459086
DOI: 10.1001/jamainternmed.2023.2986 -
Journal of the American Academy of... May 2024Drug-induced hypersensitivity syndrome, also known as drug reaction with eosinophilia and systemic symptoms, is a severe cutaneous adverse reaction characterized by an... (Review)
Review
Drug-induced hypersensitivity syndrome, also known as drug reaction with eosinophilia and systemic symptoms, is a severe cutaneous adverse reaction characterized by an exanthem, fever, and hematologic and visceral organ involvement. The differential diagnosis includes other cutaneous adverse reactions, infections, inflammatory and autoimmune diseases, and neoplastic disorders. Three sets of diagnostic criteria have been proposed; however, consensus is lacking. The cornerstone of management is immediate discontinuation of the suspected drug culprit. Systemic corticosteroids remain first-line therapy, but the literature on steroid-sparing agents is expanding. Longitudinal evaluation for sequelae is recommended. Adjunctive tests for risk stratification and drug culprit identification remain under investigation. Part II of this continuing medical education activity begins by exploring the differential diagnosis and diagnosis of drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms and concludes with an evidence-based overview of evaluation and treatment.
Topics: Humans; Drug Hypersensitivity Syndrome; Eosinophilia; Skin; Adrenal Cortex Hormones; Fever
PubMed: 37516356
DOI: 10.1016/j.jaad.2023.02.073 -
American Journal of Clinical Dermatology Jul 2023Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including... (Review)
Review
Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including infections, vaccinations, ingestion of various substances, and spider bites, have also been described. AGEP is characterized by the development of edema and erythema followed by the eruption of multiple punctate, non-follicular, sterile pustules and subsequent desquamation. AGEP typically has a rapid onset and prompt resolution within a few weeks. The differential diagnoses for AGEP are broad and include infectious, inflammatory, and drug-induced etiologies. Diagnosis of AGEP depends on both clinical and histologic criteria, as cases of overlap with other disease processes have been reported. Management includes removal of the offending drug or treatment of the underlying cause, if necessary, and supportive care, as AGEP is a self-limited disease. This review aims to provide an overview and update on the epidemiology, pathogenesis, reported precipitating factors, differentials, diagnosis, and management of AGEP.
Topics: Humans; Acute Generalized Exanthematous Pustulosis; Diagnosis, Differential; Skin; Exanthema; Erythema
PubMed: 37156992
DOI: 10.1007/s40257-023-00779-3 -
Journal of the American Academy of... May 2024Drug-induced hypersensitivity syndrome (DiHS), also known as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe cutaneous adverse reaction (SCAR)... (Review)
Review
Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part I. Epidemiology, pathogenesis, clinicopathological features, and prognosis.
Drug-induced hypersensitivity syndrome (DiHS), also known as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe cutaneous adverse reaction (SCAR) characterized by an exanthem, fever, and hematologic and visceral organ involvement. Anticonvulsants, antibiotics, and allopurinol are the most common triggers. The pathogenesis involves a complex interplay between drugs, viruses, and the immune system primarily mediated by T-cells. DiHS/DRESS typically presents with a morbilliform eruption 2-6 weeks after drug exposure, and is associated with significant morbidity, mortality, and risk of relapse. Long-term sequelae primarily relate to organ dysfunction and autoimmune diseases. Part I of this continuing medical education activity on DiHS/DRESS provides an update on epidemiology, novel insights into pathogenesis, and a description of clinicopathological features and prognosis.
Topics: Humans; Drug Hypersensitivity Syndrome; Eosinophilia; Anticonvulsants; Skin; Prognosis
PubMed: 37516359
DOI: 10.1016/j.jaad.2023.02.072 -
Clinical Microbiology and Infection :... Jul 2023Prudent handling of reported antibiotic allergies is an important aspect of antibiotic stewardship. The Dutch Working Party on Antibiotic Policy (SWAB) constituted a...
OBJECTIVES
Prudent handling of reported antibiotic allergies is an important aspect of antibiotic stewardship. The Dutch Working Party on Antibiotic Policy (SWAB) constituted a multidisciplinary expert committee to provide evidence-based recommendations for bedside decision-making in antibiotic therapy in patients that report an antibiotic allergy.
METHODS
The guideline committee generated 12 key questions, most of which were population, intervention, comparison, and outcome questions relevant to both children and adults with suspected antibiotic allergies. For each question, a systematic literature search was performed and reviewed for the best available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The quality of evidence was graded from very low to high, and recommendations were formulated in structured discussions as strong or weak.
RESULTS
Sixty recommendations were provided for suspected allergy to β-lactam antibiotics (BLAs) and non-β-lactam antibiotics. Owing to the absence of randomized controlled trials in this field, the underlying evidence was predominantly graded as low or very low. Available data support that a detailed allergy history should always be performed and critically appraised. When cross-allergy between BLA groups is not to be expected due to the absence of molecular similarity of the side chains, the patient can be safely exposed to the alternative BLA. An exception to this rule is severe delayed-type reactions in which re-exposure to a BLA should only be considered after consultation with a multidisciplinary team.
CONCLUSIONS
Accumulated scientific data now support a more liberal approach that better balances the benefits of treatment with first choice and usually smaller spectrum antibiotics with appropriate avoidance of antibiotics in case of a truly high risk of a (severe) allergic reaction. In The Netherlands, a formal guideline was developed that provides recommendations for the approach toward suspected allergy to BLA and frequently used non-β-lactam antibiotics, thereby strongly supporting antimicrobial stewardship.
Topics: Adult; Child; Humans; Anti-Bacterial Agents; Antimicrobial Stewardship; beta-Lactams; Drug Hypersensitivity; Hypersensitivity
PubMed: 37068548
DOI: 10.1016/j.cmi.2023.04.008 -
The Journal of Allergy and Clinical... Dec 2023Across all settings, women self-report more drug allergies than do men. Although there is epidemiologic evidence of increased drug allergy labeling in postpubertal... (Review)
Review
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.
Topics: Pregnancy; Female; Humans; Male; Drug Hypersensitivity; Anaphylaxis; Risk Factors; Self Report; Sex Characteristics; Anti-Bacterial Agents; Penicillins
PubMed: 37805007
DOI: 10.1016/j.jaip.2023.09.031 -
JAMA Internal Medicine Aug 2023
Topics: Humans; Penicillins; Drug Hypersensitivity; Clinical Decision-Making; Hypersensitivity; Anti-Bacterial Agents; Skin Tests
PubMed: 37338869
DOI: 10.1001/jamainternmed.2023.1572 -
Annals of Allergy, Asthma & Immunology... Oct 2023
Topics: Humans; Hypersensitivity; Drug Hypersensitivity
PubMed: 37788879
DOI: 10.1016/j.anai.2023.05.006 -
Current Opinion in Allergy and Clinical... Aug 2023The use of contrast media is increasing in recent decades. Although gadolinium-based contrast agents (GBCAs) are generally well tolerated, adverse reactions, including... (Review)
Review
PURPOSE OF REVIEW
The use of contrast media is increasing in recent decades. Although gadolinium-based contrast agents (GBCAs) are generally well tolerated, adverse reactions, including hypersensitivity reactions (HSRs), although infrequent, may occur. It is important to perform a thorough allergological evaluation in patients with suspected GBCA-HSRs to avoid potentially serious reactions in subsequent exposures.
RECENT FINDINGS
Data on GBCA-HSRs are scarce. Most published articles dealing with skin tests and drug provocation tests (DPTs) with GBCAs are case series and small cohorts. Controversies exist about the role of premedication for preventing HSRs on subsequent exposures. Selection of well tolerated alternatives is based on potential cross-reactivity among GBCAs; however, the extent of cross-reactivity among them remains unclear.
SUMMARY
As premedication is not useful because breakthrough reactions are frequent in patients with GBCA-HSRs in subsequent exposures, an allergological evaluation is required. Available data suggest a high negative predictive value of skin tests, being crucial for guiding the selection of an alternative GBCA. However, DPTs are still necessary to confirm or exclude the diagnosis or find alternative GBCAs. Cross-reactivity is high among GBCAs belonging from the same group, mainly among macrocyclic compounds, so this must be taken into account for selecting alternatives.
Topics: Humans; Gadolinium; Drug Hypersensitivity; Contrast Media; Hypersensitivity
PubMed: 37357781
DOI: 10.1097/ACI.0000000000000911