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Allergy Mar 2024In drug hypersensitivity, drug provocation testing (DPT), also called drug challenge, is the gold standard for investigation. In recent years, risk stratification has...
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.
Topics: Child; Adult; Humans; Drug Hypersensitivity; Anti-Inflammatory Agents, Non-Steroidal; Contrast Media; Monobactams; beta Lactam Antibiotics; Skin Tests; Anti-Bacterial Agents
PubMed: 38155501
DOI: 10.1111/all.15996 -
Nature Reviews. Disease Primers Apr 2024Severe cutaneous adverse reactions (SCARs), which include Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms... (Review)
Review
Severe cutaneous adverse reactions (SCARs), which include Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (also known as drug-induced hypersensitivity syndrome), acute generalized exanthematous pustulosis, and generalized bullous fixed drug eruption, are life-threatening conditions. The pathogenesis of SCARs involves T cell receptors recognizing drug antigens presented by human leukocyte antigens, triggering the activation of distinct T cell subsets. These cells interact with keratinocytes and various immune cells, orchestrating cutaneous lesions and systemic manifestations. Genetic predisposition, impaired drug metabolism, viral reactivation or infections, and heterologous immunity influence SCAR development and clinical presentation. Specific genetic associations with distinct SCAR phenotypes have been identified, leading to the implementation of genetic screening before prescription in various countries to prevent SCARs. Whilst systemic corticosteroids and conventional immunomodulators have been the primary therapeutic agents, evolving strategies, including biologics and small molecules targeting tumour necrosis factor, different cytokines, or Janus kinase signalling pathways, signify a shift towards a precision management paradigm that considers individual clinical presentations.
Topics: Humans; Stevens-Johnson Syndrome; Drug Hypersensitivity Syndrome; Drug Eruptions; Acute Generalized Exanthematous Pustulosis
PubMed: 38664435
DOI: 10.1038/s41572-024-00514-0 -
The Journal of Allergy and Clinical... May 2024When approaching a case of apparent drug allergy, the consulting clinician should consider a broad differential diagnosis. This article presents a series of cases that...
When approaching a case of apparent drug allergy, the consulting clinician should consider a broad differential diagnosis. This article presents a series of cases that could be commonly referred to an allergist for assessment as "drug allergy," however, a real diagnosis exists that mandates a different diagnostic and treatment strategy, including a case of inducible laryngeal obstruction, multiple drug intolerance syndrome, viral rash, seizure due to metastatic malignancy, and hemophagocytic lymphohistiocytosis initially diagnosed as drug reaction and eosinophilia with systemic symptoms. The initial misdiagnoses of these patients delayed or interfered with their medical care, emphasizing the importance of accurate diagnoses for the benefit of our patients.
Topics: Humans; Diagnosis, Differential; Female; Male; Drug Hypersensitivity; Middle Aged; Lymphohistiocytosis, Hemophagocytic; Adult; Aged; Diagnostic Errors; Drug Hypersensitivity Syndrome
PubMed: 38325764
DOI: 10.1016/j.jaip.2024.01.047 -
Ugeskrift For Laeger Apr 2024Perioperative anaphylaxis is rare and the diagnosis is difficult to distinguish from normal side effects from anaesthesia. Anaesthetists should be able to diagnose...
Perioperative anaphylaxis is rare and the diagnosis is difficult to distinguish from normal side effects from anaesthesia. Anaesthetists should be able to diagnose anaphylaxis and treat promptly with adrenaline and fluids. Allergy investigation should be performed subsequently. This is a case report of perioperative anaphylaxis to propofol. Propofol contains refined soya oil and egg lecithin, but no connection between allergy to soy, egg or peanut and allergy to propofol has been proven, and international guidelines recommend that propofol can be used in patients with these food allergies.
Topics: Humans; Anaphylaxis; Propofol; Anesthetics, Intravenous; Drug Hypersensitivity; Female; Epinephrine; Male
PubMed: 38704709
DOI: 10.61409/V11230746 -
The Journal of Allergy and Clinical... Oct 2023We previously developed a drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) severity (DDS) score that may...
BACKGROUND
We previously developed a drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) severity (DDS) score that may predict DIHS/DRESS-associated complications (DACs), including myocarditis, gastrointestinal bleeding, and autoimmune diseases.
OBJECTIVE
To externally confirm the predictive accuracy of the DDS score, clarify its ability to identify patients at high risk of DACs and fatal outcome, and determine which treatments might reduce or increase the risk.
METHODS
We conducted a nationwide multicenter retrospective study in which we followed 48 patients with DIHS/DRESS at 5 university hospitals in Japan for 1 year after onset. Patients were divided into mild, moderate, and severe DIHS/DRESS groups depending on their early DDS score.
RESULTS
Eight cases had DACs in the severe group (n = 17); no DACs were observed in the mild group (n = 12). Receiver-operating characteristic curve analysis showed that a cutoff DDS score of ≥4.0 and ≤2.0 could differentiate patients who would and would not develop DACs, respectively. In the moderate-to-severe disease groups, DACs occurred only in patients who received corticosteroids and not in those who received supportive care. None of the patients who received early treatment for cytomegalovirus developed DACs. Autoimmune DACs were significantly more common in patients who received pulse corticosteroid therapy. Four deaths occurred within the 1-year follow-up; all were in patients with infectious DACs who received systemic corticosteroids.
CONCLUSION
Our scoring system allows early identification of patients at increased risk for DACs. Risk factors for DACs include systemic or pulse corticosteroid therapy.
Topics: Humans; Drug Hypersensitivity Syndrome; Retrospective Studies; Eosinophilia; Adrenal Cortex Hormones; Autoimmune Diseases
PubMed: 37437776
DOI: 10.1016/j.jaip.2023.06.065 -
The Journal of Allergy and Clinical... May 2024Immediate drug-induced hypersensitivity reactions (IDHSRs) have conventionally been attributed to an immunoglobulin E (IgE)-mediated mechanism. Nevertheless, it has now... (Review)
Review
Immediate drug-induced hypersensitivity reactions (IDHSRs) have conventionally been attributed to an immunoglobulin E (IgE)-mediated mechanism. Nevertheless, it has now been acknowledged that IDHSRs can also occur independently of IgE involvement. Non-IgE-mediated IDHSRs encompass the activation of effector cells, both mast cell-dependent and -independent and the initiation of inflammatory pathways through immunogenic and nonimmunogenic mechanisms. The IDHSRs involve inflammatory mediators beyond histamine, including the platelet-activating factor, which activates multiple cell types, including smooth muscle, endothelium, and MC, and evidence supports its importance in IgE-mediated reactions in humans. Clinically, distinguishing IgE from non-IgE mechanisms is crucial for future treatment strategies, including drug(s) restriction, readministration approaches, and pretreatment considerations. However, this presents significant challenges because certain drugs can trigger both mechanisms, and their presentations can appear similarly, ranging from mild to life-threatening symptoms. Thus, history alone is often inadequate for differentiation, and skin tests lack a standardized approach. Moreover, drug-specific IgE immunoassays have favorable specificity but low sensitivity, and the usefulness of the basophil activation test remains debatable. Lastly, no biomarker reliably differentiates between both mechanisms. Whereas non-IgE-mediated mechanisms likely predominate in IDHSRs, reclassifying most drug-related IDHSRs as non-IgE-mediated, with suggested prevention through dose administration adjustments, is premature and risky. Therefore, continued research and validated diagnostic tests are crucial to improving our capacity to distinguish between these mechanisms, ultimately enhancing patient care.
Topics: Humans; Drug Hypersensitivity; Immunoglobulin E; Hypersensitivity, Immediate; Basophils; Mast Cells; Animals; Platelet Activating Factor
PubMed: 38423288
DOI: 10.1016/j.jaip.2024.02.019 -
Therapie 2024Cutaneous adverse drug reactions (ADRs) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality....
Cutaneous adverse drug reactions (ADRs) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Maculopapular exanthema and urticaria are the most common types of cutaneous ADR. Serious cutaneous ADRs, which may cause permanent sequelae or have fatal outcome, may represent 2% of all cutaneous ADR and must be quickly identified to guide their management. These serious reactions include bullous manifestations (epidermal necrolysis i.e. Stevens-Johnson syndrome and toxic epidermal necrolysis), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). Some risk factors for developing cutaneous ADRs have been identified, including immunosuppression, autoimmunity or genetic variants. All drugs can cause cutaneous ADRs, the most commonly implicated being antibiotics (especially aminopenicillins and sulfonamides), anticonvulsants, allopurinol, antineoplastic drugs, non-steroidal anti-inflammatory drugs and iodinated contrast media. Pathophysiology is related to immediate or delayed "idiosyncratic" immunologic mechanisms, i.e., usually not related to dose, and pharmacologic/toxic mechanisms, commonly dose-dependent and/or time-dependent. If an immuno-allergic mechanism is suspected, allergological explorations (including epicutaneous patch testing and/or intradermal test) are often possible to clarify drug causality, however these have a variable sensitivity according to the drug and to the ADR type. No in vivo or in vitro test can consistently confirm the drug causality. To determine the origin of a rash, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis (especially infectious etiologies) is required, completed with a literature search. Reporting to pharmacovigilance system is therefore essential both to analyze drug causality at individual level, and to contribute to knowledge of the drug at population level, especially for serious cutaneous ADRs or in cases involving newly marketed drugs.
Topics: Humans; Skin; Stevens-Johnson Syndrome; Anti-Bacterial Agents; Acute Generalized Exanthematous Pustulosis; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37980248
DOI: 10.1016/j.therap.2023.09.011 -
CMAJ : Canadian Medical Association... Jul 2023
Topics: Humans; Allopurinol; Disease Progression; Drug Hypersensitivity Syndrome
PubMed: 37460122
DOI: 10.1503/cmaj.221575-f -
Revue Medicale Suisse Oct 2023
Topics: Humans; Drug Hypersensitivity; Penicillins; Hypersensitivity
PubMed: 37819186
DOI: 10.53738/REVMED.2023.19.845.1855 -
The Journal of Allergy and Clinical... Dec 2023There is no accepted grading system classifying the severity of immediate reactions to drugs.
BACKGROUND
There is no accepted grading system classifying the severity of immediate reactions to drugs.
OBJECTIVE
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.
METHODS
The USDAR investigators sought to develop a consensus severity grading system for immediate drug reactions that is applicable to clinical care and research.
RESULTS
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.
CONCLUSION
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.
Topics: Humans; United States; Skin Tests; Drug Hypersensitivity; Anaphylaxis; Hypersensitivity, Immediate; Anti-Bacterial Agents
PubMed: 37652140
DOI: 10.1016/j.jaci.2023.08.018