PMID- 38423288
OWN - NLM
STAT- MEDLINE
DCOM- 20240509
LR  - 20240511
IS  - 2213-2201 (Electronic)
IS  - 2213-2198 (Print)
VI  - 12
IP  - 5
DP  - 2024 May
TI  - Non-IgE-Mediated Immediate Drug-Induced Hypersensitivity Reactions.
PG  - 1109-1119
LID - S2213-2198(24)00193-4 [pii]
LID - 10.1016/j.jaip.2024.02.019 [doi]
AB  - 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.
CI  - Copyright (c) 2024 American Academy of Allergy, Asthma & Immunology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Alvarez-Arango, Santiago
AU  - Alvarez-Arango S
AD  - Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins 
      University School of Medicine, Baltimore, Md; Division of Allergy and Clinical 
      Immunology, Department of Medicine, Johns Hopkins University School of Medicine, 
      Baltimore, Md; Department of Pharmacology and Molecular Science, Johns Hopkins 
      University School of Medicine, Baltimore, Md. Electronic address: 
      salvarez@jhmi.edu.
FAU - Kumar, Mukesh
AU  - Kumar M
AD  - School of Biological Sciences, University of Hong Kong, Hong Kong, SAR.
FAU - Chow, Timothy G
AU  - Chow TG
AD  - Division of Allergy and Immunology, Department of Pediatrics and Internal 
      Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
FAU - Sabato, Vito
AU  - Sabato V
AD  - Department of Immunology, Allergology and Rheumatology, Antwerp University 
      Hospital, University Antwerp, Antwerp, Belgium.
LA  - eng
GR  - KL2 TR003099/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20240228
PL  - United States
TA  - J Allergy Clin Immunol Pract
JT  - The journal of allergy and clinical immunology. In practice
JID - 101597220
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 0 (Platelet Activating Factor)
SB  - IM
MH  - Humans
MH  - *Drug Hypersensitivity/diagnosis/immunology
MH  - *Immunoglobulin E/immunology
MH  - Hypersensitivity, Immediate/immunology/diagnosis
MH  - Basophils/immunology
MH  - Mast Cells/immunology
MH  - Animals
MH  - Platelet Activating Factor/immunology
PMC - PMC11081849
MID - NIHMS1980960
OTO - NOTNLM
OT  - Anaphylaxis
OT  - Anaphylaxis mechanisms
OT  - Drug allergy
OT  - Drug hypersensitivity
OT  - Infusion reaction
OT  - Mast cells
OT  - Non-IgE-mediated immediate drug hypersensitivity reactions
COIS- Conflict of Interest: The authors declare no conflict of interest.
EDAT- 2024/03/01 01:22
MHDA- 2024/05/10 05:42
PMCR- 2025/05/01
CRDT- 2024/02/29 19:17
PHST- 2023/10/18 00:00 [received]
PHST- 2024/02/04 00:00 [revised]
PHST- 2024/02/15 00:00 [accepted]
PHST- 2025/05/01 00:00 [pmc-release]
PHST- 2024/05/10 05:42 [medline]
PHST- 2024/03/01 01:22 [pubmed]
PHST- 2024/02/29 19:17 [entrez]
AID - S2213-2198(24)00193-4 [pii]
AID - 10.1016/j.jaip.2024.02.019 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol Pract. 2024 May;12(5):1109-1119. doi: 
      10.1016/j.jaip.2024.02.019. Epub 2024 Feb 28.