Division of Allergy and Immunology, Department of Pediatrics and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Division of Allergy and Clinical Immunology, Department of Pediatrics.
Curr Opin Pediatr. 2024 Dec 1;36(6):674-683. doi: 10.1097/MOP.0000000000001395. Epub 2024 Aug 19.
Despite their prevalence and potential severity, non-IgE-mediated drug-induced hypersensitivity reactions (DHRs) are under-researched and poorly defined, particularly in children. Presentations range from mild cutaneous reactions to severe systemic diseases, with pathophysiological mechanisms and reliable diagnostic markers not well established. The lack of validated tests often leads to permanent drug restrictions, reliance on second-line drugs, and increased costs. Focusing on recent advancements and areas needing further research, this review aims to enhance children's recognition, diagnosis, and management of non-IgE-mediated DHRs.
Recent studies have enhanced the understanding of immediate and delayed non-IgE-mediated drug reactions. Key findings include the Mas-related G protein-coupled receptor X2 in mast cells and the identification of HLA alleles linked to severe cutaneous adverse reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Improved diagnostic techniques, including skin testing, show promise in identifying immediate and delayed non-IgE DHRs. Additionally, research highlights the impact of cofactors, drug metabolites, and co-infections on these DHRs and explores potential biomarkers for predicting reaction severity.
Non-IgE-mediated DHRs are a significant cause of morbidity and treatment changes in pediatric patients. Recent research underscores their clinical presentations and mechanisms, paving the way for more precise diagnostic and therapeutic strategies to improve patient outcomes.
尽管非 IgE 介导的药物引起的超敏反应(DHRs)很常见且潜在严重,但研究不足且定义不明确,尤其是在儿童中。其表现从轻度皮肤反应到严重全身疾病不等,病理生理机制和可靠的诊断标志物尚未明确。缺乏经过验证的检测方法通常会导致药物永久受限、依赖二线药物和增加成本。本综述重点关注最新进展和需要进一步研究的领域,旨在提高儿童对非 IgE 介导的 DHRs 的认识、诊断和管理。
最近的研究加深了对立即和延迟的非 IgE 介导的药物反应的理解。主要发现包括肥大细胞中的 Mas 相关 G 蛋白偶联受体 X2 和与严重皮肤不良反应(如 Stevens-Johnson 综合征和中毒性表皮坏死松解症)相关的 HLA 等位基因的鉴定。包括皮肤测试在内的改进的诊断技术有望识别立即和延迟的非 IgE DHRs。此外,研究强调了共因子、药物代谢物和合并感染对这些 DHRs 的影响,并探索了预测反应严重程度的潜在生物标志物。
非 IgE 介导的 DHRs 是儿科患者发病率和治疗变化的重要原因。最近的研究强调了它们的临床表现和机制,为更精确的诊断和治疗策略铺平了道路,以改善患者的结局。