关键词: 药物过敏, 超敏反应, 迟发型, 药物超敏反应综合征, 伴嗜酸性粒细胞增多和系统症状的药物反应, 儿童, 临床表现, 治疗, 预后

Abstract: 【Abstract】 Objective To investigate clinical characteristics, treatment approaches, and prognosis of drug-induced hypersensitivity syndrome （DIHS） in children. Methods A retrospective analysis was performed on clinical data from pediatric inpatients with DIHS in Department of Dermatology, Beijing Children's Hospital from 2009 to 2023. The clinical data included demographic characteristics, clinical manifestations, laboratory findings, treatment regimens, and outcomes. Results A total of 103 children with DIHS were included, comprising 54 males （52.4%） and 49 females （47.6%）, with ages （M ［Q1, Q3］）of 2.3 （1.2, 4.5） years. Primary causative drugs were antibiotics （52 cases, 45.2%）, antiepileptic drugs （41 cases, 35.7%）, and nonsteroidal anti-inflammatory drugs （19 cases, 16.5%）, with a median latency period of 12 days. All patients presented with rashes, including 72 （69.9%） with maculopapular rashes, 69 （67.0%） with edema （including 46 with facial edema）. Lip involvement occurred in 25 cases （24.3%）, and mucosal involvement was noted in 11 cases （10.7%）. Additionally, 102 （99.0%） patients had fever, and 79 （76.7%） presented with lymphadenectasis. Eosinophilia was present in 64 cases （62.1%）. Among 84 patients tested for atypical lymphocytes, 51 （60.7%） showed elevated percentages of atypical lymphocytes. Liver involvement was noted in 94 cases （91.3%）, followed by pulmonary involvement in 31 （30.1%）, gastrointestinal symptoms in 25 （24.3%）, cardiac involvement in 14 （13.6%）, renal involvement in 10 （9.7%）, and pancreatic involvement in 7 cases （6.8%）. Among 82 patients tested for blood immunocytes, 49 （59.8%） showed decreased percentages of B lymphocytes, and 69 （84.1%） showed decreased percentages of natural killer cells. Of 88 patients tested for serum immunoglobulins, 40 （45.5%） showed decreased IgA levels. Among 20 patients tested for serum cytokines, 15 （75.0%）, 15 （75.0%）, 13 （65.0%）, and 12 （60.0%） showed elevated levels of interleukin （IL）-5, IL-6, IL-10, and interferon-γ, respectively. All patients received systemic glucocorticoid therapy, among whom 86 additionally received intravenous immunoglobulin therapy, 4 received Janus kinase inhibitors, and 3 received dupilumab. Five patients died, 9 developed hemophagocytic lymphohistiocytosis, 6 developed bronchiolitis obliterans, and 5 experienced long-term immune-related sequelae. Conclusions Among these children with DIHS, antibiotics were the most common causative drugs, and the latency period could be shorter than 2 weeks. In addition to the common involvement of the liver and lungs, gastrointestinal and cardiac impairments were relatively frequent, while renal involvement was rare. Immunological features included decreased percentages of B lymphocytes and natural killer cells, reduced IgA levels, and elevated levels of cytokines such as IL-5, IL-6, IL-10, and interferon-γ.

Key words: Drug hypersensitivity, Hypersensitivity, delayed, Drug-induced hypersensitivity syndrome, Drug reaction with eosinophilia and systemic symptoms, Child, Clinical manifestations, Therapy, Prognosis