Abstract：
BACKGROUND: After introducing IL-1/IL-6 inhibitors, some patients with Still and Still-like disease developed unusual, often fatal, pulmonary disease. This complication was associated with scoring as DReSS (drug reaction with eosinophilia and systemic symptoms) implicating these inhibitors, although DReSS can be difficult to recognize in the setting of systemic inflammatory disease.
OBJECTIVE: To facilitate recognition of IL-1/IL-6 inhibitor-DReSS in systemic inflammatory illnesses (Still/Still-like) by looking at timing and reaction-associated features. We evaluated outcomes of stopping or not stopping IL-1/IL-6 inhibitors after DReSS reaction began.
METHODS: In an international study collaborating primarily with pediatric specialists, we characterized features of 89 drug-reaction cases versus 773 drug-exposed controls and compared outcomes of 52 cases stopping IL-1/IL-6 inhibitors with 37 cases not stopping these drugs.
RESULTS: Before the reaction began, drug-reaction cases and controls were clinically comparable, except for younger disease-onset age for reaction cases with preexisting cardiothoracic comorbidities. After the reaction began, increased rates of pulmonary complications and macrophage activation syndrome differentiated drug-reaction cases from drug-tolerant controls (P = 4.7 × 10-35 and P = 1.1 × 10-24, respectively). The initial DReSS feature was typically reported 2 to 8 weeks after initiating IL-1/IL-6 inhibition. In drug-reaction cases stopping versus not stopping IL-1/IL-6-inhibitor treatment, reaction-related features were indistinguishable, including pulmonary complication rates (75% [39 of 52] vs 76% [28 of 37]). Those stopping subsequently required fewer medications for treatment of systemic inflammation, had decreased rates of macrophage activation syndrome, and improved survival (P = .005, multivariate regression). Resolution of pulmonary complications occurred in 67% (26 of 39) of drug-reaction cases who stopped and in none who continued inhibitors.
CONCLUSIONS: In systemic inflammatory illnesses, recognition of IL-1/IL-6-inhibitor-associated reactions followed by avoidance of IL-1/IL-6 inhibitors significantly improved outcomes.
OBJECTIVE: To facilitate recognition of IL-1/IL-6 inhibitor-DReSS in systemic inflammatory illnesses (Still/Still-like) by looking at timing and reaction-associated features. We evaluated outcomes of stopping or not stopping IL-1/IL-6 inhibitors after DReSS reaction began.
METHODS: In an international study collaborating primarily with pediatric specialists, we characterized features of 89 drug-reaction cases versus 773 drug-exposed controls and compared outcomes of 52 cases stopping IL-1/IL-6 inhibitors with 37 cases not stopping these drugs.
RESULTS: Before the reaction began, drug-reaction cases and controls were clinically comparable, except for younger disease-onset age for reaction cases with preexisting cardiothoracic comorbidities. After the reaction began, increased rates of pulmonary complications and macrophage activation syndrome differentiated drug-reaction cases from drug-tolerant controls (P = 4.7 × 10-35 and P = 1.1 × 10-24, respectively). The initial DReSS feature was typically reported 2 to 8 weeks after initiating IL-1/IL-6 inhibition. In drug-reaction cases stopping versus not stopping IL-1/IL-6-inhibitor treatment, reaction-related features were indistinguishable, including pulmonary complication rates (75% [39 of 52] vs 76% [28 of 37]). Those stopping subsequently required fewer medications for treatment of systemic inflammation, had decreased rates of macrophage activation syndrome, and improved survival (P = .005, multivariate regression). Resolution of pulmonary complications occurred in 67% (26 of 39) of drug-reaction cases who stopped and in none who continued inhibitors.
CONCLUSIONS: In systemic inflammatory illnesses, recognition of IL-1/IL-6-inhibitor-associated reactions followed by avoidance of IL-1/IL-6 inhibitors significantly improved outcomes.
摘要：
背景：引入白介素（IL）-1/IL-6抑制剂后，一些Still和Still样患者出现了不寻常的，通常是致命的肺部疾病。该并发症与DReSS（嗜酸粒细胞增多和全身症状的药物反应）评分相关，涉及这些抑制剂。尽管在全身性炎症性疾病的情况下DReSS可能难以识别。
目的：我们试图通过观察时间和反应相关特征来促进对IL-1/IL-6抑制剂-DReSS在全身性炎症性疾病（Still/Still-like）中的识别。我们评估了在DReSS反应开始后停止或不停止IL-1/IL-6抑制剂的结果。
方法：在一项主要与儿科专家合作的国际研究中，我们分析了89例药物反应病例与773例药物暴露对照的特征,并比较了52例停用IL-1/IL-6抑制剂病例与37例未停用这些药物病例的结局.
结果：在反应开始之前，药物反应病例和对照在临床上具有可比性，除了年轻的疾病发病年龄与先前存在的心胸合并症的反应病例。反应开始后，肺部并发症和巨噬细胞活化综合征（MAS）的发生率增加，区分药物反应病例与药物耐受对照(分别为p=4.7x10-35;p=1.1x10-24)。通常在开始IL-1/IL-6抑制后2-8周报告初始DReSS特征。在药物反应病例中，停止与不停止IL-1/IL-6抑制剂治疗，与反应相关的特征无法区分，包括肺部并发症发生率[75%(39/52]和[76%(28/37)]。那些随后停止治疗的人需要更少的药物来治疗全身性炎症，MAS发生率下降，并改善生存率（p=0.005，多元回归）。在67％（26/39）的药物反应病例中，肺部并发症的消退发生在停止治疗的病例中，而在没有继续使用抑制剂的病例中。
结论：在全身性炎症性疾病中，识别IL-1/IL-6抑制剂相关反应,然后避免使用IL-1/IL-6抑制剂可显著改善结局.
目的：我们试图通过观察时间和反应相关特征来促进对IL-1/IL-6抑制剂-DReSS在全身性炎症性疾病（Still/Still-like）中的识别。我们评估了在DReSS反应开始后停止或不停止IL-1/IL-6抑制剂的结果。
方法：在一项主要与儿科专家合作的国际研究中，我们分析了89例药物反应病例与773例药物暴露对照的特征,并比较了52例停用IL-1/IL-6抑制剂病例与37例未停用这些药物病例的结局.
结果：在反应开始之前，药物反应病例和对照在临床上具有可比性，除了年轻的疾病发病年龄与先前存在的心胸合并症的反应病例。反应开始后，肺部并发症和巨噬细胞活化综合征（MAS）的发生率增加，区分药物反应病例与药物耐受对照(分别为p=4.7x10-35;p=1.1x10-24)。通常在开始IL-1/IL-6抑制后2-8周报告初始DReSS特征。在药物反应病例中，停止与不停止IL-1/IL-6抑制剂治疗，与反应相关的特征无法区分，包括肺部并发症发生率[75%(39/52]和[76%(28/37)]。那些随后停止治疗的人需要更少的药物来治疗全身性炎症，MAS发生率下降，并改善生存率（p=0.005，多元回归）。在67％（26/39）的药物反应病例中，肺部并发症的消退发生在停止治疗的病例中，而在没有继续使用抑制剂的病例中。
结论：在全身性炎症性疾病中，识别IL-1/IL-6抑制剂相关反应,然后避免使用IL-1/IL-6抑制剂可显著改善结局.
