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儿科抗生素难治性莱姆关节炎:一项多中心病例对照研究。

Pediatric Antibiotic-refractory Lyme Arthritis: A Multicenter Case-control Study.

机构信息

From the Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey; Rutgers Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, New Brunswick, New Jersey; Department of Biostatistics - Epidemiology, Rutgers School of Public Health, Piscataway, New Jersey; Department of Pediatrics, Brenner Children's Hospital, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina; Department of Pediatrics, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania; Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Pediatrics, Nemours/A.I. duPont Hospital for Children, Thomas Jefferson University, Wilmington, Delaware.

D.B. Horton, MD, MSCE, Division of Pediatric Rheumatology, Rutgers Robert Wood Johnson Medical School, and Rutgers Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, and Rutgers School of Public Health; A.J. Taxter, MD, MSCE, Brenner Children's Hospital, Wake Forest Baptist Medical Center; A.L. Davidow, PhD, Rutgers School of Public Health; B. Groh, MD, Penn State Milton S. Hershey Medical Center; D.D. Sherry, MD, Children's Hospital of Philadelphia, Division of Pediatric Rheumatology, Perelman School of Medicine, University of Pennsylvania; C.D. Rose, MD, Division of Rheumatology, Nemours/A.I. duPont Hospital for Children, Thomas Jefferson University.

出版信息

J Rheumatol. 2019 Aug;46(8):943-951. doi: 10.3899/jrheum.180775. Epub 2019 Mar 1.

Abstract

OBJECTIVE

Few factors have consistently been linked to antibiotic-refractory Lyme arthritis (ARLA). We sought to identify clinical and treatment factors associated with pediatric ARLA.

METHODS

We performed a case-control study in 3 pediatric rheumatology clinics in a Lyme-endemic region (2000-2013). Eligible children were aged ≤ 18 years with arthritis and had positive testing for Lyme disease by Western blot. Cases were 49 children with persistently active arthritis despite ≥ 8 weeks of oral antibiotics or ≥ 2 weeks of parenteral antibiotics; controls were 188 children whose arthritis resolved within 3 months of starting antibiotics. We compared preselected demographic, clinical, and treatment factors between groups using logistic regression.

RESULTS

Characteristics positively associated with ARLA were age ≥ 10 years, prolonged arthritis at diagnosis, knee-only arthritis, and worsening after starting antibiotics. In contrast, children with fever, severe pain, or other signs of systemic inflammation were more likely to respond quickly to treatment. Secondarily, low-dose amoxicillin and treatment nonadherence were also linked to higher risk of ARLA. Greater antibiotic use for children with ARLA was accompanied by higher rates of treatment-associated adverse events (37% vs 15%) and resultant hospitalization (6% vs 1%).

CONCLUSION

Older children and those with prolonged arthritis, arthritis limited to the knees, or poor initial response to antibiotics are more likely to have antibiotic-refractory disease and treatment-associated toxicity. Children with severe symptoms of systemic inflammation have more favorable outcomes. For children with persistently active Lyme arthritis after 2 antibiotic courses, pediatricians should consider starting antiinflammatory treatment and referring to a pediatric rheumatologist.

摘要

目的

鲜有因素与抗生素难治性莱姆关节炎(ARLA)始终相关。我们试图确定与儿科 ARLA 相关的临床和治疗因素。

方法

我们在莱姆病流行地区的 3 家儿科风湿病诊所进行了病例对照研究(2000-2013 年)。合格的儿童年龄≤18 岁,关节炎且 Western blot 检测到莱姆病阳性。病例为 49 名儿童,尽管接受了≥8 周的口服抗生素或≥2 周的静脉内抗生素治疗,但关节炎仍持续活跃;对照组为 188 名儿童,其关节炎在开始抗生素治疗后 3 个月内消退。我们使用逻辑回归比较了两组间预先选择的人口统计学、临床和治疗因素。

结果

与 ARLA 相关的特征为年龄≥10 岁、诊断时关节炎持续时间延长、仅膝关节关节炎和抗生素治疗后病情恶化。相比之下,有发热、剧烈疼痛或其他全身炎症迹象的儿童更有可能迅速对治疗做出反应。其次,低剂量阿莫西林和治疗不依从与 ARLA 风险增加有关。ARLA 儿童抗生素使用量增加与治疗相关不良事件(37% vs. 15%)和随后住院(6% vs. 1%)的发生率更高相关。

结论

年龄较大的儿童和关节炎持续时间较长、关节炎仅限于膝关节或抗生素初始反应不佳的儿童更有可能出现抗生素难治性疾病和治疗相关毒性。有严重全身炎症症状的儿童有更好的结局。对于 2 个抗生素疗程后仍持续活跃的莱姆关节炎儿童,儿科医生应考虑开始抗炎治疗并转介至儿科风湿病医生。

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本文引用的文献

1
Surveillance for Lyme Disease - United States, 2008-2015.2008 - 2015年美国莱姆病监测
MMWR Surveill Summ. 2017 Nov 10;66(22):1-12. doi: 10.15585/mmwr.ss6622a1.

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