Abstract：
BACKGROUND: Levamisole is a commonly used steroid-sparing agent (SSA), but the reported incidence of antineutrophil cytoplasmic antibody (ANCA) positivity has been concerning.
METHODS: Observational cross-sectional study wherein children aged 2 to 18 years with frequently relapsing/steroid dependent nephrotic syndrome (FRNS/SDNS) on levamisole for ≥ 12 months were tested for ANCA.
RESULTS: A total of 210 children (33% female), median age of 7.3 (IQR: 5.6-9.6) years, and a median duration of levamisole exposure of 21 (IQR: 15-30) months were tested. ANCA was positive in 18% (n = 37): 89% (n = 33) perinuclear ANCA (pANCA), 3% (n = 1) cytoplasmic ANCA (cANCA), and 8% (n = 3) both. Of ANCA-positive children, none had reduced eGFR or abnormal urinalysis. The majority of these children were asymptomatic (81%, n = 30). Rash was more common among ANCA-positive children [6/37 (16%) vs. 3/173 (2%), p = 0.0001]. On multivariate analysis, higher age (OR = 1.02, [95th CI: 1.01 to 1.03], p = 0.007) and longer duration of levamisole exposure (OR = 1.05, [95th CI: 1.02 to 1.08], p = 0.0007) were associated with ANCA positivity. Levamisole was stopped in ANCA-positive children with the resolution of any clinical manifestations if present. Repeat ANCA testing was performed in 54% (20/37), and all were ANCA negative by 18 months.
CONCLUSIONS: Children with FRNS/SDNS on longer duration of levamisole were associated with increasing prevalence of ANCA positivity, but most of these children were clinically asymptomatic. Prospective studies are required to determine the chronology of ANCA positivity and its clinical implication.
METHODS: Observational cross-sectional study wherein children aged 2 to 18 years with frequently relapsing/steroid dependent nephrotic syndrome (FRNS/SDNS) on levamisole for ≥ 12 months were tested for ANCA.
RESULTS: A total of 210 children (33% female), median age of 7.3 (IQR: 5.6-9.6) years, and a median duration of levamisole exposure of 21 (IQR: 15-30) months were tested. ANCA was positive in 18% (n = 37): 89% (n = 33) perinuclear ANCA (pANCA), 3% (n = 1) cytoplasmic ANCA (cANCA), and 8% (n = 3) both. Of ANCA-positive children, none had reduced eGFR or abnormal urinalysis. The majority of these children were asymptomatic (81%, n = 30). Rash was more common among ANCA-positive children [6/37 (16%) vs. 3/173 (2%), p = 0.0001]. On multivariate analysis, higher age (OR = 1.02, [95th CI: 1.01 to 1.03], p = 0.007) and longer duration of levamisole exposure (OR = 1.05, [95th CI: 1.02 to 1.08], p = 0.0007) were associated with ANCA positivity. Levamisole was stopped in ANCA-positive children with the resolution of any clinical manifestations if present. Repeat ANCA testing was performed in 54% (20/37), and all were ANCA negative by 18 months.
CONCLUSIONS: Children with FRNS/SDNS on longer duration of levamisole were associated with increasing prevalence of ANCA positivity, but most of these children were clinically asymptomatic. Prospective studies are required to determine the chronology of ANCA positivity and its clinical implication.
摘要：
背景：左旋咪唑是一种常用的类固醇保护剂（SSA），但报道的抗中性粒细胞胞浆抗体（ANCA）阳性的发生率令人担忧。
方法：观察性横断面研究，其中使用左旋咪唑≥12个月的2至18岁经常复发/类固醇依赖性肾病综合征（FRNS/SDNS）的儿童进行ANCA测试。
结果：共有210名儿童（33%为女性），平均年龄为7.3岁（IQR：5.6-9.6岁），测试左旋咪唑暴露的中位持续时间为21个月(IQR:15-30)。18％（n=37）的ANCA阳性：89％（n=33）的核周ANCA（pANCA），3%(n=1)细胞质ANCA(cANCA)，和8%(n=3)。在ANCA阳性儿童中，没有人出现eGFR降低或尿液分析异常。这些儿童中的大多数无症状(81%，n=30)。皮疹在ANCA阳性儿童中更为常见[6/37（16％）与3/173（2%），p=0.0001]。在多变量分析中，年龄更高(OR=1.02，[95thCI：1.01至1.03]，p=0.007）和更长的左旋咪唑暴露时间（OR=1.05，[95thCI：1.02至1.08]，p=0.0007）与ANCA阳性相关。在ANCA阳性儿童中停用左旋咪唑，并消除任何临床表现（如果存在）。在54%(20/37)中重复进行ANCA测试，并且在18个月时全部为ANCA阴性。
结论：服用左旋咪唑持续时间较长的FRNS/SDNS儿童与ANCA阳性患病率增加有关，但这些患儿大多临床无症状.需要进行前瞻性研究以确定ANCA阳性的时间顺序及其临床意义。
方法：观察性横断面研究，其中使用左旋咪唑≥12个月的2至18岁经常复发/类固醇依赖性肾病综合征（FRNS/SDNS）的儿童进行ANCA测试。
结果：共有210名儿童（33%为女性），平均年龄为7.3岁（IQR：5.6-9.6岁），测试左旋咪唑暴露的中位持续时间为21个月(IQR:15-30)。18％（n=37）的ANCA阳性：89％（n=33）的核周ANCA（pANCA），3%(n=1)细胞质ANCA(cANCA)，和8%(n=3)。在ANCA阳性儿童中，没有人出现eGFR降低或尿液分析异常。这些儿童中的大多数无症状(81%，n=30)。皮疹在ANCA阳性儿童中更为常见[6/37（16％）与3/173（2%），p=0.0001]。在多变量分析中，年龄更高(OR=1.02，[95thCI：1.01至1.03]，p=0.007）和更长的左旋咪唑暴露时间（OR=1.05，[95thCI：1.02至1.08]，p=0.0007）与ANCA阳性相关。在ANCA阳性儿童中停用左旋咪唑，并消除任何临床表现（如果存在）。在54%(20/37)中重复进行ANCA测试，并且在18个月时全部为ANCA阴性。
结论：服用左旋咪唑持续时间较长的FRNS/SDNS儿童与ANCA阳性患病率增加有关，但这些患儿大多临床无症状.需要进行前瞻性研究以确定ANCA阳性的时间顺序及其临床意义。
