Schmeling H, Seliger E, Horneff G
Department of Pediatrics, Martin-Luther University Halle-Wittenberg, Halle, Germany.
Clin Exp Rheumatol. 2003 Nov-Dec;21(6):779-84.
Growth failure is a leading problem in uncontrolled juvenile idiopathic arthritis. It also affects 10% of patients who are not treated with corticosteroids. The influence of proinflammatory cytokines like interleukin-1 beta, interleukin-6 and tumour necrosis factor on the neuroendocrine axis as well as on the production of insulin-like growth factors (IGFs) has been postulated. The objective of the current study was to evaluate effects of highly active antirheumatic treatment with tumour necrosis factor antagonist on growth retardation. Seven out of 18 patients with refractory juvenile idiopathic arthritis treated with etanercept demonstrated growth retardation leading to short stature.
Antropometric measurements and disease activity parameters--including the number of swollen and tender joints, morning stiffness, ESR and CRP levels--were monitored monthly during the first year of treatment and every 3 months thereafter. Serum levels of IGF-1 and IFG-BP were measured as well.
Upon treatment with etanercept, growth velocity increased from 3.7 +/- 1.2 cm before the beginning of the therapy to 7.6 +/- 1.2 cm in the first year of treatment (p < 0.001). The average length-standard-deviation-score (SDS) increased from -2.4 +/- 1.0 to -1.9 +/- 0.9 after one year and to -1.1 +/- 0.9 after two years (p = 0.05) indicating catch-up growth. Prior to the therapy, serum levels of insulin-like growth factor-1 and of insulin-like growth factor binding protein-3 were within the normal range but increased significantly upon treatment (p < 0.001). An inverse correlation of the IGF-1 serum level to CRP was found.
An intensified anti-inflammatory treatment using etanercept has a beneficial effect on growth in children with a so far uncontrolled inflammatory disease. This effect might be related to the cessation of the inhibitory effect of proinflammatory cytokines on the synthesis of IGF-1 and IGF-BP-3 in the liver. Growth failure should be included in the evaluation of antirheumatic treatment.
生长发育迟缓是未控制的幼年特发性关节炎的主要问题。它也影响10%未接受皮质类固醇治疗的患者。有人推测促炎细胞因子如白细胞介素-1β、白细胞介素-6和肿瘤坏死因子对神经内分泌轴以及胰岛素样生长因子（IGF）的产生有影响。本研究的目的是评估用肿瘤坏死因子拮抗剂进行的高活性抗风湿治疗对生长发育迟缓的影响。18例接受依那西普治疗的难治性幼年特发性关节炎患者中有7例出现生长发育迟缓，导致身材矮小。
在治疗的第一年每月监测人体测量指标和疾病活动参数，包括肿胀和压痛关节的数量、晨僵、血沉和CRP水平，此后每3个月监测一次。还测量了血清IGF-1和IFG-BP水平。
接受依那西普治疗后，生长速度从治疗开始前的3.7±1.2厘米增加到治疗第一年的7.6±1.2厘米（p<0.001）。平均身高标准差评分（SDS）在一年后从-2.4±1.0增加到-1.9±0.9，两年后增加到-1.1±0.9（p = 0.05），表明出现追赶生长。治疗前，胰岛素样生长因子-1和胰岛素样生长因子结合蛋白-3的血清水平在正常范围内，但治疗后显著升高（p<0.001）。发现IGF-1血清水平与CRP呈负相关。
使用依那西普进行强化抗炎治疗对迄今未控制的炎症性疾病患儿的生长有有益影响。这种作用可能与促炎细胞因子对肝脏中IGF-1和IGF-BP-3合成的抑制作用停止有关。生长发育迟缓应纳入抗风湿治疗的评估中。
