Immunomodulatory Therapy Reduces the Severity of Placental Lesions in Chronic Histiocytic Intervillositis.
Immunomodulatory Therapy Reduces the Severity of Placental Lesions in Chronic Histiocytic Intervillositis.
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免疫调节疗法可减轻慢性组织细胞绒毛间炎胎盘病变的严重程度。
DOI：
10.3389/fmed.2021.753220
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发表时间：
2021
影响因子：
3.9
通讯作者：
Heazell AEP
中科院分区：
文献类型：
--
作者：
Brady CA;Williams C;Batra G;Church E;Tower CL;Crocker IP;Heazell AEP
慢性组织细胞性绒毛炎(CHI)是一种罕见但高度复发的炎性胎盘病变，母体巨噬细胞渗入绒毛间隙。患有CHI的孕妇极有可能发生胎儿生长受限、流产或死产。目前，只有在对胎盘进行组织病理学检查后才能做出诊断。鉴于其提出的免疫病因，目前的治疗方法包括阿司匹林、肝素和免疫调节剂。然而，这些药物的基本原理很大程度上是基于小的病例系列和报告，因为缺乏调查治疗效果的更大规模的研究。因此，这项研究试图确定纳入免疫调节药物是否有效地降低了病变的严重程度，并改善了后续妊娠的妊娠结局。通过医疗记录对33名至少有一次妊娠CHI病史的妇女进行了回顾性鉴定。28名参与者首次怀孕，另有11名在流产后在一家怀孕专科诊所再次怀孕。收集了孕妇的人口学、病史、用药、妊娠结局和胎盘病理的数据，并对不同孕期进行了比较。27例(69%)的后续妊娠接受了至少一种或两种强的松龙和羟氯喹的治疗。在治疗方案中加入至少一种免疫调节剂导致总体活产率增加近25%(61.5%对86.2%)。在接受免疫调节药物治疗的妇女中，与不接受免疫调节药物治疗的妇女相比，有更大比例的胎盘病变严重程度减轻(分别为86.7%和33.3%)。与严重程度与指示病例相关的严重程度保持不变的患者相比，CHI严重程度的降低与活产率提高62.3%相关。这些数据提供了初步证据，表明在CHI的治疗中使用免疫调节药物可以改善组织病理损害和后续妊娠的活产机会。由于CHI的罕见以及伦理和可行性问题，在受影响的妇女中进行随机对照试验具有挑战性。因此，未来需要中心之间的合作来增加研究样本量，并阐明羟氯喹和强的松龙减少病理的机制。
Chronic histiocytic intervillositis (CHI) is a rare, but highly recurrent inflammatory placental lesion wherein maternal macrophages infiltrate the intervillous space. Pregnancies with CHI are at high risk of fetal growth restriction, miscarriage or stillbirth. Presently, the diagnosis can only be made after histopathological examination of the placenta. Given its proposed immunological etiology, current treatments include aspirin, heparin, and immunomodulatory agents. However, the rationale for these medications is largely based upon small case series and reports as there is a lack of larger studies investigating treatment efficacy. Therefore, this study sought to determine whether inclusion of immunomodulatory medications was effective at reducing the severity of lesions and improving pregnancy outcomes in subsequent pregnancies. Thirty-three women with a history of CHI in at least one pregnancy (index case) were identified retrospectively through medical records. Twenty-eight participants presented with a first subsequent pregnancy and a further 11 with a second subsequent pregnancy at a specialist clinic for pregnancy after loss. Data on maternal demographics, medical history, medication, pregnancy outcome, and placental pathology was collected and compared between pregnancies. Twenty-seven (69%) subsequent pregnancies were treated with at least one or both of prednisolone and hydroxychloroquine. Inclusion of at least one immunomodulatory agent in treatment regimen resulted in an almost 25% increase in overall livebirth rate (61.5 vs. 86.2%). In women treated with immunomodulatory medication a greater proportion of placentas had reduced severity of lesions compared to those treated without (86.7 vs. 33.3%, respectively). A reduction in CHI severity was associated with a 62.3% improvement in livebirth rate compared to those where severity remained unchanged in relation to the index case. These data provide preliminary evidence that the use of immunomodulatory medication in the management of CHI improves histopathological lesions and the chance of livebirth in subsequent pregnancies. Due to CHI's rarity and ethical and feasibility issues, randomized controlled trials in affected women are challenging to conduct. As a result, collaboration between centers is required in future to increase study sample sizes and elucidate the mechanisms of hydroxychloroquine and prednisolone in reducing pathology.
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