Bin Khathlan Yasir, Almutairi Sajdi, Albadr Fahad B, Alangari Abdullah A, Alsultan Abdulrahman
Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Department of Radiology and Medical Imaging, King Saud University Medical City and College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Front Pediatr. 2023 Apr 28;11:1178919. doi: 10.3389/fped.2023.1178919. eCollection 2023.
JAK inhibitors are useful in treating interferonopathies, presumably because they downregulate the JAK/STAT signaling. There are limited studies about the safety and effectiveness of using JAK inhibitors in children with -related disorders.
We report an 8-year-old female who presented at five years of age with features suggestive of hemophagocytic lymphohistiocytosis (HLH)-like disorder. The infectious disease workup was negative. Neurological assessment was normal. A brain CT scan was performed because of headache. It showed a faint subcortical calcification at right frontal lobe and almost symmetrical calcification within the basal ganglia. Brain MRI showed bilateral symmetrical globus pallidus, high T1 signal intensities, and a few scattered nonspecific FLAIR hyperintensities in subcortical and deep white matter. IVIG as an immune modulating agent was administered initially which led to the resolution of fever, improvement of blood count parameters, inflammatory markers, and normalization of liver enzymes. The child remained afebrile with no significant events for several months, then had disease flare up. The patient was started on pulse methylprednisolone 30 mg/kg for three days, then continued on 2 mg/kg. Whole exome sequencing revealed a novel heterozygous missense mutation NM_016381.3:c.223G > A p.(Glu75Lys). The child was started on ruxolitinib, 5 mg orally twice daily. The child has prolonged, durable remission after initiating ruxolitinib with no adverse effects. Steroids were tapered off and the patient is no longer on IVIG. The patient is still on ruxolitinib for more than two years.
This case highlights the potential role of ruxolitinib in the treatment of -related disorders. A longer follow-up period is required to evaluate the long-term outcome.
JAK抑制剂可用于治疗干扰素病，可能是因为它们能下调JAK/STAT信号传导。关于在患有相关疾病的儿童中使用JAK抑制剂的安全性和有效性的研究有限。
我们报告一名8岁女性，她在5岁时出现提示噬血细胞性淋巴组织细胞增生症（HLH）样疾病的特征。传染病检查结果为阴性。神经学评估正常。因头痛进行了脑部CT扫描。结果显示右额叶有轻微的皮质下钙化，基底神经节内有几乎对称的钙化。脑部MRI显示双侧对称的苍白球、T1高信号强度，以及皮质下和深部白质中有一些散在的非特异性液体衰减反转恢复序列（FLAIR）高信号。最初给予静脉注射免疫球蛋白（IVIG）作为免疫调节剂，这导致发热消退、血细胞计数参数改善、炎症标志物改善以及肝酶正常化。该儿童数月来一直无发热，无重大事件发生，随后病情复发。患者开始接受脉冲甲基强的松龙30mg/kg治疗三天，然后继续以2mg/kg治疗。全外显子测序发现一个新的杂合错义突变NM_016381.3:c.223G＞A p.(Glu75Lys)。该儿童开始口服鲁索替尼，5mg，每日两次。开始使用鲁索替尼后，该儿童获得了长期、持久的缓解，且无不良反应。逐渐减少了类固醇药物用量，患者不再使用IVIG。该患者仍在使用鲁索替尼超过两年。
本病例突出了鲁索替尼在治疗相关疾病中的潜在作用。需要更长的随访期来评估长期疗效。
