Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Laboratory of Parasitology, Department of Bacteria, Parasites, and Fungi, Statens Serum Institut, Copenhagen, Denmark.
J Intern Med. 2023 Jun;293(6):782-790. doi: 10.1111/joim.13638. Epub 2023 Apr 12.
Neoehrlichia mikurensis (N. mikurensis) is a newly discovered tick-borne pathogen that can inflict life-threatening illness in immunocompromised patients. N. mikurensis infection is only detectable by polymerase chain reaction (PCR)-based methodologies. We describe three distinct clinical manifestations of N. mikurensis infection (neoehrlichiosis) in Danish patients receiving B-lymphocyte-depleting therapy, rituximab, for underlying hematological, rheumatological, or neurological disorders. All three patients went through a protracted pre-diagnostic period.
N. mikurensis DNA was detected and confirmed using two methods. Blood was tested by specific real-time PCR targeting the groEL gene and by 16S and 18S profiling followed by sequencing. Bone marrow was analyzed by 16S and 18S profiling.
N. mikurensis was detected in blood samples in all three cases and in bone marrow from one of the three. The severity of the symptoms ranged from prolonged fever lasting more than 6 months to life-threatening hyperinflammation in the form of hemophagocytic lymphohistiocytosis (HLH). Interestingly, all patients presented with splenomegaly and two with hepatomegaly. After starting doxycycline therapy, symptoms were relieved within a few days, and biochemistry and organomegaly quickly normalized.
We present three Danish patients recognized by the same clinician over a period of 6 months, strongly suggesting that many cases are going unrecognized. Second, we describe the first case of N. mikurensis-induced HLH and emphasize the potential severity of undetected neoehrlichiosis.
新立克次体（N. mikurensis）是一种新发现的蜱传病原体，可对免疫功能低下的患者造成危及生命的疾病。N. mikurensis 感染只能通过聚合酶链反应（PCR）为基础的方法检测到。我们描述了三名丹麦患者在接受 B 淋巴细胞耗竭治疗（利妥昔单抗）时发生的三种不同临床表现（新立克次体病），这些患者存在血液学、风湿学或神经病学基础疾病。所有三名患者都经历了一个延长的预诊断期。
使用两种方法检测和确认 N. mikurensis DNA。血液通过针对 groEL 基因的特定实时 PCR 进行检测，并通过 16S 和 18S 分析进行测序。骨髓通过 16S 和 18S 分析进行分析。
在所有三个病例的血液样本中均检测到 N. mikurensis，在三个病例中的一个骨髓样本中也检测到。症状的严重程度从持续超过 6 个月的长时间发热到以噬血细胞性淋巴组织细胞增生症（HLH）形式的危及生命的过度炎症不等。有趣的是，所有患者均表现为脾肿大，两名患者表现为肝肿大。开始使用多西环素治疗后，症状在几天内得到缓解，生化和器官肿大迅速正常化。
我们提出了在 6 个月期间由同一位临床医生识别的三名丹麦患者，这强烈表明许多病例未被识别。其次，我们描述了首例由 N. mikurensis 引起的 HLH，并强调了未被发现的新立克次体病的潜在严重程度。
