Early diagnosis of early-onset sarcoidosis: a case report with functional analysis and review of the literature.
Early diagnosis of early-onset sarcoidosis: a case report with functional analysis and review of the literature.
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早发性结节病的早期诊断：功能分析和文献回顾的病例报告。
DOI：
10.1007/s10067-017-3544-6
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发表时间：
2017
影响因子：
3.4
通讯作者：
Agematsu K.
中科院分区：
文献类型：
--
作者：
Takeuchi Y;Shigemura T;Kobayashi N;Kaneko N;Iwasaki T;Minami K;Kobayashi K;Matsumoto J;Agematsu K.
本研究探讨了一例罕见nod2突变患者早发性结节病（EOS）的发病机制，并查阅文献以确定早期诊断的标志性特征。一名女婴因长时间发热及多发粉红色丘疹皮疹及结节性红斑而被转介至本院。皮肤活检和DNA测序以及患者血清和受刺激的单核细胞的细胞因子谱进行。用转染细胞分析NF-κB活化情况。在患者的皮疹活检标本中发现多个非干酪化肉芽肿包涵体。DNA测序显示一个非常罕见的杂合Met513Thr （M513T）突变inNOD2。与正常对照细胞相比，单核细胞在刺激时产生少量的IL-1β。mutatednod2转染增强NF-κB活化。我们怀疑M513T突变innod2降低了IL-1β的产生并增强了NF-κB的激活，这可能是导致患者肉芽肿的原因。对30例散发型EOS的文献进行全面回顾，发现所有患者均有皮肤表现，除一例外均有肉芽肿。大多数EOS患者为R334W/Q。但是大约一半的散发性EOS有NOD2突变，而不是R334W/Q，就像本病例一样。因此，伴有肉芽肿形成的皮疹和特定的nod2突变可能是持续炎症的婴儿EOS的早期诊断标志。
This study examined the pathogenesis of early-onset sarcoidosis (EOS) in a patient with a rareNOD2mutation and surveyed the literature to identify the hallmark features for early diagnosis. An infant girl suffering from prolonged fever and skin rash of multiple pinkish papules and subsequent erythema nodosum was referred to our institution. Skin biopsy and DNA sequencing were performed along with cytokine profiling of the patient’s serum and stimulated mononuclear cells. NF-κB activation was analyzed using transfected cells.Multiple non-caseating granuloma inclusions were recognized in biopsy specimens obtained from the patient’s rash. DNA sequencing revealed a very rare heterozygous Met513Thr (M513T) mutation inNOD2.Mononuclear cells produced a low amount of IL-1β upon stimulation as compared with normal control cells. MutatedNOD2transfection enhanced NF-κB activation. We suspected that the M513T mutation inNOD2decreased IL-1β production and enhanced NF-κB activation, which was likely responsible for the patient’s granuloma involvement. A comprehensive review of the literature on 30 cases of sporadic type of EOS revealed that all patients had cutaneous manifestations, with all but one displaying granulation. A majority of EOS patients have R334W/Q. But about half of sporadic EOS had NOD2 mutations other than R334W/Q, as in the present case. Accordingly, skin rash with granuloma formation and specificNOD2mutations may represent early diagnostic hallmarks of EOS in infants with persistent inflammation.