Delayed Neurologic Response to Dabrafenib and Trametinib in the Case of Mixed Histiocytosis (LCH/ECD): Case Report and Literature Review

混合型组织细胞增生症(朗格汉斯细胞组织细胞增生症/埃尔德海姆-切斯特病)患者对达拉非尼和曲美替尼治疗的神经系统反应延迟:病例报告及文献综述

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Abstract

Background and Clinical Significance: Histiocytosis encompasses Langerhans cell histiocytosis (LCH) and non-LCH, such as Erdheim-Chester disease (ECD). ECD or a mixed type of histiocytosis (LCH/ECD) may initially involve the central nervous system (CNS), resulting in a delayed diagnosis. More recently, dabrafenib and trametinib (Dab/Tra regimen) have become available in its treatment. Case Presentation: A 46-year-old woman with CNS involvement of mixed histiocytosis (BRAF V600E-positive LCH/ECD) was treated with combination therapy using a Dab/Tra regimen. At initial presentation, she exhibited central diabetes insipidus, dysarthria, and gait disturbance with mild spasticity and ataxia, requiring walking assistance even for short distances. The interval from the onset of central neurological symptoms to diagnosis of mixed histiocytosis was 4 years. The introduction of targeted therapy was 2 years later. After seven months of Dab/Tra therapy, partial neurological improvement was observed, as reflected by a decrease in the SARA score from 21/40 to 13/40 and the ICARS score from 33/100 to 28/100. However, further neurological recovery remained significantly delayed. Conclusions: We suspect that the limited improvement may be attributable to the delayed initiation of targeted therapy, in contrast to the more rapid and pronounced responses reported in cases where treatment was started earlier.

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