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

## TL;DR

A 46-year-old woman with mixed histiocytosis showed limited neurological improvement after delayed treatment with dabrafenib and trametinib.

## Contribution

This case highlights the importance of early diagnosis and treatment in mixed histiocytosis to improve neurological outcomes.

## Key findings

- Partial neurological improvement was observed after seven months of Dab/Tra therapy.
- The delayed initiation of treatment may have contributed to limited recovery.
- SARA and ICARS scores showed some improvement but remained significantly delayed.

## 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.