Dabrafenib and steroids for the treatment of Erdheim-Chester disease with extensive CNS involvement: a case report

Abstract

Erdheim-Chester disease (ECD) is an exceedingly rare non–Langerhans cell CD68⁺ CD1a^- S100^- histiocytic multi-organ disease. Diagnosis of ECD is often delayed due to non-specific radiographic findings and heterogeneous lesional tissue. Increasingly, the role of genomic alterations is being recognized for both diagnosis and treatment of ECD. More than half of ECD patients harbor the BRAF^V600E mutation. Evaluation for this mutation be can falsely negative on immunohistochemical staining and confirmation with molecular analyses is recommended. We present a case of the 44 year-old male with BRAF^V600E-positive ECD treated successfully with steroids followed by single-agent dabrafenib.

Plain language summary

Erdheim-Chester disease (ECD) is an exceedingly rare type of histiocytosis (a disorder of white blood cells). The diagnosis of ECD can be challenging because tissue biopsy may not provide a definitive diagnosis. Currently, genetic mutations can be used to support both diagnosis and treatment. We present a case of the 44 year-old male with BRAF V600E -positive ECD who was treated successfully with steroids followed by dabrafenib.

Executive summary

• Erdheim-Chester Disease (ECD) is exceedingly rare.

• ECD with central nervous system involvement can be refractory to conventional therapies.

• Steroids may be therapeutic for ECD.

• Molecular profiling should be obtained to assess for BRAF^V600E mutation, regardless of a negative immunohistochemical BRAF immunohistochemical staining.

• BRAF inhibitors should be considered as first-line therapy for BRAF^V600E-positive ECD patients.

Keywords: :

• BRAF V600E
• central nervous system
• CNS
• corticosteroids
• dabrafenib
• Erdheim-Chester Disease
• histiocytosis
• orbit
• pachymeninges
• steroids

Author contributions

C Yuen - study concept, data collection, analysis, interpretation, manuscript drafting, revision and final approval. S Bao - study concept, data collection, analysis, interpretation and final approval. M Sandi Aung & R Shishodia - data collection and final approval. X-T Kong - manuscript revision and final approval.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

X-T Kong received honorarium from Zai Lab for invited speeches for symposiums prior to July 2021. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved. Ethics approval and consent to participate: need for ethics approval was needed. Consent for publication: written consent was obtained. Availability of data and material: the datasets from this study are available from the corresponding author upon reasonable request. Funding: no funding was received for this manuscript.