Erdheim-Chester disease is a rare histiocytosis characterized by multi-systemic organ involvement. Immune-modulating agents such as interferon-alpha have limited success and the disorder is progressive and causes high morbidity and mortality. Treatment with the BRAF-inhibitor vemurafenib has recently produced substantial improvement in three patients with Erdheim-Chester disease expressing the p. V600E BRAF mutation. The disorder commonly affects the central nervous system and it is not yet known whether vemurafenib can reverse intra-axial infiltration and the resulting neurological impairment.

In this work, we report for the first time an excellent clinical response to vemurafenib in a Norwegian patient with debilitating progressive spastic paraparesis due to intra-axial infiltration of the thoracic spinal cord. The patient had been unresponsive to interferon-alpha. Low dose vemurafenib (720 mg daily) for a period of three months resulted in significant tumor shrinkage by >60% and regression of contrast enhancement and fluorodeoxyglucose uptake on positron-emission tomography. The patient’s spastic paraparesis and gait function improved dramatically. She currently walks unaided and reports a substantially improved quality of life.

Our findings show that vemurafenib therapy, even at low doses, can be effective for the treatment of intra-axial central nervous system involvement in BRAF-positive Erdheim-Chester disease.