Excellent response of intramedullary Erdheim-Chester disease to vemurafenib: a case report.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
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.
Department of Neurology, Haukeland University Hospital, Bergen, Norway. charalampos.tzoulis@helse-bergen.no.|Department of Clinical Medicine, University of Bergen, Bergen, Norway. charalampos.tzoulis@helse-bergen.no.
Charalampos
C
Tzoulis
Department of Clinical Medicine, University of Bergen, Bergen, Norway. thomas.schwarzlmueller@k1.uib.no.|Department of Nuclear Medicine, Haukeland University Hospital, Bergen, Norway. thomas.schwarzlmueller@k1.uib.no.
Thomas
T
Schwarzlmüller
Department of Neurology, Haukeland University Hospital, Bergen, Norway. ivar.otto.gjerde@helse-bergen.no.
Ivar Otto
IO
Gjerde
Department of Clinical Medicine, University of Bergen, Bergen, Norway. esofteland@gmail.com.|Department of Medicine, Haukeland University Hospital, Bergen, Norway. esofteland@gmail.com.
Eirik
E
Søfteland
Department of Radiology, Haukeland University Hospital, Bergen, Norway. gesche.frederike.neckelmann@helse-bergen.no.
Gesche
G
Neckelmann
Department of Clinical Medicine, University of Bergen, Bergen, Norway. martin.biermann@k1.uib.no.|Department of Nuclear Medicine, Haukeland University Hospital, Bergen, Norway. martin.biermann@k1.uib.no.
Martin
M
Biermann
Department of Internal Medicine & French reference center for rare auto-immune & systemic diseases, AP-HP. Pitié-Salpêtrière hospital, 47-83 bd de l'hôpital, 75013, Paris, France. julien.haroche@psl.aphp.fr.|Université Pierre et Marie Curie, UPMC Univ Paris 06, Paris, France. julien.haroche@psl.aphp.fr.
Julien
J
Haroche
Department of Oncology, Haukeland University Hospital, Bergen, Norway. oddbjorn.straume@helse-bergen.no.
Oddbjørn
O
Straume
Department of Pathology, Haukeland University Hospital, Bergen, Norway. olav.karsten.vintermyr@helse-bergen.no.|The Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway. olav.karsten.vintermyr@helse-bergen.no.
Olav Karsten
OK
Vintermyr
D000328:Adult; D031249:Erdheim-Chester Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D013131:Spine / Q000473:pathology*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D000077484:Vemurafenib
D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib