Treatment of Cerebral Histiocytosis With Low Dose of Cobimetinib: A Report of 2 Cases.

Autor:	Schubert C; From the Institute of Neuroimmunology and Multiple Sclerosis (INIMS) (C.S., I.S., M.A.F.); Department of Neurology (C.S., I.S., S.C.F., M.A.F.), University Medical Center Hamburg-Eppendorf, Germany; and Pathology Department (J.-F.E.), Paris-Saclay University, Versailles SQY University (UVSQ), EA4340-BECCOH, Assistance Publique-Hôpitaux de Paris (APHP), Ambroise-Paré Hospital, Boulogne-Billancourt, France., Schiffmann I; From the Institute of Neuroimmunology and Multiple Sclerosis (INIMS) (C.S., I.S., M.A.F.); Department of Neurology (C.S., I.S., S.C.F., M.A.F.), University Medical Center Hamburg-Eppendorf, Germany; and Pathology Department (J.-F.E.), Paris-Saclay University, Versailles SQY University (UVSQ), EA4340-BECCOH, Assistance Publique-Hôpitaux de Paris (APHP), Ambroise-Paré Hospital, Boulogne-Billancourt, France., Farschtschi SC; From the Institute of Neuroimmunology and Multiple Sclerosis (INIMS) (C.S., I.S., M.A.F.); Department of Neurology (C.S., I.S., S.C.F., M.A.F.), University Medical Center Hamburg-Eppendorf, Germany; and Pathology Department (J.-F.E.), Paris-Saclay University, Versailles SQY University (UVSQ), EA4340-BECCOH, Assistance Publique-Hôpitaux de Paris (APHP), Ambroise-Paré Hospital, Boulogne-Billancourt, France., Emile JF; From the Institute of Neuroimmunology and Multiple Sclerosis (INIMS) (C.S., I.S., M.A.F.); Department of Neurology (C.S., I.S., S.C.F., M.A.F.), University Medical Center Hamburg-Eppendorf, Germany; and Pathology Department (J.-F.E.), Paris-Saclay University, Versailles SQY University (UVSQ), EA4340-BECCOH, Assistance Publique-Hôpitaux de Paris (APHP), Ambroise-Paré Hospital, Boulogne-Billancourt, France., Friese MA; From the Institute of Neuroimmunology and Multiple Sclerosis (INIMS) (C.S., I.S., M.A.F.); Department of Neurology (C.S., I.S., S.C.F., M.A.F.), University Medical Center Hamburg-Eppendorf, Germany; and Pathology Department (J.-F.E.), Paris-Saclay University, Versailles SQY University (UVSQ), EA4340-BECCOH, Assistance Publique-Hôpitaux de Paris (APHP), Ambroise-Paré Hospital, Boulogne-Billancourt, France.
Jazyk:	angličtina
Zdroj:	Neurology(R) neuroimmunology & neuroinflammation [Neurol Neuroimmunol Neuroinflamm] 2024 May; Vol. 11 (3), pp. e200233. Date of Electronic Publication: 2024 Apr 08.
DOI:	10.1212/NXI.0000000000200233
Abstrakt:	Objectives: Histiocytic disorders are pathologic expansions of myeloid cells in multiple organs, including the CNS. They share activation of the MAP kinase pathway due to either BRAF V600E variant or other variants in the RAS-RAF-MEK-ERK pathway. The rarity and heterogeneity of the disease only enable therapy through pathophysiologic considerations. Methods: We present 2 histiocytosis cases without BRAF sequence variants that affect the CNS, one with Erdheim-Chester disease and the other with an unspecified histiocytosis, and their diagnostic and therapeutic challenges. Results: In both cases, comprehensive analysis of the RAS-RAF-MEK-ERK signaling pathway secured the diagnosis. Treatment with the MEK inhibitor cobimetinib brought the disease to a complete halt. However, side effects such as thrombosis and serous macular edema made it necessary to reduce cobimetinib dosage. Low-dose cobimetinib maintenance medication was successful in preventing recurrence of histiocytic disease. Discussion: CNS involvement of histiocytic disorders can lead to detrimental neurologic symptoms. MEK inhibitors are effective treatment options for some of these patients. Since side effects are common, according to our cases we propose a low-dose treatment of 20 mg per day to balance treatment effects with side effects. Classification of Evidence: This case report provides Class IV evidence. This is a single observational study without controls.
Databáze:	MEDLINE
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