Key Points• Treatment with vemurafenib induced a dramatic response in 3 patients with histiocytosis harboring BRAF V600E mutations.• Tumor response was observed in both Erdheim-Chester disease and Langerhans cell histiocytosis. IntroductionErdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, characterized by the infiltration of tissues by foamy CD68 ϩ CD1a Ϫ histiocytes. 1 It is a systemic disease with diverse manifestations: the clinical course mainly depends on the extent and distribution of the disease, and ranges from asymptomatic bone lesions to life-threatening manifestations. 2 Rare cases of ECD associated with Langerhans cell histiocytosis (LCH) have been reported. 3 Unlike ECD, LCH histiocytes are CD1a ϩ and frequently infiltrate the epidermis in skin lesions. 4 Interferon ␣ (IFN) is generally the first choice for ECD therapy and improves survival. It should be prescribed at high dose if there is central nervous system and/or cardiovascular involvement. 2 However, long-term IFN treatment can lead to severe side effects and some patients are refractory to treatment. Moreover some patients with CNS and/or cardiovascular infiltrations develop secondary resistance to high-dose of IFN. Alternative treatments include recombinant human interleukin-1 receptor antagonist, cladribine, thyrosine kinase inhibitors, autologous hematopoietic stem cell transplantation. 2 However, the optimal second line therapeutic strategy remains to be defined, mostly because these treatments have been evaluated in only small numbers of patients. Despite recent therapeutic progress the overall mortality remains high (18% of the 84 ECD patients seen at our institution). BRAF V600E mutations have been observed in 38% to 69% of cases of LCH. [5][6][7] We recently reported BRAF V600E mutations in 54% of 24 patients with ECD. 8 Vemurafenib, an inhibitor of mutant BRAF, has shown some efficacy against 2 diseases (melanoma and hairy-cell leukemia) associated with the BRAF V600E mutation. 9,10

Vemurafenib has an objective and sustained efficacy in BRAF(V600E)-mutated ECD as second-line therapy. In contrast to melanoma, no resistance has emerged to date after 6 to 16 months.

RI, et al. Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advancedstage Hodgkin lymphoma: an intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496).

Anti-NMDA-Receptor encephalitis is a severe form of encephalitis that was recently identified in the context of acute neuropsychiatric presentation. Here, we describe the case of a 17-year-old girl referred for an acute mania with psychotic features and a clinical picture deteriorated to a catatonic state. Positive diagnosis of anti-NMDA-receptor encephalitis suggested specific treatment. She improved after plasma exchange and immunosuppressive therapy. Post-cognitive sequelae (memory impairment) disappeared within 2-year follow-up and intensive cognitive rehabilitation.

Erdheim-Chester disease (ECD) is a rare, non-Langerhans histiocytosis, characterized by the infiltration of tissues by foamy CD68(+)CD1a(-) histiocytes. (99)Technetium bone scintigraphy revealing almost constant tracer uptake by the long bones is highly suggestive of ECD, and a 'hairy kidney' appearance on abdominal computed tomography scan is observed in about half of all ECD cases. CNS involvement is a strong prognostic factor and independent predictor of death. IFN-α seems to be the best initial treatment for ECD. More than half of all ECD patients carry the BRAF(V600E) mutation. More than 30 patients worldwide harboring this mutation and displaying multisystemic, refractory ECD have been treated with vemurafenib, a BRAF inhibitor, which has proven highly beneficial. Other recurrent mutations of the MAPK and PIK3 pathways (NRAS, PIK3CA) have recently been described. These mutations should lead to a new classification of histiocytic disorders such that Langerhans cell histiocytosis and ECD are classified as inflammatory myeloid neoplasms.

In patients with healthy native kidneys, long-term cyclosporine therapy, even at a low dose (5 mg/kg per day), is nephrotoxic and is associated with a high incidence of hypertension.

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Radiofrequency ablation is an effective technique in terms of pain relief and functional recovery for the treatment of bone metastases, which provides a relatively low rate of local recurrence.