Langerhans cell histiocytosis (LCH) is a rare disease, affecting subjects of any age, with extremely variable clinical manifestations. Although most patients with LCH have localized disease, requiring local or even no therapy, those patients with disseminated, 'multi-system' disease require specific therapy because they may be at risk for morbidity or even mortality. The current standard of care has developed empirically, based mainly on the experience of treating children with leukaemia and other haemo-proliferative disorders. At the time of writing, the combined use of vinblastine and prednisone remains the standard of care for children with multi-system LCH. The combination of cytarabine and cladribine is the current standard for second-line therapy of refractory cases with vital organ dysfunction. Recent advances in the knowledge of the pathogenesis of LCH may support a change in treatment strategy. Evidence of mutations that aberrantly activate RAF/MEK/ERK signalling in over two thirds of patients with LCH may direct a target therapy strategy. Vemurafenib, a small molecule widely used in the treatment of melanoma, is the main candidate for testing in prospective trials for patients with evidence of BRAF(V) (600E) mutation on lesional tissue. Additional molecules, including the recently approved trametinib, could follow. Identification of mutations in other genes in the remaining multisystem LCH cases could contribute to define a scenario in which target therapy becomes the main therapeutic choice in this intriguing disorder. However, because the long-term risks and benefits of these agents in children are unknown, and other effective treatments exist for many LCH patients, the optimal indications for administering a tyrosine kinase inhibitor to children is an open question.
Keywords: MAP2K1; RAF; histiocytosis; vemurafenib.
© 2016 John Wiley & Sons Ltd.