Langerhans cell histiocytosis LCH is a rare entity of unknown origin currently considered as an orphan disease Multisystem involvement is frequent The disease is commonly associated with central diabetes insipidus CDI and other endocrinopathies such as hypothyroidism and type diabetes mellitus Few cases have been reported in children and the incidence rate in adults is estimated at one case per million LCH may cause single system or multisystem involvement with bone and lung as the most commonly affected organs The BRAF V E mutation is present in more than half of the cases and is strongly associated with the presence of CDI Currently there are no definite treatment guidelines for adults Cases of pulmonary involvement may respond to smoking cessation although local resection or systemic chemotherapy may be required LCH shows a good response to regimens based on vinblastine VB and prednisone PDN Here we report five adult cases diagnosed and treated at the National Institute of Cancerology in Colombia between and At some time point all of the patients had multisystem disease mainly bone involvement four showed an associated endocrine disorder particularly CDI and in two patients the genital tract was affected Three patients developed a metachronous cancer First line treatments were based on etoposide VB and PDN response was good Cladribine CdA was used as a rescue therapy in four cases reaching a global response rate of response was complete in four cases Excellent response to the rescue regimen with CdA suggests this might be an excellent first line treatment strategy