Langerhans cell histiocytosis (LCH) is a rare disease of the immune system that may affect any age group. It can affect many different organs, including the skeleton, skin, lymph nodes, liver, lungs, spleen, the hematopoietic system, or central nervous system (CNS). Accordingly, the range of clinical symptoms is wide. There are two widely recognized disease extent categories: single-system LCH (SS-LCH; involvement of a single organ or system) and multisystem LCH (involvement of 2 or more organ systems). Patients with SS-LCH of the skeleton, skin, or the lymph nodes have an excellent prognosis and are felt to need a minimum or sometimes even no treatment at all.

The course of multisystem LCH (MS-LCH) is unpredictable upon diagnosis, ranging from spontaneous resolution to fulminant progression and fatal outcome. Involvement of crucial organs like the hematopoietic system, liver, or spleen has been found to herald a poor prognosis in different studies. Recent large clinical trials have shown that the response to initial treatment is a highly important prognostic factor. MS-LCH patients without involvement of “risk organs” have an excellent survival probability (>95%) when treated with a standard regimen consisting of vinblastine and steroids. In contrast, involvement of risk organs carries the risk of unfavourable outcome, particularly when combined with non-response to initial treatment.

Patients with reactivations or chronic disease may experience severe permanent consequences (hormone deficiencies, a neurodegenerative syndrome, lung fibrosis, etc.) reducing the patient’s quality of life.