Elements: in this month’s issue Langerhans Cell Histiocytosis: an orphan disease

There is no single agreed definition of a rare disease. The European Commission on Public Health defines rare diseases as those which are ‘life-threatening or chronically debilitating and which are of such low prevalence that special combined efforts are needed to address them’. The term ‘orphan’ has been used in association with rare diseases in order to emphasise their relative neglect in terms of professional awareness and available therapeutic resources to need to deal with them. ‘Low prevalence’ in this context refers to less 1 in 2,000. By this standard, Langerhans Cell Histiocytosis (LCH), the subjects of this month’s review is a rare disorder indeed with a presumed prevalence of 2–10 per million children and 1–2 per million adults. It results from clonal proliferation of Langerhans cells which are dendritic cells found in the dermis and lymph nodes. LCH belongs to the group of disorders known as the histiocytoses and has been known by a number of previous names including Leterer-Siwe Disease and Histiocytoses X; the current terminology of Langerhans Cell Histiocytosis having been agreed by the Histiocyte Society in the mid 1980s. The aetiology is not known and clinical manifestations vary according to the extent of the disease process. Two broad categories are recognised: single and multisystem LCH. The review paper considers how LCH is now considered to be a malignant rather than a reactive disease process and this is reflected by its current treatment. In early stages smoking cessation is considered to be of benefit while more advanced disease may be successfully managed by use of steroids or chemotherapy. Newer therapeutic possibilities include the use of such agents as clofarabine and thalidomide. The study of rare disease is relevant for several reasons, not merely because of the impact of associated morbidity on effected individuals and their families. While individual disease may be rare, when considered collectively they are not uncommon. It is estimated that 30 million people have a rare disease in Europe alone. As one epidemiologist stated ‘rare diseases are common’ in that every clinician will have a number of patients with rare disorders. Many patients with rare diseases have experienced either delay in correct diagnosis and some of the disorders in this category are at least partly amenable to early intervention. Furthermore, enhanced understanding of the basic molecular pathology of very rare diseases often yields benefits for patients who have more common pathology.