Langerhans cell histiocytosis (LCH), also called Histiocytosis X, is a rare disease characterized by the proliferation and accumulation of Langerhans cells in various tissues.
Langerhans cell histiocytosis may present with a variety of non-specific and specific inflammatory symptoms in various organs of the body.
Non-specific symptoms include fever, lethargy and weight loss. Involvement of organs causes specific symptoms.
The diagnosis of langerhans cell histiocytosis is confirmed histologically by biopsy. Other investigations are carried out to determine the extent of disease.
In addition, certain other tests are carried out to determine the severity and extent of the disease process. These include:
Treatment of langerhans cell histiocytosis mainly depends upon the extent of disease and the involvement of different organ systems of the body.
In case of solitary bone disease, the treatment is through excision or limited radiation. The dosage of radiation for children is 5 to 10 Gys while for adults is 24 to 30 Gys.
If there is systemic involvement, the use of steroids may be helpful in treatment. Based upon the severity of the disease, steroid therapy may be used alone or as adjunct to chemotherapy. Low to moderate doses of prednisolone, methoteraxate and vinblastin are used.
For patients with diabetes insipidus, desmopressin is an effective medication.
Other treatments may include:
The prognosis of patients with langerhans cell histiocytosis is determined by the severity of the disease. Unifocal disease carries a good prognosis while the outlook of patients with diffuse and refractory disease is poor. Complications arise in around 30 to 50% of the patients and are more common in those suffering from multifocal disease . Common complications are skeletal abnormalities, diabetes insipidus, hearing impairment, skin scarring and neurodegenerative disorders. Less frequent sequlae are pulmonary dysfunction, liver cirrhosis, malignancies and growth retardation.
Langerhans cell histiocytosis is is a non-inherited disease, although familial clustering is seen in a few cases. There is no specific infectious or hereditary cause of langerhans cell histiocytosis. Some studies suggest that activating mutation in the BRAF proto-oncogene can be responsible for this condition . This mutation has been detected in 35 of 61 biopsy samples of the patients with langerhans cell histiocytosis. Out of these, 76% of the patients were younger than 10 years and 44% were older than 10 years of age.
Langerhans cell histiocytosis is a rare disease affecting children 0 to 15 years of age. There are approximately 4 cases per million population . The estimated annual incidence rate in the United States is 0.5 to 5.4 cases per million persons. The incidence rate among adults is about 1 in 560, 000 individuals per year. The disease occurs more commonly in Caucasian males, with a male to female ratio of 1:2.
The pathophysiological mechanism of langerhans cell histiocytosis is debatable and it is not clear whether this disease is a reactive or neoplastic condition.
There are several remissions during the course of the disease which suggest that this disease is a reactive disorder . Furthermore, the elaboration of several pro-inflammatory cytokines by dendritic cells and T-cells as well as no consistent genetic abnormalities in the patients also support the idea of langerhans cell histiocytosis as a reactive disorder  .
On the contrary, there are several pathogenic mechanisms which favor the possibility of a neoplastic pathophysiology. In langerhans cell histiocytosis, organs are infiltrated by monoclonal population of abnormal langerhans cells . Also several of the anti-cancer modalities of treatment are effective against the disease.
The organ damage and characteristic lesions of langehans cell histiocytosis has been speculated to be due to proliferation of semi-mature dendritic cells. These abnormal misguided cells are recruited to specific sites in the body where they stimulate a cellular immune response which is responsible for the lesions at these anatomic sites. Specific findings from immunohistochemical and immunoflourescence analysis show a role of immune dysfunction in the pathogenesis of the disease. It is hypothesized that immature dendritic cells stimulate the regulatory T-cells which prevent the resolution of the lesions of this disease by inhibiting the immune response.
The role of interlukin-17 in causing inflammation and cellular destruction in this disease is also under investigation but it is still controversial .
There are no proven preventine measures against Langerhans cell histiocytosis.
Langerhans cell histiocytosis is a rare idiopathic disorder characterized by excessive proliferation of langerhans cells, the antigen presenting immune cells found in the skin. There is accumulation of immature langerhans cells juxtaposed against a background of T-cells, macrophages and eosinophils. In addition to the epidermal langerhans cells, other cell types like dermal langerin+ dedritic cells, lymphoid tissue-resident langerin+ dendritic cells, and monocytes can also be the potential cellular origins for langerhans cell histiocytosis because these cell types are capable of acquiring phenotypic characteristics of langerhans cells  . The disease causes a number of non-specific as well as specific inflammatory symptoms affecting bones, bone marrow, skin, lungs and endocrine organs etc. Langerhans cell histiocytosis usually affects children; the peak age of incidence being 5 to 15 years. Adults are less commonly affected.
Clinically, it is classified into three types:
Langerhans cell histiocytosis in a disorder of specific cells present in the skin and bone marrow. Their main function is to fight off infections but in this condition, there is accumulation of abnormal form of these cells in the blood and they cause damage to various organs of the body including bones, lungs, skin and liver etc. The disease commonly affects children. The treatment and prognosis depends upon severity of the disease process with an overall good outcome.