Histiocytoses affect white blood cells called histiocytes, which are important for preventing infections.

In Langerhans cell histiocytosis (LCH), abnormal histiocytes, called Langerhans dendritic cells accumulate and damage many organs.

In Haemophagocytic Lymphohistiocytosis (HLH), abnormal histiocytes accumulate in the bone marrow, liver, spleen and lymph nodes and destroy the immune system, leaving the patient vulnerable to infections.

In Rosai-Dorfman disease large numbers of histiocytes accumulate in lymph nodes.


Medical text written August 2016 by Professor P Beverley of Histio UK, UK.

Although great care has been taken in the compilation and preparation of all entries to ensure accuracy, we cannot accept responsibility for any errors or omissions. Any medical information is provided is for education/information purposes and is not designed to replace medical advice by a qualified medical professional.

What are the symptoms?

LCH may occur at any age. It is very variable, ranging from limited skin rashes or bone changes to a severe illness involving many organs, including the brain. The pituitary gland, which controls water balance is often affected, so that patients may drink large volumes of liquid and pass dilute urine. Children may not grow because of a lack of growth hormone.

HLH is a severe disease commonly triggered by infections, with symptoms depending on the infection, but patients are often very ill with a high fever. Patients may bleed or become very anaemic because of damage to the bone marrow.

Rosai-Dorman disease presents with swelling of lymph nodes (typically in the neck). There may be general ill health with fever and changes in the blood cell numbers (cell count).

What are the causes?

Fifty per cent of LCH tissue samples have a mutation in a gene (called BRAFV600E). Related mutations are usually present in the BRAFV600E negative cases. These mutations cause the proliferation of Langerhans cells.

Primary HLH, which occurs in very young children, is an inherited disorder with mutations in genes affecting the function of white blood cells. Secondary HLH occurs in association with other inherited abnormalities of immunity, in patients with tumours or those receiving immunosuppressive treatment.

How is it diagnosed?

Blood tests, examination of a tissue sample (biopsy), scans, x-rays and bone marrow or lumbar puncture may be performed. Diagnosis of LCH or HLH may be confirmed by genetic tests for mutations known to cause these diseases.

How is it treated?

Localised LCH may be treated with corticosteroids or surgery. More extensive disease is treated with combinations of cytotoxic drugs such as vinblastine, vincristine, etoposide (VP-16), methotrexate, cytosine arabinoside (Ara-C) and 6-MP. The use of Vemurafenib, which targets BRAFV600E, is being explored.

HLH is often triggered by infections, which are treated. Children with primary HLH usually require drug treatment with corticosteroids, cytotoxic chemotherapy or immunosuppressive drugs. Once the disease is under control, children with primary HLH generally receive a bone marrow transplant. Secondary HLH is controlled by treating the causes of the disease, but recurrent severe disease may require bone marrow transplantation.

Rosai-Dorfman disease may need treatment with steroids or cytotoxic drugs.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
LCH and Rosai-Dorfman are not inherited. Most primary HLH cases have an autosomal pattern of inheritance (one copy of a defective gene is inherited from each parent) and the disease is therefore more common in marriages between relatives. Secondary HLH patients may inherit mutations that predispose them to the disease.

Prenatal diagnosis
Prenatal diagnosis of HLH during pregnancy is possible if a genetic lesion has been identified in a previous affected child.

Is there support?

Histiocytosis UK (Histio UK)

Tel: 07850 740 241
Email: Histio@HistioUK.org
Website: histiouk.org

The Group is a National Registered Charity; No. 1158789. It provides information and support to individuals and families affected by histiocytic disorders. Histio UK promotes and funds scientific research into histiocytosis diseases, Langerhans’ Cell Histiocytosis and Haemophagocytic Lymphohistiocytosis.

Group details last updated August 2016.

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