Histiocytosis (HIS-tee-oh-sy-TOH-sis) is the name given to a rare family of diseases affecting only a small number of people each year in the country. This condition begins when the body produces an excessive number of white blood cells known as histiocytes. While these cells are normally part of the immune system, helping to absorb and remove bacteria and other foreign substances, in histiocytosis, they can build up and form tumours in various parts of the body, most commonly in the bones and skin.
The SSCHRC team cares for more adults with this condition than any other hospital in the country, and our SSCHRC Paediatrics team is highly experienced in the care of children with histiocytosis.
Histiocytes are a type of white blood cell produced in the bone marrow.
The condition is characterised by the overproduction of these cells, which can then accumulate to form lesions or tumours anywhere in the body.
Recent research indicates that histiocytosis is caused by genetic changes (mutations or variants). This research has classified histiocytic diseases as neoplastic (cancerous) blood disorders, which is why they are managed by cancer experts.
There are numerous types, ranging from mild forms to very severe ones. Some are more prevalent in specific age groups.
| Types of Histiocytosis | Predominant Age Group |
|---|---|
| Langerhans Cell Histiocytosis (LCH) | Most common in children (newborns up to age 4), but affects adults too. |
| Rosai-Dorfman Disease (RDD) | Most common in children, but affects adults too. |
| Juvenile Xanthogranuloma (JXG) | Rare, primarily affects infants and toddlers. |
| Erdheim-Chester Disease (ECD) | Primarily affects adults (average age of diagnosis is about 50). |
| Adult Xanthogranuloma (AXG) | Rare, starts in older people. |
| Malignant Histiocytic Disorders | Very rare and aggressive (e.g., Histiocytic Sarcoma). |
Histiocytosis symptoms often overlap with those of other diseases, making diagnosis challenging.
Histiocytosis can affect various areas of the body, leading to localised symptoms:
Rashes that may appear as red, yellow, or purplish patches or bumps. These can be painful or itchy.
Tumours in weight-bearing bones can cause intense pain and increase the risk of fractures.
Tumours near the sinuses may cause discomfort behind the face. Tumours around or behind the eyes can lead to bulging eyes or vision problems.
Can result in difficulties with balance, hormonal imbalances, headaches, weakness, reduced sensation, and impaired thinking.
Tumours in organs such as the kidneys, liver, spleen, lungs, or lymph nodes can cause swelling and compromise organ function.
Most often presents with skin rashes (sometimes very painful, affecting about half of patients) and pain and swelling in bones, particularly the skull, jaw, or hips (lesions in bones are seen in nearly 4 out of 5 patients). Rare but serious brain involvement can cause balance, speech, and coordination problems.
Common signs include swollen lymph nodes in the neck, chest, groin, or armpits. Skin lumps may be itchy and painful. Other general symptoms include fever, night sweats, and a general feeling of illness. Lesions in bones, sinuses, and internal organs are less common.
Common symptoms are pain in the bones or joints (affecting nearly everyone with ECD), weakness and extreme fatigue, fevers, and night sweats. Depending on the site, it can cause kidney, blood vessel, heart, or lung issues (leading to shortness of breath and leg/foot swelling), eye problems, and neurological issues affecting coordination, balance, speech, mood, thinking, and memory.
Both typically begin as a single skin lesion. Rarely, they can affect the bones, eyes, and brain.
A correct diagnosis can be difficult due to the disease's rarity and symptoms that mimic other health conditions. SSCHRC has experts who specialise in recognising the signs of histiocytosis. Diagnosis typically involves:
A biopsy to obtain a tissue sample is often performed on the affected areas.
Since some treatments are targeted at specific genetic changes, doctors often test the tissue sample for known histiocytosis-related gene mutations. For instance, about half of people with ECD and LCH have BRAF genetic mutations. SSCHRC utilises an advanced tumour tissue test called SSCHRC-IMPACT®, which helps doctors match patients with the best available targeted therapies.
If a tumour sample is unavailable or insufficient, SSCHRC-ACCESS® may be used. This liquid biopsy blood test checks for 129 key genes linked to cancer, helping to establish the tumour's genetic profile and monitor disease status.
Imaging tests are crucial to identify the areas affected by histiocytosis.
The necessity of these tests depends on the type of histiocytosis and the patient's symptoms.
The treatment plan for histiocytosis is highly individualised and is based on: the type of histiocytosis, the location of the disease, how many parts of the body are affected, and the speed of disease progression.
SSCHRC brings together a multidisciplinary care team of experts to discuss each case and determine a tailored plan of care, focusing on the latest therapies and managing side effects to ensure the best possible quality of life.
For mild forms (like some LCH, RDD, and ECD), or when the disease is only in the skin (in infants with LCH or JXG), the patient may only need regular exams and tests.
May be the only necessary treatment if the disease affects only one area (unifocal LCH, JXG, AXG). It can also be used to remove part of a tumour that is pressing on a vital area, such as the eye, to improve symptoms. It is rarely used for ECD and RDD.
Often used for adults with histiocytosis affecting a single area. It is effective for LCH, but less useful for multi-system diseases like ECD. Low-dose radiation may be used for JXG eye lesions to prevent vision loss. It is rarely used for RDD and AXG in general, and rarely for children with LCH.
Uses strong drugs to slow or stop the growth of abnormal cells. It is used when the disease affects multiple areas, is growing fast, or is harder to cure (e.g., LCH in the liver, spleen, brain).
Common drugs include:
Vinblastine (often combined with prednisone), 6-mercaptopurine, Methotrexate, Cytarabine, Cladribine (2-CDA), Clofarabine, and Hydroxyurea. Mild chemotherapy is often preferred for children and teens to minimise long-term organ harm.
Drugs that regulate an overactive immune system to help manage histiocytosis symptoms.
Examples include: Prednisone (a standard therapy for initial LCH diagnosis, often with vinblastine and 6-mercaptopurine), Interferon-alpha (sometimes used for ECD), and Anakinra (for ECD, helps with swelling).
These treatments target the specific gene mutations that drive the disease.
Examples include: Vemurafenib (Zelboraf®) and other BRAF inhibitors (e.g., Dabrafenib, Encorafenib) for BRAF mutations found in about half of ECD and LCH patients. Cobimetinib (Cotellic®) and other MEK inhibitors (e.g., Trametinib, Binimetinib) are also used for LCH in adults, ECD, and RDD.
Research studies that test new treatments, drug combinations, and procedures. These trials offer access to new therapies not yet widely available and are an important part of advancing treatment for histiocytosis.
After treatment, patients are monitored regularly for several years or longer to watch for signs of disease recurrence and any late side effects from the treatment, including complications that may arise as a child grows into adulthood. Follow-up may include physical exams, blood tests, biopsies, heart function tests, and imaging scans (CT and MRI).
SSCHRC offers a dedicated survivorship team to support patients in managing the lasting effects of histiocytosis and its treatment, focusing on health and wellness. Resources are available for: