Histiocytic disorders are a group of rare disorders characterised by the abnormal accumulation of histiocytes, a type of immune cell often found in tissues that regulates immune functions. There are three primary types of histiocytes, including monocytes (plays a role in inflammatory and anti-inflammatory responses during an immune response), macrophages (responsible for ingesting and eliminating foreign substances during an immune reaction), and dendritic cells (initiate and regulate the adaptive immune response).
Histiocytic disorders are broadly classified into five different groups: L group, C group, M group, R group, and H group. The L group, or Langerhans group, are classified as diseases involving Langerhans cells (an immune cell responsible for initiating an immune response when coming into contact with a foreign material), such as Langerhans cell histiocytosis (LCH). The C group, also known as cutaneous and mucocutaneous non-Langerhans cell histiocytosis, are classified as non-Langerhans cell histiocytic disorders that are localised to the skin or mucosal surfaces, such as the mouth, nose, and gastrointestinal system. The M group, also known as malignant histiocytic disorders, are classified by the presence of malignant (or cancerous) cells within the tumour(s). The R group, also known as Rosai-Dorfman disease and miscellaneous non-cutaneous non-Langerhans cell histiocytosis or sinus histiocytosis, are classified as non-Langerhans histiocytic disorders that often involve lymph nodes. The H group, also known as hemophagocytic lymphocytosis and macrophage activation syndrome, is composed entirely of hemophagocytic lymphohistiocytosis, a rare and aggressive disease caused by the overactivation of the immune system.
This page will focus specifically on H group histiocytic disorders, which is composed of hemophagocytic lymphohistiocytosis (HLH), also known as macrophage activation syndrome. HLH is a rare, life-threatening condition caused by excess production of histiocytes and lymphocytes, which accumulates and damages organs. While HLH is not cancerous, it is equally as serious.
H group histiocytic disorders are diagnosed equally among the sexes, and tends to be diagnosed before 18 months of age. However, anyone can develop this disease.
Treatment
Each patient with a H group histiocytic disorder will present with a unique disease behaviour, with varying locations, and symptoms. As such, there is no one treatment method that will work for everyone, and there is no standard staging system for this disease. Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:
- Tumour location.
- Whether or not the tumour(s) have spread.
- Your age.
- General health.
- Treatment preferences.
Your doctor may recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. Your doctor will discuss the most appropriate course of treatment for you.
Treatment options for an H group histiocytic disorder may include:
- Steroids.
- Chemotherapy.
- Immunosuppressive medications.
- Immunotherapy.
- Antibiotic drugs.
- Antiviral drugs.
- Stem cell transplant.
- Clinical trials.
- Palliative care.
For more information on the treatment options, please refer to the Rare Cancers Australia treatment options page.
Risk factors
While the cause of HLH remains unknown, the following factors may increase the likelihood of developing of the disease:
- Having a family history of HLH.
- Certain genetic mutations, potentially including:
- PRF1 gene.
- UNC13D gene.
- STX11 gene.
- STXBP2 gene.
- Having certain genetic disorders, such as:
- Griscelli syndrome type 2.
- Chediak-Higashi syndrome.
- X-linked lymphoproliferative disorder.
- XMEN disease.
- Interleukin-2-inductible T cell kinase deficiency.
- CD27 deficiency.
- Hermansky-Pudlak syndrome.
- Lysinuric protein intolerance.
- Chronic granulomatous.
- Viral infections, such as the Epstein-Barr virus.
- Bacterial infections.
- Viral infections.
- Fungal infections.
- Parasitic infections.
- Being immunocompromised.
- Autoimmune diseases.
- Autoinflammatory diseases.
- Rheumatological diseases, such as:
- Systemic juvenile idiopathic arthritis.
- Systemic lupus erythematosus.
- Vasculitis.
- Metabolic disorders.
- Having cancer, such as:
Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.
Early symptoms
Symptoms of HLH may include:
- Fever.
- Enlarged spleen (splenomegaly).
- Cytopenias, such as:
- Anaemia (low count of red blood cells, which carry oxygen).
- Neutropenia (low count of white blood cells, which fight infection).
- Thrombocytopenia (low count of platelets, which help clot blood and prevent blood loss).
- Enlarged liver (hepatomegaly).
- Swollen lymph nodes (lymphadenopathy).
- Jaundice (yellowing of the skin and the whites of the eyes).
- Skin rashes.
- Lung problems, such as:
- Coughing.
- Difficulties breathing.
- Shortness of breath.
- Digestive problems, such as:
- Abdominal pain.
- Vomiting.
- Diarrhoea.
- Headaches.
- Difficulties walking.
- Changes in vision.
- General feeling of weakness and/or unwell.
- Easy bruising.
- Swollen and/or bleeding gums.
- Seizures.
- Difficulties with coordination.
- Paralysis on one side of the body (hemiplegia).
- Anorexia.
- Irritability.
- Failure to thrive.
- Fatigue.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis/diagnosing
If your doctor suspects you have a H group histiocytic disorder, they will order a range of diagnostic tests to confirm the diagnosis, and refer you to a specialist for treatment.
Physical examination
Your doctor will collect your overall medical history, as well as your current symptoms. Following this, they may examine your body to check for any abnormalities. More specifically, they will examine the suspicious lesion, papule and/or nodule.
Neurological examination
A neurological examination assesses sensory and motor functions, and can generally be done in your GPs office. The doctor may check your vision, hearing, balance, coordination, strength, and reflexes, depending on the signs and symptoms you have described. Any problem that is detected in this exam can help determine which portion of the CNS needs further investigation.
Imaging & blood tests
The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), positron emission tomography scan (PET scan) and/or ultrasound, depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and looks for signs of metastasis. Additionally, a blood test may be taken to assess your overall health and help guide treatment decisions.
Lumbar puncture
A lumbar puncture, or spinal tap, involves inserting a needle between two vertebrae in the lower spine and extracting a sample of cerebral spinal fluid (CSF) for analysis. A local anaesthetic or sedative is given prior to the procedure. Your doctor will discuss any risks and possible complications with you prior to the procedure.
Bone Marrow Aspiration
A bone marrow aspiration is a process that involves inserting the needle into the hipbone (or breastbone in some cases) to remove samples of solid and liquid bone marrow. These samples will then be analysed for cancer cells.
Biopsy
Once the location of the cancer has been identified, the doctor will perform a biopsy to remove a section of tissue using a needle. This tissue will then be sent to the lab and analysed for cancer cells.
Prognosis (Certain factors affect the prognosis and treatment options)
While it is not possible to predict the exact course of the disease, your doctor may be able to give you a general idea based on the rate and depth of tumour growth, susceptibility to treatment, age, overall fitness, and medical history. Generally, early-stage H group histiocytic disorders have a better prognosis and survival rates. However, if the tumour has become malignant and spread, the prognosis may not be as good and there may be a higher risk of recurrence. It is very important to discuss your individual circumstances with your doctor to better understand your prognosis.
References
Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.