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 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 nodessmall bean-shaped structures that filters harmful substances from lymph fluid. 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 testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, 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:
- Corticosteroidsa type of anti-inflammatory medication that is used to treat inflammation.
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Immunosuppressive medication.
- Immunotherapya treatment that uses a person's immune system to fight cancer.
- Antibiotics.
- Antiviral medication.
- Stem cell transplanta procedure that involves replacing unhealthy blood-forming cells (stem cells) with healthy stem cells.
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
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:
- Lymphomas (especially non-Hodgkin lymphoma).
- Leukaemias.
- Myeloid neoplasms.
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.
Symptoms
Symptoms of HLH may include:
- Fever.
- Splenomegalyenlargement of the spleen.
- Cytopenialow levels of red blood cells, white blood cells or platelets in the blood; one or more blood cell type can be affected, such as:
- Anaemiaa condition where there aren't enough red blood cells in the blood, causing fatigue, weakness and pale skin and affecting how the body responds to infection.
- Neutropeniaa condition where there are low levels of neutrophils (a type of white blood cell) in the body.
- Thrombocytopenialow levels of platelets in the blood.
- Hepatomegalyenlargement of the liver.
- Lymphadenopathyswollen lymph nodes/glands, also known as adenopathy.
- Jaundiceyellowing of the skin and the whites of the eyes caused by an increase of bile in the blood.
- Skin rashes.
- Lung problems, such as:
- Coughing.
- Dyspnea.
- 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
If your doctor suspects you have a H group histiocytic disorder, they may order the following tests to confirm the diagnosis and refer you to a specialist for treatment:
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Neurological examinationan assessment of sensory and motor functions, such as vision, balance and coordination.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Bone marrow aspirationa procedure that involves inserting a needle into the hipbone (or the breastbone in some cases) to remove samples of solid and liquid bone marrow.
- Biopsyremoval of a section of tissue to analyse for cancer cells.
