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 cellsthe basic structural and functional unit of all living things (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 localisedaffecting only one area of body to the skin or mucosal surfaces, such as the mouth, nose, and gastrointestinal system. The M group, also known as malignantcancerous, may grow and spread to other areas of the body 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 on Erdheim-Chester disease (ECD), a common subtype of L group histiocytic disorder. It is defined as a is a rare cancer-like disorder that causes an abnormal increase in a type of white bloodthe red bodily fluid that transports oxygen and other nutrients around the body cell (WBC) called histiocytes, which play a significant role in many vital immune functions. It is most commonly found as lesions on the long bones of the legs, however it can also develop in the cardiovascular system, central nervous system (CNS), and other organs within the body. ECD often affects many systems within the body.
ECD is slightly more common in men, and is generally diagnosed between the ages of 50 and 60. However, anyone can develop this disease.
Treatment
Each patient with ECD 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 stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas system for this disease. Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:
- Cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs location.
- Whether or not the cancer has metastasised.
- Your age.
- General health.
- Your 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 tumoura tissue mass that forms from groups of unhealthy cells 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 patients with ECD may include:
- Watch and waitthe close monitoring of a cancer without giving treatment until symptoms appear or worsen (may be an option for some asymptomatic patients).
- 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.
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells.
- Immunotherapya treatment that uses a person's immune system to fight cancer.
- Targeted therapymedication that targets specific molecular features of cancer cells.
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence to remove as much of the tumour as possible.
- 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
Because of how rare ECD is, there has been limited research done into the riskthe possibility that something bad will happen factors of this disease. However, a genetic mutation in the BRAF gene (a protein involved in the sending of chemical signals between cells and cell growth) has been identified in a significant portion of people with this disease.
Symptoms
The symptoms of ECD will vary depending on the location(s) of the disease.
General Symptoms of ECD
General symptoms of ECD may include:
- Weight loss.
- Fever.
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
- Muscle and/or joint aches.
- General feeling of discomfort.
- Weakness.
ECD affecting bones
Most patients with ECD will experience some changes in the bones. In addition to the general symptoms listed above, patients with ECD in the bones may experience some of the following symptoms:
- Osteosclerosisabnormal hardening of the bone.
- Bone pain in affected area.
- Bone lesions.
ECD affecting the Cardiovascular System
In addition to the general symptoms listed above, patients with ECD in the cardiovascular system (such as the heart, pericardiumfluid-filled sac membrane that surrounds and protects the heart, and aorta (the largest arterya blood vessel that carries oxygenated blood from the heart to the rest of the body in the body)) may experience some of the following symptoms:
- Heart valve abnormalities.
- Heart rhythm abnormalities.
- Heart conduction defects.
- Periaortic fibrosis (inflammation of the aorta).
- Pericardial effusionabnormal fluid build-up in the pericardium.
- Myocardial infarctions (heart attacks).
- Cardiomyopathya disease of the heart that causes a loss of ability to pump blood effectively.
ECD affecting the CNS
In addition to the general symptoms listed above, patients with ECD in the CNS (including the dura (connective tissuea group of cells that work together to perform a function surrounding the brain and spinal cord), pituitary gland (one of the primary endocrine glandsglands responsible for the production and secretion of hormones of the body), other regions of the brain and/or spinal cord) may also experience some of the following symptoms:
- Diabetes insipidus (a disorder causing a fluid imbalance in the body).
- Polyuriafrequent urination.
- Polydipsiaabnormal or escessive thirst.
- Impaired muscle coordination.
- Difficulties walking.
- Slurred speech.
- Involuntary, rapid eye movements.
- Hormonea chemical substance produced by glands in the endocrine system that regulates various functions in the body imbalances.
- Loss of libido.
- Headache.
- Seizures.
- Changes in behaviour.
- Difficulty concentrating.
- Spinal cord compression.
ECD affecting Retro-orbital Tissues
In addition to the general symptoms listed above, patients with ECD in retro-orbital tissues (the tissues behind the eyes) may also experience some of the following symptoms:
- Pain behind the eyes.
- Proptosisbulging or protrusion of one or both of the eyes out of the eye sockets, also known as exophthalmos.
- Blindness.
ECD affecting the Skin
In addition to the general symptoms listed above, patients with ECD in the skin may also experience some of the following symptoms:
- Yellow plaques under the skin (most commonly on the eyelids).
- Reddish-brown nodules on the skin.
ECD affecting the Lungs
In addition to the general symptoms listed above, patients with ECD in the lungs may also experience some of the following symptoms:
- Pulmonary fibrosis (progressive scarring and thickening of lung tissue).
- Dry cough.
- Dyspneadifficulty breathing, shortness of breath.
- Decreased breathing output.
ECD affecting the Retroperitoneum
In addition to the general symptoms listed above, patients with ECD in the retroperitoneuma space located behind the abdomen that contains many important bodily structures, such as the kidneys may also experience some of the following symptoms:
- Ureteral obstruction (blockage of ureters – the tubes that carry urine from the kidneys to the bladdera hollow, muscular sac in the pelvis that stores urine).
- Abdominal swelling.
- Impaired kidneya pair of bean-shaped organs in the abdomen that are responsible for filtering excess water and waste products from the blood and converting them into urine to be removed from the body function.
- Renal failure (in extreme cases).
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 ECD, they may order the following tests to confirm the diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results 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.
- Urine teststesting done to measure the levels of certain substances in the urine.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
- X-raya type of medical imaging that uses x-ray beams to create detailed images of the body .
- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
- PET (positron emission tomography) scana type of medical imaging that uses radioactive tracers to create detailed images of the body.
- Bone scana type of medical imaging that uses a radioactive tracer to detect bone conditions or abnormalities.
- Pulmonary function testa test that examines how well your lungs are working.
- 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..
- Exploratory surgeryan exploratory surgical procedure used for conditions that cannot be confirmed by scans and tests alone, potentially including:
- Endoscopya procedure that involves inserting a long, flexible tube with a light and small camera (endoscope) into the body to view internal organs.
- Bronchoscopyan examination of the trachea and lungs with a small, flexible instrument known as a bronchoscope.
- Biopsyremoval of a section of tissue to analyse for cancer cells.
