Introduction
Erdheim-Chester disease is a rare condition characterized by excess production and accumulation of cells called histiocytes. This condition is also referred to as non-Langerhans histiocytic multisystem disorder. Histiocytes are a type of immune cell or large phagocytic cells that are found in many organs and tissues of the body. (A phagocytic cell is a type of immune cell that has the ability to digest and destroy the foreign particles entering the body). Histiocytes play a role in responding to injury and infection. Excessive production of histiocytes leads to inflammation, which can harm the body's tissues and organs, causing them to undergo fibrosis (scarring), become dense, and ultimately result in organ failure. The disease can affect the long bones, skin, lungs, brain, the tissue behind the eyeballs, the pituitary gland, and other tissues and organs. The other names by which this condition is known are lipid granulomatosis and polyostotic sclerosing histiocytosis. Erdheim-Chester disease is a rare disorder, and about 500 affected people are reported worldwide. Men are considered to be more affected by this condition than women for unknown reasons.
What Are the Signs and Symptoms of the Erdheim-Chester Disease?
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Bone pain is the most frequent symptom that affects the knees and legs, similar to both sides of the body.
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Diabetes insipidus is characterized by inadequate secretion of antidiuretic hormone (ADH) by the pituitary gland, resulting in the excretion of large volumes of urine and excessive thirst.
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Retroperitoneal fibrosis is a medical condition characterized by the development of significant scar tissue and inflammation behind the abdominal cavity's membrane that envelops the digestive system's organs.
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Xanthelasma or cutaneous xanthomas - Yellowish, soft, fatty nodules or plaque on the eyelids or skin.
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Exophthalmos (protruding eyes).
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Pulmonary fibrosis is characterized by the development of scar tissue and thickening in the lung tissues, leading to symptoms such as a persistent dry cough, shortness of breath (dyspnea) during physical activity, and potential impairment of the heart's ability to adequately pump blood to the lungs and other body parts, which can eventually lead to heart failure.
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Weight loss.
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Increased body temperature or fever.
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A feeling of discomfort.
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Weakness and fatigue (malaise).
What Is the Cause of the Erdheim-Chester Disease?
The exact cause of the Erdheim-Chester disease is still unknown. Nonetheless, the prevailing belief is that the illness is triggered by a mutation occurring in a particular gene known as BRAF (B-Raf Proto-Oncogene, serine/threonine kinase) gene. Mutations in other genes are also believed to be contributing factors to the cause of this disease. The BRAF gene is responsible for providing instructions for making a protein that helps in transmitting chemical signals to the cell’s nucleus from the outside of the cell. The mutation of the BRAF gene happens during a person’s lifetime, and it is present only in some cells. The mutation occurs in histocytes, which leads to the production of a BRAF protein that is abnormally active, resulting in disruption of the regulation of cell growth and division. This unregulated overproduction of histocytes causes their accumulation in the tissues and organs, leading to the symptoms of Erdheim-Chester disease.
What Is the Differential Diagnosis of the Erdheim-Chester Disease?
The signs and symptoms of Erdheim-Chester disease may be similar to those of the following disorders.
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Histiocytosis X or Langerhans Cell Histiocytosis (LCH) - This group of conditions is distinguished by the excessive production and buildup of Langerhans cell histiocytes. The predominant indication linked to the illness involves the occurrence of either solitary or multiple bone lesions exhibiting degenerative alterations and calcium loss in the bone (osteolysis). The most affected bone is the skull, along with the involvement of other bones, such as the spine and long bones. The affected patients are usually asymptomatic, and they might experience associated swelling and pain and certain complications such as fractures. This condition affects the patient during childhood, while Erdheim-Chester disease affects middle-aged people.
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Cerebrotendinous Xanthomatosis (CTX) - This uncommon disorder is distinguished by the buildup of excessive cholesterol in the body's tissues and is present from birth. It is an inherited form of lipid storage disease. As the excess cholesterol cannot be removed from the body, it accumulates in the brain, and the child faces difficulty in walking, mental retardation, and developmental delays. During adulthood, some patients with the condition may suffer from serious heart problems due to the build-up of cholesterol in the blood vessels surrounding the heart.
How to Diagnose the Erdheim-Chester Disease?
The diagnosis is made based on a detailed patient’s medical history, characteristic symptoms that the patient is showing through clinical evaluation, and certain specialized tests. The test recommended by the doctor are:
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Plain X-rays of Involved Bones - This shows symmetrical (same on both sides of the body) thickening and hardening. This is a distinctive feature of the Erdheim-Chester disease.
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CT (Computed Tomography) Scan - This test uses X-rays to produce images of the body parts that help in diagnosing bone disorders.
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MRI (Magnetic Resonance Imaging) Scan - In this test, a magnet, radio frequencies, and a computer are used to create a detailed image of bones, joints, and soft tissues and help in diagnosing any abnormalities.
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Bone Scan or Bone Scintigraphy - It uses nuclear imaging to diagnose the type of bone disease.
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Biopsy - In this test, tissue samples are removed and examined under a microscope.
What Are the Treatment Options for Erdheim-Chester Disease?
Recommended treatment options are:
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Corticosteroid Drugs - Prednisone helps in controlling and preventing the proliferation of abnormal cells.
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Chemotherapeutic Drugs - Vinblastine also helps in controlling the proliferating abnormal cells.
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Radiation Therapy - This therapy uses high-energy rays that may destroy or kill the proliferating cells and shrink their size.
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Immunotherapy - This therapy helps the patient’s immune system to fight the disease.
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Surgery - Surgery is not typically considered the primary treatment for Erdheim-Chester disease, as it is a systemic disorder involving multiple organs. However, in some cases, surgery may be performed to address specific complications or manifestations of the disease. The decision to perform surgery would depend on the individual patient's condition, symptoms, and the organs involved.
Conclusion
The Erdheim-Chester disease manifests as a disorder that typically emerges in adulthood, with symptoms appearing between the ages of 40 and 60, although it can occur at any stage of life. This condition is characterized by a rare, indolent form of blood cancer. The symptoms and disease course depend on the location and the extent of involvement of the disease. Some of the reports suggest various treatment options have been used but with limited success.
