Erdheim-Chester Disease (ECD) is a rare condition belonging to a group of diseases known as "histiocytic disorders." Histiocytes are cells that form part of the immune system and have the ability to engulf foreign substances, bacteria, cancer cells, and more, in a process called phagocytosis. In histiocytic disorders, there is uncontrolled proliferation of histiocytes and infiltration of tissues.
ECD was first described in 1930 by Jacob Erdheim and William Chester, hence its name. After years of debate about whether it is a neoplastic or immune disorder, recent molecular findings have confirmed that it is a neoplastic disease. Due to its rarity, it is challenging to estimate its incidence, which is approximately 1 in a million. The disease is typically diagnosed in individuals between the ages of 40 and 70, with a higher prevalence in males.
ECD is characterized by the infiltration of various tissues in the body by histiocytes. Organs commonly involved include bones, retroperitoneum (especially around the kidneys), lungs, heart and large blood vessels, central nervous system, pituitary gland, and skin. The clinical manifestations of the disease vary depending on the affected organs. For example, central nervous system involvement can lead to various neurological symptoms, while bone infiltration can cause bone pain. Skin involvement often presents with nodules around the eyes and other areas (xanthelasma), and pituitary gland involvement may result in diabetes insipidus.
Imaging studies (CT or CT-PET) may reveal characteristic findings unique to this disease, depending on the affected organs. For instance, histiocytic infiltration around the kidneys creates a distinct appearance known as a "hairy kidney," and retroperitoneal involvement may mimic pseudotumors. Bone scintigraphy can show a typical pattern of radioactive material uptake in the lower limbs.
The most common treatment for the past 15 years has been interferon-alpha, administered subcutaneously three times a week, or pegylated interferon-alpha, a similar drug with extended-release given once a week. The most troublesome side effect of these drugs is flu-like symptoms (fever, muscle aches, etc.). While these drugs have been proven effective in treating the disease, they may not work for all patients, and responses can be temporary. Other drugs that have been tried include anti-cytokine medications (e.g., anakinra, infliximab) and chemotherapeutic agents (e.g., cladribine) with limited success.
A significant breakthrough in ECD research occurred in 2010 when it was discovered that approximately 50% of ECD patients have a V600E mutation in the BRAF gene. This oncogenic mutation is well-known in melanoma and other histiocytic disorders. The importance of this discovery is twofold. First, it confirmed that ECD is a neoplastic disease and not an immune disorder. Second, it opened up avenues for new targeted therapies. Following the identification of the mutation, patients began to be treated with drugs that target the problematic gene (e.g., vemurafenib), and the results published so far are quite promising.
Despite the rarity of the disease, an organization called the ECD Global Alliance was established in the United States. This association supports patients and their families, raises public awareness of the disease, promotes research, and advocates for high-level treatment for ECD patients. One of the projects of the alliance, in collaboration with world experts in the field, was to define medical centers worldwide with adequate experience in treating the disease. As a result of our experience in treating ECD at Shaare Zedek Medical Center, the center was recognized as a designated treatment center for Erdheim-Chester Disease.
By Dr. Hazie Genazal
Image 1: "Hairy Kidney" - Histiocytic infiltration around the kidneys
Image 2: Cardiac involvement in the disease