What is Erdheim-Chester Disease?

Overview

Erdheim-Chester Disease (ECD) is an extremely rare blood cancer that can affect many different organs of the body.  It is characterized by excessive production and accumulation of specific cells whose normal functions are to fight infections and eliminate foreign bodies.  These cells, called histiocytes, infiltrate the loose connective tissue within body organs and cause inflammation.  As a result, this tissue becomes thickened, dense, and fibrotic. If the disease is not controlled, organ failure can occur. In some patients, ECD may have a relatively benign course involving a limited number of organs. In contrast, in others, the disease can be more aggressive and may affect multiple organs, including, but not limited to, the bones, skin, heart, kidney, and brain. For this reason, establishing the extent of organ involvement by a knowledgeable medical team is mandatory to guide appropriate management. This typically includes doctors from multiple specialties.

(For this reason, it is important that ECD be properly treated and managed by a knowledgeable medical team of doctors across multiple specialties).

Who typically is diagnosed with ECD?

The majority of ECD patients are typically diagnosed between the ages of 40-70 years, although occurrences in children have been exceptionally reported.  ECD can affect both men and women, with approximately 70% of reported cases occurring in men and 30% in women.

What causes ECD?

The exact cause of ECD is unknown. However, in 2016, the World Health Organization (WHO) categorized ECD as a type of blood cancer called histiocytic neoplasm.  This recognition was due to the discovery of cancer-causing DNA changes (mutations) in the ECD tissues, specifically in the genes of the mitogen activating protein kinase (MAPK) pathway, including BRAF, KRAS, MAP2K1, NRAS, etc. genes. The most common mutation is BRAF-^V600E, which is identified in about 50-60% of ECD cases. These mutations are not believed to be inherited through DNA from parents but are acquired during life (somatic) and occur in cancer cells or blood cells. Therefore, they are not considered transmissible through generations.

What issues does ECD cause?

ECD can virtually affect a variety of body parts, including the long bones of the legs and arms, skin, the tissues behind the eyes, lungs, brain, pituitary gland, the tissue around the kidneys and the ureters, abdominal cavity, the heart, blood vessels, adrenal glands, and more rarely other organs. The specific organs involved can vary; however, the most common presentation seen in over 90% of patients with ECD is the involvement of leg bones around the knees. The number of affected organs can vary between individuals, making the clinical presentation and aggressiveness differ greatly between patients.  

Brief History

There have been a very limited number of published cases of ECD in the world since it was first described in 1930 by the Austrian pathologist Jakob Erdheim and the American pathologist William Chester. Since ECD is so rare and is not discussed in common medical textbooks, many doctors have never heard of it. It is also considered difficult to diagnose. For these reasons, most feel the disease is underdiagnosed.  However, in recent years, as awareness grows, there seems to be an increasing number of diagnoses.  Moreover, treatments have improved dramatically with the discovery of MAPK pathway mutations, leading to the US FDA approval of two targeted drugs, vemurafenib and cobimetinib, for patients with ECD.

Current Efforts to learn more. 

Most published articles on ECD were initially anecdotal in nature because studies were historically extremely difficult due to the small and geographically dispersed ECD patient population. However, a significant change began when patients and caregivers joined together to form the ECD Global Alliance. As part of this effort, ECD Referral Care Centers have been formed to provide comprehensive care for patients with ECD. There are several ongoing studies ranging from the discovery of new treatments to the improvement of symptoms and survivorship experience with this disease. The World Health Organization’s declaration of ECD as a blood cancer has enabled ECD better visibility, with improved opportunities to educate patients and their medical providers. Further, the American National Comprehensive Cancer Network has issued treatment recommendations and guidelines for ECD. This has made it possible for many medical providers to familiarize themselves with treatment strategies for ECD more easily.

What is the prognosis?

The prognosis for ECD is variable and depends mainly on the extent and distribution of the disease. It ranges from asymptomatic bone lesions to multi-systemic life-threatening forms. Due to the discovery of targeted therapies, the prognosis of ECD has improved significantly, both in terms of mortality (the rate of deaths) and morbidity (the rate of illness). It is important to note that some patients with ECD have been living high-quality lives for decades. However, while targeted therapies like vemurafenib and cobimetinib have made it possible to control ECD, they are not curative in nature. Nevertheless, it is important to note that targeted therapies control disease in almost all patients, resulting in ECD being treated as more of a chronic disease for many. Patients often struggle with the side effects of treatment and/or long-term effects of their disease. Despite these challenges, the focus has shifted from mere survival to survivors’ quality of life over the last decades.  The scientific field is evolving day by day, and more effective treatment strategies and guidelines to monitor patients effectively are hoped to be available in the near future.