Photo Credit: Nambitomo

One of the rarest of rare blood cancers, Erdheim-Chester disease presents diagnosis and treatment challenges.

 Erdheim-Chester disease is a rare blood cancer that manifests itself in a variety of ways, including bone lesions, central nervous system involvement, and retroperitoneal fibrosis of the kidneys and ureters, among others. Erdheim-Chester disease, like Rosai-Dorfman disease and Langerhans cell histiocytosis, is a histiocytic neoplasm. Collectively, this group of diseases occurs in fewer than five cases per million people.

A narrative review published in Vascular Medicine described cardiac manifestations of the disease. According to those findings, cardiovascular involvement can occur in up to 70% of patients with Erdheim-Chester disease and is usually identified during CT/MRI evaluation. Cardiovascular symptoms can vary widely in presentation and may be asymptomatic, but can also include pericarditis, fatal cardiac tamponade, myocardial infarction, conduction abnormalities, heart failure, renal artery stenosis, and claudication.

“Although more cardiovascular [Erdheim-Chester disease] cases have begun to be published in the literature, more data are needed on the outcomes of these patients, as well as how cardiovascular manifestations respond to treatment of [Erdheim-Chester disease],” researchers wrote.

Physician’s Weekly (PW) spoke with Ronald Go, MD, of the Mayo Clinic, about the rarity of this disease and its management. Dr. Go studies several rare blood disorders, including Erdheim-Chester disease, Rosai-Dorfman disease, and paroxysmal nocturnal hemoglobinuria.

PW: Exactly how rare is Erdheim-Chester disease?

Dr. Go: Most doctors likely have not heard of Erdheim-Chester disease, and even hematologists or oncologists may not know of it. It’s an ultra-rare blood cancer. We don’t even know its incidence because until recently, it was not classified as a cancer. The literature reports approximately 2,000 cases in the last 100 years.

How does this disease usually present?

That is the biggest challenge with this cancer. Most cancers are easy to diagnose: If there’s a mass in the brain, it’s brain cancer; if there’s a mass in the colon, it’s colon cancer. You know what to look for. But Erdheim-Chester disease is not a single-organ problem. Almost all patients—90% to 95%—will have bone involvement picked up by bone or PET scan. Half of patients don’t have any symptoms—the nervous system [can be] involved; about 40% of patients present with falls. Speech is altered; swallowing is problematic. A quarter of patients have diabetes.

About 50% to 60% of patients will have cardiovascular involvement, but only about 10% will come in because they have cardiac problems. The most common symptoms will be bone pain, neurologic symptoms, diabetes, and orbital findings. The cardiac incidence is much lower.

How do clinicians manage Erdheim-Chester disease?

Generally, we would do next-generation sequencing to determine the type of mutation a patient has. Half of them will have BRAF mutations. The other half will have mutations in the MAP kinase pathway.

Patients with bone involvement who are asymptomatic can be monitored for years. With organ involvement or symptoms that we can treat, we typically start with drugs based on the mutation that is present. If you find that target, most patients respond to therapy quickly with the right drug. Over 90% will respond to therapy with these new targeted drugs. Before we discovered these mutations, we used traditional chemotherapy. Now, with the right drug for the right mutation, there is an almost universal response.

What barriers are there to managing this disease?

The biggest barrier is recognizing the disease. Someone may see vasculitis on a PET scan and refer patients to rheumatology. Cardiologists may see this present as pericarditis or pericardial effusion. Many pathologists don’t recognize this disease because the malignant cells are few and far between. It requires some expertise to diagnose the disease, even with the right biopsy. Otherwise, a lot of biopsies are labeled as chronic inflammation.

What are the knowledge gaps in Erdheim-Chester disease?

We don’t have a good grasp on why people get this, and we’re not aware of any certain risk factors. It’s not like cardiovascular disease, where risk factors can be minimized.

The other challenge is a cure. The targeted drugs are effective, but they have not cured people. They also have to be taken indefinitely; if you stop the drug, the disease will most likely come back.

There is also a group of patients who will have neurologic decline and deterioration of neurologic function despite the resolution of the tumors.

Is there anything else clinicians should know? 

The patient support group ECD Global Alliance has a good website with patient resources and information on locating a clinician. It’s a great group of people who support patients with Erdheim-Chester disease. These organizations also deserve credit for many of the research discoveries that have been made regarding cardiac manifestations of Erdheim-Chester disease