Just a quick preface: I am NOT a licensed physician. I am a high school student who enjoys researching interesting medical phenomena. These posts are just a summary of my research and questions I had while conducting it!
According to the U.S National Library of Medicine, Erdheim-Chester is “a rare type of slow-growing blood cancer called a histiocytic neoplasm.” So you might ask what does that really mean?....I know I did. Well first, we need to understand what a histiocyte is and what it does under normal conditions. Essentially, a histiocyte is a cell that is part of the immune system, and tasked is with two things phagocytosis, which is the consumption of a foreign bacteria or material, and antigen presentation which functions as a form of communication between cells, and is vital in helping your immune system protect you from an infection. Neoplasm is just
the word denoting an abnormal growth of tissue. Unfortunately in people that
have ECD, they produce excess histiocytes a condition called histiocytosis. As a result, there is inflammation and widespread damage to important organs and tissues which can result in organ failure, lesions, and even death. But there are many conditions that cause a form of histiocytosis, like Langerhans cell histiocytosis which essentially is histiocytosis limited to the dendritic cells or antigen-presenting cells. My next question was then what's the difference between ECD and other types of histiocytoses like LCH?
The exact difference between ECD and LCH lies in the immune-histopathological characteristics or the results of the tissue examination; think of it as the review of a biopsy. The key here is that the histiocytes in a person that has ECD are CD1a negative meaning that they don't possess the CD1a markers. The next natural question is, what does CD1a negative mean; essentially it is a T cell surface antigen or marker. CD1a specifically is important in presenting glycolipids, which are responsible for maintaining stability in the cell membrane and lipopeptide, a molecule expressed by bacteria, antigens. This is why ECD is classified as a non-Langerhans cell histiocytosis because their affected cells do not possess the antigen marker thus, they are not Langerhans or dendritic cells. Even with these differences, diagnosing ECD can still be extremely difficult. According to the U.S National Library of Medicine, “ 20% of patients with ECD also have LCH lesions, sometimes within the same biopsy.” This can present a great diagnostic challenge for physicians as the symptoms for ECD are also very general and thus applicable to a myriad of different conditions. As the symptoms of ECD are: bone pain, leg pain in the knees, upper arm pain, weight loss, fever, night sweats, fatigue, diabetes insipidus, balance issues, ataxia, dysarthria or slurred speech, involuntary rapid eye movement, reduced kidney function, exophthalmos or the bulging of the eye, and increases susceptibility to infections. One case study outlined on sciendirect.com exemplifies the diagnostic difficulty associated with diagnosing ECD: “[The child] had normal blood counts, renal and hepatic functions. As LCH was our clinical suspicion, a skeletal survey was done which showed multiple osteolytic lesions in the skull. His urine and serum osmolality favored diabetes insipidus.” The child was suspected to have LCH due to his presenting symptoms, but when the urine tests had come back he was suspected to have diabetes insipidus, which causes an imbalance of fluids in the body. It was later found out, through the immune histopathological results, that he was CD1a negative and thus ECD positive. After reading about this case, my next question was what is the prognosis of patients with ECD. According to Orphanet the prognosis for ECD has increased drastically as ”Before IFN-alpha, the mean survival after diagnosis was 19.2 months. Nowadays, with IFN-alpha treatments, the mortality rate is only 26%, and 5-year survival is 68%.” My next question upon reading this was, what is IFN-alpha, turns out it is just an abbreviation for
Interferon-alpha. Interferon Alpha has been proven to be valuable in the early stages of treatment of ECD and has helped to extend the prognosis for affected patients. Unfortunately, due to the rarity of the disease, the lack of clinical trials conducted has slowed down the research into potential cures and treatments. To provide context, there have been less than 600 cases reported in medical literature history. After researching the general information about ECD, I was still left with an important question that I had from the beginning: is Erdheim Chester disease autoimmune or is it a type of blood cancer?. At the beginning of my article, I had cited the U.S National Library of medicine and stated that they consider ECD to be blood cancer. See the thing is that technically, the way ECD affects the body is through the excess buildup of histiocytes, essentially it is the immune system attacking the body which would lend itself to the case for autoimmune. Also, patients with ECD do not have any metastases, strong indicators of cancer. For the side of cancer, most ECD patients have BRAF-V600E gene mutations, the same mutations present in other types of cancer. Other ECD patients had mutations affecting the MAPK pathway, which is responsible for cellular maintenance and growth. In doing further research, I had stumbled upon a disagreement on the subject: according to the Dana-Farber Cancer Institute, “Experts continue to debate whether or not ECD and LCH are inflammatory disorders or blood-related cancers. Recent scientific advances — including the identification of mutations specific to these diseases — have shifted opinion towards defining ECD and LCH as cancers.” So as of now, most consider ECD to be blood cancer.
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