Transcription
Far in history, this disease used to be known as retinoic acid syndrome, but unless you're living under a rock, this name is now gone. Now it's known as differentiation syndrome. It's what happens when you treat a patient with acute promyelocytic leukemia using vitamin A or arsenic trioxide. Differentiation syndrome is the topic of today's video. This is Medicos, as perfectional as we continue our talk about hematology and oncology.
I told you in the previous video that acute promyelocytic leukemia, also known as AML M3 subtype, has a good prognosis because we can treat it using vitamin A. If it's refractory to vitamin A, we can use arsenic trioxide. Cool. If we use this, sometimes the patients develop differentiation syndrome. It's a common side effect; it can be really severe.
What are the signs and symptoms of differentiation syndrome? Basically, fever and volume overload, such as pleural effusion and pericardial effusion. Pleural effusion will lead to respiratory distress, leading to hypoxia. Pericardial effusion: the heart cannot receive blood, so it cannot pump blood; you end up with hypotension. The kidney is screwed without enough tension, leading to renal problems such as pre-renal azotemia.
How to treat differentiation syndrome? First, you stop the vitamin A if the symptoms are severe enough, and of course, you give high-dose dexamethasone. Because when doctors don't have a clue, they will give steroids to you.
Do we call it differentiation syndrome? Because when we give vitamin A, vitamin A helps these immature promyelocytes develop and mature into neutrophils. These neutrophils will undergo apoptosis, which is programmed cell death, and these cells will die; rest in peace. So, development of promyelocytes into neutrophils is the process of differentiation; that's why we call this disease differentiation syndrome.
Ethogenesis: it's controversial. We have two theories; they are crazy. So normally, you have 95% of your neutrophils in the bone marrow, and we call this the storage pool. The other 5% are in the periphery, which means outside of the bone marrow. Okay, most of them are here; the minority of them are circulating in the blood, and we call them the circulatory pool. Okay, these here marginate from the blood, okay, through the process of margination into tissues, and they adhere into the endothelium, like the vascular endothelium in different organs, such as the spleen and sometimes the lung. We call this the marginating pool. So here are the neutrophils in your bloodstream; they marginate into tissues and they adhere to the vascular endothelium inside of your lungs. That's normal. If you give a drug to the patient, he has immature promyelocytes; now they will undergo maturation, and when they are mature, they can marginate into the lungs, and they will lead to pleural effusion, which is one of the symptoms of differentiation syndrome. Crazy, isn't it?
Number two: we have these promyelocytes that are immature; they produce all of these cytokines into your bloodstream. The cytokines—cyto means cell, kines means they will cause kinesis, which is movement of different inflammatory cells—and now you have a big problem on your hands. You have the fever, and you have the effusion, and all of these symptoms. This process of cytokine secretion may be independent of their differentiation; they don't have to mature in order to produce cytokines. So, therefore, the name differentiation syndrome may be—and we may have to come up with a new name—because you know, doctors, like, they get sick of their job, so they just invent new names so that students can get stuck studying all of this nonsense. I'm just kidding.
Oh, how to treat differentiation syndrome? High-dose dexamethasone. When doctors don't have a clue, they give steroids to you, and guess what? They work. Okay, stop ATRA if symptoms are severe. Symptoms are really severe; you stop the vitamin A or the arsenic trioxide, whichever one you're using.
You're ready for this case? Yes, please. 45-year-old female has extreme fatigue, mucosal bleeding, anemia, hematocrit 27, platelet is 47,000. So here we have anemia and thrombocytopenia. White blood cell count is normal, but 9% blasts on peripheral smear. Chromosomal analysis reveals translocation 15;17. Okay, treatment with ATRA is initiated, why? Because this is acute promyelocytic leukemia, also known as AML subtype M3. Two weeks after initiation of this vitamin A treatment, the patient developed fever, dyspnea, chest pain, pleural effusion, etc., etc., etc. What's the most likely diagnosis? Can you guess? Yes, this is differentiation syndrome, previously known as retinoic acid syndrome. What's the best next step in management of this patient? Of course, we stop the ATRA and give steroids. This is differentiation syndrome in a nutshell. I'll see you in the next video; stay tuned; don't forget to subscribe.