Dr. Rosmarin provides an overview of models of re-pigmentation in vitiligo.
Brett King, MD, PhD:Let's move on to segment 3 in which we are going to talk about treatment options and considerations. This is an incredibly exciting time in medicine because we have this unbelievable ability to translate discovery in lab into treatments for patients. And in vitiligo, this is absolutely the case. Let's spend some time talking about where we are with treatment, considerations around those treatment, and then emerging therapeutics. Here, David, let's start with you. Can you describe – the only way to understand treatments and why we're using any of them is to understand our current model for repigmentation. Can you walk us through this?
David Rosmarin, MD: To recap, the reason why people get vitiligo is it's an autoimmune disease where your immune system, which should fight off infections, bacteria, virus, fungus, is too active destroying those pigment cells, those melanocytes in the body. And it only takes an overactive immune system to cause the vitiligo. To get the pigment back, it's really a 2 step process. One is we need to tell the immune system to calm down and two, to try to encourage those pigment cells to come back into the area, to repopulate the depigmented patches. And the other aspect is to teach one arm of the immune system that is too active where there are high levels of interferon-gamma, chemokines, like CXCL9 and CXCL10. And many of our medicines that tell the immune system to calm down don't work as well in that arm of the immune system. And that's one of the reasons why it's so hard to treat vitiligo. Many of our treatments aren't great for the immune system. And 2, you need that second step to try to stimulate the pigment cells to come back. That's one of the key aspects to understand, and to explain to the patients which goes into why we're doing what we're doing and making certain decisions. Now, in terms of that second step of getting the pigment cells to come back, there are 2 main areas where the pigment cells can come from. The most common location is from within the hair follicle. And within the hair follicle, there are the stem cells that can then differentiate and help repopulate the area. Also, sometimes repigmentation can come from around the sides and work themselves in, but they only go so far. Those are the 2 main ways that repigmentation happens and the pigment cells come back. In areas where there are a higher density of follicles, like the face, it's easier to repigment. Areas such as acral sites, hands, and feet, where we have a very low density of follicles, much harder to repigment. And areas that are in between such as the trunk and extremities are in the middle in terms of our ability to repigment those locations. And the third aspect, which I'm sure we'll touch upon later is that sometimes we will transfer pigment cells, transfer the melanocytes from one location to another when it's particularly challenging to do that naturally.
Brett King, MD, PhD:Some important points just to recap, we need to halt T cell destruction of melanocytes, and then we need that second piece, which is repigmentation or repopulation of affected epidermis with melanocytes. And the reservoir for those melanocytes are going to be either a hair follicle or surrounding skin.
Trnascript Edited for Clarity