How can Opzelura reverse skin discoloration in vitiligo?

Teachable moment in classrooms:

1. integumentary system – layers/strata of epidermis
2. integumentary system – melanocytes produce melanin for skin pigmentation
3. immune system chapter – the white blood cells called cytotoxic (CD8) T lymphocytes can kill invaders and infected cells
4. endocrine system chapter – some hormone receptors in the cell membrane send chemical signals to the inside of the cell

The news item:  Recently the following new item appeared online:

More Vitiligo Patients Respond with Longer Use of Opzelura

Longer-term use of Opzelura was well tolerated, with no serious treatment-related adverse events, according to a poster presented at the annual dermatology meeting.

The article states that vitiligo is a disorder where skin loses color, and that it is likely an autoimmune reaction. The article also states that Opzelura is a Janus kinase (JAK) inhibitor, and that JAK signaling is responsible for inflammation in vitiligo.

So, Why Do I Care??  While vitiligo is not a life-threatening condition, the appearance of “bleached” white spots on the face or hands hinders social interactions, and may cause social withdrawal, and associated psychological stress of vitiligo sufferers. The improved coloration of the skin through medical treatment increases quality of life by lowering the psychological stress.

Plain English, Please!!!   First, let’s talk about how normal skin pigmentation is created. The deepest layer of the epidermis is called stratum basale, and in that layer, scattered among keratinocytes, we find the cells called melanocytes that make the brownish pigment called melanin. Melanin is exocytosed, secreted, from melanocytes, and then neighboring keratinocytes of stratum basale and stratum spinosum endocytose, soak up melanin. Inside the keratinocytes melanin protects the DNA from UV light.

Second, let’s talk about how vitiligo changes skin pigmentation.  People with vitiligo has melanocytes that are more sensitive to UV light or chemical stress.  The stressed melanocytes release stress-related chemicals , and those factors attract the white blood cells called cytotoxic T cells to the epidermis. In turn, those T cells secrete inflammatory cytokines, and it is those cytokines that damage and, eventually kill, the melanocytes. Because cytokines can not reach the inside of a melanocyte to cause damage, the cytokines instruct the melanocyte to begin self-destruction. The cytokine binds to a receptor in the membrane of the melanocyte, and that binding starts the damaging chemical changes inside the melanocyte. Imagine that the melanocyte is a house, and a cytokine comes to the door. The cytokine will push a doorbell (binds to the receptor). The sound from the doorbell chime wakes up a dog inside the house, and the dog starts chewing up the inside of the house. That doorbell chime is the JAK molecule that gives out a signal inside the cell to start the destruction.

Third, let’s talk about how Opzelura moderates vitiligo. The active drug in Opzelura, ruxolitinib, goes inside the cells, and disables the JAK signaling molecules. In our “house” metaphor Opzelura would plug the speakers of the doorbell chime, so even though a cytokine is pushing the doorbell, there is no sound, no signal coming from the chime, so the dog is not awakened, and the inside of the house is not chewed up. Therefore, the melanocyte stays alive, and the white patches of the vitiligo no longer spread or get bigger. In time, the melanin from the surviving melanocytes may even return brownish color to skin areas that previously were white.