The Neuroimmune Mechanisms Driving Prurigo Nodularis

Todd Schlesinger, MD (00:07):

Hi, I'm Dr. Todd Schlesinger. I'm a board-certified dermatologist and member of the American Academy of Dermatology. I practice in Charleston, South Carolina, and I founded the Clinical Research Center of the Carolinas. I also work with Epiphany Dermatology as my practice location.

(00:24):

Thinking about the neuroimmune mechanisms of prurigo nodularis, and then incorporating that when we think about atopic dermatitis, I mean, you have to think about itch. It's something we deal with so commonly in really two broad categories. One is the inflammatory version of itch and then the neuropathic version of itch. Those two pathways are oftentimes combined side by side.

(00:48):

We have not only drugs now that target one half of that pathway in evaluating drugs that can target the other half, primarily the neurogenic pathway are being looked at. But really, they go hand in hand. When you're thinking about atopic dermatitis, there's itch, psoriasis, other ones. And then you have something like prurigo nodularis where you have that thickening, those nodules in the skin that start off with some type of external trigger factor that gets the receptors going and actually then produces a very complicated pathway leading to the sensation of itch in the brain.

(01:26):

Now, of course, you have to think about itch as being something that's actually related to the pain receptors. They go along the same receptors as pain. So while the patient's scratching their skin, or you and me scratching our skin, will start out as a pleasurable sensation, it quickly becomes a painful sensation over time.

(01:44):

I think that the best way to think about these mechanisms of action, they are complicated, but that the receptors in the skin are extremely sensitive. The nociceptors in the skin, the Meissner's corpuscles in the top layers of the skin are very sensitive to external stimuli and also itch. And that's part of what drives that mechanism of action of prurigo nodularis in causing the thickening of the skin and development of keratinocyte hypertrophy and the nodules that we see on the surface of the skin.