The Ins and Outs of Itch

Chronic skin diseases affect 30–70% of people worldwide and are the most common reason people visit their primary healthcare providers.¹ Yet, they are frequently underrecognized as serious medical issues, despite their profound daily impact.^2,3 Conditions such as atopic dermatitis (AD), chronic spontaneous urticaria (CSU), prurigo nodularis, and bullous pemphigoid (BP) may appear to present only on the skin's surface, but the reality is much deeper. A defining symptom of these diseases is persistent, debilitating itch, a result of complex interactions between the immune and nervous systems.⁴ Itch perpetuates a relentless cycle of disease that can negatively impact people’s work and personal lives.⁵ To truly address this burden, it is essential to understand the underlying biological processes that contribute to the far-reaching consequences of itch.

Exploring itch, inside and out

Image Caption: 1) Immune cells, including type 2 inflammatory cells, release 2) inflammatory mediators like IL-4, IL-13, IL-31 and histamine.⁶ These interact with
3) sensory neurons to sensitize them, which means they can become hyperreactive to stimuli that would normally not lead to itch or lead to augmented itch sensations.^6,7 4) Itch sensations lead to 5) scratching, which further stimulates the immune response and sensory neuron activation, perpetuating the itch/scratch cycle.⁶ Additionally, sensory neurons can release⁷ 6) neuropeptides which further stimulate the immune response and subsequent sensory nerve cell activation to promote itch, which also ramps up the itch-scratch cycle.⁶