The Skin–Brain Axis: Emerging Evidence Transforming Dermatologic Care

Growing evidence suggests the brain and skin communicate more closely than previously understood, linking inflammatory skin disease to neurocognitive and emotional health outcomes.1 Investigators are now pointing to the skin–brain axis, a bidirectional pathway of neural, immune, and endocrine signals, as a key driver of both dermatologic and psychiatric comorbidities.

“There is a skin–brain connection,” Lisa A. Swanson, MD, a dual board-certified dermatologist and pediatric dermatologist at Ada West Dermatology, told HCPLive.“The most clear area where we have evidence for that is with atopic dermatitis in little kids. We know that patients with bad atopic dermatitis tend to have increased rates of things like ADHD, anxiety, depression, learning disabilities, even autism spectrum disorder, and for years, we wondered why.”

A 2021 Pediatric Dermatology mouse model study found that elevated interleukin-4 (IL-4), a key cytokine in atopic inflammation, was associated with delayed cognition and decreased myelination.2 This finding points to a mechanistic overlap between inflammatory signaling and neural development.

In line with this discovery, clinical data now show that IL-4 inhibition with dupilumab may reduce the need for ADHD medication among children with atopic dermatitis. A retrospective cohort study of pediatric patients found that ADHD prescription rates dropped significantly after starting dupilumab.3

“So, I think there is a brain skin connection, especially in the situation of atopic dermatitis,” Swanson said.

Mohammad Jaffarany, PhD, professor at Central Michigan University and president of the Association for Psychocutaneous Medicine of North America, said emerging research has helped explain how stress and mood disorders can trigger or exacerbate inflammatory flares.

“When there is any kind of stress due to whatever reason…our brain gets activated, and there [is] release of hormones—ACTH,” Jaffarany explained.

The brain triggers further activation of the sympathetic nervous system by influencing the adrenal cortex and increasing levels of adrenaline and norepinephrine. These hormones act on various cells, including immune cells, ultimately activating mast cells. Once activated, these mast cells release different chemical mediators, interleukins, and chemokines, which drive inflammation throughout the system.

“This has a core vicious circle,” Jaffarany said. “It goes on and on.”

Neurogenic inflammation has been observed in several dermatologic conditions, including psoriasis, prurigo nodularis, and rosacea.4 Patients frequently report discomfort even when visible inflammation is under control, suggesting a neurological component that may persist independently of skin barrier repair.5

Enzo Berardesca, MD, a professor from Miami Miller School of Medicine, investigated a topical agent that could modulate neuroactive mediators in the skin.

“This is a kind of brand-new area of investigation, and in the future, [there] could be topical products or cosmetics designed to address…internal mental well-being, not only because the skin improves, but also to affect directly our emotions,” Berardesca said.

He said the next step is to explore AI-driven skin mapping and biosensor technology to identify neurochemical patterns in skin physiology. The goal: develop personalized topical treatments that can modulate both cutaneous inflammation and mood.

Jafferany noted that extensive research has focused on the skin-brain axis, especially regarding the immune-neural connection. He highlighted that many medications are under investigation, including biologics and JAK inhibitors, which target interleukins, a key feature of various inflammatory skin conditions. This approach represents a shift toward modulating these chemical mediators to treat dermatological inflammation.

“In the past, we simply just used local applications and corticosteroids and traditional medications, but since the increase in knowledge about this basic molecular level, about the JAK inhibitors and biologics, things have changed,” Jafferany said. “Now, [many] inflammatory conditions, like atopic [dermatitis], eczema, [and] psoriasis, are being treated.”

Key Expert Perspectives:

Mohammad Jafferany, MD: professor at Central Michigan University & president of the Association for Psychocutaneous Medicine of North America

Enzo Berardesca, MD: Miami Miller School of Medicine

Lisa A. Swanson, MD: a dual-board-certified dermatologist and pediatric dermatologist at Ada West Dermatology.

Relevant disclosures include Otsuka America Pharmaceutical for Jafferany and Arcutis Biotherapeutics and LEO Pharma for Swanason. Berardesca has no relevant reported disclosures.

References

1. Scutari M, Kerob D, Salah S. Inferring skin-brain-skin connections from infodemiology data using dynamic Bayesian networks. Sci Rep. 2024;14(1):10266. Published 2024 May 4. doi:10.1038/s41598-024-60937-3

2. Jackson-Cowan L, Cole EF, Arbiser JL, Silverberg JI, Lawley LP. TH2 sensitization in the skin-gut-brain axis: How early-life Th2-mediated inflammation may negatively perpetuate developmental and psychologic abnormalities. Pediatr Dermatol. 2021;38(5):1032-1039. doi:10.1111/pde.14657

3. Yildirim AM, Pradhan T, Zinn ZA. Dupilumab treatment for atopic dermatitis is associated with decreased utilization of psychostimulants for attention deficit hyperactivity disorder: A retrospective cohort study. J Am Acad Dermatol. 2023;88(4):956-958. doi:10.1016/j.jaad.2023.01.025

4. Aitella E, De Martinis M, Romano C, Azzellino G, Ginaldi L. Neurogenic Inflammation in Allergic Contact Dermatitis. Biomedicines. 2025;13(3):656. Published 2025 Mar 7. doi:10.3390/biomedicines13030656

5. Andrus E. Jessica Hui, MD: Non-Visible Considerations for Eczema Management. Dermatologytimes.com. Published October 14, 2024. Accessed October 31, 2025. https://www.dermatologytimes.com/view/jessica-hui-md-non-visible-considerations-for-eczema-management