# Palmitoylethanolamide for Nickel Allergy: Plausible, Untested, and Worth Considering

## TL;DR

This paper suggests palmitoylethanolamide as a potential treatment for nickel allergy, focusing on its anti-inflammatory and gut-protective properties.

## Contribution

The paper proposes palmitoylethanolamide as a novel candidate for treating nickel allergy by targeting multiple pathways involved in the condition.

## Key findings

- Palmitoylethanolamide reduces mast cell degranulation and VEGF expression.
- It enhances intestinal barrier integrity and may reduce gut hyperpermeability in nickel allergy.
- The molecule shows anti-inflammatory, anti-angiogenic, and anti-allergic properties relevant to nickel allergy.

## Abstract

Nickel allergy remains the most prevalent cause of allergic contact dermatitis worldwide, imposing a substantial socio-epidemiological and economic burden. Beyond its classical cutaneous presentation, systemic nickel allergy syndrome highlights the systemic dimension of Nickel hypersensitivity, wherein dietary nickel intake may provoke both gastrointestinal and cutaneous symptoms through mechanisms involving gut barrier impairment and mucosal immune priming. Recent evidence highlights the contribution of angiogenesis and lymph-angiogenesis to Nickel-induced allergic contact dermatitis, through crosstalk among keratinocytes, mast cells, endothelial cells, and pro-angiogenic mediators such as vascular endothelial growth factor. Against this background, we propose to revisit palmitoylethanolamide, an endogenous ALIAmide with well-documented anti-inflammatory, anti-angiogenic, and anti-allergic properties. Already studied in pain and inflammatory disorders and employed in veterinary dermatology, palmitoylethanolamide down-modulates mast cell degranulation, suppresses VEGF expression via PPAR-α/Akt/mTOR signaling, and enhances intestinal barrier integrity, acting as a promising “gatekeeper” molecule that reduces gut hyperpermeability characterizing systemic nickel allergy as well as other gut disorders with systemic consequences. This paper is presented as a viewpoint intended to highlight the untapped therapeutic potential of palmitoylethanolamide, suitable for both oral and topical administration, as a candidate to address the multifactorial pathophysiology of Nickel allergic contact dermatitis and systemic nickel allergy. Our purpose is not to provide definitive answers, but to stimulate scientific debate on its rational use within emerging gut–skin therapeutic strategies. We thus encourage future experimental and clinical studies to explore its potential integration within emerging gut–skin therapeutic paradigms.