# Stratum Corneum Ceramide Abnormalities in Atopic Dermatitis: Pathophysiology and Implications for Disease Management

## TL;DR

This review explains how changes in skin barrier lipids called ceramides contribute to atopic dermatitis and how they can help guide treatment.

## Contribution

The paper highlights how ceramide abnormalities are central to atopic dermatitis and can serve as biomarkers for disease monitoring and management.

## Key findings

- Ceramide abnormalities in the stratum corneum are key contributors to atopic dermatitis pathophysiology.
- Altered ceramide composition leads to increased water loss and impaired skin hydration.
- Type 2 cytokines like IL-4 and IL-13 disrupt ceramide metabolism, worsening inflammation and barrier dysfunction.

## Abstract

The stratum corneum, as the outermost layer of the skin, functions as a critical barrier that maintains cutaneous hydration and systemic homeostasis. Among its structural lipids, ceramides constitute the most abundant and diverse component. These molecules are essential for the formation of lamellar structures that secure barrier integrity. Increasing evidence has established that abnormalities in stratum corneum ceramides are not merely epiphenomena but fundamental contributors to the pathophysiology of atopic dermatitis (AD). In this review, we provide an overview of the structure, biosynthesis, and diversity of ceramides within the stratum corneum, followed by a discussion of their pivotal role in skin barrier function. We highlight recent insights into how ceramide abnormalities manifest in AD, including reduced total content, altered class distribution, and a shift toward shorter‐chain fatty acids. Such alterations are associated with increased transepidermal water loss and impaired hydration. Mechanistic studies further reveal that type 2 cytokines, particularly IL‐4 and IL‐13, directly disrupt lipid metabolism by inhibiting enzymes, thereby establishing a vicious cycle of inflammation and barrier dysfunction. Beyond pathophysiology, advances in lipidomics and tape‐stripping techniques now enable noninvasive assessment of stratum corneum ceramides. These analyses have revealed their utility as biomarkers of disease activity, therapeutic response, and relapse risk. Collectively, ceramides of the stratum corneum provide a unique window into the biology of AD. Their accessibility, mechanistic relevance, and prognostic potential underscore their importance not only for understanding disease pathogenesis but also for advancing personalized management and the concept of disease modification in AD.