The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype

Area of Science:

• Dermatology
• Immunology
• Allergy

Background:

• Skin barrier dysfunction is common in atopic dermatitis (AD) and food allergy (FA).
• Only a subset of AD patients also have FA, suggesting distinct underlying mechanisms.
• Understanding specific skin abnormalities in AD with comorbid FA is crucial for targeted therapies.

Purpose of the Study:

• To investigate stratum corneum (SC) abnormalities in children with AD and FA (AD+FA) compared to AD without FA (AD-FA) and nonatopic (NA) controls.
• To utilize a multiomics approach and minimally invasive skin tape stripping for detailed SC analysis.
• To identify unique molecular and morphological features of the skin barrier in AD+FA.

Main Methods:

• Minimally invasive skin tape strip sampling for stratum corneum analysis.
• Multiomics approach including transcriptomics and shotgun metagenomics.
• Analysis of transepidermal water loss, lipid and protein content, epidermal morphology, and microbial composition.

Main Results:

• AD+FA showed increased transepidermal water loss and lower filaggrin and specific ceramide content in nonlesional skin.
• Morphological analysis revealed abnormalities in the epidermal lamellar bilayer architecture.
• Increased Staphylococcus aureus abundance, keratin 5/14/16 expression, and type 2 immune pathway gene expression were observed in AD+FA.
• Network analysis correlated keratins with AD+FA and filaggrin breakdown products with its absence.

Conclusions:

• Children with AD+FA exhibit unique nonlesional skin barrier abnormalities, suggesting an immature barrier.
• These abnormalities are associated with increased susceptibility to Staphylococcus aureus and type 2 immune activation.
• The findings highlight distinct pathomechanisms in AD+FA, potentially guiding future therapeutic strategies.