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The Unique Molecular Signatures of Contact Dermatitis and Implications for Treatment

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Abstract

Irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) are common skin disorders that are characterized by inflammation, oozing, crusting, and pruritus. Atopic dermatitis (AD) is an inflammatory skin disease characterized by immune and barrier abnormalities and is additionally a risk factor for acquiring ICD and ACD. New work on allergic sensitization to common allergens (e.g., nickel and fragrance) in human skin has shown that different allergens have distinct molecular fingerprinting. For example, nickel promotes strong Th1/Th17 polarization, whereas fragrance allergy causes Th2/Th22 skewing, which is similar to the phenotype of AD. While ACD has previously been considered to be constant across all allergens, largely based on mouse models involving strong sensitizers, these new data suggest that ACD differs mechanistically according to allergen. Further, ACD in the setting of concurrent AD shows a different and attenuated phenotype as compared to healthy individuals with ACD, which influences the way AD patients respond to vaccination and other treatment modalities. As in contact sensitization, skin challenged by food patch testing shows that common food allergens (e.g., peanut and barley) also cause distinct immune polarizations in the skin. Additionally, house dust mite reactions in human skin have been profiled to show unique Th2, Th9, and Th17/22 activation as compared to controls, which are similar to the phenotype of psoriasis and contact responses to nickel. Given this information, ACD patients should be treated based on their unique allergen polarity. Refined understanding of the molecular behavior of contact dermatitis and related diseases translates to improved methods of inducing tolerance in sensitized allergic patients, such as with targeted drug therapy and epicutaneous immunotherapy.

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Abbreviations

ACD:

Allergic contact dermatitis

AD:

Atopic dermatitis

CD:

Contact dermatitis

dDC:

Dermal dendritic cells

DEG:

Differentially expressed genes

DNCB:

Dinitrochlorobenzene

EPIT:

Epicutaneous immunotherapy

FLG:

Filaggrin

HDM:

House dust mite

IDEC:

Inflammatory dendritic epidermal cell

ICD:

Irritant contact dermatitis

LC:

Langerhans cells

LN:

Lymph node

MADAD:

Meta-analysis derived atopic dermatitis

SLS:

Sodium lauryl sulfate

TEWL:

Trans-epidermal water loss

Treg:

Regulatory T cell

TSLP:

Thymic stromal lymphopoietin

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  1. Department of Dermatology and the Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai Medical Center, 5 E. 98th Street, New York, NY, 10029, USA

    Alexandra Leonard & Emma Guttman-Yassky

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  1. Alexandra Leonard
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Correspondence to Emma Guttman-Yassky.

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Conflict of Interest

EGY is an employee of Mount Sinai and has received research funds (grants paid to the institution) from AbbVie, Celgene, Eli Lilly, Janssen, Medimmune/AstraZeneca, Novartis, Pfizer, Regeneron, Vitae, Glenmark, Galderma, Asana, Innovaderm, Dermira, and UCB. EGY is also a consultant for Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor, AnaptysBio, Dermira, Galderma, Glenmark, Novartis, Pfizer, Vitae, Leo Pharma, AbbVie, Eli Lilly, Kyowa, Mitsubishi Tanabe, Asana Biosciences, and Promius. AL declares no conflict of interest.

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Leonard, A., Guttman-Yassky, E. The Unique Molecular Signatures of Contact Dermatitis and Implications for Treatment. Clinic Rev Allerg Immunol 56, 1–8 (2019). https://doi.org/10.1007/s12016-018-8685-0

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