Analysis of anti-TNF-induced skin lesions reveals strong Th1 activation with some distinct immunological characteristics

Abstract

Background

Psoriasiform and eczematous eruptions are the most common dermatological adverse reaction linked to anti-TNF-α therapy. Yet, a detailed characterization of their immune phenotype is lacking.

Objectives

We sought to characterize anti-TNF-α induced inflammatory skin lesions on a histopathologic, cellular and molecular level, compared to psoriasis, eczema (atopic dermatitis), and healthy control skin.

Methods

Histopathologic evaluation, gene expression (quantitative RT-PCR) and computer-assisted immunohistologic studies (TissueFAXS) were performed on 19 skin biopsies from IBD (n=17) and rheumatoid arthritis (n=2) patients with new-onset inflammatory skin lesions during anti-TNF-α-therapy.

Results

While most biopsies showed a psoriasiform and/or spongiotic (eczematous) histopathologic architecture, these lesions were inconsistent with either psoriasis or eczema on a molecular level using an established CCL27/iNOS classifier. Despite some differences in immune skewing depending on the specific histopathologic reaction pattern, all anti-TNF-α-induced lesions showed strong IFN-γ activation, at higher levels than in psoriasis or eczema. IFN-γ was most likely produced by CD3/CD4/Tbet-positive Th1 lymphocytes.

Conclusions

New-onset anti-TNF-α-induced eruptions previously classified as psoriasis or spongiotic dermatitis (eczema) exhibit a molecular profile that is different from either of these disorders.

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