T‐helper immune phenotype may underlie 'paradoxical' tumour necrosis factor‐α inhibitor therapy‐related psoriasiform dermatitis. (22nd September 2017)

• Record Type: Journal Article
• Authors: Moy, A. P.; Murali, M.; Kroshinsky, D.; Horn, T. D.; Nazarian, R. M.
• Is Part Of: Clinical and experimental dermatology. Volume 43:Number 1(2018)
• Page Start: 19
• Page End: 26
• Publication Date: 2017-09-22
• Subjects: Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/ced.13227
• Languages: English
• ISSNs: 0307-6938

Abstract

Summary: Background: Therapeutics targeting tumour necrosis factor (TNF)‐α are effective for psoriasis; however, in patients treated for other disorders, psoriasis may worsen and psoriasiform dermatitis (PsoD) may arise. T helper (Th) cytokines in psoriasis upregulate keratin (K)17, which modulates TNF‐α transduction, leading to vascular adhesion molecule upregulation and lymphocytic extravasation. Aim: We investigated Th phenotype and expression of K17, intercellular adhesion molecule (ICAM)‐1 and vascular adhesion molecule (VCAM)‐1 in psoriasis and anti‐TNF‐α‐related PsoD. Methods: Skin biopsies from patients with psoriasis unresponsive to TNF‐α inhibitor therapy ( n = 11), PsoD‐related to TNF‐α inhibition ( n = 9), untreated psoriasis ( n = 9) or atopic dermatitis (AD; n = 9) were immunohistochemically analysed for Th1, Th2, Th17 and Th22. Expression of K17, ICAM‐1 and VCAM‐1 was also examined. Results: Anti‐TNF‐α‐unresponsive psoriasis and anti‐TNF‐α‐related PsoD showed decreased Th1 : Th2 raio and increased Th17 : Th1 ratio compared with untreated psoriasis. Anti‐TNF‐α‐unresponsive psoriasis had significantly fewer Th1 (4% vs. 12%) and more Th17 (51% vs. 20%) cells than untreated psoriasis. No difference in Th22 cells was identified. K17 was present in all cases of untreated psoriasis and anti‐TNF‐α‐related PsoD, 91% of anti‐TNF‐α‐unresponsive psoriasis, and only 22% of AD. VCAM‐1 and ICAM‐1 in anti‐TNF‐α‐related PsoD was akin to untreated psoriasis, but decreased in anti‐TNF‐α‐unresponsive psoriasis. Conclusions: These findings further the current understanding of the anti‐TNF‐α‐related psoriasiform phenotype and support a rationale for therapeutic targeting of interleukin‐17 and TNF‐α in combination.