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T‐helper immune phenotype may underlie ‘paradoxical’ tumour necrosis factor‐α inhibitor therapy‐related psoriasiform dermatitis
Author(s) -
Moy A. P.,
Murali M.,
Kroshinsky D.,
Horn T. D.,
Nazarian R. M.
Publication year - 2018
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1111/ced.13227
Subject(s) - psoriasis , tumor necrosis factor alpha , medicine , immunology , intercellular adhesion molecule 1 , cell adhesion molecule
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.