Epidermal Hyperproliferation With Less Prominent Dermal Inflammation Is the Unique Histopathological Feature of the Refractory Lesions in Psoriasis Treated With Ustekinumab.

Abstract

Although ustekinumab (UST) shows excellent efficacy in treating psoriasis, not all patients have a complete clearance rate. The purpose of this study was to investigate the histopathological characteristics of refractory psoriasis lesions in patients with excellent response to UST. Fifty-seven patients with newly diagnosed psoriasis and 66 patients with a 75% reduction in the Psoriasis Area and Severity Index score after UST treatment were included. Computer-aided image analysis was performed to measure the epidermal thickness, horny layer thickness, number of dermal vessels, and dermal inflammatory cell infiltration rate. Parakeratosis was scored using a 4-point scale. These measurements were compared between the refractory lesions of UST-treated patients and the untreated lesions of newly diagnosed patients after the adjustment for confounding factors. The dermal inflammatory cell infiltration rate was significantly lower in the refractory lesions (P = 0.022). Meanwhile, the epidermal thickness, horny layer thickness, grade of parakeratosis, and dermal vessel count did not differ between the groups (P = 0.125, 0.719, 0.542, and 0.758, respectively). Subgroup analyses were performed within the UST-treated group after dividing them into 2 groups according to the number of treatments or treatment response rates. None of these features were significantly different between the subgroups. This study suggests that the reduction of dermal inflammation by UST was not sufficient to ameliorate the epidermal changes and implies the role of the interleukin-23-independent downstream cytokine pathway in causing the refractory lesions among patients who responded well to UST. The continuation of UST treatment might not further improve epidermal alterations.