Eczematous drug eruption in patients with psoriasis under anti‐interleukin‐17A: does interleukin‐22 play a key role?

Abstract

Summary Background Eczematous drug eruption (EDE) is a spongiotic skin reaction in response to systemic medications. To date, EDE has been described in patients treated with anti‐interleukin (IL)‐17A monoclonal antibodies with a prevalence of 2.2%–12.1%. Aim To describe the clinical and histological features and the skin cytokine milieu in patients with EDE induced by anti‐IL‐17A biologics. Methods This was a prospective study, enrolling patients with psoriasis who developed EDE during treatment with two anti‐IL‐17 biologics, ixekizumab and secukinumab, from June 2019 to April 2021. Skin biopsies were taken from all patients: a 5‐mm lesional biopsy (LB) and a 3‐mm nonlesional biopsy (NLB). The LB sample was split into two parts, one for histological examination and the other for cytokine profile evaluation. Results During the study period, treatment with an anti‐IL‐17A drug was given to 289 patients of whom 8 (2.8%) developed EDE during the treatment. Histopathological evaluation suggested a diagnosis of spongiotic dermatitis in all eight patients. Cytokine gene expression showed a predominance of T helper (Th)2/Th22 cytokines in EDE lesions with a large increase in IL‐4, IL‐22 and S100A7 levels in both LB and NLB samples compared with healthy skin. IL‐4, IL‐22 and S100A7 were significantly higher in LB compared with NLB samples. IL‐26 levels were also significantly increased in both LB and NLB compared with healthy skin, whereas low levels of IL‐23A were found in both LB and NLB. Conclusion Eczematous drug eruption skin lesions have mainly Th2/Th22 features, with IL‐22 playing a major role in their pathogenesis. EDE seems to be the result of an imbalance towards a Th2/Th22 response, secondary to the blockade of IL‐17A activity.

Burning and Scaling Probably Associated with Dupilumab Therapy: A Case Report

“…7 Studies have demonstrated that eczematous drug eruption (EDE) is a reactive spongiotic skin reaction to systemic medication, with a prevalence of 2.2-12.1% in patients with psoriasis treated with anti-IL-17A biologics, and that EDE is the result of an imbalance in the Th2/Th22 response secondary to blockade of IL-17A activity. 11 Likewise, scaling and 1660 burning sensations may be rare and paradoxical reactions to biologic therapy in the case of AD treated with dupilumab. Interestingly, the patient's psoriatic lesions showed no recurrence throughout the treatment period.…”

Prurigo Nodularis Onset during IL-17A Inhibitor Treatment of Psoriasis: A Case Report

“…The diagnosis of PN was con rmed based on clinical characteristics, laboratory tests, histopathology, and history of medications. Adverse reactions such as atopic dermatitis (AD) [10], eczematous drug eruption [11], and perianal dermatomycosis [12] have been reported in the previous literature during the treatment of psoriasis with IL-17A inhibitors. However, these cases have not been reported in PN.…”

“…The Th1 and Th2 pathways are closely related in the immune response, and when the Th1 response is blocked or diminished, the Th2 response is conversely increased, as is antisense [14]. For example, AD during treatment of psoriasis in one case receiving the IL-17A inhibitors [10] and in a prospective study of 289 psoriasis patients treated with ixekizumab and secukinumab demonstrated eczematous drug eruption in 2.8% of patients [11]. The cause was suggested to be the imbalance of Th2/Th22 response to anti-IL-17A drugs by blocking the Th1/Th17 pathway.…”

The Role of T Helper 22 Cells in Dermatological Disorders

“…For example, Fania reported that three psoriasis patients developed psoriasiform skin lesions with augmented expression of IL-22 after receiving adalimumab ( 249 ). Megna also discovered increased levels of IL-22 in psoriasis patients who switched to eczematous drug eruption after treatment of anti-IL-17 biologics ( 250 ). Thus, combined therapies of anti-TNF-α (or anti-IL-23/IL-17) and anti-IL-22 intervention might be effective in anti-TNF-α (or anti-IL-23/IL-17)-resistant psoriasis individuals.…”