Biologics targeting specific cytokines and pathways have revolutionized the management of patients with chronic inflammatory diseases such as psoriasis. Although generally very safe, these treatments have their limitations and, surprisingly, can aggravate pre-existing or induce novel inflammatory diseases. Here, we present a cohort of psoriasis patients developing new onset eczema during anti-IL17 treatment, an intriguing side effect of IL-17 blockade with a largely unknown pathogenesis. The coexistence of psoriasis and eczema in a single patient is uncommon given their distinct and opposing immune mechanisms. Upon collection of their anamnestic data and evaluation of clinical and histopathological phenotypes, we performed gene expression analyses of skin biopsies using Nanostring technology in order to better define the inflammatory signatures involved. All patients showed very good clinical response of the underlying psoriasis to anti-IL17 treatment prior to developing eczematous lesions. Moreover, they carried elevated IgE levels, indicating an atopic predisposition. Gene expression analyses revealed that the predominant Th17 signature in plaque psoriasis is entirely replaced by a strong Th2 signature after the morphologic switch to eczema, a signature seen in atopic dermatitis. Intriguingly, two patients with atopic dermatitis receiving anti-IL4R treatment developed psoriasiform lesions and showed a shift from a Th2 towards a Th17 signature in the gene expression analysis. Our findings indicate a dynamic equilibrium between Th2 and Th17, with these two pathways controlling each other. Thus, we propose the “yin-yang” of Th2 and Th17, with IL-4 and IL17 representing antipodal vectors. This explains that blockade of these cytokines can lead, in predisposed patients, to the induction of the opposing inflammatory pathway via lifting the controlling mediator.

Biologics targeting specific cytokines and pathways have revolutionized the management of patients with chronic inflammatory diseases such as psoriasis or atopic eczema. Although generally very safe, these treatments have their limitations and, surprisingly, can aggravate pre-existing or induce novel inflammatory diseases. Here, we present a cohort of psoriasis patients developing new onset eczema during anti-IL17 treatment and atopic eczema patients developing dupilumab-induced psoriasis. These side effects of selective cytokine inhibitors have a largely unknown pathogenesis. The coexistence of psoriasis and eczema in a single patient is in fact uncommon given their distinct and opposing immune mechanisms. Upon collection of their anamnestic data and evaluation of clinical and histopathological phenotypes, we performed gene expression analyses of skin biopsies using Nanostring technology in order to better define the inflammatory signatures involved. All psoriatic patients showed very good clinical response of their psoriasis to anti-IL17 treatment prior to developing eczematous lesions. Moreover, they carried elevated IgE levels, indicating an atopic predisposition. Gene expression analyses revealed that the predominant Th17 signature in plaque psoriasis is entirely replaced by a strong Th2 signature after the morphologic switch to eczema, a signature seen in atopic dermatitis. On the other hand, intriguingly, patients with atopic dermatitis receiving anti-IL4R treatment developed psoriasiform lesions and showed a shift from a Th2 towards a Th17 signature in the gene expression analysis. Our findings indicate a dynamic equilibrium between Th2 and Th17, with these two pathways controlling each other. Thus, we propose the “yin-yang” of Th2 and Th17, with IL-4 and IL17 representing antipodal vectors. This explains that blockade of these cytokines can lead, in predisposed patients, to the induction of the opposing inflammatory pathway via lifting the controlling mediator.

ESDR020 - Cytokine imbalance during targeted therapies for psoriasis and atopic dermatitis – the yin yang of Th17 and Th2

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.