Abstract

Erythroderma encompasses several entities, a subset of which have overlapping clinicopathologic features (e.g. spongiotic/psoriasiform dermatitis). Assays that probe cytokine signatures in erythroderma are desirable to promote diagnostic accuracy. Thus, we performed IL-13 and IL-17A RNAscope, and IL-36 immunohistochemistry in 29 erythroderma biopsies, since these cytokines define type 2 (IL-13) and type 17 (IL-17A, IL-36) immunity, respectively. Diagnoses included psoriasis (6), pityriasis rubra pilaris (PRP; 10), spongiotic dermatitis (5), and spongiotic/psoriasiform dermatitis (8). Biopsies were quantified for epidermal IL-36 expression (scale of 0-4), and number of IL-17A- and IL-13-expressing cells. We found that IL-36 expression intensity showed strong positive correlation with the number IL-17A-expressing cells (R² = 0.25, p= 0.003) while the number of IL-13-expressing cells inversely correlated with the intensity of IL-36 expression (R² = 0.37, p= 0.0002). The number of IL-13-expressing cells showed a trend toward an inverse correlation with IL-17-expressing cells (R² = 0.07, p= 0.065). By combining IL-36 expression and IL-13-expressing cells into a classifier, cases were categorized as having type 2, type 17, or overlapping type 2/17 cytokine signatures. Spongiotic dermatitis was defined by a type 2 signature (5/5, 100%), while psoriasis (5/6, 83.3%) and PRP were largely defined by type 17 signatures (10/10 cases, 100%). For biopsies with spongiotic/psoriasiform dermatitis, five showed a type 2 (62.5%), one showed a type 17 (12.5%), and two showed a type2/17 signature (25%). Overall, we demonstrate the utility of combinatorial type 2 and 17 cytokine profiling to classify erythroderma, which may have promise in guiding clinical treatment decisions.