Abstract

Molecular therapies have revolutionized the treatment of inflammatory skin diseases. As the number of targeted medications continues to expand, the opportunity for rational treatment selection will increase. Currently, there are no biomarkers that can be used to guide molecular diagnosis or treatment selection in common inflammatory dermatoses such as atopic dermatitis (AD) and psoriasis. The development of such tissue-based biomarkers could allow dermatopathologists to provide immunologically relevant data to supplement their morphologic diagnoses and potentially facilitate progress towards personalized medicine. In this study, we used AD, which is commonly treated with dupilumab (anti-IL-4Ra), to evaluate whether levels of treatment-relevant cytokines might correlate with response to therapy. We compiled a retrospective cohort of 61 patients with eczematous dermatoses treated with dupilumab at our institution in whom archival biopsy tissue was available. We measured IL4, IL13, IL22, IFNG, IL17A, and IL17F in each case using RNA in situ hybridization (RISH). We also evaluated histomorphologic features. These findings were compared among complete responders (n=16), partial responders (n=37), and non-responders (n=8) to dupilumab. We found that increased IL13 expression differentiated complete responders from partial responders (p<0.001) and non-responders (p=0.013). When comparing partial responders to non-responders, we found that the presence of cytokines not targeted by dupilumab, IFNG (p=0.053) and IL22 (p=0.022), correlated with non-response. Histologically, non-responders tended to have increased levels of spongiosis, acanthosis, and epidermal inflammation. These findings suggest that cytokine profiles determined by RISH may aid in treatment selection for eczematous dermatoses and imply that tissue-based biomarkers may be useful in personalization of the treatment of inflammatory skin disease.

Financial Disclosure:
No current or relevant financial relationships exist.