Understanding the phenotypic switch between atopic dermatitis and psoriasis

Summary: Abstract Body: Atopic dermatitis (AD) and psoriasis (PsO) are common immune-mediated skin conditions with overlapping pathophysiological features, which is exemplified by a phenotypic switch from one to the other after the initiation of immunomodulatory therapy. This study uses a pharmacovigilance-based disproportionality analysis on the FDA Adverse Events Reporting System to investigate this phenomenon. When looking at dupilumab for the treatment of AD, eczema, or dermatitis, a signal emerges for psoriasiform dermatitis (Reporting Odds Ratio [95% Confidence Interval]=3.23 [4.39, 2.37]) as an adverse event (AE), but not psoriasis (0.56 [0.61,0.52]). For biologics used in the treatment of PsO, psoriasiform dermatitis emerged as a signal for TNF-α inhibitors=1.51 [1.69,1.35], IL-17 inhibitors=3.89 [4.58,3.30], and IL-12/23 inhibitor=1.79 [2.41,1.33]. Limiting the indication to PsO strengthened signals for psoriasiform dermatitis (TNF-α =3.01 [4.26,2.13] and IL-17 inhibitors=11.46 [14.34,9.16]), and allowed new ones to emerge for psoriasiform dermatitis (IL-23 inhibitors=2.49 [4.80,1.29] and apremilast=2.04 [3.71,1.13]), eczema (IL-17 inhibitors=1.84 [2.06,1.64]), and dermatitis (IL-17 inhibitors=1.95 [2.29,1.66]), but not AD. This suggests that paradoxical reactions create an intermediary physiologic and immunologic presentation between psoriasis and AD. For the interleukin biologics, the signal strength of IL-17 inhibitors is significantly stronger than IL-23 and IL-12/23 inhibitors, suggesting that Th17 and Th22 cells are involved in the switch. AE signals for Th2-mediated allergic conditions emerged for all biologic classes as well, providing evidence that the paradoxical reaction could potentially involve increased Th2 activity. Taken together, our study proposes a comprehensive model for the phenotypic switch between atopic dermatitis and psoriasis. Kerry Yang¹, Deborah Okusanya¹, Christopher G. Bunick², Fatemeh Jafarian³ 1. University of Calgary Cumming School of Medicine, Calgary, AB, Canada. 2. Program in Translational Biomedicine, Department of Dermatology, Yale University, New Haven, CT, United States. 3. Department of Dermatology, University of Calgary Cumming School of Medicine, Calgary, AB, Canada. Adaptive and Auto-Immunity