Palmoplantar pustular psoriasis (PPPP) is characterized by activation of the IL-17A pathway Robert Bissonnette a, *, Judilyn Fuentes-Duculan b , Shunya Mashiko c , Xuan Li b , Kathleen M. Bonifacio b , Inna Cueto b , Mayte Suárez-Fariñas d , Catherine Maari a , Chantal Bolduc a , Simon Nigen a , Marika Sarfati c , James G. Krueger b a Innovaderm Research, 1851 Sherbrooke St. East, Suite 502, Montreal, Quebec, H2K 4L5, Canada b Laboratory of Investigative Dermatology, The Rockefeller University, 1230 York Avenue, New York, NY, 10065 USA c Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), 900 Saint-Denis Street, Montreal, Quebec, H2X 0A9, Canada d Dept. of Population Health Science and Policy, Dept. of Genetics and Genomics Science and Dept. of Dermatology, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, L2-70C, Box 1077, New York, NY, 10029, USA A R T I C L E I N F O Article history: Received 12 May 2016 Received in revised form 8 September 2016 Accepted 28 September 2016 Keywords: Psoriasis Palmoplantar psoriasis Palmoplantar pustular psoriasis IL-17 IL-23 Skin biopsies A B S T R A C T Background: Palmoplantar pustular psoriasis (PPPP) is a variant of psoriasis, which has significant negative impact on quality of life. The cellular and molecular inflammatory pathways involved in PPPP have not been well studied. Objective: Study the expression of cytokines and chemokines involved in the IL-17/IL-23 axis in palmoplantar pustular psoriasis and other difficult to treat psoriasis areas (palms, scalp, elbows and lower legs). Methods: Skin biopsies were performed on a total of 80 patients with PPPP, non-pustular palmoplantar psoriasis (NPPPP), or psoriasis located on elbows, knees and scalp as well as 10 healthy subjects. RT-PCR, immunohistochemistry and flow cytometry on cells extracted from skin biopsies were used to compare PPPP to other forms of psoriasis. Results: There was a significant (p < 0.05) increase in the expression of IL-1b, IL-6, LL-37, IL-19, IL-17A, CXCL1 and CXCL2 in PPPP as compared to NPPPP. However, there was no significant difference in expression of IL-23 in PPPP as compared to NPPPP and other forms of psoriasis. The proportion of IL-22 + but not IL-17A + mast cells was higher in PPPP as compared to NPPPP (p < 0.05). Conclusion: These results suggest that the IL-17A pathway may play a more important role in PPPP than in NPPPP. ã 2016 Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology. 1. Introduction Psoriasis vulgaris is the most common clinical presentation of psoriasis, an immune-mediated multi-systemic disease. Our understanding of the pathophysiology of psoriasis vulgaris improved significantly over the past 15 years following clinical studies performed using monoclonal antibodies to treat psoriasis. These studies have shown that several cytokines, including TNF-alpha, IL-23 and IL-17, have an important role in the pathophysiology of psoriasis as evidenced by the rapid and important improvement in skin and joint disease following treatment with antagonists of IL-23 or IL-17 [1–7]. IL-23 is produced by a variety of cells including antigen presenting cells, neutrophils and macrophages [8]. IL-23 is involved in expansion and maintenance of Type 17 T-cells which are the major source of IL-17 in the skin of patients with psoriasis [7,9,10]. In addition to being produced by T cells, IL-17 is produced by other cell types including neutrophils and mast cells [9,10]. IL-17 contributes to the psoriasis phenotype by increasing the production of numerous cytokines including IL-6, IL-8, IL-36 and TNF-alpha, of chemokines including CXCL1, CXCL3, CXCL5, CXCL8 and CCL20 and of anti- microbial peptides including b-defensin and S100A7, S100A8 and S100A9 [11,12]. Palmoplantar pustular psoriasis (PPPP) is a variant of psoriasis that can limit the ability to walk, work and perform routine daily Abbreviations: PPPP, palmoplantar pustular psoriasis; NPPPP, non-pustular palmoplantar psoriasis. * Corresponding author. E-mail addresses: Rbissonnette@innovaderm.ca, alevesque@innovaderm.ca, afortier@innovaderm.ca (R. Bissonnette). http://dx.doi.org/10.1016/j.jdermsci.2016.09.019 0923-1811/ ã 2016 Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology. Journal of Dermatological Science 85 (2017) 20–26 Contents lists available at ScienceDirect Journal of Dermatological Science journal homepa ge: www.jdsjournal.com