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Pityriasis Rubra Pilaris Response to IL-17A Inhibition Is Associated with IL-17C and CCL20 Protein Levels

      Pityriasis rubra pilaris (PRP) is a rare, severe inflammatory skin disease associated with high morbidity and debilitating effects on QOL (
      • Eastham A.B.
      • Tkachenko E.Y.
      • Femia A.N.
      • Pappas-Taffer L.K.
      • Rosenbach M.
      • Joyce C.J.
      • et al.
      Pityriasis rubra pilaris: a study evaluating patient quality of life in 2 populations.
      ;
      • Ross N.A.
      • Chung H.J.
      • Li Q.
      • Andrews J.P.
      • Keller M.S.
      • Uitto J.
      Epidemiologic, clinicopathologic, diagnostic, and management challenges of pityriasis rubra pilaris: a case series of 100 patients.
      ). Classical features include follicular hyperkeratosis; erythematous plaques often progressing to erythroderma with islands of sparing; and waxy, palmoplantar keratoderma. The pathogenesis and etiology of PRP remain poorly understood. Small case series have shown dysregulation of the IL-23/IL-17 axis (
      • Adnot-Desanlis L.
      • Antonicelli F.
      • Tabary T.
      • Bernard P.
      • Reguiaï Z.
      Effectiveness of infliximab in pityriasis rubra pilaris is associated with pro-inflammatory cytokine inhibition.
      ;
      • Feldmeyer L.
      • Mylonas A.
      • Demaria O.
      • Mennella A.
      • Yawalkar N.
      • Laffitte E.
      • et al.
      Interleukin 23-helper T cell 17 axis as a treatment target for pityriasis rubra pilaris.
      ;
      • Nagai H.
      • Jimbo H.
      • Matsuura S.
      • Tatsuoka S.
      • Shiraki E.
      • Nishigori C.
      Successful treatment of pityriasis rubra pilaris with guselkumab: serum CCL20 as a potential marker for the disease activity.
      ). Importantly, there is mounting evidence for treatment efficacy with IL-17 and IL-23 inhibitors (
      • Engelmann C.
      • Elsner P.
      • Miguel D.
      Treatment of pityriasis rubra pilaris type I: a systematic review.
      ;
      • Haynes D.
      • Strunck J.L.
      • Topham C.A.
      • Ortega-Loayza A.G.
      • Kent G.
      • Cassidy P.B.
      • et al.
      Evaluation of ixekizumab treatment for patients with pityriasis rubra pilaris: a single-arm trial.
      ;
      • Kromer C.
      • Sabat R.
      • Celis D.
      • Mössner R.
      Systemic therapies of pityriasis rubra pilaris: a systematic review.
      ;
      • Maloney N.J.
      • Kim M.M.
      • Nguyen K.A.
      • Hisaw L.D.
      • Worswick S.
      Patient experiences with biologics and apremilast in pityriasis rubra pilaris: a patient survey.
      ). We sought to characterize the inflammatory landscape in patients with PRP using a proteomic panel of 92 common inflammatory biomarkers in the skin and plasma from biobanked samples collected during an open-label clinical trial with the IL-17A inhibitor, ixekizumab (
      • Haynes D.
      • Strunck J.L.
      • Topham C.A.
      • Ortega-Loayza A.G.
      • Kent G.
      • Cassidy P.B.
      • et al.
      Evaluation of ixekizumab treatment for patients with pityriasis rubra pilaris: a single-arm trial.
      ) compared with that in healthy controls (Clinicaltrials.gov identifier: NCT03485976). A high-throughput, multiplex proximity extension assay (Olink Proteomics Inflammatory Panel, www.olink.com/products/inflammation, Olink, Uppsala, Sweden) was chosen for its robust representation of established and exploratory biomarkers associated with inflammatory disease (a full list of proteins is available in Supplementary Table S1).

      Abbreviations:

      PRP (pityriasis rubra pilaris), Th (T helper type)
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