Takashi Hashimoto1, Christina Dorothy Kursewicz2, Rachel Alison Fayne2, Sonali Nanda2, Serena Maya Shah2, Leigh Nattkemper2, Hiroo Yokozeki3, Gil Yosipovitch2. 1. Miami Itch Center, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, Florida; Department of Dermatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: hashderm@tmd.ac.jp. 2. Miami Itch Center, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, Florida. 3. Department of Dermatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Abstract
BACKGROUND: One of the hallmarks of bullous pemphigoid (BP) is moderate to severe chronic itch. Managing this is difficult because little is known about the mechanisms of itch in BP. OBJECTIVE: We sought to elucidate the pathophysiologic mechanisms of itch in BP. METHODS: The expression of itch mediators in lesions of 24 patients with BP and 6 healthy individuals were examined through immunofluorescence staining. Furthermore, the expression of itch mediators and itch severity was correlated. RESULTS: Itch severity was correlated with eosinophils, substance P, neurokinin 1R, interleukin (IL) 31 receptor A, oncostatin M receptor-β, IL-13, periostin, and basophils. There was also a trend between itch severity and IL-31 expression. Most of the cells expressing IL-31 or neurokinin 1R were identified as eosinophils. Intraepidermal nerve fiber density was decreased. Other itch mediators, including mast cells, IL-4, thymic stromal lymphopoietin, transient receptor potential vanilloid 1 and ankyrin 1, and protease activated receptor 2 were not significantly correlated with itch severity. LIMITATIONS: The relatively small sample size, the examination of protein expression exclusively through immunofluorescent analysis, and lack of functional assays in patients are the limitations. CONCLUSIONS: Multiple factors are involved in BP-associated itch, including eosinophils, substance P, neurokinin 1R, IL-31, IL-31 receptor A, oncostatin M receptor-β, IL-13, periostin, and basophils. They could be useful therapeutic targets.
BACKGROUND: One of the hallmarks of bullous pemphigoid (BP) is moderate to severe chronic itch. Managing this is difficult because little is known about the mechanisms of itch in BP. OBJECTIVE: We sought to elucidate the pathophysiologic mechanisms of itch in BP. METHODS: The expression of itch mediators in lesions of 24 patients with BP and 6 healthy individuals were examined through immunofluorescence staining. Furthermore, the expression of itch mediators and itch severity was correlated. RESULTS:Itch severity was correlated with eosinophils, substance P, neurokinin 1R, interleukin (IL) 31 receptor A, oncostatin M receptor-β, IL-13, periostin, and basophils. There was also a trend between itch severity and IL-31 expression. Most of the cells expressing IL-31 or neurokinin 1R were identified as eosinophils. Intraepidermal nerve fiber density was decreased. Other itch mediators, including mast cells, IL-4, thymic stromal lymphopoietin, transient receptor potential vanilloid 1 and ankyrin 1, and protease activated receptor 2 were not significantly correlated with itch severity. LIMITATIONS: The relatively small sample size, the examination of protein expression exclusively through immunofluorescent analysis, and lack of functional assays in patients are the limitations. CONCLUSIONS: Multiple factors are involved in BP-associated itch, including eosinophils, substance P, neurokinin 1R, IL-31, IL-31 receptor A, oncostatin M receptor-β, IL-13, periostin, and basophils. They could be useful therapeutic targets.
Authors: Takashi Hashimoto; Leigh A Nattkemper; Hei Sung Kim; Christina D Kursewicz; Emilie Fowler; Serena M Shah; Sonali Nanda; Rachel A Fayne; Paolo Romanelli; Gil Yosipovitch Journal: Acta Derm Venereol Date: 2021-01-20 Impact factor: 3.875
Authors: Jana Maria Nemmer; Marcus Kuchner; Angeliki Datsi; Péter Oláh; Valérie Julia; Ulrike Raap; Bernhard Homey Journal: Front Med (Lausanne) Date: 2021-02-10