Pathophysiologic mechanisms of itch in bullous pemphigoid

Takashi Hashimoto, Christina Dorothy Kursewicz, Rachel Alison Fayne, Sonali Nanda, Serena Maya Shah, Leigh Nattkemper, Hiroo Yokozeki, Gil Yosipovitch

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)53-62
Number of pages10
JournalJournal of the American Academy of Dermatology
Issue number1
StatePublished - Jul 2020


  • IL-13
  • IL-31
  • NK1R
  • basophils
  • bullous pemphigoid
  • eosinophils
  • itch
  • periostin
  • pruritus
  • substance P

ASJC Scopus subject areas

  • Dermatology


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