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Journal of the American Academy of Dermatology
Sous presse. Epreuves corrigées par l'auteur. Disponible en ligne depuis le lundi 3 février 2020
Doi : 10.1016/j.jaad.2019.07.060
accepted : 21 July 2019
Pathophysiologic mechanisms of itch in bullous pemphigoid

Takashi Hashimoto, MD, PhD a, b, , Christina Dorothy Kursewicz, BS a, Rachel Alison Fayne, BA a, Sonali Nanda, MS a, Serena Maya Shah a, Leigh Nattkemper, PhD a, Hiroo Yokozeki, MD, PhD b, Gil Yosipovitch, MD a
a Miami Itch Center, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, Florida 
b Department of Dermatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan 

Reprint requests: Takashi Hashimoto, MD, PhD, 1600 NW 10th Ave, RMSB 2069A, Miami, FL 33130.1600 NW 10th Ave, RMSB 2069AMiamiFL33130

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.


We sought to elucidate the pathophysiologic mechanisms of itch in BP.


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.


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.


The relatively small sample size, the examination of protein expression exclusively through immunofluorescent analysis, and lack of functional assays in patients are the limitations.


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.

The full text of this article is available in PDF format.

Key words : basophils, bullous pemphigoid, eosinophils, IL-13, IL-31, itch, NK1R, periostin, pruritus, substance P

Abbreviations used : AD, BP, IENFD, IL, IL-4Rα, NK1R, NRS, OSMRβ, PAR-2, SP, Th2, TSLP, TRPA1, TRPV1

 Funding sources: This work was partially supported by Japan Society for the Promotion of Science KAKENHI Grant-in-Aid for Young Scientists (B) (#17K16328) and an unrestricted fellowship grant from Menlo Therapeutics.
 Conflicts of interest: Dr Yosipovitch is a scientific board member of Menlo, Trevi, Sienna, Sanofi, Regeneron, Galderma, Pfizer, Novartis, Bayer, Kiniksa, Eli Lilly, and Ortho, and has received research support from Pfizer, Sun Pharma, Leo,Menlo, and Kiniksa. Authors Hashimoto, Kursewicz, Fayne, Nanda, Shah, and Nattkemper have no conflicts of interest.

© 2019  American Academy of Dermatology, Inc.@@#104156@@
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