Pathophysiologic mechanisms of itch in bullous pemphigoid

大疱性类天疱疮瘙痒的病理生理机制

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

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.

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.

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.

Objective

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

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.

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