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Pruritus pp 131-144 | Cite as

Atopic Dermatitis

  • Mitsutoshi Tominaga
  • Kenji TakamoriEmail author
Chapter

Abstract

Atopic dermatitis (AD) is an inflammatory, chronically relapsing, and intensely pruritic skin disease. Antihistamines are used to treat pruritus in AD patients, although they often lack efficacy in intractable and chronic pruritus, a profound clinical problem that reduces quality of life. The development of effective treatments therefore requires a complete understanding of the fundamental mechanisms of itch. Recent studies have indicated that the pathogenic mechanisms of itch in AD involve pruritogens such as substance P, interleukin-31 and thymic stromal lymphopoietin. Some of their cognate receptors may be upregulated in the dorsal root ganglia of AD. Release of pruritogenic mediators and modulators in the periphery may directly excite itch-mediating fibers, especially C-fibers, via specific receptors on the nerve terminals. The density of epidermal nerve fibers is higher in patients and animals with than without AD, suggesting that this higher density is at least partly responsible for peripheral itch sensitization. Clinically, emollients and ultraviolet-based therapies may partly control epidermal nerve density, suppressing pruritus in patients with AD. Cyclosporine A and aprepitant have also been shown to be effective antipruritic agents in patients with AD. In animals, treatment with anti-nerve growth factor and semaphorin 3A replacement normalized the hyperinnervation in AD, partly contributing to the suppression of itch. Intrathecal minocycline suppressed itch-related behavior in an animal model of AD. Thus, new substances and classes of antipruritic agents are being developed, targeting both the peripheral and central levels. This chapter presents recent knowledge regarding the mechanisms and treatment of pruritus in AD.

Keywords

Amphiregulin Anosmin-1 Antihistamines Artemin Axon guidance molecule B-type natriuretic peptide Calcitonin-gene-related peptide Cyclosporine Dermatophagoides farinae body DRG Emollient Epidermal innervation Gastrin-releasing peptide Glutamate IL-31 Itch Keratinocytes Matrix metalloproteinases Microglia Minocycline NGF NK-1R Sema3A Sensory nerve fibers Spinal cord Substance P TSLP UV-based therapy 

Notes

Acknowledgments

This work was partly supported by KAKENHI (Grant numbers 20591354, 20790818, 25460727, 25860428 and 26860898), JSPS Research Fellowship (Grant number 10J04599), and Strategic Research Foundation Grant-aided Project for Private Universities from MEXT (Grant number S1311011).

Conflict of Interest

The authors declare they have no conflicts of interest.

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Copyright information

© Springer-Verlag London 2016

Authors and Affiliations

  1. 1.Institute for Environmental and Gender Specific MedicineJuntendo University Graduate School of MedicineUrayasuJapan
  2. 2.Department of DermatologyJuntendo University Urayasu HospitalUrayasuJapan

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