Skip to main content
SpringerLink
Log in

Factors that Exacerbate Itching in Patients with Atopic Dermatitis

  • Chapter
  • First Online:
Evolution of Atopic Dermatitis in the 21st Century

  • 888 Accesses

Abstract

Patients with atopic dermatitis (AD) exhibit different clinical symptoms, progression, and treatment responses during childhood and adulthood. In adults, itching of the skin is followed by the formation of well-circumscribed plaques or polymorphous dermatoses at the site of itching and is often accompanied by dryness. AD patients show hypersensitivity to various external stimuli that can exacerbate itching, such as heat and perspiration, which leads to scratching and further aggravation of skin lesions. This hypersensitivity exhibited by AD patients may arise from abnormal elongation of sensory nerves into the epidermis as well as sensitization of peripheral or central nerves. Itching can worsen when excess sweat is left on the skin or when insufficient sweating results in heat retention. Endogenous factors such as cytokines and chemical messengers can also induce itch by stimulating nerve fibers in the skin. Itching can be caused not only by stimulation of the skin surface but also by visual and auditory stimulation, with psychologically induced “contagious itch” being stronger in AD patients than in healthy individuals. Furthermore, itch often increases in the evening when sympathetic nerve activity decreases. This chapter discusses factors that exacerbate itching in AD and guidance for the proper management of the disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Hill LW, Sulzberger MB. Evolution of atopic dermatitis. Arch Dermatol Syphilol. 1935;32(3):451–63.

    Article  Google Scholar 

  2. Brocq L, Jacquet L. Notes pour servir a l'histories des néurodermatitis: du lichen circumscriptus des anciens auteurs, ou lichen simplex chronique de M. le Dr. E Vidal. Ann Dermatol Syphiligr. 1891;97:193–208.

    Google Scholar 

  3. Besnier E. Premiére note et observations preliminaires pour servir d'introduction à l étude diathésique. Ann Dermatol Syphiligr. 1892;23:634–48.

    Google Scholar 

  4. Hanifin JM. Pharmacophysiology of atopic dermatitis. Clin Rev Allergy. 1986;4(1):43–65.

    CAS  PubMed  Google Scholar 

  5. Wahlgren CF. Itch and atopic dermatitis: clinical and experimental studies. Acta Derm Venereol Suppl (Stockh). 1991;165:1–53.

    CAS  Google Scholar 

  6. Shiratori-Hayashi M, Koga K, Tozaki-Saitoh H, Kohro Y, Toyonaga H, Yamaguchi C, et al. STAT3-dependent reactive astrogliosis in the spinal dorsal horn underlies chronic itch. Nat Med. 2015;21(8):927–31.

    Article  CAS  PubMed  Google Scholar 

  7. Akiyama T, Carstens E. Spinal coding of itch and pain. In: Carstens E, Akiyama T, editors. Itch: mechanisms and Treatment. Boca Raton (FL): CRC Press/Taylor & Francis; 2014.

    Google Scholar 

  8. Stander S, Moormann C, Schumacher M, Buddenkotte J, Artuc M, Shpacovitch V, et al. Expression of vanilloid receptor subtype 1 in cutaneous sensory nerve fibers, mast cells, and epithelial cells of appendage structures. Exp Dermatol. 2004;13(3):129–39.

    Article  PubMed  Google Scholar 

  9. Wilson SR, Gerhold KA, Bifolck-Fisher A, Liu Q, Patel KN, Dong X, et al. TRPA1 is required for histamine-independent, mas-related G protein-coupled receptor-mediated itch. Nat Neurosci. 2011;14(5):595–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lee JH, Park CK, Chen G, Han Q, Xie RG, Liu T, et al. A monoclonal antibody that targets a NaV1.7 channel voltage sensor for pain and itch relief. Cell. 2014;157(6):1393–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Yun JW, Seo JA, Jeong YS, Bae IH, Jang WH, Lee J, et al. TRPV1 antagonist can suppress the atopic dermatitis-like symptoms by accelerating skin barrier recovery. J Dermatol Sci. 2011;62(1):8–15.

    CAS  PubMed  Google Scholar 

  12. Oh MH, Oh SY, Lu J, Lou H, Myers AC, Zhu Z, et al. TRPA1-dependent pruritus in IL-13-induced chronic atopic dermatitis. J Immunol. 2013;191(11):5371–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wilson SR, Bautista DM. Role of transient receptor potential channels in acute and chronic itch. In: Carstens E, Akiyama T, editors. Itch: mechanisms and treatment. Boca Raton (FL): CRC Press/Taylor & Francis; 2014.

    Google Scholar 

  14. Ross SE, Mardinly AR, McCord AE, Zurawski J, Cohen S, Jung C, et al. Loss of inhibitory interneurons in the dorsal spinal cord and elevated itch in Bhlhb5 mutant mice. Neuron. 2010;65(6):886–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Akiyama T, Carstens E. Neural processing of itch. Neuroscience. 2013;250:697–714.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Pereira PJ, Lerner EA. Interneurons scratch an itch. Neuron. 2014;82(3):503–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Mochizuki H, Tanaka S, Morita T, Wasaka T, Sadato N, Kakigi R. The cerebral representation of scratching-induced pleasantness. J Neurophysiol. 2014;111(3):488–98.

    Article  PubMed  Google Scholar 

  18. Paus R, Schmelz M, Biro T, Steinhoff M. Frontiers in pruritus research: scratching the brain for more effective itch therapy. J Clin Invest. 2006;116(5):1174–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Gotoh Y, Omori Y, Andoh T, Kuraishi Y. Tonic inhibition of allergic itch signaling by the descending noradrenergic system in mice. J Pharmacol Sci. 2011;115(3):417–20.

    Article  CAS  PubMed  Google Scholar 

  20. Kuraishi Y. Noradrenergic modulation of itch transmission in the spinal cord. Handb Exp Pharmacol. 2015;226:207–17.

    Article  CAS  PubMed  Google Scholar 

  21. Gotoh Y, Andoh T, Kuraishi Y. Noradrenergic regulation of itch transmission in the spinal cord mediated by alpha-adrenoceptors. Neuropharmacology. 2011;61(4):825–31.

    Article  CAS  PubMed  Google Scholar 

  22. Ishiuji Y, Coghill RC, Patel TS, Oshiro Y, Kraft RA, Yosipovitch G. Distinct patterns of brain activity evoked by histamine-induced itch reveal an association with itch intensity and disease severity in atopic dermatitis. Br J Dermatol. 2009;161(5):1072–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Yosipovitch G. Dry skin and impairment of barrier function associated with itch - new insights. Int J Cosmet Sci. 2004;26(1):1–7.

    Article  CAS  PubMed  Google Scholar 

  24. Ikoma A, Steinhoff M, Stander S, Yosipovitch G, Schmelz M. The neurobiology of itch. Nat Rev Neurosci. 2006;7(7):535–47.

    Article  CAS  PubMed  Google Scholar 

  25. Kamo A, Tominaga M, Taneda K, Ogawa H, Takamori K. Neurotropin inhibits the increase in intraepidermal nerve density in the acetone-treated dry-skin mouse model. Clin Exp Dermatol. 2013;38(6):665–8.

    Article  CAS  PubMed  Google Scholar 

  26. Tominaga M, Takamori K. Itch and nerve fibers with special reference to atopic dermatitis: therapeutic implications. J Dermatol. 2014;41(3):205–12.

    Article  CAS  PubMed  Google Scholar 

  27. Murota H, Izumi M, Abd El-Latif MI, Nishioka M, Terao M, Tani M, et al. Artemin causes hypersensitivity to warm sensation, mimicking warmth-provoked pruritus in atopic dermatitis. J Allergy Clin Immunol. 2012;130(3):671–82. e674

    Article  CAS  PubMed  Google Scholar 

  28. Feld M, Garcia R, Buddenkotte J, Katayama S, Lewis K, Muirhead G, et al. The pruritus- and TH2-associated cytokine IL-31 promotes growth of sensory nerves. J Allergy Clin Immunol. 2016;138(2):500–8. e524

    Article  CAS  PubMed  Google Scholar 

  29. Wilson SR, The L, Batia LM, Beattie K, Katibah GE, McClain SP, et al. The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch. Cell. 2013;155(2):285–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Sonkoly E, Muller A, Lauerma AI, Pivarcsi A, Soto H, Kemeny L, et al. IL-31: a new link between T cells and pruritus in atopic skin inflammation. J Allergy Clin Immunol. 2006;117(2):411–7.

    Article  CAS  PubMed  Google Scholar 

  31. Kremer AE, Martens JJ, Kulik W, Rueff F, Kuiper EM, van Buuren HR, et al. Lysophosphatidic acid is a potential mediator of cholestatic pruritus. Gastroenterology. 2010;139(3):1008–1018 e1001.

    Article  CAS  PubMed  Google Scholar 

  32. Nakao M, Sugaya M, Suga H, Kawaguchi M, Morimura S, Kai H, et al. Serum autotaxin levels correlate with pruritus in patients with atopic dermatitis. J Invest Dermatol. 2014;134(6):1745–7.

    Article  CAS  PubMed  Google Scholar 

  33. Fruhstorfer H, Hermanns M, Latzke L. The effects of thermal stimulation on clinical and experimental itch. Pain. 1986;24(2):259–69.

    Article  CAS  PubMed  Google Scholar 

  34. Yosipovitch G, Fast K, Bernhard JD. Noxious heat and scratching decrease histamine-induced itch and skin blood flow. J Invest Dermatol. 2005;125(6):1268–72.

    Article  CAS  PubMed  Google Scholar 

  35. Ikoma A, Fartasch M, Heyer G, Miyachi Y, Handwerker H, Schmelz M. Painful stimuli evoke itch in patients with chronic pruritus: central sensitization for itch. Neurology. 2004;62(2):212–7.

    Article  CAS  PubMed  Google Scholar 

  36. Murota H, Katayama I. Evolving understanding on the aetiology of thermally provoked itch. Eur J Pain. 2016;20(1):47–50.

    Article  CAS  PubMed  Google Scholar 

  37. Pfab F, Valet M, Sprenger T, Toelle TR, Athanasiadis GI, Behrendt H, et al. Short-term alternating temperature enhances histamine-induced itch: a biphasic stimulus model. J Invest Dermatol. 2006;126(12):2673–8.

    Article  CAS  PubMed  Google Scholar 

  38. Katayama I, Kohno Y, Akiyama K, Aihara M, Kondo N, Saeki H, et al. Japanese guideline for atopic dermatitis 2014. Allergol Int. 2014;63(3):377–98.

    Article  CAS  Google Scholar 

  39. Kuno Y. Human perspiration. Springfield: Illinois; 1956.

    Google Scholar 

  40. Murota H, Matsui S, Ono E, Kijima A, Kikuta J, Ishii M, et al. Sweat, the driving force behind normal skin: an emerging perspective on functional biology and regulatory mechanisms. J Dermatol Sci. 2015;77(1):3–10.

    Article  CAS  PubMed  Google Scholar 

  41. Yokozeki H, Hibino T, Sato K. Partial purification and characterization of cysteine proteinases in eccrine sweat. Am J Phys. 1987;252(6 Pt 2):R1119–29.

    CAS  Google Scholar 

  42. Yokozeki H, Hibino T, Takemura T, Sato K. Cysteine proteinase inhibitor in eccrine sweat is derived from sweat gland. Am J Phys. 1991;260(2 Pt 2):R314–20.

    CAS  Google Scholar 

  43. Hibino T, Izaki S, Izaki M. Detection of serine proteinase inhibitors in human cornified cells. Biochem Biophys Res Commun. 1981;101(3):948–55.

    Article  CAS  PubMed  Google Scholar 

  44. Kato T, Takai T, Mitsuishi K, Okumura K, Ogawa H. Cystatin a inhibits IL-8 production by keratinocytes stimulated with der p 1 and der f 1: biochemical skin barrier against mite cysteine proteases. J Allergy Clin Immunol. 2005;116(1):169–76.

    Article  CAS  PubMed  Google Scholar 

  45. Nattkemper LA, Lee HG, Valdes-Rodriguez R, Mollanazar NK, Sanders KM, Yosipovitch G. Cholinergic induction of perspiration attenuates nonhistaminergic pruritus in the skin of patients with atopic dermatitis and healthy controls. Br J Dermatol. 2015;173(1):282–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Williams JR, Burr ML, Williams HC. Factors influencing atopic dermatitis-a questionnaire survey of schoolchildren's perceptions. Br J Dermatol. 2004;150(6):1154–61.

    Article  CAS  PubMed  Google Scholar 

  47. Tanaka A, Tanaka T, Suzuki H, Ishii K, Kameyoshi Y, Hide M. Semi-purification of the immunoglobulin E-sweat antigen acting on mast cells and basophils in atopic dermatitis. Exp Dermatol. 2006;15(4):283–90.

    Article  CAS  PubMed  Google Scholar 

  48. Adachi J, Endo K, Fukuzumi T, Kojima M, Aoki T. Negative patch test reactions to sweat in atopic dermatitis. Acta Derm Venereol. 1996;76(5):410–1.

    CAS  PubMed  Google Scholar 

  49. Hiragun T, Ishii K, Hiragun M, Suzuki H, Kan T, Mihara S, et al. Fungal protein MGL_1304 in sweat is an allergen for atopic dermatitis patients. J Allergy Clin Immunol. 2013;132(3):608–15. e604

    Article  CAS  PubMed  Google Scholar 

  50. Papa C, Kligman A. Mechanism of eccrine anhidrosis. J Invest Dermatol. 1966;47:1–9.

    Article  CAS  PubMed  Google Scholar 

  51. Shiohara T, Doi T, Hayakawa J. Defective sweating responses in atopic dermatitis. Curr Probl Dermatol. 2011;41:68–79.

    Article  PubMed  Google Scholar 

  52. Eishi K, Lee JB, Bae SJ, Takenaka M, Katayama I. Impaired sweating function in adult atopic dermatitis: results of the quantitative sudomotor axon reflex test. Br J Dermatol. 2002;147(4):683–8.

    Article  CAS  PubMed  Google Scholar 

  53. Kijima A, Murota H, Matsui S, Takahashi A, Kimura A, Kitaba S, et al. Abnormal axon reflex-mediated sweating correlates with high state of anxiety in atopic dermatitis. Allergol Int. 2012;61(3):469–73.

    Article  PubMed  Google Scholar 

  54. Takahashi A, Murota H, Matsui S, Kijima A, Kitaba S, Lee JB, et al. Decreased sudomotor function is involved in the formation of atopic eczema in the cubital fossa. Allergol Int. 2013;62(4):473–8.

    Article  CAS  PubMed  Google Scholar 

  55. Matsui S, Murota H, Takahashi A, Yang L, Lee JB, Omiya K, et al. Dynamic analysis of histamine-mediated attenuation of acetylcholine-induced sweating via GSK3beta activation. J Invest Dermatol. 2014;134(2):326–34.

    Article  CAS  PubMed  Google Scholar 

  56. Saeki H, Nakahara T, Tanaka A, Kabashima K, Sugaya M, Murota H, et al. Clinical practice guidelines for the management of atopic dermatitis 2016. J Dermatol. 2016;43:1117–45.

    Article  PubMed  Google Scholar 

  57. Lavery MJ, Stull C, Kinney MO, Yosipovitch G. Nocturnal pruritus: the battle for a peaceful night's sleep. Int J Mol Sci. 2016;17(3):425.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Parsad D, Saini R. The sound of scratching: an unusual cause of neurotic excoriations. Dermatology. 1997;195(1):74.

    Article  CAS  PubMed  Google Scholar 

  59. Schut C, Grossman S, Gieler U, Kupfer J, Yosipovitch G. Contagious itch: what we know and what we would like to know. Front Hum Neurosci. 2015;9:57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Papoiu AD, Wang H, Coghill RC, Chan YH, Yosipovitch G. Contagious itch in humans: a study of visual 'transmission' of itch in atopic dermatitis and healthy subjects. Br J Dermatol. 2011;164(6):1299–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Wahlgren CF, Hagermark O, Bergstrom R. Patients’ perception of itch induced by histamine, compound 48/80 and wool fibres in atopic dermatitis. Acta Derm Venereol. 1991;71(6):488–94.

    Google Scholar 

  62. Steinhoff M, Neisius U, Ikoma A, Fartasch M, Heyer G, Skov PS, et al. Proteinase-activated receptor-2 mediates itch: a novel pathway for pruritus in human skin. J Neurosci. 2003;23(15):6176–80.

    CAS  PubMed  Google Scholar 

  63. Kempkes C, Buddenkotte J, Cevikbas F, Buhl T, Steinhoff M. Role of PAR-2 in neuroimmune communication and itch. In: Carstens E, Akiyama T, editors. Itch: mechanisms and treatment. Boca Raton (FL): CRC Press/Taylor & Francis; 2014.

    Google Scholar 

  64. Hosogi M, Schmelz M, Miyachi Y, Ikoma A. Bradykinin is a potent pruritogen in atopic dermatitis: a switch from pain to itch. Pain. 2006;126(1–3):16–23.

    Article  CAS  PubMed  Google Scholar 

  65. Bautista DM, Wilson SR, Hoon MA. Why we scratch an itch: the molecules, cells and circuits of itch. Nat Neurosci. 2014;17(2):175–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Tsybikov NN, Petrisheva IV, Kuznik BI, Magen E. Plasma endothelin-1 levels during exacerbation of atopic dermatitis. Allergy Asthma Proc. 2015;36(4):320–4.

    Article  CAS  PubMed  Google Scholar 

  67. McQueen DS, Noble MA, Bond SM. Endothelin-1 activates ETA receptors to cause reflex scratching in BALB/c mice. Br J Pharmacol. 2007;151(2):278–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Hon KL, Lam MC, Wong KY, Leung TF, Ng PC. Pathophysiology of nocturnal scratching in childhood atopic dermatitis: the role of brain-derived neurotrophic factor and substance P. Br J Dermatol. 2007;157(5):922–5.

    Article  CAS  PubMed  Google Scholar 

  69. Heyer G, Hornstein OP, Handwerker HO. Reactions to intradermally injected substance P and topically applied mustard oil in atopic dermatitis patients. Acta Derm Venereol. 1991;71(4):291–5.

    CAS  PubMed  Google Scholar 

  70. Abeck D, Andersson T, Grosshans E, Jablonska S, Kragballe K, Vahlquist A, et al. Topical application of a platelet-activating factor (PAF) antagonist in atopic dermatitis. Acta Derm Venereol. 1997;77(6):449–51.

    CAS  PubMed  Google Scholar 

  71. Andoh T, Haza S, Saito A, Kuraishi Y. Involvement of leukotriene B4 in spontaneous itch-related behaviour in NC mice with atopic dermatitis-like skin lesions. Exp Dermatol. 2011;20(11):894–8.

    Article  CAS  PubMed  Google Scholar 

  72. Wilson SR, Nelson AM, Batia L, Morita T, Estandian D, Owens DM, et al. The ion channel TRPA1 is required for chronic itch. J Neurosci. 2013;33(22):9283–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Zygmunt PM, Hogestatt ED. Trpa1. Handb Exp Pharmacol. 2014;222:583–630.

    Article  CAS  PubMed  Google Scholar 

  74. Kim DK, Kim HJ, Kim H, Koh JY, Kim KM, Noh MS, et al. Involvement of serotonin receptors 5-HT1 and 5-HT2 in 12(S)-HPETE-induced scratching in mice. Eur J Pharmacol. 2008;579(1–3):390–4.

    Article  CAS  PubMed  Google Scholar 

  75. Mollanazar NK, Smith PK, Yosipovitch G. Mediators of Chronic Pruritus in Atopic Dermatitis: Getting the Itch Out? Clin Rev Allergy Immunol. 2016;51:263–92.

    Google Scholar 

  76. Tirado-Sanchez A, Bonifaz A, Ponce-Olivera RM. Serum gastrin-releasing peptide levels correlate with disease severity and pruritus in patients with atopic dermatitis. Br J Dermatol. 2015;173(1):298–300.

    Article  CAS  PubMed  Google Scholar 

  77. Kagami S, Sugaya M, Suga H, Morimura S, Kai H, Ohmatsu H, et al. Serum gastrin-releasing peptide levels correlate with pruritus in patients with atopic dermatitis. J Invest Dermatol. 2013;133(6):1673–5.

    Article  CAS  PubMed  Google Scholar 

  78. Georgala S, Schulpis KH, Papaconstantinou ED, Stratigos J. Raised beta-endorphin serum levels in children with atopic dermatitis and pruritus. J Dermatol Sci. 1994;8(2):125–8.

    Article  CAS  PubMed  Google Scholar 

  79. Stander S, Gunzer M, Metze D, Luger T, Steinhoff M. Localization of mu-opioid receptor 1A on sensory nerve fibers in human skin. Regul Pept. 2002;110(1):75–83.

    Article  CAS  PubMed  Google Scholar 

  80. Heyer G, Vogelgsang M, Hornstein OP. Acetylcholine is an inducer of itching in patients with atopic eczema. J Dermatol. 1997;24(10):621–5.

    Article  CAS  PubMed  Google Scholar 

  81. Salomon J, Baran E. The role of selected neuropeptides in pathogenesis of atopic dermatitis. J Eur Acad Dermatol Venereol. 2008;22(2):223–8.

    CAS  PubMed  Google Scholar 

  82. Murota H, Katayama I. Exacerbating factors of itch in atopic dermatitis. Allergol Int. 2016;66:8–13. doi:10.1016/j.alit.2016.10.005.

    Article  PubMed  Google Scholar 

Download references

Conflict of Interest

The authors have nothing to declare.

Author information

Authors and Affiliations

  1. Dermatology, Department of Integrated Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita-shi, Osaka, 565-0871, Japan

    Hiroyuki Murota & Ichiro Katayama

Authors
  1. Hiroyuki Murota
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ichiro Katayama
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroyuki Murota .

Editor information

Editors and Affiliations

  1. Department of Dermatology, Integrated Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

    Ichiro Katayama

  2. Department of Dermatology, Integrated Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

    Hiroyuki Murota

  3. Department of Dermatology, National Defense Medical College, Tokorosazawa, Saitama, Japan

    Takahiro Satoh

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Cite this chapter

Murota, H., Katayama, I. (2018). Factors that Exacerbate Itching in Patients with Atopic Dermatitis. In: Katayama, I., Murota, H., Satoh, T. (eds) Evolution of Atopic Dermatitis in the 21st Century. Springer, Singapore. https://doi.org/10.1007/978-981-10-5541-6_10

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-5541-6_10

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-5540-9

  • Online ISBN: 978-981-10-5541-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation