Archives of Dermatological Research

, Volume 311, Issue 1, pp 71–82 | Cite as

Leakage of sweat into the dermo-epidermal junction as a possible trigger for lichen planus lesion development

  • Yoshiko MizukawaEmail author
  • Yoshimi Yamazaki
  • Tetsuo Shiohara
Original Paper


No previous studies have convincingly linked sweating disturbance with the subsequent development of lichen planus (LP). Therefore, we investigated whether sweating disturbance could be specifically detected in LP lesions and how it could trigger lesion development. We utilized the impression mold technique (IMT), which allows accurate quantification of individual sweat glands/ducts actively delivering sweat in a well-defined location, to evaluate sweating disturbance in LP lesions. Psoriasis vulgaris (PsV) lesions were included as controls. Leakage of sweat and subsequent induction of chemokine expression were immunohistochemically identified. Both baseline and thermal stimulus-induced sweating responses were markedly impaired in LP lesions, as well as in PsV lesions. A marked difference, however, was found in normal-appearing perilesional skin; “cold spots”, which were defined as a 1 mm2 area with no sweat droplets, were specifically and abundantly detected in perilesional LP skin, but not perilesional PsV skin. Leakage of sweat as evidenced by the immunohistochemical detection of dermcidin was specifically observed around the acrosyringium of these “cold spots” in LP, but not PsV, lesions and associated with CXCL10 induction on neighboring keratinocytes and syringotropic migration of CXCR3+ T cells. Leakage of sweat into the dermo-epidermal junction would serve not only to decrease sweat delivery to the skin surface but also to induce T-cell recruitment to the inflammatory site. Therapies for LP may be directed not only at ameliorating inflammatory responses but also at preventing the leakage of sweat into the dermo-epidermal junction.


CXCL10 CXCR3 Dermcidin Lichen planus Sweating disturbance 





Healthy control




Impression mold technique


Lichen planus


Psoriasis vulgaris


Tumor necrosis factor




Compliance with ethical standards

Conflict of interest

There is no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional (H21-008-03) and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

All subjects gave informed consent and the Institutional Review Board of Kyorin University School of Medicine approved this study (H21-008-03).


  1. 1.
    Akosa AB, Lampert IA (1990) The sweat gland in graft versus host disease. J Pathol 161:261–266CrossRefGoogle Scholar
  2. 2.
    Akosa AB, Lampert IA (1991) Sweat gland abnormalities in lichenoid dermatosis. Histopathology 19:345–349CrossRefGoogle Scholar
  3. 3.
    Braun RP, Barua D, Masouye I (1998) Zosteriform lichen planus after herpes zoster. Dermatology 197:87–88CrossRefGoogle Scholar
  4. 4.
    Dai X, Okazaki H, Hanakawa Y, Murakami M, Tohyama M, Shirakata Y, Sayama K (2013) Eccrine sweat contains IL-1α, Il-1β and IL-31 and activates epidermal keratinocytes as a danger signal. PLoS One 8:e67666. CrossRefGoogle Scholar
  5. 5.
    Didierjean L, Gruaz D, Frobert Y, Grassi J, Dayer JM, Saurat JH (1990) Biologically active inerleukin 1 in human eccrine sweat: site-dependent variations in alpha/beta ratios and stress-induced increased excretion. Cytokine 2:438–446CrossRefGoogle Scholar
  6. 6.
    Dingwell KS, Johnson DC (1998) The herpes simplex virus gE-gI complex facilitates cell-to-cell spread and binds to components of cell junctions. J Virol 72:8933–8942Google Scholar
  7. 7.
    Faulkner SH, Spilsbury KL, Harvey J, Jackson A, Huang J, Platt M, Tok A, Nimmo MA (2014) The detection and measurement of interleukin-6 in venous and capillary blood samples, and in sweat collected at rest and during exercise. Eur J Appl Physiol 114:1207–1216. CrossRefGoogle Scholar
  8. 8.
    Förster R, Schubel A, Breitfeld D, Kremmer E, Renner-Müller I, Wolf E, Lipp M (1999) CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 99:23–33CrossRefGoogle Scholar
  9. 9.
    Galen B, Cheshenko N, Tuyama A, Ramratnam B, Herold BC (2006) Access to nectin favors herpes simplex virus infection at the apical surface of polarized human epithelial cells. J Virol 80:12209–12218CrossRefGoogle Scholar
  10. 10.
    Jones AP, Webb LM, Anderson AO, Leonard EJ, Rot A (1995) Normal human sweat contains interleukin-8. J Leukoc Biol 57:434–437CrossRefGoogle Scholar
  11. 11.
    Kennedy WR, Sakuta M (1984) Collateral reinnervation of sweat glands. Ann Neurol 15:73–78CrossRefGoogle Scholar
  12. 12.
    Lehman JS, Tollefson MM, Gibson LE (2009) Lichen planus. Int J Dermatol 48:682–694. CrossRefGoogle Scholar
  13. 13.
    Meller S, Gilliet M, Homey B (2009) Chemokines in the pathogenesis of lichenoid tissue reactions. J Invest Dermatol 2009 129:315–319. CrossRefGoogle Scholar
  14. 14.
    Mizukawa Y, Horie C, Yamazaki Y, Shiohara T (2012) Detection of varicella-zoster virus antigens in lesional skin of zosteriform lichen planus but not in that of linear lichen planus. Dermatology 225:22–26. CrossRefGoogle Scholar
  15. 15.
    Murakami M, Lopez-Garcia B, Braff M, Dorschner RA, Gallo RL (2004) Postsecretory processing generates multiple cathelicidins for enhanced topical antimicrobial defense. J Immunol 172:3070–3077CrossRefGoogle Scholar
  16. 16.
    Nakai A, Hayano Y, Furuta F, Noda M, Suzuki K (2014) Control of lymphocyte egress from lymph nodes through β2-adrenergic receptors. J Exp Med 211:2583–2598. CrossRefGoogle Scholar
  17. 17.
    Niyonsaba F, Suzuki A, Ushio H, Nagaoka I, Ogawa H, Okumura K (2009) The human antimicrobial peptide dermcidin activates normal human keratinocytes. Br J Dermatol 160:239–243. CrossRefGoogle Scholar
  18. 18.
    Okiyama N, Fujimoto M (2015) Clinical perspectives and murine models of lichenoid tissue reaction/interface dermatitis. J Dermatol Sci 78:167–172. CrossRefGoogle Scholar
  19. 19.
    Rieg S, Garbe C, Sauer B, Kalbacher H, Schittek B (2004) Dermcidin is constitutively produced by eccrine sweat glands and is not induced in epidermal cells under inflammatory skin conditions. Br J Dermatol 151:534–539CrossRefGoogle Scholar
  20. 20.
    Rieg S, Steffen H, Seeber S, Humeny A, Kalbacher H, Dietz K, Garbe C, Schittek B (2005) Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo. J Immunol 174:8003–8010CrossRefGoogle Scholar
  21. 21.
    Sallusto F, Lenig D, Mackay CR, Lanzavecchia A (1998) Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. J Exp Med 187:875–883CrossRefGoogle Scholar
  22. 22.
    Sato K, Sato F (1994) Interleukin-1 alpha in human sweat is functionally active and derived from the eccrine sweat gland. Am J Physiol 266(3 Pt 2):R950–R959Google Scholar
  23. 23.
    Schittek B, Hipfel R, Sauer B, Bauer J, Kalbacher H, Stevanovic S, Schirle M, Schroeder K, Blin N, Meier F, Rassner G, Garbe C (2001) Dermcidin: a novel human antibiotic peptide secreted by sweat glands. Nat Immunol 2:1133–1137CrossRefGoogle Scholar
  24. 24.
    Shemer A, Weiss G, Trau H (2001) Wolf’s isotopic response: a case of zosteriform lichen planus on the site of healed herpes zoster. J Eur Acad Dermatol Venereol 15:445–447CrossRefGoogle Scholar
  25. 25.
    Shimoda-Komatsu Y, Sato Y, Hayashida Y, Yamazaki Y, Mizukawa Y, Nakajima K, Shiohara T, Aoyama Y (2017) Lichen amyloidosus as a sweat gland/duct-related disorder: resolution associated with restoration of sweating disturbance. Br J Dermatol 176: 1308–1315. CrossRefGoogle Scholar
  26. 26.
    Shiohara T, Doi T, Hayakawa J (2011) Defective sweating responses in atopic dermatitis. Curr Probl Dermatol 41:68–79. CrossRefGoogle Scholar
  27. 27.
    Shiohara T, Mizukawa Y, Takahashi R, Kano Y (2008) Pathomechanisms of lichen planus autoimmunity elicited by cross-reactive T cells. Curr Dir Autoimmun 10:206–226. CrossRefGoogle Scholar
  28. 28.
    Sontheimer RD (2009) Lichenoid tissue reaction/interface dermatitis: clinical and histological perspectives. J Invest Dermatol 129:1088–1099. CrossRefGoogle Scholar
  29. 29.
    Tan X, Li D, Wang X, Zeng Y, Yan Y, Yang L (2014) Clandin-2 downregulation by KSHV infection is involved in the regulation of endothelial barrier function. J Cutan Pathol 41:630–639. CrossRefGoogle Scholar
  30. 30.
    Ushigome Y, Sato Y, Shimoda Y, Yamazaki Y, Shiohara T (2017) Localized hypohidrosis is an unrecognized sequela of herpes zoster. J Am Acad Dermatol 76:160–162. CrossRefGoogle Scholar
  31. 31.
    Vilches JJ, Navarro X (2002) New silicones for the evaluation of sudomotor function with the impression mold technique. Clin Auton Res 12:20–23CrossRefGoogle Scholar
  32. 32.
    Villarroel VA, Okiyama N, Tsuji G, Linton JT, Katz SI (2014) CXCR3-mediated skin homing of autoreactive CD8 T cells is a key determinant in murine graft-versus-host disease. J Invest Dermatol 134:1552–1560. CrossRefGoogle Scholar
  33. 33.
    Wenzel J, Lucas S, Zahn S, Mikus S, Metze D, Ständer S, von Stebut E, Hillen U, Bieber T, Tűting T (2008) CXCR3 <-> lignand-mediated skin inflammation in cutaneous lichenoid graft-versus-host disease. J Am Acad Dermatol 58: 437–442. Scholar
  34. 34.
    Wenzel J, Scheler M, Proelss J, Bieber T, Tűting T (2006) Type 1 interferon-associated cytotoxic inflammation in lichen planus. J Cutan Pathol 33:672–678CrossRefGoogle Scholar
  35. 35.
    Wenzel J, Tüting T (2008) An IFN-associated cytotoxic cellular immune response against viral, self-, or tumor antigens is a common pathogenetic feature in interface dermatitis. J Invest Dermatol 128:2392–2402. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Yoshiko Mizukawa
    • 1
    Email author
  • Yoshimi Yamazaki
    • 1
  • Tetsuo Shiohara
    • 1
  1. 1.Department of DermatologyKyorin University School of MedicineTokyoJapan

Personalised recommendations