The Role of Sweat in the Pathogenesis of Atopic Dermatitis

  • Tetsuo ShioharaEmail author
  • Yurie Shimoda-Komatsu
  • Yoshiko Mizukawa
  • Yuki Hayashida
  • Yumi Aoyama


Although atopic dry skin is believed to be caused by defects in skin genes that are important for maintaining skin barrier function, the role of sweat has been apparently underestimated despite its great capacity to increase skin hydration. It has become clear that sweating responses can be divided into two types depending on their functions. Under baseline conditions, sweat glands/ducts located at the dermal folds secrete basal levels of sweat in an unrecognized fashion, which is referred to as “insensible” sweating and could serve to maintain skin hydration. In contrast, another type of sweating is called “sensible” sweating that is induced by physical exercise and hot/humid environment and could function as a major thermoregulator: this type of sweating is largely delivered from sweat glands/ducts at the dermal ridges. Atopic dermatitis (AD) would initially arise from a localized defect in “insensible” sweating responses from sweat glands/ducts at the folds: this defect could start with leakage of sweat from the glands/ducts, thereby not only providing an inflammatory milieu but also resulting in dry skin. As a next step, compensatory hyperhidrosis would occur preferentially in the sweat glands/ducts at the ridges, which may exacerbate the inflammatory responses. In the final stage, patients eventually manifest the phenotype with systemic hypohidrosis. This three-stage model for the pathogenesis of AD has significant implications both in terms of future research and therapies. Therapies directed at correcting the defects at early times, while ameliorating inflammatory responses, may prove efficacious for preventing further progression of the disease.


Atopic dermatitis Impression mold technique Insensible sweating Moisturizer Skin hydration Sweat glands Topography 



This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology (to TS) and the Health and Labour Sciences Research Grants (Research on Intractable Diseases) from the Ministry of Health, Labour and Welfare of Japan (to TS).


  1. 1.
    Augustin J, Franzke N, Augustin M, Kappas M. Does climate change affect the incidence of skin and allergic disease in Germany? J Dtsch Dermatol Ges. 2008;6:632–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Engebretsen KA, Johansen JD, Kazic S, et al. The effect of environmental humidity and temperature on skin barrier function and dermatitis. J Eur Acad Dermatol Venereol. 2016;30:223–49.CrossRefPubMedGoogle Scholar
  3. 3.
    Doi T, Mizukawa Y, Shimoda Y, et al. Importance of water content of the stratum corneum in mouse models for contact hypersensitivity. J Invest Dermatol. 2017;137:151–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Vocks E, Busch R, Fröhlich C, Borelli S, Mayer H, Ring J. Influence of weather and climate on subjective symptom intensity in atopic eczema. Int J Biometeorol. 2001;45:27–33.CrossRefPubMedGoogle Scholar
  5. 5.
    Krämer U, Weidinger S, Darsow U, Möhrenschlager M, Ring J, Behrendt H. Seasonality in symptom severity influenced by temperature or grass pollen: results of a panel study in children with eczema. J Invest Dermatol. 2005;124:514–23.CrossRefPubMedGoogle Scholar
  6. 6.
    Goldsmith LA. Biology of eccrine and apocrine sweat glands. In: Fitzpatrick TB, editor. Dermatology on general medicine. New York: McGraw-Hill; 1998. p. 155–64.Google Scholar
  7. 7.
    Cui C-Y, Schlessinger D. Eccrine sweat gland development and sweat secretion. Exp Dermatol. 2015;24:644–50.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Sato K, Kang WH, Saga K, Sato KT. Biology of sweat glands and their disorders. I. Normal sweat gland function. J Am Acad Dermatol. 1989;20:537–63.CrossRefPubMedGoogle Scholar
  9. 9.
    Sato K, Kang WH, Saga K, Sato KT. Biology of sweat glands and their disorders. II. Disorders of sweat gland function. J Am Acad Dermatol. 1989;20:713–26.CrossRefPubMedGoogle Scholar
  10. 10.
    Watabe A, Sugawara T, Kikuchi K, Yamasaki K, Sakai S, Aiba S. Sweat constitutes several natural moisturizing factors, lactate, urea, sodium, and potassium. J Dermatol Sci. 2013;72:177–82.CrossRefPubMedGoogle Scholar
  11. 11.
    Rieg S, Steffen H, Seeber S, Humeny A, Kalbacher H, Dietz K, et al. 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. 2005;174:8003–10.CrossRefPubMedGoogle Scholar
  12. 12.
    Sato K, Sato F. Interleukin-1 alpha in human sweat is functionally active and derived from the eccrine sweat gland. Am J Physiol. 1994;266:R 950–9.Google Scholar
  13. 13.
    Jones AP, Webb LM, Anderson AO, Leonard EJ, Rot A. Normal human sweat contains interleukin-8. J Leukoc Biol. 1995;57:434–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Li HH, Zhou G, Fu XB, Zhang L. Antigen expression of human eccrine sweat glands. J Cutan Pathol. 2009;36:318–24.CrossRefPubMedGoogle Scholar
  15. 15.
    Dai X, Okazaki H, Hanakawa Y, Murakami M, Tohyama M, Shirakata Y, et al. Eccrine sweat contains IL-1α, IL-1β and IL-31 and activates epidermal keratinocytes as a danger signal. PLoS One. 2013;8:e67666.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Wenzel FG, Horn TD. Non-neoplastic disorders of the eccrine glands. J Am Acad Dermatol. 1998;38:1–17.CrossRefPubMedGoogle Scholar
  17. 17.
    Shiohara T, Sato Y, Komatsu Y, Ushigome Y, Mizukawa Y. Sweat as an efficient natural moisturizer. Curr Probl Dermatol. 2016;51:30–41.CrossRefPubMedGoogle Scholar
  18. 18.
    Shiohara T, Doi T, Hayakawa J. Defective sweating responses in atopic dermatitis. Curr Probl Dermatol. 2011;41:68–79.CrossRefPubMedGoogle Scholar
  19. 19.
    Ushigome Y, Sato Y, Shimoda Y, et al. Localized hypohidrosis is an unrecognized sequela of herpes zoster. J Am Acad Dermatol. 2017;76:160–2.CrossRefPubMedGoogle Scholar
  20. 20.
    Shimoda-Komatsu Y, Sato Y, Yamazaki Y, et al. Lichen amyloidosis as a sweat gland/duct disorder: resolution associated with restoration of sweating disturbance. Br J Dermatol. 2017;176:1308–15.CrossRefGoogle Scholar
  21. 21.
    Peng Y, Cui X, Liu Y, et al. Systematic review focusing on the excretion and protection roles of sweat in the skin. Dermatology. 2014;228:115–20.CrossRefPubMedGoogle Scholar
  22. 22.
    Biehe-Hulette SJ, Kailler JM, Elstun IT, et al. Thermoregulatory vs. event sweating- comparison of clinical methodologies, physiology and results. Int J Cosmet Sci. 2014;36:102–8.CrossRefGoogle Scholar
  23. 23.
    Sulzberger MB, Herrmann F, Zak FG. Studies of sweating : preliminary report with particular emphasis of a sweat retention syndrome. J Invest Dermatol. 1947;9:221–42.CrossRefPubMedGoogle Scholar
  24. 24.
    Lobitz WC Jr, Campbell CJ. Physiologic studies in atopic dermatitis(disseminated neurodermatitis) I. The local cutaneous response to intradermally injected acetylcholine and epinephrine. Arch Dermatol Syphilol. 1953;67:575–89.CrossRefGoogle Scholar
  25. 25.
    Rovensky J, Saxl O. Differences in dynamics of sweat secretion in atopic children. J Invest Dermatol. 1964;43:171–6.CrossRefPubMedGoogle Scholar
  26. 26.
    Warndorff JA. The response of sweat gland to acetylcholine in atopic subjects. Br J Dermatol. 1970;83:306–11.CrossRefPubMedGoogle Scholar
  27. 27.
    Murphy GM, Smith SE, Smith SA, et al. Autonomic function in cholinergic urticarial and atopic eczema. Br J Dermatol. 1984;110:581–6.CrossRefPubMedGoogle Scholar
  28. 28.
    Kiistala R. Cholinergic and adrenergic sweating in atopic dermatitis. Acta Derm Venereol. 1992;72:106–8.PubMedGoogle Scholar
  29. 29.
    Candas V, Libert JP, Vogt JJ. Human skin wittedness and evaporative efficiency of sweating. J Appl Physiol. 1979;46:522–8.CrossRefPubMedGoogle Scholar
  30. 30.
    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;147:683–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Ahmed AA, Nordlind K, Schultzberg M, Lidén S. Proinflammatory cytokines and their corresponding receptor proteins in eccrine sweat glands in normal and cutaneous leishmaniasis human skin. An immunohistochemical study. Exp Dermatol. 1996;5:230–5.CrossRefPubMedGoogle Scholar
  32. 32.
    Faulkner SH, Spilsbury KL, Harvery J, Jackson A, Huang J, Platt M, et al. 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. 2014;114:1207–16.CrossRefPubMedGoogle Scholar
  33. 33.
    Marques-Deak A, Cizza G, Eskandari F, Torvik S, Christie IC, Sternberg EM, et al. Measurement of cytokines in sweat patches and plasma in healthy women: validation in controlled study. J Immunol Methods. 2006;315:99–109.CrossRefPubMedGoogle Scholar
  34. 34.
    Flores S, Davis MD, Pittelkow MR, Sandroni P, Weaver AL, Fealey RD. Abnormal sweating patterns associated with itching, burning and tingling of the skin indicate possible underlying small-fibre neuropathy. Br J Dermatol. 2015;172:412–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Adachi K, Aoki T. IgE antibody to sweat in atopic dermatitis. Arch Derm Venereol Suppl (Stockh). 1989;144:83–7.Google Scholar
  36. 36.
    Jung K, Schlenvogt G, Ladwig K, et al. The sweat of patients with atopic dermatitis contains specific Ig E antibodies to inhalant allergens. Clin Exp Dermatol. 1996;21:347–50.CrossRefPubMedGoogle Scholar
  37. 37.
    Ilves T, Virolainen A, Harvima IT. Immediate wheal reactivity to autologous sweat in atopic dermatitis is associated with clinical severity, serum total and specific IgE and sweat tryptase activity. Int Arch Allergy Immunol. 2016;170:84–91.CrossRefPubMedGoogle Scholar
  38. 38.
    Hide M, Tanaka T, Yamamura Y, et al. IgE-mediated hypersensitivity against human sweat antigen in patients with atopic dermatitis. Acta Derm Venereol. 2002;82:335–40.CrossRefPubMedGoogle Scholar
  39. 39.
    Hiragun T, Ishii K, Hiragun M, et al. Fungal protein MGL_1304 in sweat is an allergen for atopic dermatitis patients. J Allergy Clin Immunol. 2013;132:608–15.CrossRefPubMedGoogle Scholar
  40. 40.
    Reinikainen LM, Jaakola JJ. The effect of air humidification on symptoms and perception of indoor air quality in office workers: a six-period cross-over trial. Arch Environ Health. 1992;47:8–15.CrossRefPubMedGoogle Scholar
  41. 41.
    Reinikainen LM, Jaakola JJ. Significance of humidity and temperature on skin and upper airway symptoms. Indoor Air. 2003;13:344–52.CrossRefPubMedGoogle Scholar
  42. 42.
    Nilsson L, Bjorksten B, Hattevig G, et al. Season of birth as predictor of atopic manifestations. Arch Dis Child. 1997;76:341–4.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Kusunoki T, Asai K, Harazaki M, et al. Month of birth and prevalence of atopic dermatitis in school children: dry skin in early infancy as a possible etiologic factor. J Allergy Clin Immunol. 1999;103:1148–52.CrossRefPubMedGoogle Scholar
  44. 44.
    Sasaki T, Furusyo N, Shiohama A, Takeuchi S, Nakahara T, Uchi H, et al. Filaggrin loss-of-function mutations are not a predisposing factor for atopic dermatitis in an Ishigaki Island under subtropical climate. J Dermatol Sci. 2014;76:10–5.CrossRefPubMedGoogle Scholar
  45. 45.
    Scholtz J. Management of atopic dermatitis. A preliminary report. Calif Med. 1964;100:103–5.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Gutman A, Kligman A, Sciacca A, et al. Soak and smear. A standard technique revisited. Arch Dermatol. 2005;141:1556–9.CrossRefPubMedGoogle Scholar
  47. 47.
    Chiang C, Eichenfield LF. Quantitative assessment of combination bathing and moisturizing regimens on skin hydration in atopic dermatitis. Pediatr Dermatol. 2009;26:273–8.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Tetsuo Shiohara
    • 1
    Email author
  • Yurie Shimoda-Komatsu
    • 1
  • Yoshiko Mizukawa
    • 1
  • Yuki Hayashida
    • 2
    • 3
  • Yumi Aoyama
    • 2
    • 3
  1. 1.Department of DermatologyKyorin University School of MedicineTokyoJapan
  2. 2.Department of DermatologyKawasaki Medical SchoolKurashikiJapan
  3. 3.Department of DermatologyKawasaki General Medical CenterOkayamaJapan

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