Ann Dermatol.  2012 May;24(2):144-150.

A Randomized, Open-Label, Multicenter Trial of Topical Tacrolimus for the Treatment of Pruritis in Patients with Atopic Dermatitis

  • 1Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • 2Department of Dermatology, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Japan.
  • 3Department of Medical Informatics, Kyushu University Hospital, Fukuoka, Japan.
  • 4Department of Dermatology, Social Insurance Chuo General Hospital, Shinjuku-ku, Japan.
  • 5Department of Dermatology, Saitama Medical University, Iruma-gun, Japan.
  • 6Department of Dermatology, St. Marianna University School of Medicine, Kawasaki, Japan.
  • 7Department of Dermatology, Hiroshima University, Hiroshima, Japan.
  • 8Division of Dermatology, Department of Medicine, National Center for Child Health and Development, Setagaya-ku, Japan.
  • 9Division of Allergy, Department of Medicine, National Center for Child Health and Development, Setagaya-ku, Japan.


Pruritis caused by atopic dermatitis (AD) is not always well controlled by topical corticosteroid therapy, but use of tacrolimus often helps to soothe such intractable pruritis in clinical settings.
To determine the anti-pruritic efficacy of topical tacrolimus in treating AD in induction and maintenance therapy.
Prior to the study, patients were randomly allocated into two groups, induction therapy followed by tacrolimus monotherapy maintenance, and induction therapy followed by emollient-only maintenance. In the induction therapy, the patients were allowed to use topical tacrolimus and emollients in addition to a low dose (<10 g/week) of topical steroids. Patients showing relief from pruritis were allowed to proceed to maintenance therapy. Recurrence of pruritis in maintenance therapy was examined as a major endpoint.
Two-thirds of patients (44/68; 64.7%) showed relief from pruritis after induction therapy. Pruritis recurred in 23.8% (5/21) of the tacrolimus monotherapy group and in 100% (21/21) of the emollient group during maintenance period, a difference that was statistically significant.
Use of topical tacrolimus is effective in controlling pruritis of AD compared to emollient.


Atopic dermatitis; Maintenance therapy; Pruritis; Randomized trial; Tacrolimus

MeSH Terms

Dermatitis, Atopic


  • Fig. 1 Flow diagram showing subjects' progress. Patients were advance-allocated after registration, received introduction therapy (add-on tacrolimus therapy), and the responders to the introduction therapy proceeded into maintenance therapy. There were several dropouts and one refusal during the study. VAS: visual analogue scale.

  • Fig. 2 Change in visual analogue scale (VAS)-itch score and disease severity after add-on tacrolimus therapy. (A) Pruritis (mean VAS-itch score - standard deviation) reduced after add-on topical tacrolimus therapy. (B) There was no statistical difference in mean VAS-itch score between responders and non-responders before the add-on therapy. (C) There was a significant decrease in VAS-itch score in responders after the add-on therapy. (D) SCORing Atopic Dermatitis (SCORAD) score reduced after the add-on topical tacrolimus therapy.

  • Fig. 3 Cumulative recurrence of pruritis in maintenance therapy. Tacrolimus monotherapy group (solid line) showed significantly much lower recurrence of pruritis compared to that of the emollient group (dotted line).

  • Fig. 4 Efficacy of tacrolimus monotherapy in maintenance therapy. The emollient group showed more pruritis than the tacrolimus monotherapy group at the end of maintenance therapy. VAS: visual analogue scale.

  • Fig. 5 Change of SCORing Atopic Dermatitis (SCORAD) in induction therapy between treatment-responding (blue circle) and non-responding patients (red circle) in induction therapy. Forty-three treatment-responding patients showed significantly reduced SCORAD compared to that of 7 non-responding patients in induction therapy as assessed by analysis of covariance (p=0.001).


1. Takeuchi M, Ueda H. Increase of adult atopic dermatitis (AD) in recent Japan. Environ Dermatol. 2000. 7:133–136.
2. Yamamoto S. Prevalence and exacerbation factors of atopic dermatitis. Skin Allergy Frontier. 2003. 1:85–90.
3. Ikoma A, Steinhoff M, Ständer S, Yosipovitch G, Schmelz M. The neurobiology of itch. Nat Rev Neurosci. 2006. 7:535–547.
4. Rossi R, Johansson O. Cutaneous innervation and the role of neuronal peptides in cutaneous inflammation: a minireview. Eur J Dermatol. 1998. 8:299–306.
5. Ständer S, Steinhoff M, Schmelz M, Weisshaar E, Metze D, Luger T. Neurophysiology of pruritus: cutaneous elicitation of itch. Arch Dermatol. 2003. 139:1463–1470.
6. Furue M, Terao H, Rikihisa W, Urabe K, Kinukawa N, Nose Y, et al. Clinical dose and adverse effects of topical steroids in daily management of atopic dermatitis. Br J Dermatol. 2003. 148:128–133.
7. Wahlgren CF. Itch and atopic dermatitis: clinical and experimental studies. Acta Derm Venereol Suppl (Stockh). 1991. 165:1–53.
8. Boguniewicz M, Fiedler VC, Raimer S, Lawrence ID, Leung DY, Hanifin JM. Pediatric Tacrolimus Study Group. A randomized, vehicle-controlled trial of tacrolimus ointment for treatment of atopic dermatitis in children. J Allergy Clin Immunol. 1998. 102:637–644.
9. Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology. 1993. 186:23–31.
10. Furue M, Terao H, Moroi Y, Koga T, Kubota Y, Nakayama J, et al. Dosage and adverse effects of topical tacrolimus and steroids in daily management of atopic dermatitis. J Dermatol. 2004. 31:277–283.
11. Fleischer AB Jr, Ling M, Eichenfield L, Satoi Y, Jaracz E, Rico MJ, et al. Tacrolimus ointment for the treatment of atopic dermatitis is not associated with an increase in cutaneous infections. J Am Acad Dermatol. 2002. 47:562–570.
12. Rivard J, Lim HW. Ultraviolet phototherapy for pruritus. Dermatol Ther. 2005. 18:344–354.
13. Chuang TY, Heinrich LA, Schultz MD, Reizner GT, Kumm RC, Cripps DJ. PUVA and skin cancer. A historical cohort study on 492 patients. J Am Acad Dermatol. 1992. 26:173–177.
14. Hon KL, Lam MC, Leung TF, Chow CM, Wong E, Leung AK. Assessing itch in children with atopic dermatitis treated with tacrolimus: objective versus subjective assessment. Adv Ther. 2007. 24:23–28.
15. Reitamo S, Rustin M, Ruzicka T, Cambazard F, Kalimo K, Friedmann PS, et al. European Tacrolimus Ointment Study Group. Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone butyrate ointment in adult patients with atopic dermatitis. J Allergy Clin Immunol. 2002. 109:547–555.
16. Japanese FK-506 Ointment Study Group. Phase III study of FK-506 (Tacrolimus) ointment in patients with atopic dermatitis -Comparison study with 0.12% betamethasone valerate ointment for trunk and extremities lesions-. Nishinihon J Dermatol. 1997. 59:870–879. (article in Japanese).
17. Inagaki N, Shiraishi N, Igeta K, Itoh T, Chikumoto T, Nagao M, et al. Inhibition of scratching behavior associated with allergic dermatitis in mice by tacrolimus, but not by dexamethasone. Eur J Pharmacol. 2006. 546:189–196.
18. Inagaki N, Shiraishi N, Igeta K, Nagao M, Kim JF, Chikumoto T, et al. Depletion of substance P, a mechanism for inhibition of mouse scratching behavior by tacrolimus. Eur J Pharmacol. 2010. 626:283–289.
19. Inoue T, Katoh N, Kishimoto S. Prolonged topical application of tacrolimus inhibits immediate hypersensitivity reactions by reducing degranulation of mast cells. Acta Derm Venereol. 2006. 86:13–16.
20. Kido M, Takeuchi S, Esaki H, Hayashida S, Furue M. Scratching behavior does not necessarily correlate with epidermal nerve fiber sprouting or inflammatory cell infiltration. J Dermatol Sci. 2010. 58:130–135.
21. Takeuchi S, Yasukawa F, Furue M, Katz SI. Collared mice: a model to assess the effects of scratching. J Dermatol Sci. 2010. 57:44–50.
Full Text Links
  • AD
export Copy
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: