Clinics in Dermatology
Volume 28, Issue 1 , Pages 52-56 , January 2010

Malignancy concerns of topical calcineurin inhibitors for atopic dermatitis: facts and controversies

References 

  1. Chairman CR, Williams HC. Epidemiology. In:  Bieber T,  Leung D editor. Atopic dermatitis. New York: Marcel Dekker Inc; 2002;p. 21–42
  2. Hinz T, Staudacher A, Bieber T. Neues in der Pathophysiologie der atopischen Dermatitis. Hautarzt. 2006;7:567–575
  3. Fivenson D, Arnold RJ, Kaniecki DJ, Cohen JL, Frech F, Finlay AY. The effect of atopic dermatitis on total burden of illness and quality of life on adults and children in a large managed care organization. J Manag Care Pharm. 2002;8:333–342
  4. Bieber T, Cork M, Ellis C, et al. Consensus statement on the safety profile of topical calcineurin inhibitors. Dermatology. 2005;211:77–78
  5. Novartis and Fujisawa. FDA briefing statements. Pediatric Advisory Committee Meeting of the US Food and Drug Administration. Washington DC, 2005.
  6. Wang H, Diepgen TL. Atopic dermatitis and cancer risk. Br J Dermatol. 2006;154:205–210
  7. Ming ME, Levy R, Hoffstad O, et al. The lack of a relationship between atopic dermatitis and nonmelanoma skin cancers. J Am Acad Dermatol. 2004;50:357–362
  8. Sørensen HT, Mellemkjaer L, Nielsen GL, et al. Skin cancers and non-Hodgkin lymphoma among users of systemic glucocorticoids: a population-based cohort study. J Natl Cancer Inst. 2004;96:709–711
  9. Hagstroemer L, Ye W, Nyren O, et al. Incidence of cancer among patients with atopic dermatitis. Arch Dermatol. 2005;141:1123–1127
  10. Yarosh DB, Pena AV, Nay SL, et al. Calcineurin inhibitors decrease DNA repair and apoptosis in human keratinocytes following ultraviolet B irradiation. J Invest Dermatol. 2005;125:1020–1025
  11. Hultsch T, Kapp A, Spergel J. Immunomodulation and safety of topical calcineurin inhibitors for the treatment of atopic dermatitis. Dermatology. 2005;211:174–187
  12. Bos JD. Non-steroidal topical immunomodulators provide skin-selective, self-limiting treatment in atopic dermatitis. Eur J Dermatol. 2003;13:455–461
  13. Van Leent EJ, Ebelin ME, Burtin P, et al. Low systemic exposure after repeated topical application of pimecrolimus (Elidel, SDZ ASM 981) in patients with atopic dermatitis. Dermatology. 2002;204:63–68
  14. Paul C, Cork M, Rossi AB, et al. Safety and tolerability of 1% pimecrolimus cream among infants: experience with 1133 patients treated for up to 2 years. Pediatrics. 2006;117:e118–e128
  15. Patel RR, Vander Straten MR, Korman NJ. The safety and efficacy of tacrolimus therapy in patients younger than 2 years with atopic dermatitis. Arch Dermatol. 2003;139:1184–1186
  16. Alaiti S, Kang S, Fiedler VC, et al. Tacrolimus (FK506) ointment for atopic dermatitis: a phase I study in adults and children. J Am Acad Dermatol. 1998;38:69–76
  17. Harper J, Smith C, Rubins A, et al. A multicenter study of the pharmacokinetics of tacrolimus ointment after first and repeated application to children with atopic dermatitis. J Invest Dermatol. 2005;124:695–699
  18. Rubins A, Gutmane R, Valdmane N, et al. Pharmacokinetics of 0,1% tacrolimus ointment after first and repeated application to adults with moderate to severe atopic dermatitis. J Invest Dermatol. 2005;125:68–71
  19. Eichenfield LF, Thaçi D, de Prost Y, et al. Clinical management of atopic eczema with pimecrolimus cream 1% (Elidel) in paediatric patients. Dermatology. 2007;215(Suppl 1):3–17
  20. Thaçi D, Steinmeyer K, Ebelin ME, et al. Occlusive treatment of chronic hand dermatitis with pimecrolimus cream 1% results in low systemic exposure, is well tolerated, safe, and effective. An open study. Dermatology. 2003;207:37–42
  21. Spergel JM, Leung DY. Safety of topical calcineurin inhibitors in atopic dermatitis: evaluation of the evidence. Curr Allergy Asthma Rep. 2006;6:270–274
  22. Ormerod AD. Topical tacrolimus and pimecrolimus and the risk of cancer: how much cause for concern?. Br J Dermatol. 2005;153:701–705
  23. Arellano FM, Wentworth CE, Arana A, et al. Risk of lymphoma following exposure to calcineurin inhibitors and topical steroids in patients with atopic dermatitis. J Invest Dermatol. 2007;127:808–816
  24. Söderberg KC, Hagmar L, Schwarztbaum J, et al. Allergic conditions and risk of haematological malignancies in adults: a cohort study. BMC Public Health. 2004;4:51
  25. Zhang Y, Holford TR, Leaderer B, et al. Prior medical conditions and medication use and risk of non-Hodgkin lymphoma in Connecticut United States women. Cancer Causes Control. 2004;15:419–428
  26. Berger TG, Duvic M, Van Voorhees AS, et al. The use of topical calcineurin inhibitors in dermatology: safety concerns. J Am Acad Dermatol. 2006;54:818–823
  27. Margolis DJ, Hoffstad O, Bilker W. Lack of association between exposure to topical calcineurin inhibitors and skin cancer in adults. Dermatology. 2007;214:289–295
  28. Lerche CM, Philipsen PA, Poulsen T, et al. Topical tacrolimus in combination with stimulated solar radiation does not enhance photocarcinogenesis in hairless mice. Exp Dermatol. 2008;17:57–62
  29. Beck LA. The efficacy and safety of tacrolimus ointment: a clinical review. J Am Acad Dermatol. 2005;53:S165–S170
  30. Becker JC, Houben R, Vetter CS, et al. The carcinogenic potential of tacrolimus ointment beyond immune suppression: a hypothesis creating case report. BMC Cancer. 2006;6:7
  31. Ring J, Möhrenschlager M, Henkel V. The US FDA “black box” warning for topical calcineurin inhibitors: an ongoing controversy. Drug Saf. 2008;31:185–198
  32. Patel TS, Greer SC, Skinner RB. Cancer concerns with topical immunomodulators in atopic dermatitis: overview of data and recommendations to clinicians. Am J Clin Dermatol. 2007;8:189–194
  33. Luger TA, Gollnick H. Viewpoint of the German Dermatologic Society (DDG) concerning the decision of the American Food and Drug Administration (FDA) on the use of pimecrolimus cream and tacrolimus ointment in the treatment of atopic dermatitis (neurodermatitis). J Dtsch Dermatol Ges. 2005;3:415–416
  34. Fonacier L, Charlesworth EN, Spergel JM, Leung DY. The black box warning for topical calcineurin inhibitors: looking outside the box. Ann Allergy Asthma Immunol. 2006;97:117–120
  35. Thaçi D, Reitamo S, Gonzalez Ensenat MA, et al. Proactive disease management with 0.03% tacrolimus ointment for children with atopic dermatitis: results of a randomized, multicentre, comparative study. Br J Dermatol. 2008;159:1348–1356
  36. Qureshi AA, Fischer MA. Topical calcineurin inhibitors for atopic dermatitis: balancing clinical benefit and possible risk. Arch Dermatol. 2006;142:633–671

PII: S0738-081X(09)00087-X

doi: 10.1016/j.clindermatol.2009.04.001

Clinics in Dermatology
Volume 28, Issue 1 , Pages 52-56 , January 2010