No evidence of increased cancer incidence in children using topical tacrolimus for atopic dermatitis

J Am Acad Dermatol. 2020 Aug;83(2):375-381. doi: 10.1016/j.jaad.2020.03.075. Epub 2020 Apr 1.


Background: Long-term safety of topical calcineurin inhibitors is not well understood. APPLES (A Prospective Pediatric Longitudinal Evaluation to Assess the Long-Term Safety of Tacrolimus Ointment for the Treatment of Atopic Dermatitis; NCT00475605) examined incidence of lymphoma and other cancers in a pediatric population with atopic dermatitis.

Objective: To quantify incident malignancies during 10 years in children with atopic dermatitis who used topical tacrolimus for ≥6 weeks.

Methods: Standardized incidence ratios for cancer events were analyzed relative to sex-, age-, and race-matched control data from national cancer registries.

Results: There were 7954 eligible patients enrolled at 314 sites in 9 countries. During 44,629 person-years, 6 confirmed incident cancers occurred (standardized incidence ratio, 1.01; 95% confidence interval, 0.37-2.20). No lymphomas occurred.

Limitations: Observational prospective cohort study.

Conclusion: The cancer incidence was as expected, given matched background data. This finding provides no support for the hypothesis that topical tacrolimus increases long-term cancer risk in children with atopic dermatitis.

Keywords: atopic dermatitis; cancer risk; lymphoma; skin cancer; tacrolimus; topical calcineurin inhibitors.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Administration, Topical
  • Adolescent
  • Age Factors
  • Calcineurin Inhibitors / administration & dosage
  • Calcineurin Inhibitors / adverse effects*
  • Child
  • Child, Preschool
  • Dermatitis, Atopic / drug therapy*
  • Female
  • Humans
  • Incidence
  • Infant
  • Longitudinal Studies
  • Male
  • Neoplasms / chemically induced
  • Neoplasms / epidemiology*
  • Prospective Studies
  • Registries / statistics & numerical data
  • Risk Assessment / statistics & numerical data
  • Risk Factors
  • Sex Factors
  • Tacrolimus / administration & dosage
  • Tacrolimus / adverse effects*


  • Calcineurin Inhibitors
  • Tacrolimus