title: Topical calcineurin inhibitors in eczema and cancer association: A cohort study.
abstract: BACKGROUND
  Cancer risk associated with topical calcineurin inhibitors (TCIs) remains unclear.
  
  
  OBJECTIVE
  To evaluate the association between TCIs and cancer among patients with atopic and endogenous eczema.
  
  
  METHODS
  Incident cancers were identified from the National Cancer Registry. Data were analyzed using the Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals.
  
  
  RESULTS
  880 unique cases of cancer developed in 66 176 patients from 2004 to 2012. The adjusted HRs for overall malignancy were 0.82 (95%CI 0.44-1.39) for tacrolimus-exposed and 1.30 (95%CI 0.59-2.45) for pimecrolimus-exposed. The only significant cancer association observed was lymphoid leukemia among the tacrolimus-exposed: HR 7.58 (95%CI 1.64-25.8). All affected patients had young-onset B-cell leukemia. Subgroup analysis of pediatric patients (≤16 years) showed significant association between tacrolimus use and B-cell leukemia: HR 26.4 (95%CI 4.77-146).
  
  
  CONCLUSIONS
  In this first Asian study on the risk of TCIs and malignancies, we do not find an association between use of tacrolimus and pimecrolimus in atopic and endogenous eczema and the overall development of malignancies. However, the use of topical tacrolimus was found to be associated with the development of B-cell acute lymphoid leukemia in pediatric eczema patients; further studies are required to investigate if a true association indeed occurs.
authors.affiliation: a National Skin Centre , Singapore.
authors.forename: S C S
authors.initials: SC
authors.lastname: Cai
authors.affiliation: b Centre for Quantitative Medicine, Duke-NUS Graduate Medical School , Singapore.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.affiliation: a National Skin Centre , Singapore.
authors.forename: E A L
authors.initials: EA
authors.lastname: Tian
authors.affiliation: b Centre for Quantitative Medicine, Duke-NUS Graduate Medical School , Singapore.
authors.forename: J C
authors.initials: JC
authors.lastname: Allen
authors.affiliation: a National Skin Centre , Singapore.|c Lee Kong Chian School of Medicine , Singapore.
authors.forename: H L
authors.initials: HL
authors.lastname: Tey
mesh_terms: D000287:Administration, Topical; D044466:Asian People; D065095:Calcineurin Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D015331:Cohort Studies; D004485:Eczema / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D009369:Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000139:chemically induced / Q000453:epidemiology*; D012306:Risk; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; C117268:pimecrolimus; D016559:Tacrolimus
keywords: Tacrolimus; adverse; atopic; malignancy; pimecrolimus