Risk of skin cancers in thiopurines-treated and thiopurines-untreated patients with inflammatory bowel disease: A systematic review and meta-analysis

J Gastroenterol Hepatol. 2019 Mar;34(3):507-516. doi: 10.1111/jgh.14533. Epub 2018 Nov 22.


Background and aim: The thiopurines are effective in the management of patients with inflammatory bowel disease (IBD), but the association between thiopurines use and the risk of skin cancer (including nonmelanoma skin cancer [NMSC] and melanoma skin cancer) has already been sufficiently reported. However, the results of these studies are inconsistent, and thus, the objective of our analysis was to explore whether thiopurines can lead to an excess risk of skin cancer in IBD patients.

Methods: MEDLINE, EMBASE, and the Cochrane Library were searched to identify relevant studies that evaluated the risk of skin cancer in IBD patients treated with thiopurines. A random effects meta-analysis was conducted to calculate the pooled incidence rate ratios as well as risk ratios (RRs). Subgroup analysis was performed to explore the potential source of heterogeneity.

Results: Thirteen studies comprising 149 198 participants were included. The result suggested that thiopurines significantly increased the risk of overall skin cancer in IBD patients (random effects: RR = 1.80, 95% confidence interval [CI] 1.14-2.87, P = 0.013), among which NMSC showed an excess risk associated with thiopurines use (random effects: RR = 1.88, 95% CI 1.48-2.38, P < 0.001) while no increased risk was observed with respect to melanoma skin cancer (random effects: RR = 1.22, 95% CI 0.90-1.65, P = 0.206). Subgroup analysis regarding sample size and geographic distribution in skin cancer and follow-up duration in NMSC reached statistical significance, while other subgroups showed no significance.

Conclusion: Exposition of thiopurines in patients with IBD is associated with a higher risk of skin cancer. Routine skin screening and daily skin protective practice are recommended for these patients.

Keywords: immunosuppressant; inflammatory bowel disease; melanoma skin cancer; nonmelanoma skin cancer; skin cancer; thiopurines.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Azathioprine / adverse effects*
  • Azathioprine / therapeutic use
  • Databases, Bibliographic
  • Humans
  • Inflammatory Bowel Diseases / complications
  • Inflammatory Bowel Diseases / drug therapy*
  • Melanoma / etiology*
  • Melanoma / prevention & control
  • Mercaptopurine / adverse effects*
  • Mercaptopurine / therapeutic use
  • Risk
  • Skin Neoplasms / etiology*
  • Skin Neoplasms / prevention & control


  • Mercaptopurine
  • Azathioprine