The Impact of Azathioprine-Associated Lymphopenia on the Onset of Opportunistic Infections in Patients with Inflammatory Bowel Disease

PLoS One. 2016 May 23;11(5):e0155218. doi: 10.1371/journal.pone.0155218. eCollection 2016.


Background: Thiopurines are known to cause lymphopenia (<1,500 lymphocytes/μl). As severe lymphopenia (<500C/μl) is associated with opportunistic infections, we investigated severity of thiopurine-related lymphopenia and development of opportunistic infections in our tertiary referral centre.

Methods: We retrospectively screened medical records of 1,070 IBD patients and identified 100 individuals that developed a total of 161 episodes of lymphopenia during thiopurine treatment between 2002 and 2014. Occurrence of opportunistic infections was documented. A control group consisted of IBD patients receiving thiopurines but without developing lymphopenia.

Results: Of a total of 161 episodes of lymphopenia, 23% were severe (<500C/μl). In this subgroup, thiopurine dosing was modified in 64% (dosage reduction: 32%, medication discontinued: 32%). We identified 9 cases (5.5%) of opportunistic infections, of which only two occurred during severe lymphopenia. One opportunistic infection (4.5%) was identified in the control group. No association was found between opportunistic infections and severity of lymphopenia. All patients who suffered from opportunistic infections were receiving additional immunosuppressive medication.

Conclusion: Our patients treated with thiopurines rarely developed severe lymphopenia and opportunistic infections did not occur more often than in the control group. A careful monitoring of lymphocytes and prophylactic adjustment of thiopurine therapy might contribute to this low incidence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Azathioprine / adverse effects*
  • Azathioprine / therapeutic use
  • Case-Control Studies
  • Child
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Incidence
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / epidemiology*
  • Lymphopenia / chemically induced*
  • Lymphopenia / epidemiology*
  • Male
  • Middle Aged
  • Opportunistic Infections / chemically induced
  • Opportunistic Infections / epidemiology*
  • Retrospective Studies
  • Risk Factors
  • Young Adult


  • Immunosuppressive Agents
  • Azathioprine

Grant support

This research was supported by research grants from the Swiss National Science Foundation to MS (Grant No. 314730-146204 and Grant No. CRSII3 154488/1) and to GR: the Swiss IBD Cohort Study (Grant No. 3347CO-108792).