Hemophagocytic Lymphohistiocytosis Occurring in Inflammatory Bowel Disease: Systematic Review

Hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive syndrome of excessive cytokine requiring prompt recognition and aggressive therapy.

We aimed to systematically characterize HLH in moderate-to-severe inflammatory bowel disease (IBD).

We performed a systematic review of the literature (PubMED; EMBASE) and FDA Adverse Event Reporting System in accordance with the PRISMA statement. Use of biologics was used as a surrogate definition for disease severity (consistent with usual and contemporary clinical management), to enable identification of rare HLH cases with the highest fidelity.

58 cases of HLH occurring in IBD patients are known (mean age: 26.0 years, 70% male, 83% with Crohn's disease, mean disease duration 7.0 years). 34.5% of patients were undergoing induction therapy at HLH diagnosis. All cases occurred on patients exposed to anti-TNF agents, but cases with anti-integrin or anti-IL-12/23 exposure were reported. 2/3 of cases did not report prior AZA/6MP exposure. Underlying opportunistic infection or lymphoma was found in > 80% of cases. Survival was 70% if promptly recognized and treated. Five patients restarted biologics after HLH resolved, and one patient developed recurrent HLH.

HLH is rare among IBD patients exposed to biologic therapy. Most cases had an identifiable infection or malignancy at the time of diagnosis as well as history of immunomodulator use. Risk factors may include younger age, male gender, presence of Crohn's disease, and induction phase of treatment. Our study is not intended to assess risk of HLH with specific IBD therapies.