Association of Crohn's disease, thiopurines, and primary epstein-barr virus infection with hemophagocytic lymphohistiocytosis

J Pediatr. 2011 Nov;159(5):808-12. doi: 10.1016/j.jpeds.2011.04.045. Epub 2011 Jun 30.


Objective: To assess the incidence of hemophagocytic lymphohistiocytosis (HLH) in a well-defined population of children with inflammatory bowel disease (IBD) and evaluate the common clinical and laboratory characteristics of individuals with IBD who developed HLH.

Study design: We conducted a retrospective study of all children who developed HLH over an 8-year period. The incidence of HLH in patients with IBD was calculated using US census data and a statewide project examining the epidemiology of pediatric IBD.

Results: Among children in Wisconsin, 20 cases of HLH occurred during the study period; 5 cases occurred in children with IBD. Common characteristics include: Crohn's disease (CD), thiopurine administration, fever lasting more than 5 days, lymphadenopathy, splenomegaly, anemia, lymphopenia, and elevated serum triglycerides and ferritin. Of the patients, 4 had primary Epstein-Barr virus infections. The incidence of HLH among all children in Wisconsin was 1.5 per 100 000 per year. The risk was more than 100-fold greater for children with CD (P < .00001).

Conclusions: Pediatric patients with CD are at increased risk for developing HLH; primary Epstein-Barr virus infection and thiopurine administration may be risk factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anemia / complications
  • Azathioprine / therapeutic use
  • Crohn Disease / complications*
  • Crohn Disease / drug therapy
  • Crohn Disease / epidemiology
  • Epstein-Barr Virus Infections / complications*
  • Ferritins / blood
  • Fever / complications
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Incidence
  • Lymphatic Diseases / complications
  • Lymphohistiocytosis, Hemophagocytic / complications*
  • Lymphopenia / complications
  • Mercaptopurine / therapeutic use
  • Retrospective Studies
  • Splenomegaly / complications
  • Triglycerides / blood
  • Wisconsin / epidemiology


  • Immunosuppressive Agents
  • Triglycerides
  • Ferritins
  • Mercaptopurine
  • Azathioprine