Elsevier

The Journal of Pediatrics

Volume 159, Issue 5, November 2011, Pages 808-812
The Journal of Pediatrics

Original Article
Association of Crohn’s Disease, Thiopurines, and Primary Epstein-Barr Virus Infection with Hemophagocytic Lymphohistiocytosis

https://doi.org/10.1016/j.jpeds.2011.04.045Get rights and content

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.

Section snippets

Methods

We conducted a retrospective chart review of all individuals with IBD who developed HLH at Children’s Hospital of Wisconsin between January 2000 and June 2008. Cases of HLH were identified through a database maintained by the Children’s Hospital of Wisconsin Hematology/Oncology and Bone Marrow Transplant Department. Patients with HLH and a diagnosis of IBD were extracted for analysis.

The data extracted included patients’ demographics, presenting symptoms, medical and surgical records,

Results

Between January 2000 and June 2008, 20 cases of HLH were identified and 5 of those patients had IBD. According to the 2005-2007 US Census Bureau data, the Wisconsin population was 5.5 million persons, and 24% were younger than 19 years of age (1.3 million).19 Based on these figures, the overall incidence rate was 1.5 cases of HLH per 100 000 children. In the multicenter IBD epidemiology project, 992 children were documented to have IBD, and 5 cases of HLH occurred in this population.18 The

Discussion

The incidence of HLH treated at our institution appears to be similar to that reported in the general population, which ranges from 1 in 50 000 to 12 in 1 000 000.2, 7, 15, 22 The results in our pediatric population experiencing IBD suggests that there is more than a 100-fold greater risk for their developing HLH than exists in the general population. Possible explanations for this discrepancy are that the data assume that all pediatric patients diagnosed with IBD were included in our

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    Supported by NIH/NIGMS (5K08GM077395 to M. Stephens). M. Stephens has received research grants from the Centocor Inc, Abbott Laboratories, and Schwartz Biosciences. All other authors declare no conflicts of interest.

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