HLH is difficult to diagnose –patients without HLH can meet the established criteria (see links below); and, especially early in the disease, patients with HLH may not meet the established criteria. A study which will help with this difficulty has been published (J Pediatr 2012; 160: 984-90 and summary pg A1). For pediatric gastroenterologists, HLH is important because some of our IBD patients may develop HLH and because some patients presenting with liver disease have HLH.
This study examined 756 consecutive patients with fever in Hematology/Oncology unit of China’s Children’s Hospital of Zhejiang between 2005-2010. Three control groups also were studied: hematology-oncology patients without fever (n=202), healthy children (n=100), and previously-healthy children with bacterial sepsis (n=85).
A highly discriminating cytokine pattern was identified in 71 episodes of HLH.
- Highly elevated IFN-γ : 94% sensitivity, 97% specificity for HLH using a cutoff of 100 pg/mL
- Highly elevated IL-10
- Modestly elevated IL -6
- Combined use of IFN-γ (>75 pg/mL) & IL-10 (>60 pg/mL) had sensitivity of 93% and specificity of 99% for HLH
Using these cytokines may help establish a more rapid diagnosis of HLH and allow institution of critical therapy while avoiding implementation of the wrong treatment in patients who have other conditions. In other studies (see below), there are other useful markers that have been identified.
- -J Pediatr 2011; 159: 808. HLH increased with Crohn’s Rx. If fever >5days, can screen for HLH with ferritin (>500mcg/L) & lymphopenia. Need to discontinue immunosuppression. 100-fold increase risk of HLH. Diagnostic criteria for HLH pg 809. Newer criteria: molecular, low/absent NK activity & soluble CD-25 (ie. soluble IL-2 receptor) >2400 U/mL.
- Hemophagocytic Syndrome Link with powerpoint case presentation including diagnostic criteria for primary and secondary HLH.
- Hemophagocytic lymphohistiocytosis (HLH) and related disorders Link with review article by leader in field (A Filipovich, 2009).
- -J Peds 2006; 149: 134-7. Aftrican-american infants c HLH often have a specific defect in perforin gene -50delT-PRF1
- -NEJM 2004; 351: 1120. case of twins c FELS. Impaired NK cell activity is key with absence of NK intracytoplasmic perforin in 20-40%.
- -JPGN 2002; 34: 3A (pg 433.) Liver failure with HLH. mortality 84%, n=25.